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Sun YW, Lei XY, Lyu XY, Yin Y, Kan SJ, Wang ZM, Gao B. Decoupling of Neurochemical and White Matter Microstructural Integrity in Posterior Cingulate Cortex Predicts Early Alzheimer's Disease Progression. Neurochem Res 2025; 50:159. [PMID: 40343631 DOI: 10.1007/s11064-025-04405-y] [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: 11/18/2024] [Revised: 04/14/2025] [Accepted: 04/22/2025] [Indexed: 05/11/2025]
Abstract
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by early metabolic and structural brain changes. These alterations are often detectable during mild cognitive impairment due to AD (AD-MCI), a prodromal stage of the disease. The posterior cingulate cortex (PCC), a critical brain region involved in memory and self-referential processing, is particularly vulnerable to these changes. We recruited 21 healthy controls (HC) and 20 AD-MCI patients to participate in this study. Point-Resolved Echo Spin Spectroscopy (PRESS) combined with MEGA-PRESS was employed to accurately measure levels of Gamma-Aminobutyric Acid (GABA) and Glx (Combination of Glutamate and Glutamine) in the PCC. Additionally, diffusion tensor imaging (DTI) was utilized to assess white matter (WM) microstructure integrity. Key metabolites, including N-acetylaspartate (NAA), choline (Cho), and myo-inositol (mI), were quantified to provide insights into neuronal health and metabolic status, while WM integrity was evaluated using fractional anisotropy (FA) and mean diffusivity (MD) metrics. In the PCC, AD-MCI patients exhibited a significant reduction in tNAA/tCr (1.22 ± 0.09 vs. HC 1.32 ± 0.07, p < 0.001) and NAA/mI (1.22 ± 0.12 vs. HC 1.44 ± 0.12, p < 0.001), along with an increase in mI/Cr (1.84 ± 0.28 vs. HC 1.60 ± 0.29, p = 0.012) and decreased GABA+/water (2.23 ± 0.78 vs. HC 2.98 ± 0.73, p = 0.003). Diffusion metrics revealed higher mean diffusivity in PCC-connected gray matter (GM_MD: 10.40 ± 0.79 vs. 9.53 ± 0.80 × 10⁻⁴ mm²/s, p < 0.01) and white matter (WM_MD: 0.09 ± 0.01 vs. 0.08 ± 0.01 × 10⁻² mm²/s, p < 0.01). Notably, in AD-MCI, NAA/mI was negatively correlated with WM_MD (r = - 0.462, p = 0.047), and tNAA/tCr was positively correlated with WM_FA (r = 0.580, p = 0.009). PCC neurochemical-microstructural decoupling (NAA/mI-MD dissociation with preserved tNAA/tCr-FA coupling) marks early AD progression. This dissociation pattern, reflecting concurrent neuronal dysfunction and compensatory glial responses, proposes a novel multimodal biomarker for tracking axonal degeneration prior to overt cognitive decline.
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Affiliation(s)
- Yong-Wen Sun
- Department of Radiology, The Affiliated Hospital of Guizhou Medical University, Guiyang, China
- Department of Radiology, Qiandongnan Prefecture People's Hospital, Kaili, China
| | - Xiao-Yang Lei
- Department of Neurology, The Affiliated Hospital of Guizhou Medical University, Guiyang, China
| | - Xin-Yue Lyu
- Department of Radiology, The Affiliated Hospital of Guizhou Medical University, Guiyang, China
| | - Yi Yin
- Department of Radiology, The Affiliated Hospital of Guizhou Medical University, Guiyang, China
| | - Shi-Ji Kan
- Department of Radiology, The Affiliated Hospital of Guizhou Medical University, Guiyang, China
| | - Zhen-Min Wang
- Department of Radiology, The Affiliated Hospital of Guizhou Medical University, Guiyang, China
| | - Bo Gao
- Department of Radiology, The Affiliated Hospital of Guizhou Medical University, Guiyang, China.
- Key Laboratory of Brain Imaging, Guizhou Medical University, Guiyang, China.
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Boscarino JJ, Weitzner DS, Bailey EK, Kamper JE, Vanderbleek EN. Utility of learning ratio scores from the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Word List Memory Test in distinguishing patterns of cognitive decline in veterans referred for neuropsychological evaluation. Clin Neuropsychol 2024; 38:1967-1979. [PMID: 38494420 DOI: 10.1080/13854046.2024.2330144] [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: 10/26/2023] [Accepted: 03/07/2024] [Indexed: 03/19/2024]
Abstract
Background: The Learning Ratio (LR) is a novel learning score that has shown improved utility over other learning metrics in detecting Alzheimer's disease (AD) across multiple memory tasks. However, its utility on the Consortium to Establish a Registry for Alzheimer's Disease Word List Memory Test (CERAD WLMT), a widely used list learning measure sensitive to decline in neurodegenerative disease, is unknown. The goal of the current study was to determine the utility of LR on the CERAD WLMT in differentiating between diagnostic (MiNCD vs MaNCD) and etiologic groups (VaD vs AD) in a veteran sample. Methods: Raw learning slope (RLS) and LR scores were examined in 168 veterans diagnosed with major neurocognitive disorder (MaNCD), mild neurocognitive disorder (MiNCD), or normal aging following neuropsychological evaluation. Patients with MaNCD were further classified by suspected etiology (i.e. microvascular disease vs AD). Results: Whereas RLS scores were not significantly different between MiNCD and MaNCD, LR scores were significantly different between all diagnostic groups (p's < .05). Those with AD had lower LR scores and RLS scores compared to those with VaD (p's < .05). LR classification accuracy was acceptable for MiNCD (AUC = .76), excellent for MaNCD (AUC = .86) and VaD (AUC = .81), and outstanding for AD (AUC = .91). Optimal cutoff scores for WLMT LR were derived from Youden's index. Conclusion: Results support the use of LR scores over RLS when interpreting the CERAD WLMT and highlight the clinical utility of LR in differentiating between diagnostic groups and identifying suspected etiology.
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Affiliation(s)
- Joseph J Boscarino
- Mental Health and Behavioral Service, James A. Haley Veterans' Hospital, Tampa, Florida, USA
| | - Daniel S Weitzner
- Mental Health and Behavioral Service, James A. Haley Veterans' Hospital, Tampa, Florida, USA
| | - Erin K Bailey
- Mental Health and Behavioral Service, James A. Haley Veterans' Hospital, Tampa, Florida, USA
- Department of Psychiatry, University of South Florida Morsani College of Medicine, Tampa, Florida, USA
| | - Joel E Kamper
- Mental Health and Behavioral Service, James A. Haley Veterans' Hospital, Tampa, Florida, USA
| | - Emily N Vanderbleek
- Mental Health and Behavioral Service, James A. Haley Veterans' Hospital, Tampa, Florida, USA
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Alzola P, Carnero C, Bermejo-Pareja F, Sánchez-Benavides G, Peña-Casanova J, Puertas-Martín V, Fernández-Calvo B, Contador I. Neuropsychological Assessment for Early Detection and Diagnosis of Dementia: Current Knowledge and New Insights. J Clin Med 2024; 13:3442. [PMID: 38929971 PMCID: PMC11204334 DOI: 10.3390/jcm13123442] [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: 05/15/2024] [Revised: 06/06/2024] [Accepted: 06/10/2024] [Indexed: 06/28/2024] Open
Abstract
Dementia remains an underdiagnosed syndrome, and there is a need to improve the early detection of cognitive decline. This narrative review examines the role of neuropsychological assessment in the characterization of cognitive changes associated with dementia syndrome at different states. The first section describes the early indicators of cognitive decline and the major barriers to their identification. Further, the optimal cognitive screening conditions and the most widely accepted tests are described. The second section analyzes the main differences in cognitive performance between Alzheimer's disease and other subtypes of dementia. Finally, the current challenges of neuropsychological assessment in aging/dementia and future approaches are discussed. Essentially, we find that current research is beginning to uncover early cognitive changes that precede dementia, while continuing to improve and refine the differential diagnosis of neurodegenerative disorders that cause dementia. However, neuropsychology faces several barriers, including the cultural diversity of the populations, a limited implementation in public health systems, and the adaptation to technological advances. Nowadays, neuropsychological assessment plays a fundamental role in characterizing cognitive decline in the different stages of dementia, but more efforts are needed to develop harmonized procedures that facilitate its use in different clinical contexts and research protocols.
