|
1
|
Horowitz T, Doyen M, Caminiti SP, Yakushev I, Verger A, Guedj E. Metabolic Brain PET Connectivity. PET Clin 2025; 20:1-10. [PMID: 39482220 DOI: 10.1016/j.cpet.2024.09.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2024]
Abstract
This review examines the role of metabolic connectivity based on fluorodeoxyglucose-PET in understanding brain network organization across neurologic disorders, with a focus on neurodegenerative diseases. The article explores key methodologies for metabolic connectivity study and highlights altered connectivity patterns in Alzheimer's, Parkinson's, frontotemporal dementia, and other conditions. It also discusses emerging applications, including single-subject analyses and brain-organ interactions.
Collapse
Affiliation(s)
- Tatiana Horowitz
- Aix Marseille Univ, Marseille, France; CERIMED, CNRS, Centrale Marseille, Institut Fresnel, Marseille, France; Nuclear Medicine Department, AP-HM, Timone Hospital, Marseille, France.
| | - Matthieu Doyen
- University of Lorraine, IADI, INSERM U1254, Nancy, France
| | | | - Igor Yakushev
- Department of Nuclear Medicine, School of Medicine, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany
| | - Antoine Verger
- Department of Nuclear Medicine and Nancyclotep Imaging Platform, Université de Lorraine, CHRU Nancy, Nancy, France
| | - Eric Guedj
- Aix Marseille Univ, Marseille, France; CERIMED, CNRS, Centrale Marseille, Institut Fresnel, Marseille, France; Nuclear Medicine Department, AP-HM, Timone Hospital, Marseille, France
| |
Collapse
|
|
2
|
Power SK, Venkatesan S, Qu S, McLaurin J, Lambe EK. Enhanced prefrontal nicotinic signaling as evidence of active compensation in Alzheimer's disease models. Transl Neurodegener 2024; 13:58. [PMID: 39623428 PMCID: PMC11613856 DOI: 10.1186/s40035-024-00452-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2023] [Accepted: 08/22/2024] [Indexed: 12/06/2024] Open
Abstract
BACKGROUND Cognitive reserve allows for resilience to neuropathology, potentially through active compensation. Here, we examine ex vivo electrophysiological evidence for active compensation in Alzheimer's disease (AD) focusing on the cholinergic innervation of layer 6 in prefrontal cortex. Cholinergic pathways are vulnerable to neuropathology in AD and its preclinical models, and their modulation of deep layer prefrontal cortex is essential for attention and executive function. METHODS We functionally interrogated cholinergic modulation of prefrontal layer 6 pyramidal neurons in two preclinical models: a compound transgenic AD mouse model that permits optogenetically-triggered release of endogenous acetylcholine and a transgenic AD rat model that closely recapitulates the human trajectory of AD. We then tested the impact of therapeutic interventions to further amplify the compensated responses and preserve the typical kinetic profile of cholinergic signaling. RESULTS In two AD models, we found potentially compensatory upregulation of functional cholinergic responses above non-transgenic controls after onset of pathology. To identify the locus of this enhanced cholinergic signal, we dissected key pre- and post-synaptic components with pharmacological strategies. We identified a significant and selective increase in post-synaptic nicotinic receptor signalling on prefrontal cortical neurons. To probe the additional impact of therapeutic intervention on the adapted circuit, we tested cholinergic and nicotinic-selective pro-cognitive treatments. Inhibition of acetylcholinesterase further enhanced endogenous cholinergic responses but greatly distorted their kinetics. Positive allosteric modulation of nicotinic receptors, by contrast, enhanced endogenous cholinergic responses and retained their rapid kinetics. CONCLUSIONS We demonstrate that functional nicotinic upregulation occurs within the prefrontal cortex in two AD models. Promisingly, this nicotinic signal can be further enhanced while preserving its rapid kinetic signature. Taken together, our work suggests that compensatory mechanisms are active within the prefrontal cortex that can be harnessed by nicotinic receptor positive allosteric modulation, highlighting a new direction for cognitive treatment in AD neuropathology.
Collapse
Affiliation(s)
- Saige K Power
- Department of Physiology, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, M5S 1A8, Canada
| | - Sridevi Venkatesan
- Department of Physiology, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, M5S 1A8, Canada
| | - Sarah Qu
- Department of Physiology, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, M5S 1A8, Canada
| | - JoAnne McLaurin
- Department of Laboratory Medicine and Pathobiology, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, M5S 1A8, Canada
- Biological Sciences, Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute, Toronto, ON, M4N 3M5, Canada
| | - Evelyn K Lambe
- Department of Physiology, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, M5S 1A8, Canada.
- Department of Obstetrics and Gynaecology, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, M5G 1E2, Canada.
- Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, M5T 1R8, Canada.
| |
Collapse
|
|
3
|
Bartos LM, Kunte ST, Wagner S, Beumers P, Schaefer R, Zatcepin A, Li Y, Griessl M, Hoermann L, Wind-Mark K, Bartenstein P, Tahirovic S, Ziegler S, Brendel M, Gnörich J. Astroglial glucose uptake determines brain FDG-PET alterations and metabolic connectivity during healthy aging in mice. Neuroimage 2024; 300:120860. [PMID: 39332748 DOI: 10.1016/j.neuroimage.2024.120860] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2024] [Revised: 08/24/2024] [Accepted: 09/18/2024] [Indexed: 09/29/2024] Open
Abstract
PURPOSE 2-Fluorodeoxyglucose-PET (FDG-PET) is a powerful tool to study glucose metabolism in mammalian brains, but cellular sources of glucose uptake and metabolic connectivity during aging are not yet understood. METHODS Healthy wild-type mice of both sexes (2-21 months of age) received FDG-PET and cell sorting after in vivo tracer injection (scRadiotracing). FDG uptake per cell was quantified in isolated microglia, astrocytes and neurons. Cerebral FDG uptake and metabolic connectivity were determined by PET. A subset of mice received measurement of blood glucose levels to study associations with cellular FDG uptake during aging. RESULTS Cerebral FDG-PET signals in healthy mice increased linearly with age. Cellular FDG uptake of neurons increased between 2 and 12 months of age, followed by a strong decrease towards late ages. Contrarily, FDG uptake in microglia and astrocytes exhibited a U-shaped function with respect to age, comprising the predominant cellular source of higher cerebral FDG uptake in the later stages. Metabolic connectivity was closely associated with the ratio of glucose uptake in astroglial cells relative to neurons. Cellular FDG uptake was not associated with blood glucose levels and increasing FDG brain uptake as a function of age was still observed after adjusting for blood glucose levels. CONCLUSION Trajectories of astroglial glucose uptake drive brain FDG-PET alterations and metabolic connectivity during aging.
Collapse
Affiliation(s)
- Laura M Bartos
- Department of Nuclear Medicine, LMU University Hospital, LMU Munich, Munich, Germany
| | - Sebastian T Kunte
- Department of Nuclear Medicine, LMU University Hospital, LMU Munich, Munich, Germany
| | - Stephan Wagner
- Department of Nuclear Medicine, LMU University Hospital, LMU Munich, Munich, Germany
| | - Philipp Beumers
- Department of Nuclear Medicine, LMU University Hospital, LMU Munich, Munich, Germany
| | - Rebecca Schaefer
- Department of Nuclear Medicine, LMU University Hospital, LMU Munich, Munich, Germany
| | - Artem Zatcepin
- Department of Nuclear Medicine, LMU University Hospital, LMU Munich, Munich, Germany; German Center for Neurodegenerative Diseases (DZNE) Munich, Germany
| | - Yunlei Li
- Department of Nuclear Medicine, LMU University Hospital, LMU Munich, Munich, Germany
| | - Maria Griessl
- Department of Nuclear Medicine, LMU University Hospital, LMU Munich, Munich, Germany
| | - Leonie Hoermann
- Department of Nuclear Medicine, LMU University Hospital, LMU Munich, Munich, Germany
| | - Karin Wind-Mark
- Department of Nuclear Medicine, LMU University Hospital, LMU Munich, Munich, Germany; German Center for Neurodegenerative Diseases (DZNE) Munich, Germany
| | - Peter Bartenstein
- Department of Nuclear Medicine, LMU University Hospital, LMU Munich, Munich, Germany; Munich Cluster for Systems Neurology (SyNergy), Munich, Germany
| | - Sabina Tahirovic
- German Center for Neurodegenerative Diseases (DZNE) Munich, Germany
| | - Sibylle Ziegler
- Department of Nuclear Medicine, LMU University Hospital, LMU Munich, Munich, Germany; Munich Cluster for Systems Neurology (SyNergy), Munich, Germany
| | - Matthias Brendel
- Department of Nuclear Medicine, LMU University Hospital, LMU Munich, Munich, Germany; German Center for Neurodegenerative Diseases (DZNE) Munich, Germany; Munich Cluster for Systems Neurology (SyNergy), Munich, Germany
| | - Johannes Gnörich
- Department of Nuclear Medicine, LMU University Hospital, LMU Munich, Munich, Germany; German Center for Neurodegenerative Diseases (DZNE) Munich, Germany.
| |
Collapse
|
|
4
|
Pappalettera C, Carrarini C, Miraglia F, Vecchio F, Rossini PM. Cognitive resilience/reserve: Myth or reality? A review of definitions and measurement methods. Alzheimers Dement 2024; 20:3567-3586. [PMID: 38477378 PMCID: PMC11095447 DOI: 10.1002/alz.13744] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2023] [Revised: 12/27/2023] [Accepted: 12/28/2023] [Indexed: 03/14/2024]
Abstract
INTRODUCTION This review examines the concept of cognitive reserve (CR) in relation to brain aging, particularly in the context of dementia and its early stages. CR refers to an individual's ability to maintain or regain cognitive function despite brain aging, damage, or disease. Various factors, including education, occupation complexity, leisure activities, and genetics are believed to influence CR. METHODS We revised the literature in the context of CR. A total of 842 articles were identified, then we rigorously assessed the relevance of articles based on titles and abstracts, employing a systematic approach to eliminate studies that did not align with our research objectives. RESULTS We evaluate-also in a critical way-the methods commonly used to define and measure CR, including sociobehavioral proxies, neuroimaging, and electrophysiological and genetic measures. The challenges and limitations of these measures are discussed, emphasizing the need for more targeted research to improve the understanding, definition, and measurement of CR. CONCLUSIONS The review underscores the significance of comprehending CR in the context of both normal and pathological brain aging and emphasizes the importance of further research to identify and enhance this protective factor for cognitive preservation in both healthy and neurologically impaired older individuals. HIGHLIGHTS This review examines the concept of cognitive reserve in brain aging, in the context of dementia and its early stages. We have evaluated the methods commonly used to define and measure cognitive reserve. Sociobehavioral proxies, neuroimaging, and electrophysiological and genetic measures are discussed. The review emphasizes the importance of further research to identify and enhance this protective factor for cognitive preservation.
Collapse
Affiliation(s)
- Chiara Pappalettera
- Brain Connectivity LaboratoryDepartment of Neuroscience and NeurorehabilitationIRCCS San Raffaele RomaRomeItaly
- Department of Theoretical and Applied ScienceseCampus UniversityNovedrateItaly
| | - Claudia Carrarini
- Brain Connectivity LaboratoryDepartment of Neuroscience and NeurorehabilitationIRCCS San Raffaele RomaRomeItaly
- Department of NeuroscienceCatholic University of Sacred HeartRomeItaly
| | - Francesca Miraglia
- Brain Connectivity LaboratoryDepartment of Neuroscience and NeurorehabilitationIRCCS San Raffaele RomaRomeItaly
- Department of Theoretical and Applied ScienceseCampus UniversityNovedrateItaly
| | - Fabrizio Vecchio
- Brain Connectivity LaboratoryDepartment of Neuroscience and NeurorehabilitationIRCCS San Raffaele RomaRomeItaly
- Department of Theoretical and Applied ScienceseCampus UniversityNovedrateItaly
| | - Paolo M. Rossini
- Brain Connectivity LaboratoryDepartment of Neuroscience and NeurorehabilitationIRCCS San Raffaele RomaRomeItaly
| |
Collapse
|
|
5
|
Fernández‐Rodríguez B, Rodríguez‐Rojas R, Guida P, Angulo‐Díaz‐Parreño S, Trompeta C, Mata‐Marín D, Obeso I, Vela L, Plaza de las Heras I, Obeso JA, Gasca‐Salas C. Cognitive Reserve in Parkinson's Disease without Dementia: β-Amyloid and Metabolic Assessment. Mov Disord Clin Pract 2024; 11:282-288. [PMID: 38169114 PMCID: PMC10928358 DOI: 10.1002/mdc3.13967] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2023] [Revised: 11/14/2023] [Accepted: 12/09/2023] [Indexed: 01/05/2024] Open
Abstract
BACKGROUND Cognitive reserve (CR) is the mismatch between preserved cognition and neuropathological damage. Amyloidopathy in Parkinson's disease (PD) could be associated with faster progression to dementia, but the putative protective effect of CR is unknown. OBJECTIVES To evaluate the effect of CR on β-amyloid burden and brain metabolism in non-demented PD subjects. METHODS Participants with PD (n = 53) underwent a clinical evaluation, [18 F]-fluorodeoxyglucose and [18 F]-flutemetamol positron emission tomography magnetic resonances, and were classified according to CR. The metabolic pattern of 16 controls was compared to PD subjects. RESULTS The PD subjects showed hypometabolism mainly in the bilateral posterior cortex. Superior-CR subjects (n = 22) exhibited better cognitive performance, increased amyloid burden, and higher metabolism in several right hemisphere areas compared to low-medium-CR subjects (n = 31). CONCLUSIONS Higher CR in non-demented PD is associated with better cognitive performance, which might reduce vulnerability to the effect of β-amyloid. Whether superior CR leads to protection against metabolic deterioration, and predominantly right hemisphere involvement, deserves further exploration.
Collapse
Affiliation(s)
- Beatriz Fernández‐Rodríguez
- HM CINAC (Centro Integral de Neurociencias Abarca Campal), Hospital Universitario HM Puerta del Sur, HM HospitalesMadridSpain
- PhD Program in Neuroscience, Autonoma de Madrid University‐Cajal InstituteMadridSpain
| | - Rafael Rodríguez‐Rojas
- HM CINAC (Centro Integral de Neurociencias Abarca Campal), Hospital Universitario HM Puerta del Sur, HM HospitalesMadridSpain
- Network Center for Biomedical Research on Neurodegenerative Diseases (CIBERNED), Instituto Carlos IIIMadridSpain
| | - Pasqualina Guida
- HM CINAC (Centro Integral de Neurociencias Abarca Campal), Hospital Universitario HM Puerta del Sur, HM HospitalesMadridSpain
- PhD Program in Neuroscience, Autonoma de Madrid University‐Cajal InstituteMadridSpain
| | - Santiago Angulo‐Díaz‐Parreño
- CEMBIO, Centro de Excelencia en Metabolómica y Bioanálisis, Facultad de Farmacia, Universidad San Pablo CEUMadridSpain
- Departamento de Matemática Aplicada y EstadísticaUniversidad San Pablo CEUMadridSpain
| | - Clara Trompeta
- HM CINAC (Centro Integral de Neurociencias Abarca Campal), Hospital Universitario HM Puerta del Sur, HM HospitalesMadridSpain
- PhD Program in Health SciencesUniversity of Alcala de HenaresAlcalá de HenaresSpain
| | - David Mata‐Marín
- HM CINAC (Centro Integral de Neurociencias Abarca Campal), Hospital Universitario HM Puerta del Sur, HM HospitalesMadridSpain
- PhD Program in Neuroscience, Autonoma de Madrid University‐Cajal InstituteMadridSpain
| | - Ignacio Obeso
- HM CINAC (Centro Integral de Neurociencias Abarca Campal), Hospital Universitario HM Puerta del Sur, HM HospitalesMadridSpain
- Network Center for Biomedical Research on Neurodegenerative Diseases (CIBERNED), Instituto Carlos IIIMadridSpain
| | - Lydia Vela
- Hospital Universitario Fundación AlcorcónAlcorcónSpain
| | | | - José A. Obeso
- HM CINAC (Centro Integral de Neurociencias Abarca Campal), Hospital Universitario HM Puerta del Sur, HM HospitalesMadridSpain
- Network Center for Biomedical Research on Neurodegenerative Diseases (CIBERNED), Instituto Carlos IIIMadridSpain
| | - Carmen Gasca‐Salas
- HM CINAC (Centro Integral de Neurociencias Abarca Campal), Hospital Universitario HM Puerta del Sur, HM HospitalesMadridSpain
- Network Center for Biomedical Research on Neurodegenerative Diseases (CIBERNED), Instituto Carlos IIIMadridSpain
- University CEU‐San PabloMadridSpain
| |
Collapse
|
|
6
|
Di Tella S, Isernia S, Cabinio M, Rossetto F, Borgnis F, Pagliari C, Cazzoli M, Navarro J, Silveri MC, Baglio F. Cognitive Reserve proxies can modulate motor and non-motor basal ganglia circuits in early Parkinson's Disease. Brain Imaging Behav 2024; 18:220-230. [PMID: 37993754 PMCID: PMC10844415 DOI: 10.1007/s11682-023-00829-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/19/2023] [Indexed: 11/24/2023]
Abstract
Parkinson's Disease (PD) is hallmarked by dysfunctional circuitry between the basal ganglia and dorsolateral-prefrontal cortex. Recently progress has been made in understanding factors contributing to differential susceptibility to pathology mitigating disease-related cognitive decline. Cognitive reserve, the brain processing resources accumulated throughout life while engaged in mentally stimulating activities, can play an important protective role in cognitive performance. We tested the hypothesis that Cognitive Reserve proxies may exert an impact on the basal ganglia and dorsolateral-prefrontal atrophy in early PD. Forty-five early patients with PD and 20 age-gender-matched healthy controls (HC) completed the Cognitive Reserve Index questionnaire to quantify Cognitive Reserve proxies by three indexes (CRI-Education, CRI-Working Activity, CRI-Leisure Time) and a structural MRI examination (3T). Morphometrical indexes for basal ganglia (bilateral putamen, caudate, pallidum volume) and dorsolateral-prefrontal cortex (cortical thickness) were computed. Significant differences between HC and PD were tested by direct comparisons in demographics, cognitive level, and cognitive reserve proxies indexes. Then two multiple regression analyses were performed to identify predictors of the basal ganglia and dorsolateral-prefrontal cortex structural integrity. Regression analysis revealed that basal ganglia volume was significantly predicted by CRI-Education (pFDR = 0.029), sex (pFDR = 0.029), and Total Intracranial Volume (pFDR < 0.001). Instead, the dorsolateral-prefrontal thickness was predicted by CRI-Leisure Time (pFDR = 0.030) and age (pFDR = 0.010). Cognitive Reserve proxies, especially education and leisure-time activities, can play a protective role on the structural integrity of the basal ganglia and dorsolateral-prefrontal cortex, respectively, critical regions hallmarking brain status of early phases of PD.
Collapse
Affiliation(s)
- Sonia Di Tella
- Department of Psychology, Università Cattolica del Sacro Cuore, Milan, Italy
- IRCCS Fondazione Don Carlo Gnocchi ONLUS, Milan, Italy
| | - Sara Isernia
- IRCCS Fondazione Don Carlo Gnocchi ONLUS, Milan, Italy.
| | - Monia Cabinio
- IRCCS Fondazione Don Carlo Gnocchi ONLUS, Milan, Italy
| | | | | | | | - Marta Cazzoli
- IRCCS Fondazione Don Carlo Gnocchi ONLUS, Milan, Italy
| | - Jorge Navarro
- IRCCS Fondazione Don Carlo Gnocchi ONLUS, Milan, Italy
| | | | | |
Collapse
|
|
7
|
Kim HB, Kim SH, Um YH, Wang SM, Kim REY, Choe YS, Lee J, Kim D, Lim HK, Lee CU, Kang DW. Modulation of associations between education years and cortical volume in Alzheimer's disease vulnerable brain regions by Aβ deposition and APOE ε4 carrier status in cognitively normal older adults. Front Aging Neurosci 2023; 15:1248531. [PMID: 37829142 PMCID: PMC10565031 DOI: 10.3389/fnagi.2023.1248531] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2023] [Accepted: 09/05/2023] [Indexed: 10/14/2023] Open
Abstract
Background Education years, as a measure of cognitive reserve, have been shown to affect the progression of Alzheimer's disease (AD), both pathologically and clinically. However, inconsistent results have been reported regarding the association between years of education and intermediate structural changes in AD-vulnerable brain regions, particularly when AD risk factors were not considered during the preclinical phase. Objective This study aimed to examine how Aβ deposition and APOE ε4 carrier status moderate the relationship between years of education and cortical volume in AD-vulnerable regions among cognitively normal older adults. Methods A total of 121 participants underwent structural MRI, [18F] flutemetamol PET-CT imaging, and neuropsychological battery assessment. Multiple regression analysis was conducted to examine the interaction between years of education and the effects of potential modifiers on cortical volume. The associations between cortical volume and neuropsychological performance were further explored in subgroups categorized based on AD risk factors. Results The cortical volume of the left lateral occipital cortex and bilateral fusiform gyrus demonstrated a significant differential association with years of education, depending on the presence of Aβ deposition and APOE ε4 carrier status. Furthermore, a significant relationship between the cortical volume of the bilateral fusiform gyrus and AD-nonspecific cognitive function was predominantly observed in individuals without AD risk factors. Conclusion AD risk factors exerted varying influences on the association between years of education and cortical volume during the preclinical phase. Further investigations into the long-term implications of these findings would enhance our understanding of cognitive reserves in the preclinical stages of AD.