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Affiliation(s)
- Patricia Alzola
- Department of Basic Psychology, Psychobiology and Methodology of Behavioral Sciences, University of Salamanca, 37005 Salamanca, Spain;
| | - Cristóbal Carnero
- Neurology Department, Granada University Hospital Complex, 18014 Granada, Spain
| | - Félix Bermejo-Pareja
- Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Institute of Health Carlos III, 28029 Madrid, Spain
- Institute of Research i+12, University Hospital “12 de Octubre”, 28041 Madrid, Spain
| | | | | | | | | | - Israel Contador
- Department of Basic Psychology, Psychobiology and Methodology of Behavioral Sciences, University of Salamanca, 37005 Salamanca, Spain;
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Yang T, Wei F, Guo Y, Zhu M, Hou H, Guo Z, Liu X. The increased effective connectivity from left middle occipital gyrus to right medial septum/diagonal bands in AD patients after donepezil intervention. Front Aging Neurosci 2024; 16:1362790. [PMID: 38659702 PMCID: PMC11039922 DOI: 10.3389/fnagi.2024.1362790] [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: 12/29/2023] [Accepted: 03/27/2024] [Indexed: 04/26/2024] Open
Abstract
Introduction Donepezil enhances the function of cholinergic nerves by increasing the concentration of acetylcholine, thereby improving clinical symptoms in patients with Alzheimer's disease (AD). However, the neural mechanisms of how donepezil modulates the effective connectivity (EC) network of cholinergic system in AD patients remain unknown. We speculated that the effective network of the cholinergic system changes in AD patients after donepezil intervention. Methods We employed resting-state functional magnetic resonance imaging and Granger causality analysis approach to explore changes in the effective connectivity network of the basal forebrain in AD patients before and after donepezil intervention. This study included 32 participants, including 16 healthy controls (HCs) and 16 AD patients. In a 3T MRI scanner, the 16 AD patients were scanned before and after the donepezil intervention. To compare EC differences between the three groups of participants, ANOVA and post-hoc t-tests analysis were employed. Results Compared to baseline status, AD patients after donepezil intervention had an increased EC from left middle occipital gyrus to right medial septum/diagonal bands. Compared to HCs, AD patients after donepezil intervention had an increased EC from right inferior frontal gyrus/orbit part to right medial septum/diagonal bands, AD patients before donepezil intervention had a reduced EC from right precuneus to right medial septum/diagonal bands. A significant positive correlation was found between EC values in right precuneus and Mini-Mental State Examination in pre-intervention AD patients (r = 0.7338, p = 0.0012). Discussion Our study showed that effective connectivity of brain regions associated with the default mode network in the cholinergic pathway was enhanced after donepezil intervention. The results of this study will help us to better understand the neural mechanisms of donepezil intervention in AD and to find clinical targets for intervention.
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Affiliation(s)
- Ting Yang
- The Second Affiliated Hospital and Yuying Children’s Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Fuquan Wei
- Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang, China
| | - Yufei Guo
- The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Mengxiao Zhu
- The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Hongtao Hou
- Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang, China
| | - Zhongwei Guo
- Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang, China
| | - Xiaozheng Liu
- The Second Affiliated Hospital and Yuying Children’s Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China
- Wenzhou Key Laboratory of Structural and Functional Imaging, Wenzhou, Zhejiang, China
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von Rennenberg R, Nolte CH, Liman TG, Hellwig S, Riegler C, Scheitz JF, Georgakis MK, Fang R, Bode FJ, Petzold GC, Hermann P, Zerr I, Goertler M, Bernkopf K, Wunderlich S, Dichgans M, Endres M. High-Sensitivity Cardiac Troponin T and Cognitive Function Over 12 Months After Stroke-Results of the DEMDAS Study. J Am Heart Assoc 2024; 13:e033439. [PMID: 38456438 PMCID: PMC11010029 DOI: 10.1161/jaha.123.033439] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2023] [Accepted: 01/24/2024] [Indexed: 03/09/2024]
Abstract
BACKGROUND Subclinical myocardial injury in form of hs-cTn (high-sensitivity cardiac troponin) levels has been associated with cognitive impairment and imaging markers of cerebral small vessel disease (SVD) in population-based and cardiovascular cohorts. Whether hs-cTn is associated with domain-specific cognitive decline and SVD burden in patients with stroke remains unknown. METHODS AND RESULTS We analyzed patients with acute stroke without premorbid dementia from the prospective multicenter DEMDAS (DZNE [German Center for Neurodegenerative Disease]-Mechanisms of Dementia after Stroke) study. Patients underwent neuropsychological testing 6 and 12 months after the index event. Test results were classified into 5 cognitive domains (language, memory, executive function, attention, and visuospatial function). SVD markers (lacunes, cerebral microbleeds, white matter hyperintensities, and enlarged perivascular spaces) were assessed on cranial magnetic resonance imaging to constitute a global SVD score. We examined the association between hs-cTnT (hs-cTn T levels) and cognitive domains as well as the global SVD score and individual SVD markers, respectively. Measurement of cognitive and SVD-marker analyses were performed in 385 and 466 patients with available hs-cTnT levels, respectively. In analyses adjusted for demographic characteristics, cardiovascular risk factors, and cognitive status at baseline, higher hs-cTnT was negatively associated with the cognitive domains "attention" up to 12 months of follow-up (beta-coefficient, -0.273 [95% CI, -0.436 to -0.109]) and "executive function" after 12 months. Higher hs-cTnT was associated with the global SVD score (adjusted odds ratio, 1.95 [95% CI, 1.27-3.00]) and the white matter hyperintensities and lacune subscores. CONCLUSIONS In patients with stroke, hs-cTnT is associated with a higher burden of SVD markers and cognitive function in domains linked to vascular cognitive impairment. REGISTRATION URL: https://www.clinicaltrials.gov; Unique identifier: NCT01334749.
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Affiliation(s)
- Regina von Rennenberg
- Department of Neurology (Klinik und Hochschulambulanz für Neurologie)Charité—Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt‐Universität zu BerlinBerlinGermany
- Center for Stroke Research Berlin (CSB)Charité—Universitätsmedizin BerlinBerlinGermany
- German Center for Neurodegenerative Diseases (Deutsches Zentrum für Neurodegenerative Erkrankungen), partner site BerlinBerlinGermany
| | - Christian H. Nolte
- Department of Neurology (Klinik und Hochschulambulanz für Neurologie)Charité—Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt‐Universität zu BerlinBerlinGermany
- Center for Stroke Research Berlin (CSB)Charité—Universitätsmedizin BerlinBerlinGermany
- German Center for Neurodegenerative Diseases (Deutsches Zentrum für Neurodegenerative Erkrankungen), partner site BerlinBerlinGermany
- German Center for Cardiovascular Research (Deutsches Zentrum für Herz‐Kreislaufforschung), partner site Berlin, Charité‐Universitätsmedizin BerlinBerlinGermany
- Berlin Institute of Health at Charité –Universitätsmedizin Berlin, BIH Biomedical Innovation AcademyBerlinGermany
| | - Thomas G. Liman
- Department of Neurology (Klinik und Hochschulambulanz für Neurologie)Charité—Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt‐Universität zu BerlinBerlinGermany
- Center for Stroke Research Berlin (CSB)Charité—Universitätsmedizin BerlinBerlinGermany
- German Center for Neurodegenerative Diseases (Deutsches Zentrum für Neurodegenerative Erkrankungen), partner site BerlinBerlinGermany
- Department of Neurology, School of Medicine and Health SciencesCarl von Ossietzky University of OldenburgOldenburgGermany
| | - Simon Hellwig
- Department of Neurology (Klinik und Hochschulambulanz für Neurologie)Charité—Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt‐Universität zu BerlinBerlinGermany
- Center for Stroke Research Berlin (CSB)Charité—Universitätsmedizin BerlinBerlinGermany
- Berlin Institute of Health at Charité –Universitätsmedizin Berlin, BIH Biomedical Innovation AcademyBerlinGermany
| | - Christoph Riegler
- Department of Neurology (Klinik und Hochschulambulanz für Neurologie)Charité—Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt‐Universität zu BerlinBerlinGermany
- Center for Stroke Research Berlin (CSB)Charité—Universitätsmedizin BerlinBerlinGermany
| | - Jan F. Scheitz
- Department of Neurology (Klinik und Hochschulambulanz für Neurologie)Charité—Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt‐Universität zu BerlinBerlinGermany
- Center for Stroke Research Berlin (CSB)Charité—Universitätsmedizin BerlinBerlinGermany
- German Center for Cardiovascular Research (Deutsches Zentrum für Herz‐Kreislaufforschung), partner site Berlin, Charité‐Universitätsmedizin BerlinBerlinGermany
- Berlin Institute of Health at Charité –Universitätsmedizin Berlin, BIH Biomedical Innovation AcademyBerlinGermany
| | - Marios K. Georgakis
- Institute for Stroke and Dementia Research (ISD), University Hospital, LMU MunichMunichGermany
- German Center for Neurodegenerative Diseases (Deutsches Zentrum für Neurodegenerative Erkrankungen), partner site MunichMunichGermany
| | - Rong Fang
- Institute for Stroke and Dementia Research (ISD), University Hospital, LMU MunichMunichGermany
- German Center for Neurodegenerative Diseases (Deutsches Zentrum für Neurodegenerative Erkrankungen), partner site MunichMunichGermany
| | - Felix J. Bode
- Division of Vascular Neurology, Department of NeurologyUniversity Hospital BonnBonnGermany
| | - Gabor C. Petzold
- Division of Vascular Neurology, Department of NeurologyUniversity Hospital BonnBonnGermany
- German Center for Neurodegenerative Diseases (Deutsches Zentrum für Neurodegenerative Erkrankungen), partner site BonnBonnGermany
| | - Peter Hermann
- German Center for Neurodegenerative Diseases (DZNE) GöttingenGöttingenGermany
- Clinical Dementia Center, Department of NeurologyUniversity Medical CenterGöttingenGermany
| | - Inga Zerr
- German Center for Neurodegenerative Diseases (DZNE) GöttingenGöttingenGermany
- Clinical Dementia Center, Department of NeurologyUniversity Medical CenterGöttingenGermany
| | - Michael Goertler
- Department of NeurologyMagdeburg University Vascular and Stroke CentreMagdeburgGermany
- German Center for Neurodegenerative Diseases (Deutsches Zentrum für Neurodegenerative Erkrankungen), partner site MagdeburgMagdeburgGermany
| | - Kathleen Bernkopf
- Department of Neurology, School of MedicineKlinikum rechts der Isar, Technical University of MunichMunichGermany
| | - Silke Wunderlich
- Department of Neurology, School of MedicineKlinikum rechts der Isar, Technical University of MunichMunichGermany
| | - Martin Dichgans
- Institute for Stroke and Dementia Research (ISD), University Hospital, LMU MunichMunichGermany
- German Center for Neurodegenerative Diseases (Deutsches Zentrum für Neurodegenerative Erkrankungen), partner site MunichMunichGermany
| | - Matthias Endres
- Department of Neurology (Klinik und Hochschulambulanz für Neurologie)Charité—Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt‐Universität zu BerlinBerlinGermany
- Center for Stroke Research Berlin (CSB)Charité—Universitätsmedizin BerlinBerlinGermany