Collapse
Affiliation(s)
- Hak-Bin Kim
- Department of Psychiatry, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Sung-Hwan Kim
- Department of Psychiatry, Yeouido St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Yoo Hyun Um
- Department of Psychiatry, St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Suwon, Republic of Korea
| | - Sheng-Min Wang
- Department of Psychiatry, Yeouido St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | | | - Yeong Sim Choe
- Research Institute, NEUROPHET Inc., Seoul, Republic of Korea
| | - Jiyeon Lee
- Research Institute, NEUROPHET Inc., Seoul, Republic of Korea
| | - Donghyeon Kim
- Research Institute, NEUROPHET Inc., Seoul, Republic of Korea
| | - Hyun Kook Lim
- Department of Psychiatry, Yeouido St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- Research Institute, NEUROPHET Inc., Seoul, Republic of Korea
| | - Chang Uk Lee
- Department of Psychiatry, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Dong Woo Kang
- Department of Psychiatry, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| |
Collapse
|
|
8
|
Horowitz T, Doche E, Philip M, Cammilleri S, Suissa L, Guedj E. Regional brain glucose metabolism is differentially affected by ketogenic diet: a human semiquantitative positron emission tomography. Eur J Nucl Med Mol Imaging 2023; 50:2047-2055. [PMID: 36867201 DOI: 10.1007/s00259-023-06156-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2023] [Accepted: 02/14/2023] [Indexed: 03/04/2023]
Abstract
PURPOSE Ketogenic diet (KD) is recommended to avoid intense [18F]FDG myocardial physiologic uptake in PET imaging. Neuroprotective and anti-seizure effects of KD have been suggested, but their mechanisms remain to be elucidated. This [18F]FDG PET study aims to evaluate the effect of KD on glucose brain metabolism. METHOD Subjects who underwent KD prior to whole-body and brain [18F]FDG PET between January 2019 and December 2020 in our department for suspected endocarditis were retrospectively included. Myocardial glucose suppression (MGS) on whole-body PET was analyzed. Patients with brain abnormalities were excluded. Thirty-four subjects with MGS (mean age: 61.8 ± 17.2 years) were included in the KD population, and 14 subjects without MGS were considered for a partial KD group (mean age: 62.3 ± 15.1 years). Brain SUVmax was first compared between these two KD groups to determine possible global uptake difference. Semiquantitative voxel-based intergroup analyses were secondarily performed to determine possible inter-regional differences by comparing KD groups with and without MGS, separately, to 27 healthy subjects fasting for at least 6 h (mean age of 62.4 ± 10.9 years), and KD groups between them (p-voxel < 0.001, and p-cluster < 0.05, FWE-corrected). RESULTS A 20% lower brain SUVmax was found in subjects under KD with MGS in comparison to those without MGS (Student's t-test, p = 0.02). Whole-brain voxel-based intergroup analysis revealed that patients under KD with and without MGS had relative hypermetabolism of limbic regions including medial temporal cortices and cerebellum lobes and relative hypometabolism of bilateral posterior regions (occipital), without significant difference between them. CONCLUSION KD globally reduces brain glucose metabolism but with regional differences, requiring special attention to clinical interpretation. On a pathophysiological perspective, these findings could help understand underlying neurological effects of KD through possible decrease of oxidative stress in posterior regions and functional compensation in the limbic regions.
Collapse
Affiliation(s)
- Tatiana Horowitz
- APHM, CNRS, Centrale Marseille, Institut Fresnel, AP-HM, La Timone Hospital, CERIMED, Nuclear Medicine Department, Aix Marseille Univ, Marseille, France.
- Service Central de Biophysique Et Médecine Nucléaire, Hôpital de La Timone, 264 Rue Saint Pierre, 13005, Marseille, France.
| | - Emilie Doche
- Center for CardioVascular and Nutrition Research (C2VN), Stroke Unit, AP-HM, La Timone Hospital, Marseille, France
| | - Mary Philip
- Cardiology Department, APHM, La Timone Hospital, Marseille, France
| | - Serge Cammilleri
- APHM, CNRS, Centrale Marseille, Institut Fresnel, AP-HM, La Timone Hospital, CERIMED, Nuclear Medicine Department, Aix Marseille Univ, Marseille, France
- Service Central de Biophysique Et Médecine Nucléaire, Hôpital de La Timone, 264 Rue Saint Pierre, 13005, Marseille, France
| | - Laurent Suissa
- Center for CardioVascular and Nutrition Research (C2VN), Stroke Unit, AP-HM, La Timone Hospital, Marseille, France
| | - Eric Guedj
- APHM, CNRS, Centrale Marseille, Institut Fresnel, AP-HM, La Timone Hospital, CERIMED, Nuclear Medicine Department, Aix Marseille Univ, Marseille, France
- Service Central de Biophysique Et Médecine Nucléaire, Hôpital de La Timone, 264 Rue Saint Pierre, 13005, Marseille, France
| |
Collapse
|
|
9
|
Hoenig MC, Drzezga A. Clear-headed into old age: Resilience and resistance against brain aging-A PET imaging perspective. J Neurochem 2023; 164:325-345. [PMID: 35226362 DOI: 10.1111/jnc.15598] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2021] [Revised: 02/18/2022] [Accepted: 02/22/2022] [Indexed: 11/28/2022]
Abstract
With the advances in modern medicine and the adaptation towards healthier lifestyles, the average life expectancy has doubled since the 1930s, with individuals born in the millennium years now carrying an estimated life expectancy of around 100 years. And even though many individuals around the globe manage to age successfully, the prevalence of aging-associated neurodegenerative diseases such as sporadic Alzheimer's disease has never been as high as nowadays. The prevalence of Alzheimer's disease is anticipated to triple by 2050, increasing the societal and economic burden tremendously. Despite all efforts, there is still no available treatment defeating the accelerated aging process as seen in this disease. Yet, given the advances in neuroimaging techniques that are discussed in the current Review article, such as in positron emission tomography (PET) or magnetic resonance imaging (MRI), pivotal insights into the heterogenous effects of aging-associated processes and the contribution of distinct lifestyle and risk factors already have and are still being gathered. In particular, the concepts of resilience (i.e. coping with brain pathology) and resistance (i.e. avoiding brain pathology) have more recently been discussed as they relate to mechanisms that are associated with the prolongation and/or even stop of the progressive brain aging process. Better understanding of the underlying mechanisms of resilience and resistance may one day, hopefully, support the identification of defeating mechanism against accelerating aging.
Collapse
Affiliation(s)
- Merle C Hoenig
- Research Center Juelich, Institute for Neuroscience and Medicine II, Molecular Organization of the Brain, Juelich, Germany.,Department of Nuclear Medicine, Faculty of Medicine, University Hospital Cologne, Cologne, Germany
| | - Alexander Drzezga
- Research Center Juelich, Institute for Neuroscience and Medicine II, Molecular Organization of the Brain, Juelich, Germany.,Department of Nuclear Medicine, Faculty of Medicine, University Hospital Cologne, Cologne, Germany.,German Center for Neurodegenerative Diseases, Bonn/Cologne, Germany
| |
Collapse
|
|
10
|
Ersoezlue E, Rauchmann BS, Schneider-Axmann T, Wagner M, Ballarini T, Tato M, Utecht J, Kurz C, Papazov B, Guersel S, Burow L, Koller G, Stöcklein S, Keeser D, Bartels C, Brosseron F, Buerger K, Cetindag AC, Dechent P, Dobisch L, Ewers M, Fliessbach K, Frommann I, Haynes JD, Heneka MT, Janowitz D, Kilimann I, Kleinedam L, Laske C, Maier F, Metzger CD, Munk MH, Peters O, Preis L, Priller J, Ramirez A, Roeske S, Roy N, Scheffler K, Schneider A, Spottke A, Spruth EJ, Teipel S, Wiltfang J, Wolfsgruber S, Yakupov R, Duezel E, Jessen F, Perneczky R. Lifelong experiences as a proxy of cognitive reserve moderate the association between connectivity and cognition in Alzheimer's disease. Neurobiol Aging 2023; 122:33-44. [PMID: 36476760 DOI: 10.1016/j.neurobiolaging.2022.05.015] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2021] [Revised: 04/08/2022] [Accepted: 05/30/2022] [Indexed: 11/05/2022]
Abstract
Alzheimer's disease (AD) is associated with alterations in functional connectivity (FC) of the brain. The FC underpinnings of CR, that is, lifelong experiences, are largely unknown. Resting-state FC and structural MRI were performed in 76 CSF amyloid-β (Aβ) negative healthy controls and 152 Aβ positive individuals as an AD spectrum cohort (ADS; 55 with subjective cognitive decline, SCD; 52 with mild cognitive impairment; 45 with AD dementia). Following a region-of-interest (ROI) FC analysis, intrinsic network connectivity within the default-mode network (INC-DMN) and anti-correlation in INC between the DMN and dorsal attention network (DMN:DAN) were obtained as composite scores. CR was estimated by education and Lifetime Experiences Questionnaire (LEQ). The association between INC-DMN and MEM was attenuated by higher LEQ scores in the entire ADS group, particularly in SCD. In ROI analyses, higher LEQ scores were associated with higher FC within the DMN in ADS group. INC-DMN remains relatively intact despite memory decline in individuals with higher lifetime activity estimates, supporting a role for functional networks in maintaining cognitive function in AD.
Collapse
Affiliation(s)
- Ersin Ersoezlue
- Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich, Munich, Germany
| | - Boris-Stephan Rauchmann
- Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich, Munich, Germany; German Center for Neurodegenerative Diseases (DZNE), Munich, Germany; Sheffield Institute for Translational Neurology (SITraN), University of Sheffield, Sheffield, UK
| | - Thomas Schneider-Axmann
- Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich, Munich, Germany
| | - Michael Wagner
- German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany; Department for Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital Bonn, Germany
| | - Tommaso Ballarini
- German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany; Department for Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital Bonn, Germany
| | - Maia Tato
- Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich, Munich, Germany
| | - Julia Utecht
- Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich, Munich, Germany
| | - Carolin Kurz
- Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich, Munich, Germany
| | - Boris Papazov
- Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich, Munich, Germany
| | - Selim Guersel
- Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich, Munich, Germany
| | - Lena Burow
- Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich, Munich, Germany
| | - Gabriele Koller
- Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich, Munich, Germany
| | - Sophia Stöcklein
- Department of Radiology, University Hospital, LMU Munich, Munich, Germany
| | - Daniel Keeser
- Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich, Munich, Germany
| | - Claudia Bartels
- Department of Psychiatry and Psychotherapy, University Medical Center Goettingen, University of Goettingen, Goettingen, Germany
| | - Frederic Brosseron
- German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany; Department for Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital Bonn, Germany
| | - Katharina Buerger
- German Center for Neurodegenerative Diseases (DZNE), Munich, Germany; Institute for Stroke and Dementia Research (ISD), University Hospital, LMU Munich, Munich, Germany
| | - Arda C Cetindag
- Charité - Universitätsmedizin Berlin, Department of Psychiatry and Psychotherapy, Campus Benjamin Franklin, Berlin, Germany
| | - Peter Dechent
- MR-Research in Neurology and Psychiatry, Georg-August-University Göttingen, Germany
| | - Laura Dobisch
- German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany
| | - Michael Ewers
- German Center for Neurodegenerative Diseases (DZNE), Munich, Germany
| | - Klaus Fliessbach
- German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany; Department for Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital Bonn, Germany
| | - Ingo Frommann
- German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany; Department for Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital Bonn, Germany
| | - John D Haynes
- Bernstein Center for Computational Neuroscience, Charité - Universitätsmedizin, Berlin, Germany
| | - Michael T Heneka
- German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany; Department for Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital Bonn, Germany
| | - Daniel Janowitz
- German Center for Neurodegenerative Diseases (DZNE), Munich, Germany
| | - Ingo Kilimann
- German Center for Neurodegenerative Diseases (DZNE), Rostock, Germany; Department of Psychosomatic Medicine, Rostock University Medical Center, Rostock, Germany
| | - Luca Kleinedam
- German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany
| | - Christoph Laske
- German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany; Section for Dementia Research, Hertie Institute for Clinical Brain Research and Department of Psychiatry and Psychotherapy, University of Tübingen, Tübingen, Germany
| | - Franziska Maier
- Department of Psychiatry, University of Cologne, Medical Faculty, Cologne, Germany
| | - Coraline D Metzger
- German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany; Institute of Cognitive Neurology and Dementia Research (IKND), Otto-von-Guericke University, Magdeburg, Germany; Department of Psychiatry and Psychotherapy, Otto-von-Guericke University, Magdeburg, Germany
| | - Matthias H Munk
- German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany; Section for Dementia Research, Hertie Institute for Clinical Brain Research and Department of Psychiatry and Psychotherapy, University of Tübingen, Tübingen, Germany
| | - Oliver Peters
- Charité - Universitätsmedizin Berlin, Department of Psychiatry and Psychotherapy, Campus Benjamin Franklin, Berlin, Germany; German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany
| | - Lukas Preis
- German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany
| | - Josef Priller
- German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany; Department of Psychiatry and Psychotherapy, Charité, Berlin, Germany; Department of Psychiatry and Psychotherapy, Technical University Munich, Munich, Germany
| | - Alfredo Ramirez
- German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany; Department for Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital Bonn, Germany; Division of Neurogenetics and Molecular Psychiatry, Department of Psychiatry, University of Cologne, Medical Faculty, Cologne, Germany
| | - Sandra Roeske
- German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany
| | - Nina Roy
- German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany
| | - Klaus Scheffler
- Department for Biomedical Magnetic Resonance, University of Tübingen, Tübingen, Germany
| | - Anja Schneider
- German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany; Department for Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital Bonn, Germany
| | - Annika Spottke
- German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany; Department of Neurology, University of Bonn, Bonn, Germany
| | - Eike J Spruth
- Department of Psychiatry and Psychotherapy, Charité, Berlin, Germany
| | - Stefan Teipel
- German Center for Neurodegenerative Diseases (DZNE), Rostock, Germany; Department of Psychosomatic Medicine, Rostock University Medical Center, Rostock, Germany
| | - Jens Wiltfang
- Department of Psychiatry and Psychotherapy, University Medical Center Goettingen, University of Goettingen, Goettingen, Germany; Department of Psychosomatic Medicine, Rostock University Medical Center, Rostock, Germany; Neurosciences and Signaling Group, Institute of Biomedicine (iBiMED), Department of Medical Sciences, University of Aveiro, Aveiro, Portugal
| | - Steffen Wolfsgruber
- German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany; Department for Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital Bonn, Germany
| | - Renat Yakupov
- German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany
| | - Emrah Duezel
- German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany; Institute of Cognitive Neurology and Dementia Research (IKND), Otto-von-Guericke University, Magdeburg, Germany
| | - Frank Jessen
- German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany; Department of Psychiatry, University of Cologne, Medical Faculty, Cologne, Germany; Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Köln, Germany
| | - Robert Perneczky
- Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich, Munich, Germany; German Center for Neurodegenerative Diseases (DZNE), Munich, Germany; Munich Cluster for Systems Neurology (SyNergy) Munich, Munich, Germany; Ageing Epidemiology Research Unit (AGE), School of Public Health, Imperial College London, London, UK; Sheffield Institute for Translational Neurology (SITraN), University of Sheffield, Sheffield, UK.
| |
Collapse
|
|
11
|
Wang M, Schutte M, Grimmer T, Lizarraga A, Schultz T, Hedderich DM, Diehl-Schmid J, Rominger A, Ziegler S, Navab N, Yan Z, Jiang J, Yakushev I, Shi K. Reducing instability of inter-subject covariance of FDG uptake networks using structure-weighted sparse estimation approach. Eur J Nucl Med Mol Imaging 2022; 50:80-89. [PMID: 36018359 DOI: 10.1007/s00259-022-05949-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2022] [Accepted: 08/18/2022] [Indexed: 11/04/2022]
Abstract
PURPOSE Sparse inverse covariance estimation (SICE) is increasingly utilized to estimate inter-subject covariance of FDG uptake (FDGcov) as proxy of metabolic brain connectivity. However, this statistical method suffers from the lack of robustness in the connectivity estimation. Patterns of FDGcov were observed to be spatially similar with patterns of structural connectivity as obtained from DTI imaging. Based on this similarity, we propose to regularize the sparse estimation of FDGcov using the structural connectivity. METHODS We retrospectively analyzed the FDG-PET and DTI data of 26 healthy controls, 41 patients with Alzheimer's disease (AD), and 30 patients with frontotemporal lobar degeneration (FTLD). Structural connectivity matrix derived from DTI data was introduced as a regularization parameter to assign individual penalties to each potential metabolic connectivity. Leave-one-out cross validation experiments were performed to assess the differential diagnosis ability of structure weighted SICE approach. A few approaches of structure weighted were compared with the standard SICE. RESULTS Compared to the standard SICE, structural weighting has shown more stable performance in the supervised classification, especially in the differentiation AD vs. FTLD (accuracy of 89-90%, while unweighted SICE only 85%). There was a significant positive relationship between the minimum number of metabolic connection and the robustness of the classification accuracy (r = 0.57, P < 0.001). Shuffling experiments showed significant differences between classification score derived with true structural weighting and those obtained by randomized structure (P < 0.05). CONCLUSION The structure-weighted sparse estimation can enhance the robustness of metabolic connectivity, which may consequently improve the differentiation of pathological phenotypes.
Collapse
Affiliation(s)
- Min Wang
- Institute of Biomedical Engineering, School of Life Science, Shanghai University, Shanghai, China
- Computer-Aided Medical Procedures and Augmented Reality, Technical University of Munich, Munich, Germany
| | - Michael Schutte
- The Bonn-Aachen International Center for Information Technology (b-it) and Institute of Computer Science II, University of Bonn, Bonn, Germany
| | - Timo Grimmer
- Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany
| | - Aldana Lizarraga
- Department of Nuclear Medicine, Klinikum rechts der Isar, Technical University of Munich, Ismaninger Str. 22, 81675, Munich, Germany
| | - Thomas Schultz
- Department for Visual Computing, University of Bonn, Bonn, Germany
| | - Dennis M Hedderich
- Department of Nuclear Medicine, Klinikum rechts der Isar, Technical University of Munich, Ismaninger Str. 22, 81675, Munich, Germany
| | - Janine Diehl-Schmid
- Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany
| | - Axel Rominger
- Department of Nuclear Medicine, University of Bern, Bern, Switzerland
| | - Sybille Ziegler
- Department of Nuclear Medicine, Ludwig Maximilian University of Munich, Munich, Germany
| | - Nassir Navab
- Computer-Aided Medical Procedures and Augmented Reality, Technical University of Munich, Munich, Germany
| | - Zhuangzhi Yan
- Institute of Biomedical Engineering, School of Life Science, Shanghai University, Shanghai, China
| | - Jiehui Jiang
- Institute of Biomedical Engineering, School of Life Science, Shanghai University, Shanghai, China.
| | - Igor Yakushev
- Department of Nuclear Medicine, Klinikum rechts der Isar, Technical University of Munich, Ismaninger Str. 22, 81675, Munich, Germany.
| | - Kuangyu Shi
- Computer-Aided Medical Procedures and Augmented Reality, Technical University of Munich, Munich, Germany
- Department of Nuclear Medicine, University of Bern, Bern, Switzerland
| |
Collapse
|
|
12
|
Curreri C, Trevisan C, Grande G, Giantin V, Ceolin C, Maggi S, Noale M, Baggio G, Sergi G. The influence of occupation type and complexity on cognitive performance in older adults. Psychiatry Res Neuroimaging 2022; 326:111542. [PMID: 36137478 DOI: 10.1016/j.pscychresns.2022.111542] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2022] [Revised: 08/11/2022] [Accepted: 09/01/2022] [Indexed: 11/29/2022]
Abstract
Sociodemographic factors, such as education and occupation, may influence the individual's cognitive reserve. We explored the extent to which the type and complexity of previous work activities influence cognitive performance (evaluated with Mini-Mental State Examination, MMSE, and the Animal Naming Test, ANT) in 799 older people with or without brain damage. The presence of cortical/subcortical ischemic brain lesions and right/left hippocampal atrophy was derived from magnetic resonance imaging. We found that individuals who had done intellectual work had better MMSE and ANT scores than their counterparts in the presence of brain lesions or hippocampal atrophy. Among the manual workers there were significant differences between the MMSE scores of individuals with and without brain damage (mean MMSE difference (2.09 [SD: 0.68], p=0.01), but not among the intellectuals (0.19 [SD: 0.29], p=0.36) nor the service providers (1.67 [SD: 0.55], p=0.21). Occupations involving more complex dealings with people were associated with better MMSE scores in the presence of brain lesions [β=-0.41, 95%CI: -0.72,-0.09] and hippocampal atrophy [β=-0.29, 95%CI:-0.58,-0.001]. These results indicate that in more cognitively stimulating work with greater social interaction may help older individuals preserve cognitive functions, even in the presence of brain damage.