- German Center for Neurodegenerative Diseases (Deutsches Zentrum für Neurodegenerative Erkrankungen), partner site BerlinBerlinGermany
- German Center for Cardiovascular Research (Deutsches Zentrum für Herz‐Kreislaufforschung), partner site Berlin, Charité‐Universitätsmedizin BerlinBerlinGermany
- Berlin Institute of Health at Charité –Universitätsmedizin Berlin, BIH Biomedical Innovation AcademyBerlinGermany
- German Center for Mental Health (DZPG), partner site BerlinBerlinGermany
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Owens CD, Bonin Pinto C, Mukli P, Szarvas Z, Peterfi A, Detwiler S, Olay L, Olson AL, Li G, Galvan V, Kirkpatrick AC, Balasubramanian P, Tarantini S, Csiszar A, Ungvari Z, Prodan CI, Yabluchanskiy A. Vascular mechanisms leading to progression of mild cognitive impairment to dementia after COVID-19: Protocol and methodology of a prospective longitudinal observational study. PLoS One 2023; 18:e0289508. [PMID: 37535668 PMCID: PMC10399897 DOI: 10.1371/journal.pone.0289508] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2023] [Accepted: 07/19/2023] [Indexed: 08/05/2023] Open
Abstract
INTRODUCTION Mild cognitive impairment (MCI) is a prodromal stage to dementia, affecting up to 20% of the aging population worldwide. Patients with MCI have an annual conversion rate to dementia of 15-20%. Thus, conditions that increase the conversion from MCI to dementia are of the utmost public health concern. The COVID-19 pandemic poses a significant impact on our aging population with cognitive decline as one of the leading complications following recovery from acute infection. Recent findings suggest that COVID-19 increases the conversion rate from MCI to dementia in older adults. Hence, we aim to uncover a mechanism for COVID-19 induced cognitive impairment and progression to dementia to pave the way for future therapeutic targets that may mitigate COVID-19 induced cognitive decline. METHODOLOGY A prospective longitudinal study is conducted at the University of Oklahoma Health Sciences Center. Patients are screened in the Department of Neurology and must have a formal diagnosis of MCI, and MRI imaging prior to study enrollment. Patients who meet the inclusion criteria are enrolled and followed-up at 18-months after their first visit. Visit one and 18-month follow-up will include an integrated and cohesive battery of vascular and cognitive measurements, including peripheral endothelial function (flow-mediated dilation, laser speckle contrast imaging), retinal and cerebrovascular hemodynamics (dynamic vessel retinal analysis, functional near-infrared spectroscopy), and fluid and crystalized intelligence (NIH-Toolbox, n-back). Multiple logistic regression will be used for primary longitudinal data analysis to determine whether COVID-19 related impairment in neurovascular coupling and increases in white matter hyperintensity burden contribute to progression to dementia.
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Affiliation(s)
- Cameron D. Owens
- Oklahoma Center for Geroscience and Healthy Brain Aging, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States of America
- Department of Neurosurgery, Vascular Cognitive Impairment, Neurodegeneration and Healthy Brain Aging Program, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States of America
| | - Camila Bonin Pinto
- Oklahoma Center for Geroscience and Healthy Brain Aging, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States of America
- Department of Neurosurgery, Vascular Cognitive Impairment, Neurodegeneration and Healthy Brain Aging Program, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States of America
| | - Peter Mukli
- Oklahoma Center for Geroscience and Healthy Brain Aging, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States of America
- Department of Neurosurgery, Vascular Cognitive Impairment, Neurodegeneration and Healthy Brain Aging Program, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States of America
- Doctoral School of Basic and Translational Medicine/Departments of Public Health, International Training Program in Geroscience, Translational Medicine and Physiology, Semmelweis University, Budapest, Hungary
| | - Zsofia Szarvas
- Oklahoma Center for Geroscience and Healthy Brain Aging, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States of America
- Department of Neurosurgery, Vascular Cognitive Impairment, Neurodegeneration and Healthy Brain Aging Program, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States of America
- Doctoral School of Basic and Translational Medicine/Departments of Public Health, International Training Program in Geroscience, Translational Medicine and Physiology, Semmelweis University, Budapest, Hungary
| | - Anna Peterfi
- Oklahoma Center for Geroscience and Healthy Brain Aging, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States of America
- Department of Neurosurgery, Vascular Cognitive Impairment, Neurodegeneration and Healthy Brain Aging Program, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States of America
- Doctoral School of Basic and Translational Medicine/Departments of Public Health, International Training Program in Geroscience, Translational Medicine and Physiology, Semmelweis University, Budapest, Hungary
| | - Sam Detwiler
- Oklahoma Center for Geroscience and Healthy Brain Aging, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States of America
- Department of Neurosurgery, Vascular Cognitive Impairment, Neurodegeneration and Healthy Brain Aging Program, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States of America
| | - Lauren Olay
- Oklahoma Center for Geroscience and Healthy Brain Aging, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States of America
- Department of Neurosurgery, Vascular Cognitive Impairment, Neurodegeneration and Healthy Brain Aging Program, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States of America
| | - Ann L. Olson
- Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States of America
| | - Guangpu Li
- Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States of America
| | - Veronica Galvan
- Oklahoma Center for Geroscience and Healthy Brain Aging, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States of America
- Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States of America
- Veterans Affairs Medical Center, Oklahoma City, OK, United States of America
| | - Angelia C. Kirkpatrick
- Veterans Affairs Medical Center, Oklahoma City, OK, United States of America
- Department of Medicine, Cardiovascular Section, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States of America
| | - Priya Balasubramanian
- Oklahoma Center for Geroscience and Healthy Brain Aging, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States of America
- Department of Neurosurgery, Vascular Cognitive Impairment, Neurodegeneration and Healthy Brain Aging Program, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States of America
- Department of Medicine, Cardiovascular Section, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States of America
| | - Stefano Tarantini
- Oklahoma Center for Geroscience and Healthy Brain Aging, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States of America
- Department of Neurosurgery, Vascular Cognitive Impairment, Neurodegeneration and Healthy Brain Aging Program, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States of America
- Doctoral School of Basic and Translational Medicine/Departments of Public Health, International Training Program in Geroscience, Translational Medicine and Physiology, Semmelweis University, Budapest, Hungary
- The Peggy and Charles Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States of America
- Department of Health Promotion Sciences, College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States of America
| | - Anna Csiszar
- Oklahoma Center for Geroscience and Healthy Brain Aging, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States of America
- Department of Neurosurgery, Vascular Cognitive Impairment, Neurodegeneration and Healthy Brain Aging Program, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States of America
- Doctoral School of Basic and Translational Medicine/Departments of Public Health, International Training Program in Geroscience, Translational Medicine and Physiology, Semmelweis University, Budapest, Hungary
| | - Zoltan Ungvari
- Oklahoma Center for Geroscience and Healthy Brain Aging, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States of America
- Department of Neurosurgery, Vascular Cognitive Impairment, Neurodegeneration and Healthy Brain Aging Program, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States of America
- Doctoral School of Basic and Translational Medicine/Departments of Public Health, International Training Program in Geroscience, Translational Medicine and Physiology, Semmelweis University, Budapest, Hungary
- Department of Health Promotion Sciences, College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States of America
| | - Calin I. Prodan
- Veterans Affairs Medical Center, Oklahoma City, OK, United States of America
- Department of Neurology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States of America
| | - Andriy Yabluchanskiy
- Oklahoma Center for Geroscience and Healthy Brain Aging, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States of America
- Department of Neurosurgery, Vascular Cognitive Impairment, Neurodegeneration and Healthy Brain Aging Program, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States of America
- The Peggy and Charles Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States of America
- Department of Health Promotion Sciences, College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States of America
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Fredi BM, De Labio RW, Rasmussen LT, Chagas EFB, Chen ES, Turecki G, Smith MDAC, Payão SLM. CDK10, CDK11, FOXO1, and FOXO3 Gene Expression in Alzheimer's Disease Encephalic Samples. Cell Mol Neurobiol 2023; 43:2953-2962. [PMID: 36988771 PMCID: PMC11410123 DOI: 10.1007/s10571-023-01341-9] [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: 11/27/2022] [Accepted: 03/22/2023] [Indexed: 03/30/2023]
Abstract
Alzheimer's disease (AD) is a progressive neuroinflammatory and neurodegenerative disorder that affects different regions of the brain. Its pathophysiology includes the accumulation of β-amyloid protein, formation of neurofibrillary tangles, and inflammatory processes. Genetic factors are involved in the onset of AD, but they are not fully elucidated. Identification of gene expression in encephalic tissues of patients with AD may help elucidate its development. Our objectives were to characterize and compare the gene expression of CDK10, CDK11, FOXO1, and FOXO3 in encephalic tissue samples from AD patients and elderly controls, from the auditory cortex and cerebellum. RT-qPCR was used on samples from 82 individuals (45 with AD and 37 controls). We observed a statistically significant increase in CDK10 (p = 0.029*) and CDK11 (p = 0.048*) gene expression in the AD group compared to the control, which was most evident in the cerebellum. Furthermore, the Spearman test demonstrated the presence of a positive correlation of gene expression both in the auditory cortex in the AD group (r = 0.046/p = 0.004) and control group (r = 0.454/p = 0.005); and in the cerebellum in the AD group (r = 0.654 /p < 0.001). There was no statistically significant difference and correlation in the gene expression of FOXO1 and FOXO3 in the AD group and the control. In conclusion, CDK10 and CDK11 have high expression in AD patients compared to control, and they present a positive correlation of gene expression in the analyzed groups and tissues, which suggests that they play an important role in the pathogenesis of AD.