Collapse
Affiliation(s)
- Chiara Curreri
- Geriatrics Division, Department of Medicine, University of Padua, Padua, Italy.
| | - Caterina Trevisan
- Geriatrics Division, Department of Medicine, University of Padua, Padua, Italy; Aging Research Center, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet and Stockholm University, Stockholm, Sweden
| | - Giulia Grande
- Aging Research Center, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet and Stockholm University, Stockholm, Sweden
| | - Valter Giantin
- Geriatrics Division, Department of Medicine, University of Padua, Padua, Italy
| | - Chiara Ceolin
- Geriatrics Division, Department of Medicine, University of Padua, Padua, Italy
| | - Stefania Maggi
- Neuroscience Institute, National Research Council, Padua, Italy
| | - Marianna Noale
- Neuroscience Institute, National Research Council, Padua, Italy
| | - Giovanella Baggio
- Italian Center for Studies on Gender Health and Medicine, Padua, Italy
| | - Giuseppe Sergi
- Geriatrics Division, Department of Medicine, University of Padua, Padua, Italy
| |
Collapse
|
|
13
|
McKenzie C, Bucks RS, Weinborn M, Bourgeat P, Salvado O, Gavett BE. Residual reserve index modifies the effect of amyloid pathology on fluorodeoxyglucose metabolism: Implications for efficiency and capacity in cognitive reserve. Front Aging Neurosci 2022; 14:943823. [PMID: 36034126 PMCID: PMC9413056 DOI: 10.3389/fnagi.2022.943823] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2022] [Accepted: 07/25/2022] [Indexed: 11/13/2022] Open
Abstract
Background The residual approach to measuring cognitive reserve (using the residual reserve index) aims to capture cognitive resilience conferred by cognitive reserve, but may be confounded by factors representing brain resilience. We sought to distinguish between brain and cognitive resilience by comparing interactions between the residual reserve index and amyloid, tau, and neurodegeneration ["AT(N)"] biomarkers when predicting executive function. We hypothesized that the residual reserve index would moderate at least one path from an AT(N) biomarker to executive function (consistent with cognitive resilience), as opposed to moderating a path between two AT(N) biomarkers (suggestive of brain resilience). Methods Participants (N = 332) were from the Alzheimer's Disease Neuroimaging Initiative. The residual reserve index represented the difference between observed and predicted memory performance (a positive residual reserve index suggests higher cognitive reserve). AT(N) biomarkers were: CSF β-amyloid1-42/β-amyloid1-40 (A), plasma phosphorylated tau-181 (T), and FDG metabolism in AD-specific regions ([N]). AT(N) biomarkers (measured at consecutive time points) were entered in a sequential mediation model testing the indirect effects from baseline amyloid to executive function intercept (third annual follow-up) and slope (baseline to seventh follow-up), via tau and/or FDG metabolism. The baseline residual reserve index was entered as a moderator of paths between AT(N) biomarkers (e.g., amyloid-tau), and paths between AT(N) biomarkers and executive function. Results The residual reserve index interacted with amyloid pathology when predicting FDG metabolism: the indirect effect of amyloid → FDG metabolism → executive function intercept and slope varied as a function of the residual reserve index. With lower amyloid pathology, executive function performance was comparable at different levels of the residual reserve index, but a higher residual reserve index was associated with lower FDG metabolism. With higher amyloid pathology, a higher residual reserve index predicted better executive function via higher FDG metabolism. Conclusion The effect of the residual reserve index on executive function performance via FDG metabolism was consistent with cognitive resilience. This suggests the residual reserve index captures variation in cognitive reserve; specifically, neural efficiency, and neural capacity to upregulate metabolism to enhance cognitive resilience in the face of greater amyloid pathology. Implications for future research include the potential bidirectionality between neural efficiency and amyloid accumulation.
Collapse
Affiliation(s)
- Cathryn McKenzie
- School of Psychological Science, The University of Western Australia, Perth, WA, Australia
| | - Romola S. Bucks
- School of Psychological Science, The University of Western Australia, Perth, WA, Australia
| | - Michael Weinborn
- School of Psychological Science, The University of Western Australia, Perth, WA, Australia
| | - Pierrick Bourgeat
- Australian e-Health Research Centre, Commonwealth Scientific and Industrial Research Organisation (CSIRO) Health and Biosecurity, Brisbane, QLD, Australia
| | - Olivier Salvado
- Data61, Commonwealth Scientific and Industrial Research Organisation (CSIRO), Sydney, NSW, Australia
| | - Brandon E. Gavett
- School of Psychological Science, The University of Western Australia, Perth, WA, Australia
| |
Collapse
|
|
14
|
Zhu Y, Ruan G, Cheng Z, Zou S, Zhu X. Lateralization of the crossed cerebellar diaschisis-associated metabolic connectivities in cortico-ponto-cerebellar and cortico-rubral pathways. Neuroimage 2022; 260:119487. [PMID: 35850160 DOI: 10.1016/j.neuroimage.2022.119487] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2021] [Revised: 06/21/2022] [Accepted: 07/14/2022] [Indexed: 11/16/2022] Open
Abstract
This study aimed to explore the glucose metabolic profile of extrapyramidal system in patients with crossed cerebellar diaschisis (CCD). Furthermore, the metabolic connectivities in cortico-ponto-cerebellar and cortico-rubral pathways associated with CCD were also investigated. A total of 130 CCD positive (CCD+) and 424 CCD negative (CCD-) patients with unilateral cerebral hemisphere hypometabolism on 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) were enrolled. Besides, the control group consisted of 56 subjects without any brain structural and metabolic abnormalities. Apart from the "autocorrelation", metabolic connectivity pattern of right or left affected cerebellar hemisphere involved unilateral (left or right, respectively) caudate, pallidum, putamen, thalamus and red nucleus, in CCD+ patients with left or right supratentorial lesions, respectively (Puncorrected < 0.001, cluster size > 200). CCD+ group had significantly lower asymmetry index (AI) in cortico-ponto-cerebellar pathway (including ipsilateral cerebral white matter, ipsilateral pons, contralateral cerebellum white matter and contralateral cerebellum exterior cortex) and cortico-rubral pathway (including ipsilateral caudate, thalamus proper, pallidum, putamen, ventral diencephalon and red nucleus) than those of both CCD- and control groups (all P < 0.05). AI in contralateral cerebellum exterior cortex was significantly positively correlated with that in ipsilateral caudate, putamen, pallidum, thalamus proper, ventral diencephalon, red nucleus and pons among CCD+ group (all P < 0.01), but only with that in ipsilateral caudate and putamen among CCD- group (both P < 0.001). These results provide additional insight into the involvement of both cortico-ponto-cerebellar and cortico-rubral pathways in the presence of CCD, underlining the need for further investigation about the role of their aberrant metabolic connectivities in the associated symptoms of CCD.
Collapse
Affiliation(s)
- Yuankai Zhu
- Department of Nuclear Medicine and PET Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Ave, Wuhan 430030, China
| | - Ge Ruan
- Department of Radiology, Hospital, Hubei University, Wuhan 430062, China
| | - Zhaoting Cheng
- Department of Nuclear Medicine and PET Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Ave, Wuhan 430030, China
| | - Sijuan Zou
- Department of Nuclear Medicine and PET Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Ave, Wuhan 430030, China
| | - Xiaohua Zhu
- Department of Nuclear Medicine and PET Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Ave, Wuhan 430030, China.
| |
Collapse
|
|
15
|
Varela-López B, Cruz-Gómez ÁJ, Lojo-Seoane C, Díaz F, Pereiro A, Zurrón M, Lindín M, Galdo-Álvarez S. Cognitive reserve, neurocognitive performance, and high-order resting-state networks in cognitively unimpaired aging. Neurobiol Aging 2022; 117:151-164. [DOI: 10.1016/j.neurobiolaging.2022.05.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2021] [Revised: 05/06/2022] [Accepted: 05/07/2022] [Indexed: 10/18/2022]
|
|
16
|
Modifiable lifestyle factors and cognitive reserve: A systematic review of current evidence. Ageing Res Rev 2022; 74:101551. [PMID: 34952208 PMCID: PMC8794051 DOI: 10.1016/j.arr.2021.101551] [Citation(s) in RCA: 123] [Impact Index Per Article: 41.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2021] [Revised: 11/12/2021] [Accepted: 12/17/2021] [Indexed: 02/03/2023]
Abstract
This systematic review aims to summarize cognitive reserve (CR) evaluation approaches and to examine the role of seven selected modifiable lifestyle factors (diet, smoking, alcohol consumption, physical activity, cognitive leisure activity, sleep, and meditation) in mitigating the impacts of age- or disease-related brain changes on cognition. Eighteen population-based English empirical studies were included. We summarize the study designs and identify three CR models that were broadly used in these studies, including a residual model assessing lifestyle factors in relation to unexplained variance in cognition after accounting for brain markers, a moderation model testing whether lifestyle factors moderate the relationship between brain status and cognition, and a controlling model examining the associations between lifestyle factors and cognition when controlling for brain measures. We also present the findings for the impact of each lifestyle factor. No studies examined diet, sleep, or meditation, and only two studies focused on smoking and alcohol consumption each. Overall, the studies suggest lifestyle activity factors (physical and cognitive leisure activities) may contribute to CR and attenuate the damaging impact of brain changes on cognition. Standardized measurements of lifestyle factors and CR are needed, and mechanisms underlying CR need to be further addressed as well.
Collapse
|
|
17
|
Sala A, Malpetti M, Farsad M, Lubian F, Magnani G, Frasca Polara G, Epiney J, Abutalebi J, Assal F, Garibotto V, Perani D. Lifelong bilingualism and mechanisms of neuroprotection in Alzheimer dementia. Hum Brain Mapp 2022; 43:581-592. [PMID: 34729858 PMCID: PMC8720191 DOI: 10.1002/hbm.25605] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Revised: 06/28/2021] [Accepted: 07/14/2021] [Indexed: 11/08/2022] Open
Abstract
Lifelong bilingualism is associated with delayed dementia onset, suggesting a protective effect on the brain. Here, we aim to study the effects of lifelong bilingualism as a dichotomous and continuous phenomenon, on brain metabolism and connectivity in individuals with Alzheimer's dementia. Ninety-eight patients with Alzheimer's dementia (56 monolinguals; 42 bilinguals) from three centers entered the study. All underwent an [18F]-fluorodeoxyglucose positron emission tomography (PET) imaging session. A language background questionnaire measured the level of language use for conversation and reading. Severity of brain hypometabolism and strength of connectivity of the major neurocognitive networks was compared across monolingual and bilingual individuals, and tested against the frequency of second language life-long usage. Age, years of education, and MMSE score were included in all above mentioned analyses as nuisance covariates. Cerebral hypometabolism was more severe in bilingual compared to monolingual patients; severity of hypometabolism positively correlated with the degree of second language use. The metabolic connectivity analyses showed increased connectivity in the executive, language, and anterior default mode networks in bilingual compared to monolingual patients. The change in neuronal connectivity was stronger in subjects with higher second language use. All effects were most pronounced in the left cerebral hemisphere. The neuroprotective effects of lifelong bilingualism act both against neurodegenerative processes and through the modulation of brain networks connectivity. These findings highlight the relevance of lifelong bilingualism in brain reserve and compensation, supporting bilingual education and social interventions aimed at usage, and maintenance of two or more languages, including dialects, especially crucial in the elderly people.
Collapse
Affiliation(s)
- Arianna Sala
- San Raffaele UniversityMilanItaly
- Division of NeuroscienceIRCCS San RaffaeleMilanItaly
| | - Maura Malpetti
- Division of NeuroscienceIRCCS San RaffaeleMilanItaly
- Department of Clinical NeurosciencesUniversity of CambridgeCambridgeUK
| | - Mohsen Farsad
- Nuclear Medicine UnitAzienda Sanitaria dell'Alto Adige BolzanoBolzanoItaly
| | - Francesca Lubian
- Nuclear Medicine UnitAzienda Sanitaria dell'Alto Adige BolzanoBolzanoItaly
| | | | | | | | | | - Frédéric Assal
- Neurology DepartmentUniversity Hospitals GenevaGenevaSwitzerland
| | - Valentina Garibotto
- Division of Nuclear Medicine and Molecular Imaging, Diagnostic DepartmentUniversity Hospitals GenevaGenevaSwitzerland
- NIMTLab, Faculty of MedicineUniversity of GenevaGenevaSwitzerland
| | - Daniela Perani
- San Raffaele UniversityMilanItaly
- Division of NeuroscienceIRCCS San RaffaeleMilanItaly
- Nuclear Medicine UnitSan Raffaele HospitalMilanItaly
| |
Collapse
|
|
18
|
Zhu W, Li X, Li X, Wang H, Li M, Gao Z, Wu X, Tian Y, Zhou S, Wang K, Yu Y. The protective impact of education on brain structure and function in Alzheimer's disease. BMC Neurol 2021; 21:423. [PMID: 34717581 PMCID: PMC8557004 DOI: 10.1186/s12883-021-02445-9] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2020] [Accepted: 10/13/2021] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND The Cognitive Reserve (CR) theory posits that brains with higher reserve can cope with more cerebral damage to minimize clinical manifestations. The aim of this study was to examine the effect of education (CR proxy) on brain structure and function in Alzheimer's disease (AD) and amnestic mild cognitive impairment (aMCI) patients and in cognitively healthy elderly (HC) individuals. METHODS Fifty-seven AD patients, 57 aMCI patients and 48 HCs were included to investigate the relationships between education years and gray matter volume (GMV), regional homogeneity (ReHo) and functional connectivity (FC) in brain regions to show associations with both structure and function. Taking the severity of the disease into account, we further assessed the relationships in AD stratified analyses. RESULTS In AD group, the GMV of the dorsal anterior cingulate cortex (dACC) and ReHo in the left inferior temporal cortex (ITC) were inversely associated with education years, after adjustment for age, sex, Mini-Mental State Examination (MMSE), and total intracranial volume or head motion parameters. Seed-based FC analyses revealed that education years were negatively correlated with the FC between the left anterior ITC and left mid frontal cortex as well as right superior frontal cortex and right angular gyrus. Stratified analyses results indicated that this negative relation between education and GMV, ReHo, FC was mainly present in mild AD, which was attenuated in moderate AD and aMCI groups. CONCLUSIONS Our results support the CR theory, and suggest that CR may be protective against AD related brain pathology at the early stage of clinical dementia. These findings could provide the locus of CR-related functional brain mechanisms and a specific time-window for therapeutic interventions to help AD patients to cope better with the brain pathological damage by increasing CR.
Collapse
Affiliation(s)
- Wanqiu Zhu
- Department of Radiology, The First Affiliated Hospital of Anhui Medical University, No. 218, Jixi Road, Shushan District, Hefei, 230022, China
| | - Xiaoshu Li
- Department of Radiology, The First Affiliated Hospital of Anhui Medical University, No. 218, Jixi Road, Shushan District, Hefei, 230022, China
| | - Xiaohu Li
- Department of Radiology, The First Affiliated Hospital of Anhui Medical University, No. 218, Jixi Road, Shushan District, Hefei, 230022, China
| | - Haibao Wang
- Department of Radiology, The First Affiliated Hospital of Anhui Medical University, No. 218, Jixi Road, Shushan District, Hefei, 230022, China
| | - Meiqin Li
- Department of Radiology, The First Affiliated Hospital of Anhui Medical University, No. 218, Jixi Road, Shushan District, Hefei, 230022, China
| | - Ziwen Gao
- Department of Radiology, The First Affiliated Hospital of Anhui Medical University, No. 218, Jixi Road, Shushan District, Hefei, 230022, China
| | - Xingqi Wu
- Department of Neurology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China
| | - Yanghua Tian
- Department of Neurology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China
| | - Shanshan Zhou
- Department of Neurology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China
| | - Kai Wang
- Department of Neurology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China.
| | - Yongqiang Yu
- Department of Radiology, The First Affiliated Hospital of Anhui Medical University, No. 218, Jixi Road, Shushan District, Hefei, 230022, China.
| |
Collapse
|
|
19
|
Yakushev I, Ripp I, Wang M, Savio A, Schutte M, Lizarraga A, Bogdanovic B, Diehl-Schmid J, Hedderich DM, Grimmer T, Shi K. Mapping covariance in brain FDG uptake to structural connectivity. Eur J Nucl Med Mol Imaging 2021; 49:1288-1297. [PMID: 34677627 PMCID: PMC8921091 DOI: 10.1007/s00259-021-05590-y] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2021] [Accepted: 10/11/2021] [Indexed: 11/25/2022]
Abstract
PURPOSE Inter-subject covariance of regional 18F-fluorodeoxyglucose (FDG) PET measures (FDGcov) as proxy of brain connectivity has been gaining an increasing acceptance in the community. Yet, it is still unclear to what extent FDGcov is underlied by actual structural connectivity via white matter fiber tracts. In this study, we quantified the degree of spatial overlap between FDGcov and structural connectivity networks. METHODS We retrospectively analyzed neuroimaging data from 303 subjects, both patients with suspected neurodegenerative disorders and healthy individuals. For each subject, structural magnetic resonance, diffusion tensor imaging, and FDG-PET data were available. The images were spatially normalized to a standard space and segmented into 62 anatomical regions using a probabilistic atlas. Sparse inverse covariance estimation was employed to estimate FDGcov. Structural connectivity was measured by streamline tractography through fiber assignment by continuous tracking. RESULTS For the whole brain, 55% of detected connections were found to be convergent, i.e., present in both FDGcov and structural networks. This metric for random networks was significantly lower, i.e., 12%. Convergent were 80% of intralobe connections and only 30% of interhemispheric interlobe connections. CONCLUSION Structural connectivity via white matter fiber tracts is a relevant substrate of FDGcov, underlying around a half of connections at the whole brain level. Short-range white matter tracts appear to be a major substrate of intralobe FDGcov connections.
Collapse
Affiliation(s)
- Igor Yakushev
- Department of Nuclear Medicine, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Ismaninger Str. 22, Munich, 81675, Germany.
- Klinikum rechts der Isar, School of Medicine, Neuroimaging Center (TUM-NIC), Technical University of Munich, Munich, Germany.
| | - Isabelle Ripp
- Department of Nuclear Medicine, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Ismaninger Str. 22, Munich, 81675, Germany
- Klinikum rechts der Isar, School of Medicine, Neuroimaging Center (TUM-NIC), Technical University of Munich, Munich, Germany
| | - Min Wang
- Shanghai Institute for Advanced Communication and Data Science, Shanghai, China
| | - Alex Savio
- Department of Nuclear Medicine, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Ismaninger Str. 22, Munich, 81675, Germany
| | - Michael Schutte
- Department of Nuclear Medicine, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Ismaninger Str. 22, Munich, 81675, Germany
- Department Biology II, Ludwig Maximilian University of Munich, Munich, Germany
| | - Aldana Lizarraga
- Department of Nuclear Medicine, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Ismaninger Str. 22, Munich, 81675, Germany
- Klinikum rechts der Isar, School of Medicine, Neuroimaging Center (TUM-NIC), Technical University of Munich, Munich, Germany
| | - Borjana Bogdanovic
- Department of Nuclear Medicine, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Ismaninger Str. 22, Munich, 81675, Germany
| | - Janine Diehl-Schmid
- Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany
| | - Dennis M Hedderich
- Department of Neuroradiology, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany
| | - Timo Grimmer
- Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany
| | - Kuangyu Shi
- Department of Nuclear Medicine, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Ismaninger Str. 22, Munich, 81675, Germany
- Department of Nuclear Medicine, University Hospital Bern, Bern, Switzerland
| |
Collapse
|
|
20
|
Effect of education on functional network edge efficiency in Alzheimer's disease. Sci Rep 2021; 11:17255. [PMID: 34446742 PMCID: PMC8390462 DOI: 10.1038/s41598-021-96361-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2021] [Accepted: 07/29/2021] [Indexed: 11/24/2022] Open
Abstract
We investigated the effect of education on the edge efficiency in resting state functional networks (RSFNs) in amnestic mild cognitive impairment (aMCI) and Alzheimer’s disease dementia (ADD). We collected the data of 57 early aMCI, 141 late aMCI, 173 mild ADD, and 39 moderate-to-severe ADD patients. We used years of education as a proxy for cognitive reserve. We measured edge efficiency for each edge in RSFNs, and performed simple slope analyses to discover their associations with education level among the four groups. In the late aMCI, a sub-network that had hub nodes in the right middle frontal gyrus and the right posterior cingulate gyrus, showed a positive association between RSFN edge efficiency and education (threshold = 2.5, p = 0.0478). There was no negative effect of education on the RSFN edge efficiency. In the early aMCI, mild ADD, and moderate-to-severe ADD, there were no sub-networks showing positive or negative correlation between education and RSFN edge efficiency. There was a positive effect of higher education on RSFN edge efficiency in the late aMCI, but not in the early aMCI or ADD. This indicates that in late aMCI, those who have higher education level have greater ability to resist collapsed functional network.