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Affiliation(s)
| | | | | | | | - Elizabeth Suchi Chen
- Escola Paulista de Medicina, Federal University of São Paulo, São Paulo, São Paulo, Brazil
| | - Gustavo Turecki
- The Douglas-Bell Canada Brain Bank, Douglas Mental Health University, Montreal, QC, Canada
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8
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Li KY, Chien CF, Huang TW, Yang YH. The Use of Verbal and Nonverbal Memory Tests for Alzheimer's Disease Screening in Taiwan Chinese. Am J Alzheimers Dis Other Demen 2023; 38:15333175231201036. [PMID: 37683179 PMCID: PMC10623994 DOI: 10.1177/15333175231201036] [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] [Indexed: 09/10/2023]
Abstract
Patients with Alzheimer's disease typically have initial deficits in memory. Memory testing can be categorized as verbal or nonverbal by the modality of the stimuli used. We compared the discriminative validity of selected verbal and nonverbal memory tests between non-dementia and Alzheimer's disease in Taiwan. Ninety-eight patients with mild Alzheimer's disease and 269 non-dementia individuals underwent story recall test (immediate and delayed recall), and constructional praxis test (copy and delayed recall). The receiver-operating characteristic curve and area under the curve were evaluated to compare between tests. Patients with Alzheimer's disease performed poorly across all memory tests, and the receiver-operating characteristic curve analysis indicated that story recall immediate and relayed recall, and constructional praxis delayed recall had good classification accuracy with area under the curve of .90, .87 and .87 respectively. These results provide support that both verbal and nonverbal memory tests are reliable measure for screening patients with Alzheimer's disease.
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Affiliation(s)
- Kuan-Ying Li
- Department of Neurology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Neuroscience Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Neurology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Ching-Fang Chien
- Department of Neurology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Neuroscience Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Neurology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Tang-Wei Huang
- School of Post-Baccalaureate Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Yuan-Han Yang
- Department of Neurology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Neuroscience Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Neurology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- School of Post-Baccalaureate Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
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9
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Cejudo JC, Samaniego M, Almeria M, Castrillo S, Medina L, Gil D. Ikos Test: New Tool for the Assessment of Semantic Knowledge in Early Alzheimer Disease. J Alzheimers Dis 2022; 90:151-160. [DOI: 10.3233/jad-220516] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Background: Semantic memory (SM) constitutes a cognitive system that is seriously affected by Alzheimer’s disease (AD). There are several tests for assessing SM, but a tool is needed to assess AD in the early stages of the illness. Objective: The study aimed to create, validate, and normalize a new test to assess SM, called the Ikos test, for AD and early AD in clinical practice. Methods: 62 healthy adults as a control group (CG), 62 AD, and 60 amnestic mild cognitive impairment (aMCI) subdivided into a group that progresses to AD, and another group that does not progress to AD were selected. The internal consistency (IC), the construct validity (CV), and reliability between raters and the test-retest were analyzed. We used the Bayesian approach to establish the accuracy of the diagnosis of the Ikos test in AD and early AD. Results: IC showed a Kuder-Richardson index of r = 0.945. The CV between the Ikos test and Pyramids and Palm Trees; Intraclass Correlation Coefficient (ICC) index was 0.897. The Kappa index was between 0.865 and 0.912, and the ICC index was 0.873 for the test-retest reliability. The Area Under the Curve was 0.981, sensitivity (SE) was 0.95, and specificity (SP) was 0.96 in AD/CG. In contrast, in the MCI-AD/CG group, SE = 0.77 and SP = 0.80. Conclusion: The Ikos test accomplishes the criteria of validity and reliability with high correlation indexes. Therefore, it can be considered a valid, reliable, and easily applicable tool for SM assessment in diagnosing AD and the early stages of clinical disease.
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Affiliation(s)
- Juan Carlos Cejudo
- Cognitive Impairment and Dementia Unit, Hospital Sagrat Cor. Hermanas Hospitalarias, Martorell, (Barcelona), Spain
| | - Melissa Samaniego
- Cognitive Impairment and Dementia Unit, Hospital Sagrat Cor. Hermanas Hospitalarias, Martorell, (Barcelona), Spain
| | - Marta Almeria
- Cognition and Behavior Unit, Department of Neurology, Hospital Universitari Mútua Terrassa, Terrassa(Barcelona), Spain
- Department of Medicine, Autonomous University of Barcelona, (Barcelona), Spain
| | - Susana Castrillo
- RGG Sant Roc (DGPS), Drets Socials Dep, Generalitat de Catalunya, Spain
| | - Lidia Medina
- Cognitive Impairment and Dementia Unit. Hospital Atenció Intermedia MutuamGüell, EAPS Mutuam Barcelona, Barcelona, Spain
| | - Domènec Gil
- Cognitive Impairment and Dementia Unit, Hospital Sagrat Cor. Hermanas Hospitalarias, Martorell, (Barcelona), Spain
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10
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Williamson J, Yabluchanskiy A, Mukli P, Wu DH, Sonntag W, Ciro C, Yang Y. Sex differences in brain functional connectivity of hippocampus in mild cognitive impairment. Front Aging Neurosci 2022; 14:959394. [PMID: 36034134 PMCID: PMC9399646 DOI: 10.3389/fnagi.2022.959394] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2022] [Accepted: 07/19/2022] [Indexed: 11/13/2022] Open
Abstract
Mild cognitive impairment (MCI) is the prodromal stage of Alzheimer's Disease (AD). Prior research shows that females are more impacted by MCI than males. On average females have a greater incidence rate of any dementia and current evidence suggests that they suffer greater cognitive deterioration than males in the same disease stage. Recent research has linked these sex differences to neuroimaging markers of brain pathology, such as hippocampal volumes. Specifically, the rate of hippocampal atrophy affects the progression of AD in females more than males. This study was designed to extend our understanding of the sex-related differences in the brain of participants with MCI. Specifically, we investigated the difference in the hippocampal connectivity to different areas of the brain. The Resting State fMRI and T2 MRI of cognitively normal individuals (n = 40, female = 20) and individuals with MCI (n = 40, female = 20) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) were analyzed using the Functional Connectivity Toolbox (CONN). Our results demonstrate that connectivity of hippocampus to the precuneus cortex and brain stem was significantly stronger in males than in females. These results improve our current understanding of the role of hippocampus-precuneus cortex and hippocampus-brainstem connectivity in sex differences in MCI. Understanding the contribution of impaired functional connectivity sex differences may aid in the development of sex specific precision medicine to manipulate hippocampal-precuneus cortex and hippocampal-brainstem connectivity to decrease the progression of MCI to AD.
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Affiliation(s)
- Jordan Williamson
- Neural Control and Rehabilitation Laboratory, Stephenson School of Biomedical Engineering, University of Oklahoma, Norman, OK, United States
| | - Andriy Yabluchanskiy
- Vascular Cognitive Impairment and Neurodegeneration Program, Oklahoma Center for Geroscience and Healthy Brain Aging, Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States
| | - Peter Mukli
- Vascular Cognitive Impairment and Neurodegeneration Program, Oklahoma Center for Geroscience and Healthy Brain Aging, Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States
| | - Dee H. Wu
- Department of Radiological Science and Medical Physics, University of Oklahoma Health Science Center, Oklahoma City, OK, United States
- Data Institute for Societal Challenges, University of Oklahoma, Norman, OK, United States
- School of Computer Science, Gallogly College of Engineering, University of Oklahoma, Norman, OK, United States
- School of Electrical and Computer Engineering, Gallogly College of Engineering, University of Oklahoma, Norman, OK, United States
| | - William Sonntag
- Vascular Cognitive Impairment and Neurodegeneration Program, Oklahoma Center for Geroscience and Healthy Brain Aging, Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States
| | - Carrie Ciro
- Department of Rehabilitation Sciences, University of Oklahoma Health Science Center, Oklahoma City, OK, United States
| | - Yuan Yang
- Neural Control and Rehabilitation Laboratory, Stephenson School of Biomedical Engineering, University of Oklahoma, Norman, OK, United States
- Data Institute for Societal Challenges, University of Oklahoma, Norman, OK, United States
- Department of Rehabilitation Sciences, University of Oklahoma Health Science Center, Oklahoma City, OK, United States
- School of Electrical and Computer Engineering, University of Oklahoma, Tulsa, OK, United States
- Department of Physical Therapy and Human Movement Sciences, Northwestern University, Chicago, IL, United States
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11
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Disrupted Value-Directed Strategic Processing in Individuals with Mild Cognitive Impairment: Behavioral and Neural Correlates. Geriatrics (Basel) 2022; 7:geriatrics7030056. [PMID: 35645279 PMCID: PMC9149834 DOI: 10.3390/geriatrics7030056] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2022] [Revised: 05/09/2022] [Accepted: 05/09/2022] [Indexed: 02/05/2023] Open
Abstract
Value-directed strategic processing involves attending to higher-value information while inhibiting lower-value information. This preferential processing is relatively preserved in cognitively normal older adults but is impaired in individuals with dementia. No studies have investigated whether value-directed strategic processing is disrupted in earlier stages of cognitive decline, namely, mild cognitive impairment (MCI). The current study examined behavioral and EEG differences in value-directed strategic processing between 18 individuals with MCI and 18 cognitively normal older controls using a value-directed list learning task. Behaviorally, individuals with MCI recalled fewer total and high-value words compared to controls, but no group differences were observed in low-value word recall. Neurally, individuals with MCI had reduced theta synchronization relative to controls between 100 and 200 ms post-stimulus. Greater alpha desynchronization was observed for high- versus low-value words between 300 and 400 ms in controls but not in the MCI group. The groups showed some processing similarities, with greater theta synchronization for low-value words between 700 and 800 ms and greater alpha desynchronization for high-value words between 500 and 1100 ms. Overall, value-directed strategic processing was compromised in individuals with MCI on both behavioral and neural measures relative to controls. These findings add to the growing body of literature on differences between typical cognitive aging and MCI.
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12
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Isella V, Rosazza C, Ferri F, Gazzotti M, Impagnatiello V, Mapelli C, Morzenti S, Crivellaro C, Appollonio IM, Ferrarese C. Learning From Mistakes: Cognitive and Metabolic Correlates of Errors on Picture Naming in the Alzheimer’s Disease Spectrum. J Alzheimers Dis 2022; 87:1033-1053. [DOI: 10.3233/jad-220053] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Abstract
Background: Analysis of subtypes of picture naming errors produced by patients with Alzheimer’s disease (AD) have seldom been investigated yet may clarify the cognitive and neural underpinnings of naming in the AD spectrum. Objective: To elucidate the neurocognitive bases of picture naming in AD through a qualitative analysis of errors. Methods: Over 1000 naming errors produced by 70 patients with amnestic, visuospatial, linguistic, or frontal AD were correlated with general cognitive tests and with distribution of hypometabolism on FDG-PET. Results: Principal component analysis identified 1) a Visual processing factor clustering visuospatial tests and unrecognized stimuli, pure visual errors and visual-semantic errors, associated with right parieto-occipital hypometabolism; 2) a Concept-Lemma factor grouping language tests and anomias, circumlocutions, superordinates, and coordinates, correlated with left basal temporal hypometabolism; 3) a Lemma-Phonology factor including the digit span and phonological errors, linked with left temporo-parietal hypometabolism. Regression of brain metabolism on individual errors showed that errors due to impairment of basic and higher-order processing of object visual attributes or of their interaction with semantics, were related with bilateral occipital and left occipito-temporal dysfunction. Omissions and superordinates were linked to degradation of broad and basic concepts in the left basal temporal cortex. Semantic-lexical errors derived from faulty semantically- and phonologically-driven lexical retrieval in the left superior and middle temporal gyri. Generation of nonwords was underpinned by of phonological impairment within the left inferior parietal cortex. Conclusion: Analysis of individual naming errors allowed to outline a comprehensive anatomo-functional model of picture naming in classical and atypical AD.
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Affiliation(s)
- Valeria Isella
- Department of Neurology, S. Gerardo Hospital, Monza, University of Milano - Bicocca, Italy
- NeuroMI, University of Milano - Bicocca, Italy
| | - Cristina Rosazza
- Dipartimento di Studi Umanistici (DISTUM), Università degli Studi di Urbino Carlo Bo, Urbino, Italy
- Neuroradiology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy
| | - Francesca Ferri
- Department of Neurology, S. Gerardo Hospital, Monza, University of Milano - Bicocca, Italy
- NeuroMI, University of Milano - Bicocca, Italy
| | - Maria Gazzotti
- Department of Neurology, S. Gerardo Hospital, Monza, University of Milano - Bicocca, Italy
| | | | - Cristina Mapelli
- Department of Neurology, S. Gerardo Hospital, Monza, University of Milano - Bicocca, Italy
- NeuroMI, University of Milano - Bicocca, Italy
| | - Sabrina Morzenti
- Medical Physics, S. Gerardo Hospital, Monza, Italy
- NeuroMI, University of Milano - Bicocca, Italy
| | - Cinzia Crivellaro
- Nuclear Medicine, S. Gerardo Hospital, Monza, Italy
- NeuroMI, University of Milano - Bicocca, Italy
| | - Ildebrando M. Appollonio
- Department of Neurology, S. Gerardo Hospital, Monza, University of Milano - Bicocca, Italy
- NeuroMI, University of Milano - Bicocca, Italy
| | - Carlo Ferrarese
- Department of Neurology, S. Gerardo Hospital, Monza, University of Milano - Bicocca, Italy
- NeuroMI, University of Milano - Bicocca, Italy
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13
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Pan FF, Cui L, Li QJ, Guo QH. Validation of a modified Chinese version of Mini-Addenbrooke's Cognitive Examination for detecting mild cognitive impairment. Brain Behav 2022; 12:e2418. [PMID: 34843170 PMCID: PMC8785624 DOI: 10.1002/brb3.2418] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2021] [Accepted: 10/16/2021] [Indexed: 11/17/2022] Open
Abstract
BACKGROUND For detecting mild cognitive impairment (MCI), brief cognitive screening tools are increasingly required for the advantage of time saving and no need for special equipment or trained raters. We aimed to develop a modified Chinese version of Mini-Addenbrooke's Cognitive Examination (C-MACE) and further evaluate its validation in detecting MCI. METHODS A total of 716 individuals aged from 50 to 90 years old were recruited, including 431 cognitively normal controls (NC) and 285 individuals with MCI. The effect size of Cramer's V was used to explore which items in the Chinese version of Addenbrooke's Cognitive Examination-III (ACE-III-CV) best associated with MCI and to form the C-MACE. Receiver operating characteristic (ROC) analyses were carried out to explore the ability of C-MACE, ACE-III-CV, Chinese version of Montreal Cognitive Assessment-Basic (MoCA-BC), and Mini-Mental State Examination (MMSE) in discriminating MCI from NC. RESULTS Five items with greatest effect sizes of Cramer's V were selected from ACE-III-CV to form the C-MACE: Memory Immediate Recall, Memory Delayed Recall, Memory Recognition, Verbal Fluency Animal and Language Naming. With a total score of 38, the C-MACE had a satisfactory classification accuracy in detecting MCI (area under the ROC curve, AUC = 0.892), superior to MMSE (AUC = 0.782) and comparable to ACE-III-CV (AUC = 0.901) and MoCA-BC (AUC = 0.916). In the subgroup of Age > 70 years, Education ≤ 12 years, the C-MACE got a highest classification accuracy (AUC = 0.958) for detecting MCI. CONCLUSION In the Chinese-speaking population, C-MACE derived from ACE-III-CV may identify MCI with a good classification accuracy, especially in aged people with low education.
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Affiliation(s)
- Feng-Feng Pan
- Department of Gerontology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China
| | - Liang Cui
- Department of Gerontology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China
| | - Qing-Jie Li
- Department of Gerontology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China
| | - Qi-Hao Guo
- Department of Gerontology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China
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14
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Duff K, Suhrie KR, Dalley BCA, Porter SM, Dixon AM. Recognition subtests for the Repeatable Battery for the Assessment of Neuropsychological Status: Preliminary data in cognitively intact older adults, amnestic Mild Cognitive Impairment, and Alzheimer's disease. Clin Neuropsychol 2021; 35:1415-1425. [PMID: 32883179 PMCID: PMC7925698 DOI: 10.1080/13854046.2020.1812724] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2020] [Revised: 08/13/2020] [Accepted: 08/14/2020] [Indexed: 10/23/2022]
Abstract
Objective: The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) has three delayed recall subtests (list, story, figure), but only one delayed recognition subtest (list). Since comparisons between delayed recall and recognition can be useful in clinical neuropsychology, the current study sought to develop and preliminarily examine two proposed new subtests for Form A of the RBANS, Story Recognition and Figure Recognition. Method: A sample of older adults who were cognitively intact (n = 48) or classified with amnestic Mild Cognitive Impairment (MCI, n = 29) or mild Alzheimer's disease (AD, n = 24) were administered the RBANS and the two new recognition subtests. Results: In the primary analyses, cognitively intact participants performed significantly better than the two memory-impaired groups on all twelve scores (one recall and three recognition [total, hits, false positive errors] for the list, story, and figure). For amnestic MCI and AD participants, they showed statistically comparable scores on 7 of the 12 variables, where those with MCI performed better than those with AD on the other five scores. Across the three groups, effect sizes were large (e.g., Cohen's d = 1.0-2.9). In secondary analyses, all of the List Recall and Recognition scores significantly correlated with one another, and this pattern was observed for all of the Story Recall and Recognition scores and most of the Figure Recall and Recognition scores. Conclusions: Although preliminary, these new recognition scores appear to provide useful information and may improve the sensitivity of the RBANS in identifying cortical/subcortical profiles in clinical and research settings.