Collapse
|
|
21
|
Iaccarino L, Sala A, Caminiti SP, Presotto L, Perani D. In vivo MRI Structural and PET Metabolic Connectivity Study of Dopamine Pathways in Alzheimer's Disease. J Alzheimers Dis 2021; 75:1003-1016. [PMID: 32390614 DOI: 10.3233/jad-190954] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND Alzheimer's disease (AD) is characterized by an involvement of brain dopamine (DA) circuitry, the presence of which has been associated with emergence of both neuropsychiatric symptoms and cognitive deficits. OBJECTIVE In order to investigate whether and how the DA pathways are involved in the pathophysiology of AD, we assessed by in vivo neuroimaging the structural and metabolic alterations of subcortical and cortical DA pathways and targets. METHODS We included 54 healthy control participants, 53 amyloid-positive subjects with mild cognitive impairment due to AD (MCI-AD), and 60 amyloid-positive patients with probable dementia due to AD (ADD), all with structural 3T MRI and 18F-FDG-PET scans. We assessed MRI-based gray matter reductions in the MCI-AD and ADD groups within an anatomical a priori-defined Nigrostriatal and Mesocorticolimbic DA pathways, followed by 18F-FDG-PET metabolic connectivity analyses to evaluate network-level metabolic connectivity changes. RESULTS We found significant tissue loss in the Mesocorticolimbic over the Nigrostriatal pathway. Atrophy was evident in the ventral striatum, orbitofrontal cortex, and medial temporal lobe structures, and already plateaued in the MCI-AD stage. Degree of atrophy in Mesocorticolimbic regions positively correlated with the severity of depression, anxiety, and apathy in MCI-AD and ADD subgroups. Additionally, we observed significant alterations of metabolic connectivity between the ventral striatum and fronto-cingulate regions in ADD, but not in MCI-AD. There were no metabolic connectivity changes within the Nigrostriatal pathway. CONCLUSION Our cross-sectional data support a clinically-meaningful, yet stage-dependent, involvement of the Mesocorticolimbic system in AD. Longitudinal and clinical correlation studies are needed to further establish the relevance of DA system involvement in AD.
Collapse
Affiliation(s)
- Leonardo Iaccarino
- Vita-Salute San Raffaele University, Milan, Italy.,In vivo Human Molecular and Structural Neuroimaging Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.,Memory and Aging Center, Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA, USA
| | - Arianna Sala
- Vita-Salute San Raffaele University, Milan, Italy.,In vivo Human Molecular and Structural Neuroimaging Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Silvia Paola Caminiti
- Vita-Salute San Raffaele University, Milan, Italy.,In vivo Human Molecular and Structural Neuroimaging Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Luca Presotto
- In vivo Human Molecular and Structural Neuroimaging Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.,Nuclear Medicine Unit, San Raffaele Hospital, Milan, Italy
| | - Daniela Perani
- Vita-Salute San Raffaele University, Milan, Italy.,In vivo Human Molecular and Structural Neuroimaging Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.,Nuclear Medicine Unit, San Raffaele Hospital, Milan, Italy
| | | |
Collapse
|
|
22
|
Grosch M, Beyer L, Lindner M, Kaiser L, Ahmadi SA, Stockbauer A, Bartenstein P, Dieterich M, Brendel M, Zwergal A, Ziegler S. Metabolic connectivity-based single subject classification by multi-regional linear approximation in the rat. Neuroimage 2021; 235:118007. [PMID: 33831550 DOI: 10.1016/j.neuroimage.2021.118007] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2020] [Revised: 03/15/2021] [Accepted: 03/18/2021] [Indexed: 10/21/2022] Open
Abstract
Metabolic connectivity patterns on the basis of [18F]-FDG positron emission tomography (PET) are used to depict complex cerebral network alterations in different neurological disorders and therefore may have the potential to support diagnostic decisions. In this study, we established a novel statistical classification method taking advantage of differential time-dependent states of whole-brain metabolic connectivity following unilateral labyrinthectomy (UL) in the rat and explored its classification accuracy. The dataset consisted of repeated [18F]-FDG PET measurements at baseline and 1, 3, 7, and 15 days (= maximum of 5 classes) after UL with 17 rats per measurement day. Classification in different stages after UL was performed by determining connectivity patterns for the different classes by Pearson's correlation between uptake values in atlas-based segmented brain regions. Connections were fitted with a linear function, with which different thresholds on the correlation coefficient (r = [0.5, 0.85]) were investigated. Rats were classified by determining the congruence of their PET uptake pattern with the fitted connectivity patterns in the classes. Overall, the classification accuracy with this method was 84.3% for 3 classes, 75.0% for 4 classes, and 54.1% for 5 classes and outperformed random classification as well as machine learning classification on the same dataset. The optimal classification thresholds of the correlation coefficient and distance-to-fit were found to be |r| > 0.65 and d = 4 when using Siegel's slope estimator for fitting. This connectivity-based classification method can compete with machine learning classification and may have methodological advantages when applied to support PET-based diagnostic decisions in neurological network disorders (such as neurodegenerative syndromes).
Collapse
Affiliation(s)
- Maximilian Grosch
- German Center for Vertigo and Balance Disorders, DSGZ, University Hospital, Ludwig-Maximilians-University Munich, Marchioninistrasse 15, D-81377 Munich, Germany; Department of Nuclear Medicine, University Hospital, LMU Munich, Munich Germany.
| | - Leonie Beyer
- Department of Nuclear Medicine, University Hospital, LMU Munich, Munich Germany
| | - Magdalena Lindner
- German Center for Vertigo and Balance Disorders, DSGZ, University Hospital, Ludwig-Maximilians-University Munich, Marchioninistrasse 15, D-81377 Munich, Germany; Department of Nuclear Medicine, University Hospital, LMU Munich, Munich Germany
| | - Lena Kaiser
- Department of Nuclear Medicine, University Hospital, LMU Munich, Munich Germany
| | - Seyed-Ahmad Ahmadi
- German Center for Vertigo and Balance Disorders, DSGZ, University Hospital, Ludwig-Maximilians-University Munich, Marchioninistrasse 15, D-81377 Munich, Germany
| | - Anna Stockbauer
- Department of Nuclear Medicine, University Hospital, LMU Munich, Munich Germany
| | - Peter Bartenstein
- Department of Nuclear Medicine, University Hospital, LMU Munich, Munich Germany; Munich Cluster of Systems Neurology, SyNergy, Munich, Germany
| | - Marianne Dieterich
- German Center for Vertigo and Balance Disorders, DSGZ, University Hospital, Ludwig-Maximilians-University Munich, Marchioninistrasse 15, D-81377 Munich, Germany; Department of Neurology, University Hospital, LMU Munich, Munich, Germany; Munich Cluster of Systems Neurology, SyNergy, Munich, Germany
| | - Matthias Brendel
- Department of Nuclear Medicine, University Hospital, LMU Munich, Munich Germany; Munich Cluster of Systems Neurology, SyNergy, Munich, Germany
| | - Andreas Zwergal
- German Center for Vertigo and Balance Disorders, DSGZ, University Hospital, Ludwig-Maximilians-University Munich, Marchioninistrasse 15, D-81377 Munich, Germany; Department of Neurology, University Hospital, LMU Munich, Munich, Germany
| | - Sibylle Ziegler
- Department of Nuclear Medicine, University Hospital, LMU Munich, Munich Germany
| |
Collapse
|
|
23
|
Carli G, Tondo G, Boccalini C, Perani D. Brain Molecular Connectivity in Neurodegenerative Conditions. Brain Sci 2021; 11:brainsci11040433. [PMID: 33800680 PMCID: PMC8067093 DOI: 10.3390/brainsci11040433] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2021] [Revised: 03/15/2021] [Accepted: 03/23/2021] [Indexed: 12/28/2022] Open
Abstract
Positron emission tomography (PET) allows for the in vivo assessment of early brain functional and molecular changes in neurodegenerative conditions, representing a unique tool in the diagnostic workup. The increased use of multivariate PET imaging analysis approaches has provided the chance to investigate regional molecular processes and long-distance brain circuit functional interactions in the last decade. PET metabolic and neurotransmission connectome can reveal brain region interactions. This review is an overview of concepts and methods for PET molecular and metabolic covariance assessment with evidence in neurodegenerative conditions, including Alzheimer’s disease and Lewy bodies disease spectrum. We highlight the effects of environmental and biological factors on brain network organization. All of the above might contribute to innovative diagnostic tools and potential disease-modifying interventions.
Collapse
Affiliation(s)
- Giulia Carli
- School of Psychology, Vita-Salute San Raffaele University, 20121 Milan, Italy; (G.C.); (G.T.); (C.B.)
- In Vivo Human Molecular and Structural Neuroimaging Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, 20121 Milan, Italy
| | - Giacomo Tondo
- School of Psychology, Vita-Salute San Raffaele University, 20121 Milan, Italy; (G.C.); (G.T.); (C.B.)
- In Vivo Human Molecular and Structural Neuroimaging Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, 20121 Milan, Italy
| | - Cecilia Boccalini
- School of Psychology, Vita-Salute San Raffaele University, 20121 Milan, Italy; (G.C.); (G.T.); (C.B.)
- In Vivo Human Molecular and Structural Neuroimaging Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, 20121 Milan, Italy
| | - Daniela Perani
- School of Psychology, Vita-Salute San Raffaele University, 20121 Milan, Italy; (G.C.); (G.T.); (C.B.)
- In Vivo Human Molecular and Structural Neuroimaging Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, 20121 Milan, Italy
- Nuclear Medicine Unit, San Raffaele Hospital, 20121 Milan, Italy
- Correspondence: ; Tel.: +39-02-26432224
| |
Collapse
|
|
24
|
Babiloni C, Ferri R, Noce G, Lizio R, Lopez S, Lorenzo I, Panzavolta A, Soricelli A, Nobili F, Arnaldi D, Famà F, Orzi F, Buttinelli C, Giubilei F, Cipollini V, Marizzoni M, Güntekin B, Aktürk T, Hanoğlu L, Yener G, Özbek Y, Stocchi F, Vacca L, Frisoni GB, Del Percio C. Abnormalities of Cortical Sources of Resting State Alpha Electroencephalographic Rhythms are Related to Education Attainment in Cognitively Unimpaired Seniors and Patients with Alzheimer's Disease and Amnesic Mild Cognitive Impairment. Cereb Cortex 2021; 31:2220-2237. [PMID: 33251540 DOI: 10.1093/cercor/bhaa356] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2020] [Revised: 10/23/2020] [Accepted: 10/26/2020] [Indexed: 12/21/2022] Open
Abstract
In normal old (Nold) and Alzheimer's disease (AD) persons, a high cognitive reserve (CR) makes them more resistant and resilient to brain neuropathology and neurodegeneration. Here, we tested whether these effects may affect neurophysiological oscillatory mechanisms generating dominant resting state electroencephalographic (rsEEG) alpha rhythms in Nold and patients with mild cognitive impairment (MCI) due to AD (ADMCI). Data in 60 Nold and 70 ADMCI participants, stratified in higher (Edu+) and lower (Edu-) educational attainment subgroups, were available in an Italian-Turkish archive. The subgroups were matched for age, gender, and education. RsEEG cortical sources were estimated by eLORETA freeware. As compared to the Nold-Edu- subgroup, the Nold-Edu+ subgroup showed greater alpha source activations topographically widespread. On the contrary, in relation to the ADMCI-Edu- subgroup, the ADMCI-Edu+ subgroup displayed lower alpha source activations topographically widespread. Furthermore, the 2 ADMCI subgroups had matched cerebrospinal AD diagnostic biomarkers, brain gray-white matter measures, and neuropsychological scores. The current findings suggest that a high CR may be related to changes in rsEEG alpha rhythms in Nold and ADMCI persons. These changes may underlie neuroprotective effects in Nold seniors and subtend functional compensatory mechanisms unrelated to brain structure alterations in ADMCI patients.
Collapse
Affiliation(s)
- Claudio Babiloni
- Department of Physiology and Pharmacology "Vittorio Erspamer", Sapienza University of Rome, Rome, Italy.,San Raffaele of Cassino, Cassino, Italy
| | | | | | | | - Susanna Lopez
- Nephrology, Dialysis and Transplantation Unit, Department of Emergency and Organ Transplantation, Aldo Moro University of Bari, Bari, Italy
| | | | - Andrea Panzavolta
- Department of Physiology and Pharmacology "Vittorio Erspamer", Sapienza University of Rome, Rome, Italy
| | - Andrea Soricelli
- IRCCS SDN, Napoli, Italy.,Department of Motor Sciences and Healthiness, University of Naples Parthenope, Naples, Italy
| | - Flavio Nobili
- Clinica Neurologica, IRCCS Ospedale Policlinico San Martino, Genova, Italy.,Dipartimento di Neuroscienze, Oftalmologia, Genetica, Riabilitazione e Scienze Materno-infantili (DiNOGMI), Università di Genova, Italy
| | - Dario Arnaldi
- Clinica Neurologica, IRCCS Ospedale Policlinico San Martino, Genova, Italy.,Dipartimento di Neuroscienze, Oftalmologia, Genetica, Riabilitazione e Scienze Materno-infantili (DiNOGMI), Università di Genova, Italy
| | - Francesco Famà
- Dipartimento di Neuroscienze, Oftalmologia, Genetica, Riabilitazione e Scienze Materno-infantili (DiNOGMI), Università di Genova, Italy
| | - Francesco Orzi
- Department of Neuroscience, Mental Health and Sensory Organs, Sapienza University of Rome, Rome, Italy
| | - Carla Buttinelli
- Department of Neuroscience, Mental Health and Sensory Organs, Sapienza University of Rome, Rome, Italy
| | - Franco Giubilei
- Department of Neuroscience, Mental Health and Sensory Organs, Sapienza University of Rome, Rome, Italy
| | - Virginia Cipollini
- Department of Neuroscience, Mental Health and Sensory Organs, Sapienza University of Rome, Rome, Italy
| | - Moira Marizzoni
- Laboratory of Alzheimer's Neuroimaging and Epidemiology, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy
| | - Bahar Güntekin
- Department of Biophysics, School of Medicine, Istanbul Medipol University, Istanbul, Turkey.,REMER, Clinical Electrophysiology, Neuroimaging and Neuromodulation Lab., Istanbul Medipol University, Istanbul, Turkey
| | - Tuba Aktürk
- REMER, Clinical Electrophysiology, Neuroimaging and Neuromodulation Lab., Istanbul Medipol University, Istanbul, Turkey
| | - Lutfu Hanoğlu
- Department of Neurology, School of Medicine, Istanbul Medipol University, Istanbul, Turkey
| | - Görsev Yener
- Izmir Biomedicine and Genome Center, Dokuz Eylul University Health Campus, Izmir, Turkey.,Department of Neurosciences, Institute of Health Sciences, Dokuz Eylul University, Izmir, Turkey
| | - Yağmur Özbek
- Department of Neurosciences, Institute of Health Sciences, Dokuz Eylul University, Izmir, Turkey
| | - Fabrizio Stocchi
- Institute for Research and Medical Care, IRCCS San Raffaele Pisana, Rome, Italy
| | - Laura Vacca
- Institute for Research and Medical Care, IRCCS San Raffaele Pisana, Rome, Italy
| | - Giovanni B Frisoni
- Laboratory of Alzheimer's Neuroimaging and Epidemiology, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy.,Memory Clinic and LANVIE-Laboratory of Neuroimaging of Aging, University Hospitals and University of Geneva, Geneva, Switzerland
| | - Claudio Del Percio
- Department of Physiology and Pharmacology "Vittorio Erspamer", Sapienza University of Rome, Rome, Italy
| |
Collapse
|
|
25
|
Bauckneht M, Chincarini A, Brendel M, Rominger A, Beyer L, Bruffaerts R, Vandenberghe R, Kramberger MG, Trost M, Garibotto V, Nicastro N, Frisoni GB, Lemstra AW, van Berckel BNM, Pilotto A, Padovani A, Ochoa-Figueroa MA, Davidsson A, Camacho V, Peira E, Arnaldi D, Pardini M, Donegani MI, Raffa S, Miceli A, Sambuceti G, Aarsland D, Nobili F, Morbelli S. Associations among education, age, and the dementia with Lewy bodies (DLB) metabolic pattern: A European-DLB consortium project. Alzheimers Dement 2021; 17:1277-1286. [PMID: 33528089 DOI: 10.1002/alz.12294] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2020] [Revised: 12/29/2020] [Accepted: 12/31/2020] [Indexed: 12/22/2022]
Abstract
INTRODUCTION We assessed the influence of education as a proxy of cognitive reserve and age on the dementia with Lewy bodies (DLB) metabolic pattern. METHODS Brain 18F-fluorodeoxyglucose positron emission tomography and clinical/demographic information were available in 169 probable DLB patients included in the European DLB-consortium database. Principal component analysis identified brain regions relevant to local data variance. A linear regression model was applied to generate age- and education-sensitive maps corrected for Mini-Mental State Examination score, sex (and either education or age). RESULTS Age negatively covaried with metabolism in bilateral middle and superior frontal cortex, anterior and posterior cingulate, reducing the expression of the DLB-typical cingulate island sign (CIS). Education negatively covaried with metabolism in the left inferior parietal cortex and precuneus (making the CIS more prominent). DISCUSSION These findings point out the importance of tailoring interpretation of DLB biomarkers considering the concomitant effect of individual, non-disease-related variables such as age and cognitive reserve.
Collapse
Affiliation(s)
- Matteo Bauckneht
- Nuclear Medicine Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Andrea Chincarini
- National Institute of Nuclear Physics (INFN), Genoa Section, Genoa, Italy
| | - Matthias Brendel
- Department of Nuclear Medicine, University Hospital, LMU Munich, Munich, Germany
| | - Axel Rominger
- Department of Nuclear Medicine, University Hospital, LMU Munich, Munich, Germany.,Department of Nuclear Medicine, Inselspital, University Hospital Bern, Bern, Switzerland
| | - Leonie Beyer
- Department of Nuclear Medicine, University Hospital, LMU Munich, Munich, Germany
| | - Rose Bruffaerts
- Laboratory for Cognitive Neurology, Department of Neurosciences, KU Leuven, Leuven, Belgium.,Neurology Department, University Hospitals Leuven, Leuven, Belgium.,Biomedical Research Institute, Hasselt University, Hasselt, Belgium
| | - Rik Vandenberghe
- Laboratory for Cognitive Neurology, Department of Neurosciences, KU Leuven, Leuven, Belgium.,Neurology Department, University Hospitals Leuven, Leuven, Belgium
| | - Milica G Kramberger
- Department of Neurology, University Medical Centre Ljubljana, Ljubljana, Slovenia.,Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
| | - Maja Trost
- Department of Neurology, University Medical Centre Ljubljana, Ljubljana, Slovenia.,Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
| | - Valentina Garibotto
- Division of Nuclear Medicine and Molecular Imaging, Geneva University Hospitals and NIMTLab, Geneva University, Geneva, Switzerland
| | - Nicolas Nicastro
- Department of Clinical Neurosciences, Geneva University Hospitals, Geneva, Switzerland.,Department of Psychiatry, University of Cambridge, Cambridge, UK
| | - Giovanni B Frisoni
- LANVIE (Laboratoire de Neuroimagerie du Vieillissement), Department of Psychiatry, Geneva University Hospitals, Geneva, Switzerland
| | - Afina W Lemstra
- Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands
| | - Bart N M van Berckel
- Department of Radiology & Nuclear Medicine, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands
| | - Andrea Pilotto
- Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.,Parkinson's Disease Rehabilitation Centre, FERB ONLUS-S, Isidoro Hospital, Trescore Balneario, Italy
| | - Alessandro Padovani
- Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy
| | - Miguel A Ochoa-Figueroa
- Department of Clinical Physiology in Linköping, Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden.,Department of Diagnostic Radiology, Linköping University Hospital, Linköping, Sweden.,Center for Medical Image Science and Visualization (CMIV), Linköping University, Linköping, Sweden
| | - Anette Davidsson
- Department of Clinical Physiology in Linköping, Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden
| | - Valle Camacho
- Servicio de Medicina Nuclear, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Enrico Peira
- National Institute of Nuclear Physics (INFN), Genoa Section, Genoa, Italy.,Department of Neuroscience (DINOGMI), University of Genoa, Genoa, Italy
| | - Dario Arnaldi
- Department of Neuroscience (DINOGMI), University of Genoa, Genoa, Italy.,Clinical Neurology, IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Matteo Pardini
- Department of Neuroscience (DINOGMI), University of Genoa, Genoa, Italy.,Clinical Neurology, IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | | | - Stefano Raffa
- Department of Health Sciences, University of Genoa, Italy
| | - Alberto Miceli
- Department of Health Sciences, University of Genoa, Italy
| | - Gianmario Sambuceti
- Nuclear Medicine Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy.,Department of Health Sciences, University of Genoa, Italy
| | - Dag Aarsland
- Centre for Age-Related Medicine (SESAM), Stavanger University Hospital, Stavanger, Norway.,Department of Old Age Psychiatry, Institute of Psychiatry, Psychology, and Neuroscience, King's College, London, UK
| | - Flavio Nobili
- Department of Neuroscience (DINOGMI), University of Genoa, Genoa, Italy.,Clinical Neurology, IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Silvia Morbelli
- Nuclear Medicine Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy.,Department of Health Sciences, University of Genoa, Italy
| |
Collapse
|
|
26
|
Canosa A, Palumbo F, Iazzolino B, Peotta L, Di Pede F, Manera U, Vasta R, Grassano M, Solero L, Arena V, Moglia C, Calvo A, Chiò A, Pagani M. The interplay among education, brain metabolism, and cognitive impairment suggests a role of cognitive reserve in Amyotrophic Lateral Sclerosis. Neurobiol Aging 2020; 98:205-213. [PMID: 33316576 DOI: 10.1016/j.neurobiolaging.2020.11.010] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2020] [Revised: 11/08/2020] [Accepted: 11/10/2020] [Indexed: 01/09/2023]
Abstract
We tested the Cognitive Reserve (CR) hypothesis in Amyotrophic Lateral Sclerosis (ALS), enrolling 111 patients, using education as CR proxy, 18F-FDG-PET to assess brain damage, and ECAS to measure cognition. Education was regressed out against brain metabolism, including age, sex, spinal/bulbar onset, ALSFRS-R, and ECAS as covariates. Clusters showing a significant correlation were used as seed regions in an interregional correlation analysis (IRCA) in the ALS group and in 40 controls. In the ALS group, we found a negative correlation between brain metabolism and education in the right anterior cingulate and bilateral medial frontal gyrus. In the IRCA in the ALS group, the medial frontal cluster metabolism positively correlated with that of frontotemporal regions (right > left), bilateral caudate nuclei, and right insula, and negatively correlated with that of corticospinal tracts, cerebellum, and pons. In controls, the IRCA showed significant positive correlations in the same regions but less extended. Our results agree with the CR hypothesis. The negative correlation between the medial frontal cluster and the cerebellum found only in ALS patients might reflect cerebellar compensation.
Collapse
Affiliation(s)
- Antonio Canosa
- ALS Centre, "Rita Levi Montalcini" Department of Neuroscience, University of Turin, Turin, Italy; Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, SC Neurologia 1U, Turin, Italy.
| | - Francesca Palumbo
- ALS Centre, "Rita Levi Montalcini" Department of Neuroscience, University of Turin, Turin, Italy
| | - Barbara Iazzolino
- ALS Centre, "Rita Levi Montalcini" Department of Neuroscience, University of Turin, Turin, Italy
| | - Laura Peotta
- ALS Centre, "Rita Levi Montalcini" Department of Neuroscience, University of Turin, Turin, Italy
| | - Francesca Di Pede
- ALS Centre, "Rita Levi Montalcini" Department of Neuroscience, University of Turin, Turin, Italy
| | - Umberto Manera
- ALS Centre, "Rita Levi Montalcini" Department of Neuroscience, University of Turin, Turin, Italy
| | - Rosario Vasta
- ALS Centre, "Rita Levi Montalcini" Department of Neuroscience, University of Turin, Turin, Italy
| | - Maurizio Grassano
- ALS Centre, "Rita Levi Montalcini" Department of Neuroscience, University of Turin, Turin, Italy
| | - Luca Solero
- ALS Centre, "Rita Levi Montalcini" Department of Neuroscience, University of Turin, Turin, Italy
| | - Vincenzo Arena
- Positron Emission Tomography Centre AFFIDEA-IRMET S.P.A., Turin, Italy
| | - Cristina Moglia
- ALS Centre, "Rita Levi Montalcini" Department of Neuroscience, University of Turin, Turin, Italy; Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, SC Neurologia 1U, Turin, Italy
| | - Andrea Calvo
- ALS Centre, "Rita Levi Montalcini" Department of Neuroscience, University of Turin, Turin, Italy; Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, SC Neurologia 1U, Turin, Italy; Neuroscience Institute of Turin (NIT), Turin, Italy
| | - Adriano Chiò
- ALS Centre, "Rita Levi Montalcini" Department of Neuroscience, University of Turin, Turin, Italy; Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, SC Neurologia 1U, Turin, Italy; Neuroscience Institute of Turin (NIT), Turin, Italy; Institute of Cognitive Sciences and Technologies, C.N.R., Rome, Italy
| | - Marco Pagani
- Institute of Cognitive Sciences and Technologies, C.N.R., Rome, Italy; Department of Medical Radiation Physics and Nuclear Medicine, Karolinska University Hospital, Stockholm, Sweden
| |
Collapse
|
|
27
|
Staekenborg SS, Kelly N, Schuur J, Koster P, Scherder E, Tielkes CE, Scheltens P, Claus JJ. Education as Proxy for Cognitive Reserve in a Large Elderly Memory Clinic: ‘Window of Benefit’. J Alzheimers Dis 2020; 76:671-679. [DOI: 10.3233/jad-191332] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
Affiliation(s)
| | - Naomi Kelly
- Department of Medical Psychology, Neuroscience Campus Amsterdam, Amsterdam University Medical Center, Amsterdam, The Netherlands
| | - Jacqueline Schuur
- Department of Geriatrics, Tergooi Hospital, Blaricum, The Netherlands
| | - Pieter Koster
- Department of Radiology, Tergooi Hospital, Blaricum, The Netherlands
| | - Erik Scherder
- Department of Medical Psychology, Neuroscience Campus Amsterdam, Amsterdam University Medical Center, Amsterdam, The Netherlands
| | | | - Philip Scheltens
- Department of Neurology, Alzheimer Center, Amsterdam Neuroscience, Amsterdam University Medical Center, Amsterdam, The Netherlands
| | - Jules J. Claus
- Department of Neurology, Tergooi Hospital, Blaricum, The Netherlands
| |
Collapse
|
|
28
|
Brugnolo A, De Carli F, Pagani M, Morbelli S, Jonsson C, Chincarini A, Frisoni GB, Galluzzi S, Perneczky R, Drzezga A, van Berckel BNM, Ossenkoppele R, Didic M, Guedj E, Arnaldi D, Massa F, Grazzini M, Pardini M, Mecocci P, Dottorini ME, Bauckneht M, Sambuceti G, Nobili F. Head-to-Head Comparison among Semi-Quantification Tools of Brain FDG-PET to Aid the Diagnosis of Prodromal Alzheimer's Disease. J Alzheimers Dis 2020; 68:383-394. [PMID: 30776000 DOI: 10.3233/jad-181022] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
BACKGROUND Several automatic tools have been implemented for semi-quantitative assessment of brain [18]F-FDG-PET. OBJECTIVE We aimed to head-to-head compare the diagnostic performance among three statistical parametric mapping (SPM)-based approaches, another voxel-based tool (i.e., PALZ), and a volumetric region of interest (VROI-SVM)-based approach, in distinguishing patients with prodromal Alzheimer's disease (pAD) from controls. METHODS Sixty-two pAD patients (MMSE score = 27.0±1.6) and one hundred-nine healthy subjects (CTR) (MMSE score = 29.2±1.2) were enrolled in five centers of the European Alzheimer's Disease Consortium. The three SPM-based methods, based on different rationales, included 1) a cluster identified through the correlation analysis between [18]F-FDG-PET and a verbal memory test (VROI-1), 2) a VROI derived from the comparison between pAD and CTR (VROI-2), and 3) visual analysis of individual maps obtained by the comparison between each subject and CTR (SPM-Maps). The VROI-SVM approach was based on 6 VROI plus 6 VROI asymmetry values derived from the pAD versus CTR comparison thanks to support vector machine (SVM). RESULTS The areas under the ROC curves between pAD and CTR were 0.84 for VROI-1, 0.83 for VROI-2, 0.79 for SPM maps, 0.87 for PALZ, and 0.95 for VROI-SVM. Pairwise comparisons of Youden index did not show statistically significant differences in diagnostic performance between VROI-1, VROI-2, SPM-Maps, and PALZ score whereas VROI-SVM performed significantly (p < 0.005) better than any of the other methods. CONCLUSION The study confirms the good accuracy of [18]F-FDG-PET in discriminating healthy subjects from pAD and highlights that a non-linear, automatic VROI classifier based on SVM performs better than the voxel-based methods.
Collapse
Affiliation(s)
- Andrea Brugnolo
- Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, and Mother-Child health (DINOGMI), University of Genoa, Italy.,Clinical Psychology Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Fabrizio De Carli
- Institute of Bioimaging and Molecular Physiology, Consiglio Nazionale delle Ricerche (CNR), Genoa, Italy
| | - Marco Pagani
- Institute of Cognitive Sciences and Technologies, Consiglio Nazionale delle Ricerche (CNR), Rome, Italy.,Department of Nuclear Medicine, Karolinska Hospital, Stockholm, Sweden
| | - Slivia Morbelli
- Department of Health Sciences (DISSAL), University of Genoa, Italy.,Nuclear Medicine Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Cathrine Jonsson
- Medical Radiation Physics and Nuclear Medicine, Imaging and Physiology, Karolinska University Hospital, Stockholm, Sweden
| | | | - Giovanni B Frisoni
- LENITEM Laboratory of Epidemiology and Neuroimaging, IRCCS S. Giovanni di Dio-FBF, Brescia, Italy.,University Hospitals and University of Geneva, Geneva, Switzerland
| | - Samantha Galluzzi
- LENITEM Laboratory of Epidemiology and Neuroimaging, IRCCS S. Giovanni di Dio-FBF, Brescia, Italy
| | - Robert Perneczky
- Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich, Germany.,Department of Psychiatry and Psychotherapy, Technische Universität München, Munich, Germany.,German Center for Neurodegenerative Diseases (DZNE) Munich, Germany.,Neuroepidemiology and Ageing Research Unit, School of Public Health, Faculty of Medicine, The Imperial College London of Science, Technology and Medicine, London, UK
| | - Alexander Drzezga
- Department of Nuclear Medicine, University Hospital of Cologne, Germany; previously at Department of Nuclear Medicine, Technische Universität, Munich, Germany
| | - Bart N M van Berckel
- Department of Nuclear Medicine & PET Research, VU University Medical Center, Amsterdam, The Netherlands
| | - Rik Ossenkoppele
- Department of Nuclear Medicine & PET Research, VU University Medical Center, Amsterdam, The Netherlands
| | - Mira Didic
- APHM, CHU Timone, Service de Neurologie et Neuropsychologie, Aix-Marseille University, Marseille, France
| | - Eric Guedj
- APHM, CHU Timone, Service de Médecine Nucléaire, CERIMED, Institut Fresnel, CNRS, Ecole Centrale Marseille, Aix-Marseille University, France
| | - Dario Arnaldi
- Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, and Mother-Child health (DINOGMI), University of Genoa, Italy.,Neurology Clinics, IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Federico Massa
- Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, and Mother-Child health (DINOGMI), University of Genoa, Italy
| | - Matteo Grazzini
- Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, and Mother-Child health (DINOGMI), University of Genoa, Italy
| | - Matteo Pardini
- Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, and Mother-Child health (DINOGMI), University of Genoa, Italy.,Neurology Clinics, IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Patrizia Mecocci
- Section of Gerontology and Geriatrics, University of Perugia, Perugia, Italy
| | - Massimo E Dottorini
- Department of Diagnostic Imaging, Nuclear Medicine Unit, Perugia General Hospital, Perugia, Italy
| | - Matteo Bauckneht
- Department of Health Sciences (DISSAL), University of Genoa, Italy.,Nuclear Medicine Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Gianmario Sambuceti
- Department of Health Sciences (DISSAL), University of Genoa, Italy.,Nuclear Medicine Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Flavio Nobili
- Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, and Mother-Child health (DINOGMI), University of Genoa, Italy.,Neurology Clinics, IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| |
Collapse
|
|
29
|
Rosa G, Giannotti C, Martella L, Massa F, Serafini G, Pardini M, Nobili FM, Monacelli F. Brain Aging, Cardiovascular Diseases, Mixed Dementia, and Frailty in the Oldest Old: From Brain Phenotype to Clinical Expression. J Alzheimers Dis 2020; 75:1083-1103. [DOI: 10.3233/jad-191075] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Affiliation(s)
- Gianmarco Rosa
- Department of Internal Medicine and Medical Specialties, DIMI, Section of Cardiovascular Diseases, University of Genoa, Genoa, Italy
- IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Chiara Giannotti
- Department of Internal Medicine and Medical Specialties, DIMI, Section of Geriatrics, Genoa, Italy
- IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Lucia Martella
- Department of Internal Medicine and Medical Specialties, DIMI, Section of Geriatrics, Genoa, Italy
- IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Federico Massa
- Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health DINOGMI, Section of Psychiatry, University of Genoa, Genoa, Italy
- IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Gianluca Serafini
- Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health DINOGMI, Section of Psychiatry, University of Genoa, Genoa, Italy
- IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Matteo Pardini
- Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health DINOGMI, Section of Psychiatry, University of Genoa, Genoa, Italy
- IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Flavio Mariano Nobili
- Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health DINOGMI, Section of Psychiatry, University of Genoa, Genoa, Italy
- IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Fiammetta Monacelli
- Department of Internal Medicine and Medical Specialties, DIMI, Section of Geriatrics, Genoa, Italy
- IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | | |
Collapse
|
|
30
|
Canosa A, D'Ovidio F, Calvo A, Moglia C, Manera U, Torrieri MC, Vasta R, Cistaro A, Gallo S, Iazzolino B, Nobili FM, Casale F, Chiò A, Pagani M. Lifetime sport practice and brain metabolism in Amyotrophic Lateral Sclerosis. NEUROIMAGE-CLINICAL 2020; 27:102312. [PMID: 32622315 PMCID: PMC7334468 DOI: 10.1016/j.nicl.2020.102312] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/15/2020] [Revised: 06/08/2020] [Accepted: 06/09/2020] [Indexed: 12/12/2022]
Abstract
The possible impact of lifetime physical activity on the risk of ALS is debated. Brain18F-FDG-PET is a marker of neuronal integrity in vivo. We compared cases who did not practice sport (N), cases who did (Y) and controls. N had more extensive changes in areas involved in ALS at the same disability level. N might cope better with the neurodegenerative process compared to Y. Objective To evaluate the metabolic correlates of lifetime sport practice in ALS through brain 18F-FDG-PET. Methods 131 patients completed a questionnaire about lifetime exposures, including physical activity related to sports, hobbies and occupations, and underwent brain 18F-FDG-PET. Exposure to sports was expressed as MET (Metabolic Equivalent of Task). We considered only regular practice (at least 2 h/week, for at least three months). We compared brain metabolism between two groups: subjects who did not report regular sport practice during life (N-group) and patients who did (Y-group). The resulting significant clusters were used in each group as seed regions in an interregional correlation analysis (IRCA) to evaluate the impact of lifetime sport practice on brain networks typically involved by the neurodegenerative process of ALS. Each group was compared to healthy controls (HC, n = 40). Results We found a significant, relative cerebellar hypermetabolism in the N-group compared to the Y-group. The metabolism of such cerebellar cluster resulted correlated to more significant and widespread metabolic changes in areas known to be affected by ALS (i.e. frontotemporal regions and corticospinal tracts) in the N-group as compared to the Y-group, despite the same level of disability as expressed by the ALS FRS-R. Such findings resulted independent of age, sex, site of onset (bulbar/spinal), presence/absence of C9ORF72 expansion, cognitive status and physical activity related to hobbies and occupations. When compared to HC, the N-group showed more widespread metabolic changes than the Y-group in cortical regions known to be relatively hypometabolic in ALS patients as compared to HC. Conclusions We hypothesize that patients of the N-group might cope better with the neurodegenerative process, since they show more widespread metabolic changes as compared to the Y-group, despite the same level of disability. Nevertheless, further studies are necessary to corroborate this hypothesis.
Collapse
Affiliation(s)
- Antonio Canosa
- ALS Centre, "Rita Levi Montalcini" Department of Neuroscience, University of Turin, Turin, Italy; Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, SC Neurologia 1U, Turin, Italy.
| | - Fabrizio D'Ovidio
- ALS Centre, "Rita Levi Montalcini" Department of Neuroscience, University of Turin, Turin, Italy
| | - Andrea Calvo
- ALS Centre, "Rita Levi Montalcini" Department of Neuroscience, University of Turin, Turin, Italy; Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, SC Neurologia 1U, Turin, Italy; Neuroscience Institute of Turin (NIT), Turin, Italy
| | - Cristina Moglia
- ALS Centre, "Rita Levi Montalcini" Department of Neuroscience, University of Turin, Turin, Italy; Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, SC Neurologia 1U, Turin, Italy
| | - Umberto Manera
- ALS Centre, "Rita Levi Montalcini" Department of Neuroscience, University of Turin, Turin, Italy
| | - Maria Claudia Torrieri
- ALS Centre, "Rita Levi Montalcini" Department of Neuroscience, University of Turin, Turin, Italy
| | - Rosario Vasta
- ALS Centre, "Rita Levi Montalcini" Department of Neuroscience, University of Turin, Turin, Italy
| | - Angelina Cistaro
- ALS Centre, "Rita Levi Montalcini" Department of Neuroscience, University of Turin, Turin, Italy; Nuclear Medicine Advisor for the ALS Centre, "Rita Levi Montalcini" Department of Neuroscience, University of Turin, Turin, Italy
| | - Silvia Gallo
- ALS Centre, "Rita Levi Montalcini" Department of Neuroscience, University of Turin, Turin, Italy
| | - Barbara Iazzolino
- ALS Centre, "Rita Levi Montalcini" Department of Neuroscience, University of Turin, Turin, Italy
| | - Flavio Mariano Nobili
- Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa, Genoa, Italy; Clinica Neurologica, IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Federico Casale
- ALS Centre, "Rita Levi Montalcini" Department of Neuroscience, University of Turin, Turin, Italy
| | - Adriano Chiò
- ALS Centre, "Rita Levi Montalcini" Department of Neuroscience, University of Turin, Turin, Italy; Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, SC Neurologia 1U, Turin, Italy; Neuroscience Institute of Turin (NIT), Turin, Italy; Institute of Cognitive Sciences and Technologies, C.N.R., Rome, Italy
| | - Marco Pagani
- Institute of Cognitive Sciences and Technologies, C.N.R., Rome, Italy; Department of Nuclear Medicine, Karolinska Hospital, Stockholm, Sweden
| |
Collapse
|
|
31
|
Angelelli P, Macchitella L, Toraldo DM, Abbate E, Marinelli CV, Arigliani M, De Benedetto M. The Neuropsychological Profile of Attention Deficits of Patients with Obstructive Sleep Apnea: An Update on the Daytime Attentional Impairment. Brain Sci 2020; 10:brainsci10060325. [PMID: 32471112 PMCID: PMC7349097 DOI: 10.3390/brainsci10060325] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2020] [Revised: 04/20/2020] [Accepted: 05/22/2020] [Indexed: 11/16/2022] Open
Abstract
Introduction: Patients with obstructive sleep apnea (OSA) suffer from several neurocognitive disturbances. One of the neuropsychological processes most investigated in OSA patients is attention, but the results have been controversial. Here, we update the attention profile of OSA patients with the final aim to improve attention assessment, with a possible impact on clinical and medical-legal practices, in terms of which attention subdomains and parameters need consideration and which one is a high-risk OSA phenotype for attention dysfunctions. Method: For this purpose, we assessed 32 previously untreated OSA patients (26 men and 6 women) under 65 years of age (mean age 53.2 ± 7.3; mean education level 10.4 ± 3.4 years) suffering from moderate to severe sleep apnea and hypopnea (mean apnea-hypopnea index (AHI) 45.3 ± 22.9, range 16.1–69.6). A control group of 34 healthy participants matched with OSA patients for age, education level, and general cognitive functioning were also enrolled. The OSA patients and healthy participants were tested through an extensive computerized battery (Test of Attentional Performance, TAP) that evaluated intensive (i.e., alertness and vigilance) and selective (i.e., divided and selective) dimensions of attention and returned different outcome parameters (i.e., reaction time, stability of performance, and various types of errors). Data analysis: The data were analyzed by ANCOVA which compared the speed and accuracy performance of the OSA and control participants (cognitive reserve was treated as a covariate). The possible mechanisms underlying attention deficits in OSA patients were examined through correlation analysis among AHI, oxygenation parameters, sleepiness scores, and TAP outcomes and by comparing the following three phenotypes of patients: severe OSA and severe nocturnal desaturators (AHI++D+), severe OSA nondesaturators (AHI++D−), and moderate OSA nondesaturators (AHI+D−). Results: The results suggest that the OSA patients manifest deficits in both intensive and selective attention processes and that reaction time (RT) alone is ineffective for detecting and characterizing their problems, for which error analysis and stability of performance also have to be considered. Patients with severe OSA and severe hypoxemia underperformed on alertness and vigilance attention subtests. Conclusions: The data suggest the importance of evaluating attention deficits among OSA patients through several parameters (including performance instability). Moreover, the data suggest a multifaceted mechanism underlying attention dysfunction in OSA patients.
Collapse
Affiliation(s)
- Paola Angelelli
- Lab of Applied Psychology and Intervention, Department of History, Society and Human Studies, University of Salento, 73100 Lecce, Italy; (L.M.); (E.A.); (C.V.M.)