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Affiliation(s)
- Kevin Duff
- Center for Alzheimer's Care, Imaging and Research, Department of Neurology, University of Utah, Salt Lake City, UT, USA
| | - Kayla R Suhrie
- Center for Alzheimer's Care, Imaging and Research, Department of Neurology, University of Utah, Salt Lake City, UT, USA
| | - Bonnie C A Dalley
- Center for Alzheimer's Care, Imaging and Research, Department of Neurology, University of Utah, Salt Lake City, UT, USA
| | - Sariah M Porter
- Center for Alzheimer's Care, Imaging and Research, Department of Neurology, University of Utah, Salt Lake City, UT, USA
| | - Ava M Dixon
- Center for Alzheimer's Care, Imaging and Research, Department of Neurology, University of Utah, Salt Lake City, UT, USA
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15
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Gellersen HM, Coughlan G, Hornberger M, Simons JS. Memory precision of object-location binding is unimpaired in APOE ε4-carriers with spatial navigation deficits. Brain Commun 2021; 3:fcab087. [PMID: 33987536 PMCID: PMC8108563 DOI: 10.1093/braincomms/fcab087] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2020] [Revised: 03/09/2021] [Accepted: 03/29/2021] [Indexed: 12/19/2022] Open
Abstract
Research suggests that tests of memory fidelity, feature binding and spatial navigation are promising for early detection of subtle behavioural changes related to Alzheimer's disease. In the absence of longitudinal data, one way of testing the early detection potential of cognitive tasks is through the comparison of individuals at different genetic risk for Alzheimer's dementia. Most studies have done so using samples aged 70 years or older. Here, we tested whether memory fidelity of long-term object-location binding may be a sensitive marker even among cognitively healthy individuals in their mid-60s by comparing participants at low and higher risk based on presence of the ε4-allele of the apolipoprotein gene (n = 26 ε3ε3, n = 20 ε3ε4 carriers). We used a continuous report paradigm in a visual memory task that required participants to recreate the spatial position of objects in a scene. We employed mixture modelling to estimate the two distinct memory processes that underpin the trial-by-trial variation in localization errors: retrieval success which indexes the proportion of trials where participants recalled any information about an object's position and the precision with which participants retrieved this information. Prior work has shown that these memory paradigms that separate retrieval success from precision are capable of detecting subtle differences in mnemonic fidelity even when retrieval success could not. Nonetheless, Bayesian analyses found good evidence that ε3ε4 carriers did not remember fewer object locations [F(1, 42) = 0.450, P = 0.506, BF01 = 3.02], nor was their precision for the spatial position of objects reduced compared to ε3ε3 carriers [F(1, 42) = 0.12, P = 0.726, BF01 = 3.19]. Because the participants in the sample presented here were a subset of a study on apolipoprotein ε4-carrier status and spatial navigation in the Sea Hero Quest game [Coughlan et al., 2019. PNAS, 116(9)], we obtained these data to contrast genetic effects on the two tasks within the same sample (n = 33). Despite the smaller sample size, wayfinding deficits among ε3ε4 carriers could be replicated [F(1, 33) = 5.60, P = 0.024, BF10 = 3.44]. Object-location memory metrics and spatial navigation scores were not correlated (all r < 0.25, P > 0.1, 0 < BF10 < 3). These findings show spared object-location binding in the presence of a detrimental apolipoprotein ε4 effect on spatial navigation. This suggests that the sensitivity of memory fidelity and binding tasks may not extend to individuals with one ε4-allele in their early to mid-60s. The results provide further support to prior proposals that spatial navigation may be a sensitive marker for the earliest cognitive changes in Alzheimer's disease, even before episodic memory.
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Affiliation(s)
- Helena M Gellersen
- Department of Psychology, University of Cambridge, Cambridge CB2 3EB, UK
| | - Gillian Coughlan
- Rotman Research Institute, Baycrest Hospital, Toronto, ON M6A 1W1, Canada
| | | | - Jon S Simons
- Department of Psychology, University of Cambridge, Cambridge CB2 3EB, UK
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16
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Yang SY, Lee HC, Huang CM, Chen JJ. Efficacy of Tai Chi-Style Multi-Component Exercise on Frontal-Related Cognition and Physical Health in Elderly With Amnestic Mild Cognitive Impairment. FRONTIERS IN AGING 2021; 2:636390. [PMID: 35822039 PMCID: PMC9261301 DOI: 10.3389/fragi.2021.636390] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/01/2020] [Accepted: 02/17/2021] [Indexed: 02/06/2023]
Abstract
Early prevention from accelerated neurocognitive declines with advanced aging and the delay of the onset of dementia have became paramount for the achievement of active aging. The present study examined whether the proposed non-pharmaceutical, multi-component exercise training which combined Tai-Chi exercise, Aerobic fitness, and thera-band therapy protects against age-related neurocognitive and physical deterioration in the older participants with amnestic mild cognitive impairment (aMCI). Participants with aMCI in the quasi-experimental design were assigned to the multi-component exercise group or care control group. Evaluations of neuropsychological function and functional fitness were performed before and after 12-weeks intervention, and after 24-weeks follow-up. Our results showed that the multi-component intervention significantly improved various domains of neurocognitive function, particularly in memory- and frontal-related cognition, and better performance on functional fitness, including muscle strength, cardiopulmonary endurance, and agility. Furthermore, such beneficial effects were preserved after 24 weeks. The findings provide supportive evidence that non-pharmaceutically multi-component intervention with Tai-Chi style practice as a core exercise may protect against age-related neurocognitive and physical deficits and lay the path on developing age-friendly intervention programs to delay, or even reverse, the progression of MCI to dementia.
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Affiliation(s)
- Shao-Yun Yang
- Department of Physical Therapy and Assistive Technology, National Yang Ming Chiao Tung University, Taipei, Taiwan
- Sports and Health Science Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Hsuei-Chen Lee
- Department of Physical Therapy and Assistive Technology, National Yang Ming Chiao Tung University, Taipei, Taiwan
- Sports and Health Science Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Chih-Mao Huang
- Department of Biological Science and Technology, National Yang Ming Chiao Tung University, Hsinchu, Taiwan
- Center for Intelligent Drug Systems and Smart Bio-devices (IDSB), National Yang Ming Chiao Tung University, Hsinchu, Taiwan
- *Correspondence: Chih-Mao Huang, ; Jin-Jong Chen,
| | - Jin-Jong Chen
- Department of Physical Therapy and Assistive Technology, National Yang Ming Chiao Tung University, Taipei, Taiwan
- Sports and Health Science Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan
- Innovation Center of Artificial Intelligence for Precision Exercise and Health Promotion, Yuanpei University of Medical Technology, Hsinchu, Taiwan
- *Correspondence: Chih-Mao Huang, ; Jin-Jong Chen,
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17
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Schütz H, Caspers S, Moebus S, Lux S. Prevalence and psychosocial correlates of subjectively perceived decline in five cognitive domains: Results from a population-based cohort study in Germany. Int J Geriatr Psychiatry 2020; 35:1219-1227. [PMID: 32510658 DOI: 10.1002/gps.5359] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2019] [Revised: 05/20/2020] [Accepted: 05/30/2020] [Indexed: 11/11/2022]
Abstract
OBJECTIVE Subjective cognitive decline (SCD) was frequently investigated for memory in healthy aging or in relation to diseases like dementia. It was found to be related to sociodemographic and psychological variables as well as cognitive abilities. The prevalence of SCD in other cognitive domains and their relation to these variables is largely unknown to date. The present study aimed to fill this gap. METHODS A total of 807 subjects (18-85 years of age, M = 57.8 years, female: 43%) completed the Juelich Questionnaire on Subjective Cognitive Decline, to investigate SCD in memory, attention, language, motor, and executive functions. Logistic regression analyses were used to estimate association of depressive symptomatology, emotionality, and general cognitive performance as well as age, gender, and educational attainment with domain-specific SCD. RESULTS The highest prevalence rate was obtained for the memory domain (65.9%), followed by the attention (54.6%), motor (52.9%), executive (39.7%), and language domain (31.5%). Of the psychosocial factors, only age, depressive symptomatology and emotionality were consistently and strongly associated with domain-specific SCD prevalence. CONCLUSIONS SCD is prevalent not only in the memory domain, but also in other major cognitive domains. Our results also suggest that the suspicion from previous research, that subjective memory decline might be more strongly associated with depressive symptomatology and emotionality than with actual decline of cognitive performance, might also apply to the attention, motor, executive, and language domain. Further investigations using neuropsychological testing for specific cognitive functions and employing longitudinal designs are required for substantiating this suspicion.