- Correspondence:
| | - Luigi Macchitella
- Lab of Applied Psychology and Intervention, Department of History, Society and Human Studies, University of Salento, 73100 Lecce, Italy; (L.M.); (E.A.); (C.V.M.)
| | | | - Elena Abbate
- Lab of Applied Psychology and Intervention, Department of History, Society and Human Studies, University of Salento, 73100 Lecce, Italy; (L.M.); (E.A.); (C.V.M.)
| | - Chiara Valeria Marinelli
- Lab of Applied Psychology and Intervention, Department of History, Society and Human Studies, University of Salento, 73100 Lecce, Italy; (L.M.); (E.A.); (C.V.M.)
| | | | | |
Collapse
|
|
32
|
Shi Z, Fu LP, Zhang N, Zhao X, Liu S, Zuo C, Cai L, Wang Y, Gao S, Ai L, Guan YH, Xu B, Ji Y. Amyloid PET in Dementia Syndromes: A Chinese Multicenter Study. J Nucl Med 2020; 61:1814-1819. [PMID: 32385166 DOI: 10.2967/jnumed.119.240325] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2019] [Accepted: 03/28/2020] [Indexed: 12/15/2022] Open
Abstract
Cerebral β-amyloid deposits and regional glucose metabolism assessed by PET are used to distinguish between Alzheimer disease (AD) and other dementia syndromes. In the present multicenter study, we estimated the prevalence of β-amyloid deposits on PET imaging in a wide variety of dementia syndromes and mild cognitive impairment (MCI) within a memory clinic population. Methods: Of the 1,193 consecutive patients with cognitive impairment (CI) who received 1 11C-PIB PET or 18F-AV45 PET or both 11C-PIB PET and 18F-AV45 PET, 960 were diagnosed with AD, 36 with frontotemporal dementia (FTD), 5 with dementia with Lewy bodies, 144 with MCI, 29 with vascular dementia, 4 with corticobasal syndrome, and 15 with unclassifiable dementia. Baseline clinical diagnoses were independently established without access to PET imaging results. Apolipoprotein E (ApoE) genotype analysis was performed on CI patients and 231 sex- and age-matched controls. Results: Of the 1,193 CI patients, 860 (72.1%) were amyloid-positive. The prevalence of amyloid positivity in AD and MCI patients was 86.8% (833/960) and 9.7% (14/144), respectively. In FTD patients, the prevalence of β-amyloid deposits was 5.6% (2/36). In the 4 corticobasal syndrome patients, 2 were amyloid-positive. Three of the 5 patients with dementia with Lewy bodies showed amyloid positivity, as did 6 of the 29 vascular dementia (20.7%) patients. The ApoEε4 allele frequency was significantly increased in amyloid-positive CI patients (30.5%) as compared with other amyloid-negative CI patients (14%) or controls (7.3%). Conclusion: Amyloid imaging may potentially be the most helpful parameter for differential diagnosis in dementia, particularly to distinguish between AD and FTD. Amyloid PET can be used in conjunction with the ApoEε4 allele genetic risk test for amyloid deposits.
Collapse
Affiliation(s)
- Zhihong Shi
- Tianjin Key Laboratory of Cerebrovascular and Neurodegenerative Diseases, Department of Neurology, Tianjin Dementia Institute, Tianjin Huanhu Hospital, Tianjin, China
| | - Li-Ping Fu
- Department of Nuclear Medicine, 1st Medical Center, Chinese PLA (People's Liberation Army) General Hospital, Beijing, China.,Department of Nuclear Medicine, China-Japan Friendship Hospital, Beijing, China
| | - Nan Zhang
- Department of Neurology, General Hospital of Tianjin Medical University, Tianjin, China
| | - Xiaobin Zhao
- Department of Nuclear Medicine, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Shuai Liu
- Tianjin Key Laboratory of Cerebrovascular and Neurodegenerative Diseases, Department of Neurology, Tianjin Dementia Institute, Tianjin Huanhu Hospital, Tianjin, China
| | - Chuantao Zuo
- PET Center, Huashan Hospital, Fudan University, Shanghai, China
| | - Li Cai
- Department of PET-CT Diagnostics, Tianjin Medical University General Hospital, Tianjin, China
| | - Ying Wang
- Department of PET-CT Diagnostics, Tianjin Medical University General Hospital, Tianjin, China
| | - Shuo Gao
- Department of PET-CT Diagnostics, Tianjin Medical University General Hospital, Tianjin, China
| | - Lin Ai
- Department of Nuclear Medicine, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Yi-Hui Guan
- PET Center, Huashan Hospital, Fudan University, Shanghai, China
| | - Baixuan Xu
- Department of Nuclear Medicine, 1st Medical Center, Chinese PLA (People's Liberation Army) General Hospital, Beijing, China
| | - Yong Ji
- Tianjin Key Laboratory of Cerebrovascular and Neurodegenerative Diseases, Department of Neurology, Tianjin Dementia Institute, Tianjin Huanhu Hospital, Tianjin, China .,China National Clinical Research Center for Neurological Diseases, Beijing, China; and.,Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| |
Collapse
|
|
33
|
Neth BJ, Graff-Radford J, Mielke MM, Przybelski SA, Lesnick TG, Schwarz CG, Reid RI, Senjem ML, Lowe VJ, Machulda MM, Petersen RC, Jr. CRJ, Knopman DS, Vemuri P. Relationship Between Risk Factors and Brain Reserve in Late Middle Age: Implications for Cognitive Aging. Front Aging Neurosci 2020; 11:355. [PMID: 31998113 PMCID: PMC6962238 DOI: 10.3389/fnagi.2019.00355] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2019] [Accepted: 12/05/2019] [Indexed: 12/16/2022] Open
Abstract
Background Brain reserve can be defined as the individual variation in the brain structural characteristics that later in life are likely to modulate cognitive performance. Late midlife represents a point in aging where some structural brain imaging changes have become manifest but the effects of cognitive aging are minimal, and thus may represent an ideal opportunity to determine the relationship between risk factors and brain imaging biomarkers of reserve. Objective We aimed to assess neuroimaging measures from multiple modalities to broaden our understanding of brain reserve, and the late midlife risk factors that may make the brain vulnerable to age related cognitive disorders. Methods We examined multimodal [structural and diffusion Magnetic Resonance Imaging (MRI), FDG PET] neuroimaging measures in 50-65 year olds to examine the associations between risk factors (Intellectual/Physical Activity: education-occupation composite, physical, and cognitive-based activity engagement; General Health Factors: presence of cardiovascular and metabolic conditions (CMC), body mass index, hemoglobin A1c, smoking status (ever/never), CAGE Alcohol Questionnaire (>2, yes/no), Beck Depression Inventory score), brain reserve measures [Dynamic: genu corpus callosum fractional anisotropy (FA), posterior cingulate cortex FDG uptake, superior parietal cortex thickness, AD signature cortical thickness; Static: intracranial volume], and cognition (global, memory, attention, language, visuospatial) from a population-based sample. We quantified dynamic proxies of brain reserve (cortical thickness, glucose metabolism, microstructural integrity) and investigated various protective/risk factors. Results Education-occupation was associated with cognition and total intracranial volume (static measure of brain reserve), but was not associated with any of the dynamic neuroimaging biomarkers. In contrast, many general health factors were associated with the dynamic neuroimaging proxies of brain reserve, while most were not associated with cognition in this late middle aged group. Conclusion Brain reserve, as exemplified by the four dynamic neuroimaging features studied here, is itself at least partly influenced by general health status in midlife, but may be largely independent of education and occupation.
Collapse
Affiliation(s)
- Bryan J. Neth
- Department of Neurology, Mayo Clinic, Rochester, MN, United States
| | | | - Michelle M. Mielke
- Department of Neurology, Mayo Clinic, Rochester, MN, United States
- Department of Health Sciences Research, Mayo Clinic, Rochester, MN, United States
| | - Scott A. Przybelski
- Department of Health Sciences Research, Mayo Clinic, Rochester, MN, United States
| | - Timothy G. Lesnick
- Department of Health Sciences Research, Mayo Clinic, Rochester, MN, United States
| | | | - Robert I. Reid
- Department of Information Technology, Mayo Clinic, Rochester, MN, United States
| | - Matthew L. Senjem
- Department of Radiology, Mayo Clinic, Rochester, MN, United States
- Department of Information Technology, Mayo Clinic, Rochester, MN, United States
| | - Val J. Lowe
- Department of Radiology, Mayo Clinic, Rochester, MN, United States
| | - Mary M. Machulda
- Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, United States
| | | | | | - David S. Knopman
- Department of Neurology, Mayo Clinic, Rochester, MN, United States
| | | |
Collapse
|
|
34
|
Elias A, Cummins T, Lamb F, Tyrrell R, Dore V, Williams R, Rosenfeld JV, Hopwood M, Villemagne VL, Rowe CC. Amyloid-β, Tau, and 18F-Fluorodeoxyglucose Positron Emission Tomography in Posttraumatic Stress Disorder. J Alzheimers Dis 2020; 73:163-173. [DOI: 10.3233/jad-190913] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Affiliation(s)
- Alby Elias
- Department of Molecular Imaging and Therapy, Austin Health, The University of Melbourne, Melbourne, VIC, Australia
- Department of Psychiatry, The University of Melbourne, Melbourne, VIC, Australia
| | - Tia Cummins
- Department of Molecular Imaging and Therapy, Austin Health, The University of Melbourne, Melbourne, VIC, Australia
- Florey Institute of Neuroscience and Mental Health, Parkville, VIC, Australia
| | - Fiona Lamb
- Department of Molecular Imaging and Therapy, Austin Health, The University of Melbourne, Melbourne, VIC, Australia
| | - Regan Tyrrell
- Department of Molecular Imaging and Therapy, Austin Health, The University of Melbourne, Melbourne, VIC, Australia
| | - Vincent Dore
- Commonwealth Scientific and Industrial Research Organization (CSIRO), Australia
| | - Rob Williams
- Florey Institute of Neuroscience and Mental Health, Parkville, VIC, Australia
| | - Jeffrey V. Rosenfeld
- Department of Surgery, Monash University, VIC, Australia
- Department of Neurosurgery, Alfred Hospital, Melbourne, VIC, Australia
| | - Malcolm Hopwood
- Department of Psychiatry, The University of Melbourne, Melbourne, VIC, Australia
| | - Victor L. Villemagne
- Department of Molecular Imaging and Therapy, Austin Health, The University of Melbourne, Melbourne, VIC, Australia
| | - Christopher C. Rowe
- Department of Molecular Imaging and Therapy, Austin Health, The University of Melbourne, Melbourne, VIC, Australia
| |
Collapse
|
|
35
|
Smith PJ. Pathways of Prevention: A Scoping Review of Dietary and Exercise Interventions for Neurocognition. Brain Plast 2019; 5:3-38. [PMID: 31970058 PMCID: PMC6971820 DOI: 10.3233/bpl-190083] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Alzheimer's disease and related dementias (ADRD) represent an increasingly urgent public health concern, with an increasing number of baby boomers now at risk. Due to a lack of efficacious therapies among symptomatic older adults, an increasing emphasis has been placed on preventive measures that can curb or even prevent ADRD development among middle-aged adults. Lifestyle modification using aerobic exercise and dietary modification represents one of the primary treatment modalities used to mitigate ADRD risk, with an increasing number of trials demonstrating that exercise and dietary change, individually and together, improve neurocognitive performance among middle-aged and older adults. Despite several optimistic findings, examination of treatment changes across lifestyle interventions reveals a variable pattern of improvements, with large individual differences across trials. The present review attempts to synthesize available literature linking lifestyle modification to neurocognitive changes, outline putative mechanisms of treatment improvement, and discuss discrepant trial findings. In addition, previous mechanistic assumptions linking lifestyle to neurocognition are discussed, with a focus on potential solutions to improve our understanding of individual neurocognitive differences in response to lifestyle modification. Specific recommendations include integration of contemporary causal inference approaches for analyzing parallel mechanistic pathways and treatment-exposure interactions. Methodological recommendations include trial multiphase optimization strategy (MOST) design approaches that leverage individual differences for improved treatment outcomes.
Collapse
Affiliation(s)
- Patrick J. Smith
- Department of Psychiatry and Behavioral Sciences (Primary), Duke University Medical Center, NC, USA
- Department of Medicine (Secondary), Duke University Medical Center, NC, USA
- Department of Population Health Sciences (Secondary), Duke University, NC, USA
| |
Collapse
|
|
36
|
Huber M, Beyer L, Prix C, Schönecker S, Palleis C, Rauchmann B, Morbelli S, Chincarini A, Bruffaerts R, Vandenberghe R, Van Laere K, Kramberger MG, Trost M, Grmek M, Garibotto V, Nicastro N, Frisoni GB, Lemstra AW, Zande J, Pilotto A, Padovani A, Garcia‐Ptacek S, Savitcheva I, Ochoa‐Figueroa MA, Davidsson A, Camacho V, Peira E, Arnaldi D, Bauckneht M, Pardini M, Sambuceti G, Vöglein J, Schnabel J, Unterrainer M, Perneczky R, Pogarell O, Buerger K, Catak C, Bartenstein P, Cumming P, Ewers M, Danek A, Levin J, Aarsland D, Nobili F, Rominger A, Brendel M. Metabolic Correlates of Dopaminergic Loss in Dementia with Lewy Bodies. Mov Disord 2019; 35:595-605. [DOI: 10.1002/mds.27945] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2019] [Revised: 10/21/2019] [Accepted: 10/23/2019] [Indexed: 12/14/2022] Open
Affiliation(s)
- Maria Huber
- Department of Nuclear Medicine University Hospital of Munich, LMU Munich Munich Germany
| | - Leonie Beyer
- Department of Nuclear Medicine University Hospital of Munich, LMU Munich Munich Germany
| | - Catharina Prix
- Department of Neurology University Hospital of Munich, LMU Munich Munich Germany
| | - Sonja Schönecker
- Department of Neurology University Hospital of Munich, LMU Munich Munich Germany
| | - Carla Palleis
- Department of Neurology University Hospital of Munich, LMU Munich Munich Germany
| | - Boris‐Stephan Rauchmann
- Department of Psychiatry and Psychotherapy University Hospital, LMU Munich Munich Germany
- Department of Radiology University Hospital of Munich, LMU Munich Munich Germany
| | - Silvia Morbelli
- IRCCS Ospedale Policlinico San Martino Genoa Italy
- Nuclear Medicine Unit, Department of Health Sciences University of Genoa Genoa Italy
| | - Andrea Chincarini
- National Institute of Nuclear Physics (INFN), Genoa section Genoa Genoa Italy
| | - Rose Bruffaerts
- Department of Neurosciences Faculty of Medicine, KU Leuven Leuven Belgium
- Department of Neurology University Hospitals Leuven Leuven Belgium
| | - Rik Vandenberghe
- Department of Neurosciences Faculty of Medicine, KU Leuven Leuven Belgium
- Department of Neurology University Hospitals Leuven Leuven Belgium
| | - Koen Van Laere
- Department of Nuclear Medicine University Hospitals Leuven Leuven Belgium
| | | | - Maja Trost
- Department of Neurology University Medical Centre Ljubljana Slovenia
- Department for Nuclear Medicine University Medical Centre Ljubljana Slovenia
| | - Marko Grmek
- Department for Nuclear Medicine University Medical Centre Ljubljana Slovenia
| | - Valentina Garibotto
- Division of Nuclear Medicine and Molecular Imaging, Geneva University Hospitals and NIMTLab Geneva University Geneva Switzerland
| | - Nicolas Nicastro
- Department of Clinical Neurosciences Geneva University Hospitals Geneva Switzerland
- Department of Psychiatry University of Cambridge Cambridge United Kingdom
| | - Giovanni B. Frisoni
- LANVIE (Laboratoire de Neuroimagerie du Vieillissement), Department of Psychiatry Geneva University Hospitals Geneva Switzerland
| | | | - Jessica Zande
- VU Medical Center Alzheimer Center Amsterdam The Netherlands
| | - Andrea Pilotto
- Neurology Unit University of Brescia Brescia Italy
- Parkinson's Disease Rehabilitation Centre FERB ONLUS–S. Isidoro Hospital Trescore Balneario (BG) Italy
| | | | - Sara Garcia‐Ptacek
- Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society Karolinska Institutet Stockholm Sweden
- Internal Medicine, section for Neurology Sädersjukhuset Stockholm Sweden
| | - Irina Savitcheva
- Medical Radiation Physics and Nuclear Medicine Karolinska University Hospital Stockholm Sweden
| | - Miguel A. Ochoa‐Figueroa
- Department of Clinical Physiology, Institution of Medicine and Health Sciences Linköping University Hospital Linköping Sweden
- Department of Diagnostic Radiology Linköping University Hospital Linköping Sweden
- Center for Medical Image Science and Visualization (CMIV) Linköping University Linköping Sweden
| | - Anette Davidsson
- Department of Clinical Physiology, Institution of Medicine and Health Sciences Linköping University Hospital Linköping Sweden
| | - Valle Camacho
- Servicio de Medicina Nuclear, Hospital de la Santa Creu i Sant Pau Universitat Autònoma de Barcelona Barcelona España
| | - Enrico Peira
- National Institute of Nuclear Physics (INFN), Genoa section Genoa Genoa Italy
- Clinical Neurology, Department of Neuroscience (DINOGMI) University of Genoa Genoa Italy
| | - Dario Arnaldi
- IRCCS Ospedale Policlinico San Martino Genoa Italy
- Clinical Neurology, Department of Neuroscience (DINOGMI) University of Genoa Genoa Italy
| | - Matteo Bauckneht
- IRCCS Ospedale Policlinico San Martino Genoa Italy
- Nuclear Medicine Unit, Department of Health Sciences University of Genoa Genoa Italy
| | - Matteo Pardini
- IRCCS Ospedale Policlinico San Martino Genoa Italy
- Clinical Neurology, Department of Neuroscience (DINOGMI) University of Genoa Genoa Italy
| | - Gianmario Sambuceti
- IRCCS Ospedale Policlinico San Martino Genoa Italy
- Nuclear Medicine Unit, Department of Health Sciences University of Genoa Genoa Italy
| | - Jonathan Vöglein
- Department of Neurology University Hospital of Munich, LMU Munich Munich Germany
- DZNE–German Center for Neurodegenerative Diseases Munich Germany
| | - Jonas Schnabel
- Department of Nuclear Medicine University Hospital of Munich, LMU Munich Munich Germany
| | - Marcus Unterrainer
- Department of Nuclear Medicine University Hospital of Munich, LMU Munich Munich Germany
| | - Robert Perneczky
- Department of Psychiatry and Psychotherapy University Hospital, LMU Munich Munich Germany
- DZNE–German Center for Neurodegenerative Diseases Munich Germany
- Ageing Epidemiology Research Unit (AGE) School of Public Health, Imperial College London United Kingdom
- Institut for Stroke and Dementia Research University of Munich Munich Germany
| | - Oliver Pogarell
- Department of Psychiatry and Psychotherapy University Hospital, LMU Munich Munich Germany
| | - Katharina Buerger
- DZNE–German Center for Neurodegenerative Diseases Munich Germany
- Institut for Stroke and Dementia Research University of Munich Munich Germany
| | - Cihan Catak
- Institut for Stroke and Dementia Research University of Munich Munich Germany
| | - Peter Bartenstein
- Department of Nuclear Medicine University Hospital of Munich, LMU Munich Munich Germany
- Munich Cluster for Systems Neurology (SyNergy) Munich Germany
| | - Paul Cumming
- Department of Nuclear Medicine University of Bern Inselspital Bern Switzerland
- School of Psychology and Counselling and IHBI Queensland University of Technology Brisbane Australia
| | - Michael Ewers
- DZNE–German Center for Neurodegenerative Diseases Munich Germany
| | - Adrian Danek
- Department of Neurology University Hospital of Munich, LMU Munich Munich Germany
| | - Johannes Levin
- Department of Neurology University Hospital of Munich, LMU Munich Munich Germany
- DZNE–German Center for Neurodegenerative Diseases Munich Germany
- Munich Cluster for Systems Neurology (SyNergy) Munich Germany
| | - Dag Aarsland
- Centre for Age‐Related Medicine (SESAM) Stavanger University Hospital Stavanger Norway
- Wolfson Centre for Age‐Related Diseases King's College London London United Kingdom
| | - Flavio Nobili
- IRCCS Ospedale Policlinico San Martino Genoa Italy
- Clinical Neurology, Department of Neuroscience (DINOGMI) University of Genoa Genoa Italy
| | - Axel Rominger
- Department of Nuclear Medicine University Hospital of Munich, LMU Munich Munich Germany
- Munich Cluster for Systems Neurology (SyNergy) Munich Germany
- Department of Nuclear Medicine University of Bern Inselspital Bern Switzerland
| | - Matthias Brendel
- Department of Nuclear Medicine University Hospital of Munich, LMU Munich Munich Germany
- Munich Cluster for Systems Neurology (SyNergy) Munich Germany
| |
Collapse
|
|
37
|
Nicolas B, Alessandra D, Daniela P, Osman R, Sara T, Giovanni B F, Valentina G. Basal forebrain metabolism in Alzheimer's disease continuum: relationship with education. Neurobiol Aging 2019; 87:70-77. [PMID: 32008856 DOI: 10.1016/j.neurobiolaging.2019.11.013] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2019] [Revised: 11/19/2019] [Accepted: 11/20/2019] [Indexed: 10/25/2022]
Abstract
We analyzed education, as a proxy of cognitive reserve, and the cholinergic pathway in Alzheimer's disease (AD), to test the hypothesis that education might modulate the relationship between clinical symptoms and metabolic and structural changes in AD. We included 84 subjects and compared between diagnostic groups and different educational levels the glucose metabolism of basal forebrain (BFM) and volume of the basal forebrain, the major cholinergic structure, and hippocampus (HM) (and hippocampal volume), a relevant projection site for the basal forebrain. Correlations with the global cognitive status and education in the whole sample were also performed. Patients with AD dementia showed reduced basal forebrain volume, hippocampal volume, and HM compared with controls. In the whole group, the global cognitive status was positively correlated with BFM and HM. Among high-educated subjects, mild cognitive impairment showed higher BFM and HM in comparison to other diagnostic groups. Our results suggest that in mild cognitive impairment subjects with a higher educational level, cholinergic activity is upregulated and this appears to have a compensatory effect, which may be lost in later symptomatic stages.