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Affiliation(s)
- Holger Schütz
- Research Center Jülich, Institute of Neuroscience and Medicine, INM-8, Jülich, Germany
| | - Svenja Caspers
- Research Center Jülich, Institute of Neuroscience and Medicine, INM-1, Jülich, Germany.,Institute for Anatomy I, Medical Faculty, University Düsseldorf, Düsseldorf, Germany.,JARA-BRAIN, Jülich-Aachen Research Alliance, Jülich, Germany
| | - Susanne Moebus
- Institute for Urban Public Health, University Hospitals, University Duisburg-Essen, Duisburg, Germany
| | - Silke Lux
- Department of Psychiatry and Psychotherapy, University Clinic Bonn, Bonn, Germany
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18
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Dasgupta A, Acharya K. Mushrooms: an emerging resource for therapeutic terpenoids. 3 Biotech 2019; 9:369. [PMID: 31588393 DOI: 10.1007/s13205-019-1906-2] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2019] [Accepted: 09/19/2019] [Indexed: 12/22/2022] Open
Abstract
Mankind has always been fascinated with nature and have heavily explored natural products since the ancient times. Evolution of diseases led to research on synthetic structure, specificity and activity-guided treatment. To combat threats of new developing diseases and the deleterious side effects posed by modern therapy, researchers have once again looked back towards natural resources. Although plants have been the main source of natural drugs, lower fungi are being recently paid attention to. Among them, mushrooms have emerged as an under-explored yet immensely rich resource, especially for bioactive terpenoids. A lot of research is going on around the world with mushroom-derived terpenoids especially their medicinal properties, some of which have even been used in pre- and post-clinical studies. From the literatures that are available, it was found that mushroom terpenoids have activity against a wide range of diseases. In this review, we have summarized different mushroom-derived terpenoids and their therapeutic properties.
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Affiliation(s)
- Adhiraj Dasgupta
- Molecular and Applied Mycology and Plant Pathology Laboratory, Department of Botany, University of Calcutta, 35, Ballygunge Circular Road, Kolkata, West Bengal 700019 India
| | - Krishnendu Acharya
- Molecular and Applied Mycology and Plant Pathology Laboratory, Department of Botany, University of Calcutta, 35, Ballygunge Circular Road, Kolkata, West Bengal 700019 India
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Symbol Comprehension in Patients With Alzheimer Disease Dementia, Mild Cognitive Impairment, and Major Depressive Disorder. Alzheimer Dis Assoc Disord 2019; 34:85-93. [DOI: 10.1097/wad.0000000000000347] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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21
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Rubin LH, Sundermann EE, Moore DJ. The current understanding of overlap between characteristics of HIV-associated neurocognitive disorders and Alzheimer's disease. J Neurovirol 2019; 25:661-672. [PMID: 30671777 DOI: 10.1007/s13365-018-0702-9] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2018] [Revised: 11/04/2018] [Accepted: 11/13/2018] [Indexed: 12/11/2022]
Abstract
The advent of effective antiretroviral medications (ARVs) has led to an aging of the HIV population with approximately 50% of people with HIV (PWH) being over the age of 50 years. Neurocognitive complications, typically known as HIV-associated neurocognitive disorders (HAND), persist in the era of ARVs and, in addition to risk of HAND, older PWH are also at risk for age-associated, neurodegenerative disorders including Alzheimer's disease (AD). It has been postulated that risk for AD may be greater among PWH due to potential compounding effects of HIV and aging on mechanisms of neural insult. We are now faced with the challenge of disentangling AD from HAND, which has important prognostic and treatment implications given the more rapidly debilitating trajectory of AD. Herein, we review the evidence to date demonstrating both parallels and differences in the profiles of HAND and AD. We specifically address similarities and difference of AD and HAND as it relates to (1) neuropsychological profiles (cross-sectional/longitudinal), (2) AD-associated neuropathological features as evidenced from neuropathological, cerebrospinal fluid and neuroimaging assessments, (3) biological mechanisms underlying cortical amyloid deposition, (4) parallels in mechanisms of neural insult, and (5) common risk factors. Our current understanding of the similarities and dissimilarities of AD and HAND should be further delineated and leveraged in the development of differential diagnostic methods that will allow for the early identification of AD and more suitable and effective treatment interventions among graying PWH.
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Affiliation(s)
- Leah H Rubin
- Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.,Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA
| | - Erin E Sundermann
- Department of Psychiatry, University of California, San Diego (UCSD) School of Medicine, La Jolla, CA, USA.
| | - David J Moore
- Department of Psychiatry, University of California, San Diego (UCSD) School of Medicine, La Jolla, CA, USA
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22
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Li Y, Liu Q, Sun J, Wang J, Liu X, Gao J. Mitochondrial protective mechanism of simvastatin protects against amyloid β peptide-induced injury in SH-SY5Y cells. Int J Mol Med 2018; 41:2997-3005. [PMID: 29436584 DOI: 10.3892/ijmm.2018.3456] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2016] [Accepted: 01/25/2018] [Indexed: 11/06/2022] Open
Abstract
Mitochondrial dysfunction is implicated in the pathology of neuronal damage during Alzheimer's disease (AD). Previous studies suggest that simvastatin (SV) ameliorates amyloid β (Aβ)‑mediated cognitive impairment in AD patients and transgenic mice; however, the mechanisms remain unknown. To investigate the potential mechanisms by which SV protects against AD neurotoxicity, the present study used a series of cellular and molecular assays to analyze the effects of SV in an in vitro model of Aβ1‑42-induced injury. The results demonstrated that SV protected against Aβ1‑42‑induced SH‑SY5Y cell injury by inhibiting the release of cytochrome c from the mitochondria to the cytoplasm, and reducing the production of intracellular reactive oxygen species. In addition, SV downregulated cleaved‑caspase‑3 protein levels, increased the ratio of B cell lymphoma 2 (Bcl-2) to Bcl-2-associated X protein, and increased the protein levels of peroxisome proliferator-activated receptor γ coactivator-1α in the Aβ1‑42‑treated cells. Furthermore, SV increased the mitochondrial membrane potential and adenosine triphosphate levels, and enhanced the cell respiratory function and mitochondrial mass of the cells. In conclusion, the present study revealed that SV protected SH‑SY5Y cells against Aβ1‑42-induced injury through regulating the mitochondrial apoptosis pathway and mitochondrial function.
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Affiliation(s)
- Yunzi Li
- School of Pharmacy, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China
| | - Qian Liu
- Department of Neurology, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210002, P.R. China
| | - Jing Sun
- School of Pharmacy, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China
| | - Jin Wang
- School of Pharmacy, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China
| | - Xinfeng Liu
- Department of Neurology, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210002, P.R. China
| | - Jing Gao
- School of Pharmacy, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China
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Abstract
Notwithstanding tremendous research efforts, the cause of Alzheimer's disease (AD) remains elusive and there is no curative treatment. The cholinergic hypothesis presented 35 years ago was the first major evidence-based hypothesis on the etiology of AD. It proposed that the depletion of brain acetylcholine was a primary cause of cognitive decline in advanced age and AD. It relied on a series of observations obtained in aged animals, elderly, and AD patients that pointed to dysfunctions of cholinergic basal forebrain, similarities between cognitive impairments induced by anticholinergic drugs and those found in advanced age and AD, and beneficial effects of drugs stimulating cholinergic activity. This review revisits these major results to show how this hypothesis provided the drive for the development of anticholinesterase inhibitor-based therapies of AD, the almost exclusively approved treatment in use despite transient and modest efficacy. New ideas for improving cholinergic therapies are also compared and discussed in light of the current revival of the cholinergic hypothesis on the basis of two sets of evidence from new animal models and refined imagery techniques in humans. First, human and animal studies agree in detecting signs of cholinergic dysfunctions much earlier than initially believed. Second, alterations of the cholinergic system are deeply intertwined with its reactive responses, providing the brain with efficient compensatory mechanisms to delay the conversion into AD. Active research in this field should provide new insight into development of multitherapies incorporating cholinergic manipulation, as well as early biomarkers of AD enabling earlier diagnostics. This is of prime importance to counteract a disease that is now recognized to start early in adult life.
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Contador I, Fernández-Calvo B, Boycheva E, Rueda L, Bermejo-Pareja F. Normative Data of the Story and Six-Object Memory Recall Tests in Older Spanish Adults: NEDICES Population-Based Cohort. Arch Clin Neuropsychol 2017; 32:992-1000. [PMID: 28184429 DOI: 10.1093/arclin/acx015] [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: 08/12/2016] [Accepted: 01/22/2017] [Indexed: 11/13/2022] Open
Abstract
Objective We provide normative data for the story and six-object recall tasks, stratified by age and education in a large population-based cohort of older Spanish adults. Method The sample consisted of 2,581 participants without dementia (age range: 67-98 years) from different socioeconomic areas of central Spain. Normative data are presented in percentile ranks and divided into four overlapping age tables with different midpoints. Results Spearman correlations and shared variances were calculated to evaluate the effects of sociodemographic variables on both tasks. Our findings showed that age and education influence the scores in the story and six-object recall tasks, whereas sex had null effect on story recall and an almost negligible on object recall, respectively. Conclusion The norms presented herein are important for the correct interpretation of scores in the story and six-object recall tasks when assessing older adults in Spain.