Collapse
Affiliation(s)
- Brandt Nicolas
- Faculty of Medicine, Geneva University, Geneva, Switzerland.
| | - Dodich Alessandra
- NIMTlab, Neuroimaging and Innovative Molecular Tracers Laboratory, University of Geneva, Geneva, Switzerland
| | - Perani Daniela
- Vita-Salute San Raffaele University and Division of Neuroscience San Raffaele Scientific Institute, Milan, Italy; Nuclear Medicine Unit, San Raffaele Hospital, Milan, Italy
| | - Ratib Osman
- Faculty of Medicine, Geneva University, Geneva, Switzerland; Department of Radiology and Medical informatics, Geneva University Hospitals and University of Geneva, Geneva, Switzerland
| | - Trombella Sara
- NIMTlab, Neuroimaging and Innovative Molecular Tracers Laboratory, University of Geneva, Geneva, Switzerland; Memory Center and LANVIE-Laboratory of Neuroimaging of Aging, Geneva University Hospitals, Geneva, Switzerland
| | - Frisoni Giovanni B
- Memory Center and LANVIE-Laboratory of Neuroimaging of Aging, Geneva University Hospitals, Geneva, Switzerland; Laboratory of Alzheimer's Neuroimaging and Epidemiology, IRCCS Fatebenefratelli, Brescia, Italy
| | - Garibotto Valentina
- Faculty of Medicine, Geneva University, Geneva, Switzerland; NIMTlab, Neuroimaging and Innovative Molecular Tracers Laboratory, University of Geneva, Geneva, Switzerland; Department of Radiology and Medical informatics, Geneva University Hospitals and University of Geneva, Geneva, Switzerland.
| | | |
Collapse
|
|
38
|
Menardi A, Pascual-Leone A, Fried PJ, Santarnecchi E. The Role of Cognitive Reserve in Alzheimer's Disease and Aging: A Multi-Modal Imaging Review. J Alzheimers Dis 2019; 66:1341-1362. [PMID: 30507572 DOI: 10.3233/jad-180549] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Comforts in modern society have generally been associated with longer survival rates, enabling individuals to reach advanced age as never before in history. With the increase in longevity, however, the incidence of neurodegenerative diseases, especially Alzheimer's disease, has also doubled. Nevertheless, most of the observed variance, in terms of time of clinical diagnosis and progression, often remains striking. Only recently, differences in the social, educational and occupational background of the individual, as proxies of cognitive reserve (CR), have been hypothesized to play a role in accounting for such discrepancies. CR is a well-established concept in literature; lots of studies have been conducted in trying to better understand its underlying neural substrates and associated biomarkers, resulting in an incredible amount of data being produced. Here, we aimed to summarize recent relevant published work addressing the issue, gathering evidence for the existence of a common path across research efforts that might ease future investigations by providing a general perspective on the actual state of the arts. An innovative model is hereby proposed, addressing the role of CR across structural and functional evidences, as well as the potential implementation of non-invasive brain stimulation techniques in the causal validation of such theoretical frame.
Collapse
Affiliation(s)
- Arianna Menardi
- Brain Investigation and Neuromodulation Lab, Department of Medicine, Surgery and Neuroscience, Neurology and Clinical Neurophysiology Section, University of Siena, Italy.,Berenson-Allen Center for Noninvasive Brain Stimulation, Division of Cognitive Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Alvaro Pascual-Leone
- Berenson-Allen Center for Noninvasive Brain Stimulation, Division of Cognitive Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Peter J Fried
- Berenson-Allen Center for Noninvasive Brain Stimulation, Division of Cognitive Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Emiliano Santarnecchi
- Brain Investigation and Neuromodulation Lab, Department of Medicine, Surgery and Neuroscience, Neurology and Clinical Neurophysiology Section, University of Siena, Italy.,Berenson-Allen Center for Noninvasive Brain Stimulation, Division of Cognitive Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| |
Collapse
|
|
39
|
Giovacchini G, Giovannini E, Borsò E, Lazzeri P, Riondato M, Leoncini R, Duce V, Mansi L, Ciarmiello A. The brain cognitive reserve hypothesis: A review with emphasis on the contribution of nuclear medicine neuroimaging techniques. J Cell Physiol 2019; 234:14865-14872. [PMID: 30784080 DOI: 10.1002/jcp.28308] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2018] [Revised: 01/09/2019] [Accepted: 01/24/2019] [Indexed: 01/24/2023]
Abstract
Neuropathological and clinical evidence indicates that the clinical expression of Alzheimer's disease (AD) occurs as neuropathology exceeds the brain reserve capacity. The brain or cognitive reserve (BCR) hypothesis states that high premorbid intelligence, education, and an active and stimulating lifestyle provide reserve capacity, which acts as a buffer against the cognitive deficits due to accumulating neuropathology. Neuroimaging studies that assessed the BCR hypothesis are critically reviewed with emphasis on study design and statistical analysis. Many studies were performed in the last two decades owing to the increasing availability of positron emission tomography (PET) and PET/computed tomography scanners and to the synthesis of new radiopharmaceuticals, including tracers for amyloid and tau proteins. Studies with different tracers provided complementary consistent results supporting the BCR hypothesis. Many studies were appropriately designed with a measure of reserve, a measure of brain anatomy/function/neuropathology, and a measure of cognitive functions that are necessary. Most of the early studies were performed with PET and [ 18 F]fluorodeoxyglucose, and occasionally with [ 15 O]water, reporting a significant association between higher occupation/education and lower glucose metabolism (blood flow) in associative temporo-parietal cortex in patients with AD and also in patients with MCI, after correcting for the degree in the cognitive impairment. On the contrary, performances on several neuropsychological tests increased with increasing education for participants with elevated [ 11 C]PiB uptake. Studies with the tracers specific for tau protein showed that patients with AD with elevated tau deposits had higher cognitive performances compared with patients with similar levels of tau deposits. BCR in AD is also associated with a preserved cholinergic function. The BCR hypothesis has been validated with methodologically sound study designs and sophisticated neuroimaging techniques using different radiotracers and providing an explanation for neuropathological and clinical observations on patients with AD.
Collapse
Affiliation(s)
| | | | - Elisa Borsò
- Department of Nuclear Medicine, S. Andrea Hospital, La Spezia, Italy
| | - Patrizia Lazzeri
- Department of Nuclear Medicine, S. Andrea Hospital, La Spezia, Italy
| | - Mattia Riondato
- Department of Nuclear Medicine, S. Andrea Hospital, La Spezia, Italy
| | - Rossella Leoncini
- Department of Nuclear Medicine, S. Andrea Hospital, La Spezia, Italy
| | - Valerio Duce
- Department of Nuclear Medicine, S. Andrea Hospital, La Spezia, Italy
| | - Luigi Mansi
- Department of Nuclear Medicine, S. Andrea Hospital, La Spezia, Italy
| | - Andrea Ciarmiello
- Department of Nuclear Medicine, S. Andrea Hospital, La Spezia, Italy
| |
Collapse
|
|
40
|
Benvenutto A, Giusiano B, Koric L, Gueriot C, Didic M, Felician O, Guye M, Guedj E, Ceccaldi M. Imaging Biomarkers of Neurodegeneration in Alzheimer's Disease: Distinct Contributions of Cortical MRI Atrophy and FDG-PET Hypometabolism. J Alzheimers Dis 2019; 65:1147-1157. [PMID: 30124446 DOI: 10.3233/jad-180292] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
BACKGROUND Neurodegeneration biomarkers are routinely used in the diagnosis of Alzheimer's disease (AD). OBJECTIVE To evaluate the respective contributions of two neuroimaging biomarkers, structural MRI and 18FDG-PET, in the assessment of neurodegeneration in AD dementia. METHODS Patients with mild AD dementia diagnosed based on clinical and cerebrospinal fluid criteria and cognitively healthy subjects, from the Marseille cohort ADAge with cognitive, structural MRI and 18FDG-PET assessments, were included. Extent of atrophy on MRI and of hypometabolism on 18FDG-PET were individually evaluated in each patient using a voxel-based analysis on whole-brain approach and compared to healthy subjects. Patients were divided in distinct groups according to their atrophy extent on the one hand and to their hypometabolism extent on the other, then, to their imaging profile combining the extent of the two biomarkers. RESULTS Fifty-two patients were included. The MMSE score was significantly lower in the "Extensive hypometabolism" group than in the "Limited hypometabolism" group (respectively 19.5/30 versus 23/30). A lower Innotest Amyloid Tau Index was associated with an extensive hypometabolism (p = 0.04). There were more patients with low educational level in the "Extensive atrophy" group, while a higher educational level was more found in the "Limited atrophy" group (p = 0.005). CONCLUSION 18FDG-PET hypometabolism extent is associated with the pathological processes and clinical severity of AD, while MRI atrophy seems to be influenced by the cognitive reserve. In the context of mild AD dementia, these two biomarkers of neurodegeneration are thus not interchangeable and require to be considered in combination rather than in isolation.
Collapse
Affiliation(s)
- Agnès Benvenutto
- Neurology and Neuropsychology Department and CMMR PACA Ouest, Assistance Publique-Hôpitaux de Marseille, Marseille, France
| | - Bernard Giusiano
- Department of Public Health, Assistance Publique-Hôpitaux de Marseille, Marseille, France.,Institut de Neurosciences des Systèmes, Aix-Marseille Univ, INSERM UMR 1106, Marseille, France
| | - Lejla Koric
- Neurology and Neuropsychology Department and CMMR PACA Ouest, Assistance Publique-Hôpitaux de Marseille, Marseille, France.,Aix Marseille Univ, CNRS, Centrale Marseille, Institut Fresnel, Marseille, France
| | - Claude Gueriot
- Neurology and Neuropsychology Department and CMMR PACA Ouest, Assistance Publique-Hôpitaux de Marseille, Marseille, France
| | - Mira Didic
- Neurology and Neuropsychology Department and CMMR PACA Ouest, Assistance Publique-Hôpitaux de Marseille, Marseille, France.,Institut de Neurosciences des Systèmes, Aix-Marseille Univ, INSERM UMR 1106, Marseille, France
| | - Olivier Felician
- Neurology and Neuropsychology Department and CMMR PACA Ouest, Assistance Publique-Hôpitaux de Marseille, Marseille, France.,Institut de Neurosciences des Systèmes, Aix-Marseille Univ, INSERM UMR 1106, Marseille, France
| | - Maxime Guye
- Aix Marseille Univ, CNRS, CRMBM, Marseille, France.,AP-HM, Timone University Hospital, CEMEREM, Marseille, France
| | - Eric Guedj
- Aix Marseille Univ, CNRS, Centrale Marseille, Institut Fresnel, Marseille, France.,Department of Nuclear Medecine, Assistance Publique-Hôpitaux de Marseille, Marseille, France.,CERIMED, Aix-Marseille Univ, Marseille, France
| | - Mathieu Ceccaldi
- Neurology and Neuropsychology Department and CMMR PACA Ouest, Assistance Publique-Hôpitaux de Marseille, Marseille, France.,Institut de Neurosciences des Systèmes, Aix-Marseille Univ, INSERM UMR 1106, Marseille, France
| |
Collapse
|
|
41
|
Biomarker-Based Signature of Alzheimer's Disease in Pre-MCI Individuals. Brain Sci 2019; 9:brainsci9090213. [PMID: 31450744 PMCID: PMC6769621 DOI: 10.3390/brainsci9090213] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2019] [Revised: 08/10/2019] [Accepted: 08/20/2019] [Indexed: 12/11/2022] Open
Abstract
Alzheimer’s disease (AD) pathology begins decades before the onset of clinical symptoms. It is recognized as a clinicobiological entity, being detectable in vivo independently of the clinical stage by means of pathophysiological biomarkers. Accordingly, neuropathological studies that were carried out on healthy elderly subjects, with or without subjective experience of cognitive decline, reported evidence of AD pathology in a high proportion of cases. At present, mild cognitive impairment (MCI) represents the only clinically diagnosed pre-dementia stage. Several attempts have been carried out to detect AD as early as possible, when subtle cognitive alterations, still not fulfilling MCI criteria, appear. Importantly, pre-MCI individuals showing the positivity of pathophysiological AD biomarkers show a risk of progression similar to MCI patients. In view of successful treatment with disease modifying agents, in a clinical setting, a timely diagnosis is mandatory. In clinical routine, biomarkers assessment should be taken into consideration whenever a subject with subtle cognitive deficits (pre-MCI), who is aware of his/her decline, requests to know the cause of such disturbances. In this review, we report the available neuropsychological and biomarkers data that characterize the pre-MCI patients, thus proposing pre-MCI as the first clinical manifestation of AD.
Collapse
|
|
42
|
Caldwell JZK, Zhuang X, Leavitt MJ, Banks SJ, Cummings J, Cordes D. Sex Moderates Amyloid and Apolipoprotein ε4 Effects on Default Mode Network Connectivity at Rest. Front Neurol 2019; 10:900. [PMID: 31481928 PMCID: PMC6710397 DOI: 10.3389/fneur.2019.00900] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2019] [Accepted: 08/02/2019] [Indexed: 12/12/2022] Open
Abstract
Women are more likely to have Alzheimer's disease (AD) and decline more rapidly once diagnosed despite greater verbal memory early in the disease compared to men—an advantage that has been termed “memory reserve.” Resting state functional MRI (fMRI) investigations demonstrate interactions between sex and AD risk factors in default mode network (DMN) connectivity, a network of brain regions showing progressive dysfunction in AD. Separate work suggests connectivity of left prefrontal cortex (PFC) may correlate with more general cognitive reserve in healthy aging. It is unknown whether left prefrontal functional connectivity with anterior and posterior default mode network (aDMN, pDMN) might differ by sex in AD. This study employed group independent component analysis (ICA) to analyze resting state fMRI data from 158 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) with baseline diagnoses of normal cognition or early mild cognitive impairment (eMCI). pDMN and aDMN were defined on a subject-specific basis; prefrontal areas were selected from the Brodmann atlas (BA 6, 44, 8, and 9). Moderation regression analyses examined whether sex and amyloid PET positivity (A+/–) moderated effects of apolipoprotein ε4 (APOE ε4) on connectivity between left PFC, aDMN, and pDMN; and between aDMN and pDMN. Significant analyses were followed up with partial correlations assessing relationship of connectivity to verbal memory on the Rey Auditory Verbal Learning Test (RAVLT), and with preliminary analyses within NC and eMCI groups separately. Results showed no sex moderation of effects of A+ and APOE ε4 on left prefrontal/DMN connectivity in the full sample. However, sex significantly moderated impact of A+ and APOE ε4 on connectivity between aDMN and pDMN (p < 0.01). Women with an APOE allele (ε4+) and A+ showed greater aDMN/pDMN connectivity than their ε4- counterparts. No significant results were observed in men. Subgroup analyses suggested the aDMN/pDMN finding was true for those with NC, not eMCI. Partial correlations controlling for age and education showed increased aDMN/pDMN connectivity related to better verbal learning in women (p < 0.01) and not men (p = 0.18). In women at risk for AD or in early symptomatic stages who also have evidence of amyloid burden, stronger aDMN/pDMN connectivity may support verbal learning.
Collapse
Affiliation(s)
| | - Xiaowei Zhuang
- Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, NV, United States
| | - MacKenzie J Leavitt
- Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, NV, United States
| | - Sarah J Banks
- Department of Neurosciences, University of California, San Diego, San Diego, CA, United States
| | - Jeffrey Cummings
- Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, NV, United States.,UNLV School of Allied Health Sciences, Las Vegas, NV, United States
| | - Dietmar Cordes
- Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, NV, United States
| | | |
Collapse
|
|
43
|
Sala A, Perani D. Brain Molecular Connectivity in Neurodegenerative Diseases: Recent Advances and New Perspectives Using Positron Emission Tomography. Front Neurosci 2019; 13:617. [PMID: 31258466 PMCID: PMC6587303 DOI: 10.3389/fnins.2019.00617] [Citation(s) in RCA: 48] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2019] [Accepted: 05/29/2019] [Indexed: 12/12/2022] Open
Abstract
Positron emission tomography (PET) represents a unique molecular tool to get in vivo access to a wide spectrum of biological and neuropathological processes, of crucial relevance for neurodegenerative conditions. Although most PET findings are based on massive univariate approaches, in the last decade the increasing interest in multivariate methods has paved the way to the assessment of unexplored cerebral features, spanning from resting state brain networks to whole-brain connectome properties. Currently, the combination of molecular neuroimaging techniques with multivariate connectivity methods represents one of the most powerful, yet still emerging, approach to achieve novel insights into the pathophysiology of neurodegenerative diseases. In this review, we will summarize the available evidence in the field of PET molecular connectivity, with the aim to provide an overview of how these studies may increase the understanding of the pathogenesis of neurodegenerative diseases, over and above "traditional" structural/functional connectivity studies. Considering the available evidence, a major focus will be represented by molecular connectivity studies using [18F]FDG-PET, today applied in the major neuropathological spectra, from amyloidopathies and tauopathies to synucleinopathies and beyond. Pioneering studies using PET tracers targeting brain neuropathology and neurotransmission systems for connectivity studies will be discussed, their strengths and limitations highlighted with reference to both applied methodology and results interpretation. The most common methods for molecular connectivity assessment will be reviewed, with particular emphasis on the available strategies to investigate molecular connectivity at the single-subject level, of potential relevance for not only research but also diagnostic purposes. Finally, we will highlight possible future perspectives in the field, with reference in particular to newly available PET tracers, which will expand the application of molecular connectivity to new, exciting, unforeseen possibilities.
Collapse
Affiliation(s)
- Arianna Sala
- Faculty of Medicine and Surgery, Vita-Salute San Raffaele University, Milan, Italy.,Division of Neuroscience, Faculty of Psychology, San Raffaele Scientific Institute (IRCCS), Milan, Italy
| | - Daniela Perani
- Division of Neuroscience, Faculty of Psychology, San Raffaele Scientific Institute (IRCCS), Milan, Italy.,Faculty of Psychology, Vita-Salute San Raffaele University, Milan, Italy.,Nuclear Medicine Unit, Faculty of Psychology, San Raffaele Hospital (IRCCS), Milan, Italy
| |
Collapse
|
|
44
|
Morbelli S, Chincarini A, Brendel M, Rominger A, Bruffaerts R, Vandenberghe R, Kramberger MG, Trost M, Garibotto V, Nicastro N, Frisoni GB, Lemstra AW, van der Zande J, Pilotto A, Padovani A, Garcia-Ptacek S, Savitcheva I, Ochoa-Figueroa MA, Davidsson A, Camacho V, Peira E, Arnaldi D, Bauckneht M, Pardini M, Sambuceti G, Aarsland D, Nobili F. Metabolic patterns across core features in dementia with lewy bodies. Ann Neurol 2019; 85:715-725. [PMID: 30805951 DOI: 10.1002/ana.25453] [Citation(s) in RCA: 43] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2018] [Revised: 02/22/2019] [Accepted: 02/22/2019] [Indexed: 12/14/2022]
Abstract
OBJECTIVE To identify brain regions whose metabolic impairment contributes to dementia with Lewy bodies (DLB) clinical core features expression and to assess the influence of severity of global cognitive impairment on the DLB hypometabolic pattern. METHODS Brain fluorodeoxyglucose positron emission tomography and information on core features were available in 171 patients belonging to the imaging repository of the European DLB Consortium. Principal component analysis was applied to identify brain regions relevant to the local data variance. A linear regression model was applied to generate core-feature-specific patterns controlling for the main confounding variables (Mini-Mental State Examination [MMSE], age, education, gender, and center). Regression analysis to the locally normalized intensities was performed to generate an MMSE-sensitive map. RESULTS Parkinsonism negatively covaried with bilateral parietal, precuneus, and anterior cingulate metabolism; visual hallucinations (VH) with bilateral dorsolateral-frontal cortex, posterior cingulate, and parietal metabolism; and rapid eye movement sleep behavior disorder (RBD) with bilateral parieto-occipital cortex, precuneus, and ventrolateral-frontal metabolism. VH and RBD shared a positive covariance with metabolism in the medial temporal lobe, cerebellum, brainstem, basal ganglia, thalami, and orbitofrontal and sensorimotor cortex. Cognitive fluctuations negatively covaried with occipital metabolism and positively with parietal lobe metabolism. MMSE positively covaried with metabolism in the left superior frontal gyrus, bilateral-parietal cortex, and left precuneus, and negatively with metabolism in the insula, medial frontal gyrus, hippocampus in the left hemisphere, and right cerebellum. INTERPRETATION Regions of more preserved metabolism are relatively consistent across the variegate DLB spectrum. By contrast, core features were associated with more prominent hypometabolism in specific regions, thus suggesting a close clinical-imaging correlation, reflecting the interplay between topography of neurodegeneration and clinical presentation in DLB patients. Ann Neurol 2019;85:715-725.
Collapse
Affiliation(s)
- Silvia Morbelli
- IRCCS Ospedale Policlinico San Martino, Genoa, Italy.,Nuclear Medicine Unit, Department of Health Sciences, University of Genoa
| | - Andrea Chincarini
- National Institute of Nuclear Physics (INFN), Genoa section, Genoa, Italy
| | - Matthias Brendel
- Department of Nuclear Medicine, University Hospital, LMU Munich, Munich, Germany
| | - Axel Rominger
- Department of Nuclear Medicine, University Hospital, LMU Munich, Munich, Germany.,Department of Nuclear Medicine, Inselspital, University Hospital Bern, Bern, Switzerland
| | - Rose Bruffaerts
- Laboratory for Cognitive Neurology, Department of Neurosciences, KU Leuven, Belgium.,Neurology Department, University Hospitals Leuven, Leuven, Belgium
| | - Rik Vandenberghe
- Laboratory for Cognitive Neurology, Department of Neurosciences, KU Leuven, Belgium.,Neurology Department, University Hospitals Leuven, Leuven, Belgium
| | | | - Maja Trost
- Department of Neurology, University Medical Centre, Ljubljana, Slovenia.,Faculty of Medicine, University of Ljubljana, Slovenia
| | - Valentina Garibotto
- Division of Nuclear Medicine and Molecular Imaging, Geneva University Hospitals and NIMTLab, Geneva University
| | - Nicolas Nicastro
- Department of Clinical Neurosciences, Geneva University Hospitals, Switzerland.,Department of Psychiatry, University of Cambridge, United Kingdom
| | - Giovanni B Frisoni
- LANVIE (Laboratoire de Neuroimagerie du Vieillissement), Department of Psychiatry, Geneva University Hospitals, Geneva, Switzerland
| | - Afina W Lemstra
- VU Medical Center Alzheimer Center, Amsterdam, The Netherlands
| | | | - Andrea Pilotto
- Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.,Parkinson's Disease Rehabilitation Centre, FERB ONLUS - S. Isidoro Hospital, Trescore Balneario (BG), Italy
| | - Alessandro Padovani
- Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy
| | - Sara Garcia-Ptacek
- Department of Clinical Geriatrics, division of Neurobiology, Care Sciences and Society, Karolinska Institutet.,Internal Medicine, section for Neurology, Sädersjukhuset, Stockholm, Sweden
| | - Irina Savitcheva
- Department of Radiology, Karolinska Institutet, Stockholm, Sweden
| | - Miguel A Ochoa-Figueroa
- Department of Clinical Physiology, Institution of Medicine and Health Sciences, Linköping, Sweden.,Department of Diagnostic Radiology, Linköping University Hospital, Linköping, Sweden.,Center for Medical Image Science and Visualization (CMIV), Linköping University, Linköping, Sweden
| | - Annette Davidsson
- Department of Clinical Physiology, Institution of Medicine and Health Sciences, Linköping, Sweden
| | - Valle Camacho
- Servicio de Medicina Nuclear, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, España
| | - Enrico Peira
- National Institute of Nuclear Physics (INFN), Genoa section, Genoa, Italy.,Clinical Neurology, Department of Neuroscience (DINOGMI), University of Genoa, Italy
| | - Dario Arnaldi
- IRCCS Ospedale Policlinico San Martino, Genoa, Italy.,Clinical Neurology, Department of Neuroscience (DINOGMI), University of Genoa, Italy
| | - Matteo Bauckneht
- IRCCS Ospedale Policlinico San Martino, Genoa, Italy.,Nuclear Medicine Unit, Department of Health Sciences, University of Genoa
| | - Matteo Pardini
- IRCCS Ospedale Policlinico San Martino, Genoa, Italy.,Clinical Neurology, Department of Neuroscience (DINOGMI), University of Genoa, Italy
| | - Gianmario Sambuceti
- IRCCS Ospedale Policlinico San Martino, Genoa, Italy.,Nuclear Medicine Unit, Department of Health Sciences, University of Genoa
| | - Dag Aarsland
- Centre for Age-Related Medicine (SESAM), Stavanger University Hospital, Stavanger, Norway.,Department of Old Age Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King's College London
| | - Flavio Nobili
- IRCCS Ospedale Policlinico San Martino, Genoa, Italy.,Clinical Neurology, Department of Neuroscience (DINOGMI), University of Genoa, Italy
| |
Collapse
|
|
45
|
Perneczky R, Kempermann G, Korczyn AD, Matthews FE, Ikram MA, Scarmeas N, Chetelat G, Stern Y, Ewers M. Translational research on reserve against neurodegenerative disease: consensus report of the International Conference on Cognitive Reserve in the Dementias and the Alzheimer's Association Reserve, Resilience and Protective Factors Professional Interest Area working groups. BMC Med 2019; 17:47. [PMID: 30808345 PMCID: PMC6391801 DOI: 10.1186/s12916-019-1283-z] [Citation(s) in RCA: 63] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2018] [Accepted: 02/06/2019] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND The concept of reserve was established to account for the observation that a given degree of neurodegenerative pathology may result in varying degrees of symptoms in different individuals. There is a large amount of evidence on epidemiological risk and protective factors for neurodegenerative diseases and dementia, yet the biological mechanisms that underpin the protective effects of certain lifestyle and physiological variables remain poorly understood, limiting the development of more effective preventive and treatment strategies. Additionally, different definitions and concepts of reserve exist, which hampers the coordination of research and comparison of results across studies. DISCUSSION This paper represents the consensus of a multidisciplinary group of experts from different areas of research related to reserve, including clinical, epidemiological and basic sciences. The consensus was developed during meetings of the working groups of the first International Conference on Cognitive Reserve in the Dementias (24-25 November 2017, Munich, Germany) and the Alzheimer's Association Reserve and Resilience Professional Interest Area (25 July 2018, Chicago, USA). The main objective of the present paper is to develop a translational perspective on putative mechanisms underlying reserve against neurodegenerative disease, combining evidence from epidemiological and clinical studies with knowledge from animal and basic research. The potential brain functional and structural basis of reserve in Alzheimer's disease and other brain disorders are discussed, as well as relevant lifestyle and genetic factors assessed in both humans and animal models. CONCLUSION There is an urgent need to advance our concept of reserve from a hypothetical model to a more concrete approach that can be used to improve the development of effective interventions aimed at preventing dementia. Our group recommends agreement on a common dictionary of terms referring to different aspects of reserve, the improvement of opportunities for data sharing across individual cohorts, harmonising research approaches across laboratories and groups to reduce heterogeneity associated with human data, global coordination of clinical trials to more effectively explore whether reducing epidemiological risk factors leads to a reduced burden of neurodegenerative diseases in the population, and an increase in our understanding of the appropriateness of animal models for reserve research.
Collapse
Affiliation(s)
- Robert Perneczky
- Division of Mental Health in Older Adults and Alzheimer Therapy and Research Center, Department of Psychiatry and Psychotherapy, University Hospital, Ludwig Maximilian University Munich, 80336, Munich, Germany. .,German Center for Neurodegenerative Diseases (DZNE) Munich, Munich, Germany. .,Ageing Epidemiology (AGE) Research Unit, School of Public Health, Imperial College London, London, UK. .,Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.
| | - Gerd Kempermann
- German Center for Neurodegenerative Diseases (DZNE) Dresden, Dresden, Germany.,Center for Regenerative Therapies Dresden (CRTD), Technische Universität Dresden, Dresden, Germany
| | - Amos D Korczyn
- Sackler School of Medicine, Tel- Aviv University, Ramat Aviv, Israel
| | - Fiona E Matthews
- Institute of Health and Society, Newcastle University Institute for Ageing, Newcastle University, Newcastle, UK.,MRC Biostatistics Unit, Cambridge University, Cambridge, UK
| | - M Arfan Ikram
- Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands
| | - Nikolaos Scarmeas
- Department of Social Medicine, Psychiatry and Neurology, 1st Department of Neurology, Aeginition University Hospital, National and Kapodistrian University of Athens, Athens, Greece.,Cognitive Neuroscience Division, Department of Neurology and The Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, NY, USA
| | - Gael Chetelat
- Université Normandie, Inserm, Université de Caen-Normandie, Inserm UMR-S U1237, GIP Cyceron, Caen, France
| | - Yaakov Stern
- Cognitive Neuroscience Division, Department of Neurology and The Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, NY, USA
| | - Michael Ewers
- Institute for Stroke and Dementia Research, University Hospital, LMU Munich, Munich, Germany
| |
Collapse
|
|
46
|
Topiwala A, Suri S, Allan C, Valkanova V, Filippini N, Sexton CE, Heise V, Zsoldos E, Mahmood A, Singh-Manoux A, Mackay CE, Kivimäki M, Ebmeier KP. Predicting cognitive resilience from midlife lifestyle and multi-modal MRI: A 30-year prospective cohort study. PLoS One 2019; 14:e0211273. [PMID: 30779761 PMCID: PMC6380585 DOI: 10.1371/journal.pone.0211273] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2018] [Accepted: 01/10/2019] [Indexed: 01/08/2023] Open
Abstract
BACKGROUND There is significant heterogeneity in the clinical expression of structural brain abnormalities, including Alzheimer's disease biomarkers. Some individuals preserve their memory despite the presence of risk factors or pathological brain changes, indicating resilience. We aimed to test whether resilient individuals could be distinguished from those who develop cognitive impairment, using sociodemographic variables and neuroimaging. METHODS We included 550 older adults participating in the Whitehall II study with longitudinal data, cognitive test results, and multi-modal MRI. Hippocampal atrophy was defined as Scheltens Scores >0. Resilient individuals (n = 184) were defined by high cognitive performance despite hippocampal atrophy (HA). Non-resilient participants (n = 133) were defined by low cognitive performance (≥1.5 standard deviations (S.D.) below the group mean) in the presence of HA. Dynamic and static exposures were evaluated for their ability to predict later resilience status using multivariable logistic regression. In a brain-wide analysis we tested for group differences in the integrity of white matter (structural connectivity) and resting-state networks (functional connectivity). FINDINGS Younger age (OR: 0.87, 95% CI: 0.83 to 0.92, p<0.001), higher premorbid FSIQ (OR: 1.06, 95% CI: 1.03 to 1.10, p<0.0001) and social class (OR 1 vs. 3: 4.99, 95% CI: 1.30 to 19.16, p = 0.02, OR 2 vs. 3: 8.43, 95% CI: 1.80 to 39.45, p = 0.007) were independently associated with resilience. Resilient individuals could be differentiated from non-resilient participants by higher fractional anisotropy (FA), and less association between anterior and posterior resting state networks. Higher FA had a significantly more positive effect on cognitive performance in participants with HA, compared to those without. CONCLUSIONS Resilient individuals could be distinguished from those who developed impairments on the basis of sociodemographic characteristics, brain structural and functional connectivity, but not midlife lifestyles. There was a synergistic deleterious effect of hippocampal atrophy and poor white matter integrity on cognitive performance. Exploiting and supporting neural correlates of resilience could offer a fresh approach to postpone or avoid the appearance of clinical symptoms.
Collapse
Affiliation(s)
- Anya Topiwala
- Department of Psychiatry, University of Oxford, Oxford, United Kingdom
| | - Sana Suri
- Department of Psychiatry, University of Oxford, Oxford, United Kingdom
- Wellcome Centre for Integrative Neuroimaging, Oxford, United Kingdom
| | - Charlotte Allan
- Department of Psychiatry, University of Oxford, Oxford, United Kingdom
| | - Vyara Valkanova
- Department of Psychiatry, University of Oxford, Oxford, United Kingdom
| | - Nicola Filippini
- Department of Psychiatry, University of Oxford, Oxford, United Kingdom
| | - Claire E. Sexton
- Department of Psychiatry, University of Oxford, Oxford, United Kingdom
| | - Verena Heise
- Department of Psychiatry, University of Oxford, Oxford, United Kingdom
| | - Enikő Zsoldos
- Department of Psychiatry, University of Oxford, Oxford, United Kingdom
| | - Abda Mahmood
- Department of Psychiatry, University of Oxford, Oxford, United Kingdom
| | - Archana Singh-Manoux
- Centre for Research in Epidemiology and Population Health, INSERM, Villejuif, France
- Department of Epidemiology and Public Health, University College London, London, United Kingdom
| | - Clare E. Mackay
- Department of Psychiatry, University of Oxford, Oxford, United Kingdom
| | - Mika Kivimäki
- Department of Epidemiology and Public Health, University College London, London, United Kingdom
| | - Klaus P. Ebmeier
- Department of Psychiatry, University of Oxford, Oxford, United Kingdom
| |
Collapse
|
|
47
|
Modular architecture of metabolic brain network and its effects on the spread of perturbation impact. Neuroimage 2019; 186:146-154. [DOI: 10.1016/j.neuroimage.2018.11.003] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2018] [Revised: 09/16/2018] [Accepted: 11/03/2018] [Indexed: 12/25/2022] Open
|
|
48
|
Jung NY, Cho H, Kim YJ, Kim HJ, Lee JM, Park S, Kim ST, Kim EJ, Kim JS, Moon SH, Lee JH, Ewers M, Na DL, Seo SW. The impact of education on cortical thickness in amyloid-negative subcortical vascular dementia: cognitive reserve hypothesis. ALZHEIMERS RESEARCH & THERAPY 2018; 10:103. [PMID: 30261914 PMCID: PMC6161352 DOI: 10.1186/s13195-018-0432-5] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/03/2018] [Accepted: 09/17/2018] [Indexed: 01/22/2023]
Abstract
Background The protective effect of education has been well established in Alzheimer’s disease, whereas its role in patients with isolated cerebrovascular diseases remains unclear. We examined the correlation of education with cortical thickness and cerebral small vessel disease markers in patients with pure subcortical vascular mild cognitive impairment (svMCI) and patients with pure subcortical vascular dementia (SVaD). Methods We analyzed 45 patients with svMCI and 47 patients with SVaD with negative results on Pittsburgh compound B positron emission tomographic imaging who underwent structural brain magnetic resonance imaging. The main outcome was cortical thickness measured using surface-based morphometric analysis. We also assessed the volumes of white matter hyperintensities (WMH) and numbers of lacunes as other outcomes. To investigate the correlation of education with cortical thickness, WMH volume, and number of lacunes, multiple linear regression analyses were performed after controlling for covariates, including Mini Mental State Examination, in the svMCI and SVaD groups. Results In the SVaD group, higher education was correlated with more severe cortical thinning in the bilateral dorsolateral frontal, left medial frontal, and parahippocampal areas, whereas there was no correlation of education with cortical thickness in the svMCI group. There was no correlation between education and cerebral small vessel disease, including WMH and lacunes, in both patients with svMCI and patients with SVaD. Conclusions Our findings suggest that the compensatory effects of education on cortical thinning apply to patients with SVaD, which might be explained by the cognitive reserve hypothesis.
Collapse
Affiliation(s)
- Na-Yeon Jung
- Pusan National University Yangsan Hospital, Pusan National University School of Medicine and Research Institute for Convergence of Biomedical Science and Technology, Yangsan, Korea.,Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.,Neuroscience Center, Samsung Medical Center, Seoul, Korea
| | - Hanna Cho
- Department of Neurology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Yeo Jin Kim
- Department of Neurology, Chuncheon Sacred Heart Hospital, Hallym University College of Medicine, Chuncheon, Korea
| | - Hee Jin Kim
- Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.,Neuroscience Center, Samsung Medical Center, Seoul, Korea
| | - Jong Min Lee
- Department of Biomedical Engineering, Hanyang University, Seoul, Korea
| | - Seongbeom Park
- Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.,Neuroscience Center, Samsung Medical Center, Seoul, Korea
| | - Sung Tae Kim
- Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Eun-Joo Kim
- Department of Neurology, Pusan National University Hospital, Busan, Korea
| | - Jae Seung Kim
- Department of Nuclear Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Seung Hwan Moon
- Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jae-Hong Lee
- Department of Neurology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Michael Ewers
- Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität LMU, Munich, Germany
| | - Duk L Na
- Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.,Neuroscience Center, Samsung Medical Center, Seoul, Korea
| | - Sang Won Seo
- Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. .,Neuroscience Center, Samsung Medical Center, Seoul, Korea.
| |
Collapse
|
|
49
|
Malpetti M, Sala A, Vanoli EG, Gianolli L, Luzi L, Perani D. Unfavourable gender effect of high body mass index on brain metabolism and connectivity. Sci Rep 2018; 8:12584. [PMID: 30135519 PMCID: PMC6105632 DOI: 10.1038/s41598-018-30883-y] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2018] [Accepted: 07/18/2018] [Indexed: 12/25/2022] Open
Abstract
The influence of Body Mass Index (BMI) on neurodegeneration in dementia has yet to be elucidated. We aimed at exploring the effects of BMI levels on cerebral resting-state metabolism and brain connectivity, as crucial measures of synaptic function and activity, in a large group of patients with Alzheimer's Dementia (AD) (n = 206), considering gender. We tested the correlation between BMI levels and brain metabolism, as assessed by 18F-FDG-PET, and the modulation of the resting-state functional networks by BMI. At comparable dementia severity, females with high BMI can withstand a lower degree of brain metabolism dysfunction, as shown by a significant BMI-brain metabolism correlation in the temporal-parietal regions, which are typically vulnerable to AD pathology (R = 0.269, p = 0.009). Of note, high BMI was also associated with reduced connectivity in frontal and limbic brain networks, again only in AD females (p < 0.05 FDR-corrected, k = 100 voxels). This suggests a major vulnerability of neural systems known to be selectively involved in brain compensatory mechanisms in AD females. These findings indicate a strong gender effect of high BMI and obesity in AD, namely reducing the available reserve mechanisms in female patients. This brings to considerations for medical practice and health policy.
Collapse
Affiliation(s)
- Maura Malpetti
- Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy
| | - Arianna Sala
- Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy
- Vita-Salute San Raffaele University, Milan, Italy
| | | | - Luigi Gianolli
- Nuclear Medicine Unit, San Raffaele Hospital, Milan, Italy
| | - Livio Luzi
- Metabolism Research Center and Endocrinology Unit, IRCCS Policlinico San Donato Milanese, Milan, Italy
| | - Daniela Perani
- Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy.
- Vita-Salute San Raffaele University, Milan, Italy.
- Nuclear Medicine Unit, San Raffaele Hospital, Milan, Italy.
| |
Collapse
|
|
50
|
Dumurgier J, Hanseeuw BJ, Hatling FB, Judge KA, Schultz AP, Chhatwal JP, Blacker D, Sperling RA, Johnson KA, Hyman BT, Gómez-Isla T. Alzheimer's Disease Biomarkers and Future Decline in Cognitive Normal Older Adults. J Alzheimers Dis 2018; 60:1451-1459. [PMID: 29036824 DOI: 10.3233/jad-170511] [Citation(s) in RCA: 53] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
BACKGROUND Identifying older adults at risk of cognitive decline represents a challenge as Alzheimer's disease (AD) modifying therapies move toward preclinical stages. OBJECTIVE To investigate the relationship between AD biomarkers and subsequent change in cognition in a cohort of cognitively intact older adults. METHODS 84 cognitively normal subjects (mean age 72.0 years, 59% women) were recruited through the Massachusetts Alzheimer's Disease Research Center and the Harvard Aging Brain Study and followed over 3 years. Measurements of amyloid-β 1-42 (Aβ42), total Tau (t-Tau), and Tau phosphorylated at threonine 181 (p-Tau181) in the cerebrospinal fluid (CSF) at study entry were available in all cases. Baseline brain MRI, FDG-PET, and PiB-PET data were available in the majority of participants. Relationship between baseline AD biomarkers and longitudinal change in cognition was assessed using Cox proportional hazard regression and linear mixed models. RESULTS 14% participants increased their global Clinical Dementia Rating (CDR) score from 0 to 0.5 during follow-up. A CDR score increase was associated with higher baseline CSF t-Tau and p-Tau181, higher global cortical PiB retention, and lower hippocampal volume. The combination of high CSF t-Tau and low Aβ42 or low hippocampal volume was more strongly related to cognitive outcome than each single biomarker. Higher CSF t-Tau was the only biomarker associated with subsequent decline in MMSE score. CONCLUSIONS Baseline CSF t-Tau and p-Tau181, in vivo amyloid load, and hippocampal volume were all independently associated with future decline in cognition. The discriminatory ability of these biomarkers to predict risk of cognitive decline, however, was only modest.
Collapse
Affiliation(s)
- Julien Dumurgier
- Department of Neurology, Massachusetts Alzheimer Disease Research Center, Massachusetts General Hospital, Boston, MA, USA.,INSERM U942 and Memory Clinical Center, Saint Louis - Lariboisiere - Fernand Widal Hospital, AP-HP, University Paris VII Denis Diderot, Paris, France
| | - Bernard J Hanseeuw
- Department of Neurology, Massachusetts Alzheimer Disease Research Center, Massachusetts General Hospital, Boston, MA, USA
| | - Frances B Hatling
- Department of Neurology, Massachusetts Alzheimer Disease Research Center, Massachusetts General Hospital, Boston, MA, USA
| | - Kelly A Judge
- Department of Radiology, Massachusetts Alzheimer Disease Research Center, Massachusetts General Hospital, Boston, MA, USA.,Department of Neurology, Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Boston, MA, USA
| | - Aaron P Schultz
- Department of Neurology, Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Boston, MA, USA
| | - Jasmeer P Chhatwal
- Department of Neurology, Massachusetts Alzheimer Disease Research Center, Massachusetts General Hospital, Boston, MA, USA
| | - Deborah Blacker
- Department of Psychiatry, Massachusetts Alzheimer Disease Research Center, Massachusetts General Hospital, Boston, MA, USA
| | - Reisa A Sperling
- Department of Neurology, Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Boston, MA, USA
| | - Keith A Johnson
- Department of Radiology, Massachusetts Alzheimer Disease Research Center, Massachusetts General Hospital, Boston, MA, USA
| | - Bradley T Hyman
- Department of Neurology, Massachusetts Alzheimer Disease Research Center, Massachusetts General Hospital, Boston, MA, USA
| | - Teresa Gómez-Isla
- Department of Neurology, Massachusetts Alzheimer Disease Research Center, Massachusetts General Hospital, Boston, MA, USA
| |
Collapse
|