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Affiliation(s)
- Israel Contador
- Department of Basic Psychology, Psychobiology and Methodology of Behavioral Science, University of Salamanca, Salamanca, Spain
| | | | - Elina Boycheva
- Research Institute of Hospital "12 de Octubre" (i+12), Madrid, Spain
| | - Laura Rueda
- Department of Basic Psychology, Psychobiology and Methodology of Behavioral Science, University of Salamanca, Salamanca, Spain
| | - Félix Bermejo-Pareja
- The Biomedical Research Centre Network for Neurodegenerative Diseases (CIBERNED), Carlos III Research Institute, Madrid, Spain.,Faculty of Medicine, Complutense University, Madrid, Spain
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25
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Cerami C, Dubois B, Boccardi M, Monsch AU, Demonet JF, Cappa SF. Clinical validity of delayed recall tests as a gateway biomarker for Alzheimer's disease in the context of a structured 5-phase development framework. Neurobiol Aging 2017; 52:153-166. [PMID: 28317646 DOI: 10.1016/j.neurobiolaging.2016.03.034] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2015] [Revised: 03/05/2016] [Accepted: 03/22/2016] [Indexed: 11/27/2022]
Abstract
Although Alzheimer's disease criteria promote the use of biomarkers, their maturity in clinical routine still needs to be assessed. In the light of the oncology framework, we conducted a literature review on measures used to assess delayed recall impairment due to medial temporal lobe dysfunction (i.e., free and cued word list recall tests). Ample evidence is available for phases 1 (rationale for use), 2 (discriminative ability), and 3 (early detection ability) for many of the tests in routine use. Evidence about phase 4 (performance in real world) and phase 5 (quantify impact and costs) is yet to come. Administration procedures have been standardized and cutoff scores are well validated in large Alzheimer's disease and mild cognitive impaired series. Some aspects (e.g., different task formats), however, hamper the comparability of results among different populations and the reproducibility between laboratories. No definite guideline for their use can thus be proposed at the moment. Accordingly, the maturity of such markers is not yet sufficient and requires future investigation to promote the proper use of memory measures in clinical settings.
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26
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Weissberger GH, Melrose RJ, Fanale CM, Veliz JV, Sultzer DL. Cortical Metabolic and Cognitive Correlates of Disorientation in Alzheimer’s Disease. J Alzheimers Dis 2017; 60:707-719. [DOI: 10.3233/jad-170420] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Affiliation(s)
- Gali H. Weissberger
- Brain Behavior and Aging Research Center, VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA
- Geriatric Research Education and Clinical Center, VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA
| | - Rebecca J. Melrose
- Brain Behavior and Aging Research Center, VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA
- Geriatric Research Education and Clinical Center, VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA
- Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | - Candace M. Fanale
- Brain Behavior and Aging Research Center, VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA
| | - Joseph V. Veliz
- Brain Behavior and Aging Research Center, VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA
| | - David L. Sultzer
- Brain Behavior and Aging Research Center, VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA
- Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
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27
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The midlife cognitive profiles of adults at high risk of late-onset Alzheimer's disease: The PREVENT study. Alzheimers Dement 2017; 13:1089-1097. [PMID: 28365321 DOI: 10.1016/j.jalz.2017.02.008] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2016] [Revised: 02/15/2017] [Accepted: 02/15/2017] [Indexed: 11/20/2022]
Abstract
INTRODUCTION Although biomarker studies of late-onset Alzheimer's disease suggest pathology to be present decades before diagnosis, little is known about cognitive performance at this stage. METHODS A sample of 210 adults (aged 40-59) of whom 103 have a parent diagnosed with dementia (family history subgroup) underwent computerized cognitive testing. Apolipoprotein E (apoE) status was determined, and 193 subjects had magnetic resonance imaging. Distance from dementia onset was estimated in relation to age of parental diagnosis, and Cardiovascular Risk Factors, Aging, and Incidence of Dementia Risk Scores were calculated. RESULTS Lower hippocampal volumes (P = .04) were associated with poorer spatial location recall and higher Dementia Risk Scores with poorer visual recognition (P = .0005), and lower brain and hippocampal volume (P < .0001, P = .04, respectively). Family history subgroup participants closer to dementia onset had lower scores on visual working memory (P = .05), whereas those with an APOE ε4 allele performed better on form perception (P = .005). DISCUSSION Middle-aged adults at risk of dementia show evidence of poorer cognitive performance, principally in visuospatial functions.
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28
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Toepper M. Dissociating Normal Aging from Alzheimer's Disease: A View from Cognitive Neuroscience. J Alzheimers Dis 2017; 57:331-352. [PMID: 28269778 PMCID: PMC5366251 DOI: 10.3233/jad-161099] [Citation(s) in RCA: 90] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/23/2017] [Indexed: 02/07/2023]
Abstract
Both normal aging and Alzheimer's disease (AD) are associated with changes in cognition, grey and white matter volume, white matter integrity, neural activation, functional connectivity, and neurotransmission. Obviously, all of these changes are more pronounced in AD and proceed faster providing the basis for an AD diagnosis. Since these differences are quantitative, however, it was hypothesized that AD might simply reflect an accelerated aging process. The present article highlights the different neurocognitive changes associated with normal aging and AD and shows that, next to quantitative differences, there are multiple qualitative differences as well. These differences comprise different neurocognitive dissociations as different cognitive deficit profiles, different weights of grey and white matter atrophy, and different gradients of structural decline. These qualitative differences clearly indicate that AD cannot be simply described as accelerated aging process but on the contrary represents a solid entity.
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Affiliation(s)
- Max Toepper
- Department of Psychiatry and Psychotherapy Bethel, Research Division, Evangelisches Krankenhaus Bielefeld (EvKB), Bielefeld, Germany
- Department of Psychiatry and Psychotherapy Bethel, Department of Geriatric Psychiatry, Evangelisches Krankenhaus Bielefeld (EvKB), Bielefeld, Germany
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29
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Detecting cognitive changes in preclinical Alzheimer's disease: A review of its feasibility. Alzheimers Dement 2016; 13:468-492. [PMID: 27702618 DOI: 10.1016/j.jalz.2016.06.2365] [Citation(s) in RCA: 125] [Impact Index Per Article: 13.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2016] [Revised: 05/31/2016] [Accepted: 06/18/2016] [Indexed: 11/23/2022]
Abstract
Significant progress has been made in characterizing the biological changes occurring in preclinical Alzheimer's disease (AD). Cognitive dysfunction has been viewed, however, as a late-stage phenomenon, despite increasing evidence that changes may be detected in the decades preceding dementia. In the absence of comprehensive evidence-based guidelines for preclinical cognitive assessment, longitudinal cohort and neuroimaging studies have been reviewed to determine the temporal order and brain biomarker correlates of specific cognitive functions. Episodic memory decline was observed to be the most salient cognitive function, correlating with high levels of amyloid deposition and hypoconnectivity across large-scale brain networks. Prospective studies point to early decline in both episodic and semantic memory processing as well as executive functions in the predementia period. The cognitive tests have, however, been principally those used to diagnose dementia. New procedures are required which target more finely the medial temporal lobe subregions first affected by clinically silent AD pathology.
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Mistridis P, Krumm S, Monsch AU, Berres M, Taylor KI. The 12 Years Preceding Mild Cognitive Impairment Due to Alzheimer's Disease: The Temporal Emergence of Cognitive Decline. J Alzheimers Dis 2016; 48:1095-107. [PMID: 26402083 PMCID: PMC4927842 DOI: 10.3233/jad-150137] [Citation(s) in RCA: 69] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Abstract
Background: The identification of the type and sequence of cognitive decline in preclinical mild cognitive impairment (MCI) prior to Alzheimer’s disease (AD) is crucial for understanding AD pathogenesis and implementing therapeutic interventions. Objective: To model the longitudinal courses of different neuropsychological functions in MCI due to AD. Methods: We investigated the prodromal phase of MCI over a 12-year period in 27 initially healthy participants with subsequent MCI preceding AD (NC-MCI) and 60 demographically matched healthy individuals (NC-NC). The longitudinal courses of cognitive performance (verbal and visual episodic memory, semantic memory, executive functioning, constructional praxis, psychomotor speed, language, and informant-based reports) were analyzed with linear mixed effects models. Results: The sequence with which different cognitive functions declined in the NC-MCI relative to the NC-NC group began with verbal memory and savings performance approximately eight years, and verbal episodic learning, visual memory, and semantic memory (animal fluency) circa four years prior to the MCI diagnosis. Executive functioning, psychomotor speed, and informant-based reports of the NC-MCI group declined approximately two years preceding the MCI diagnosis. Conclusions: Measurable neuropsychological deterioration occurs up to approximately eight years preceding MCI due to AD.
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Affiliation(s)
- Panagiota Mistridis
- Memory Clinic, University Center for Medicine of Aging Basel, Felix Platter Hospital, Basel, Switzerland.,University of Basel, Basel, Switzerland
| | - Sabine Krumm
- Memory Clinic, University Center for Medicine of Aging Basel, Felix Platter Hospital, Basel, Switzerland.,University of Basel, Basel, Switzerland
| | - Andreas U Monsch
- Memory Clinic, University Center for Medicine of Aging Basel, Felix Platter Hospital, Basel, Switzerland.,University of Basel, Basel, Switzerland
| | - Manfred Berres
- Department of Mathematics and Technology, University of Applied Sciences Koblenz, Koblenz, Germany
| | - Kirsten I Taylor
- Memory Clinic, University Center for Medicine of Aging Basel, Felix Platter Hospital, Basel, Switzerland.,University of Basel, Basel, Switzerland.,Centre for Speech, Language and the Brain, Department of Experimental Psychology, University of Cambridge, Cambridge, UK
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Laws KR, Irvine K, Gale TM. Sex differences in cognitive impairment in Alzheimer’s disease. World J Psychiatry 2016; 6:54-65. [PMID: 27014598 PMCID: PMC4804268 DOI: 10.5498/wjp.v6.i1.54] [Citation(s) in RCA: 212] [Impact Index Per Article: 23.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2015] [Revised: 11/14/2015] [Accepted: 01/22/2016] [Indexed: 02/05/2023] Open
Abstract
Sex differences in neurocognitive abilities have been extensively explored both in the healthy population and in many disorders. Until recently, however, little work has examined such differences in people with Alzheimer’s disease (AD). This is despite clear evidence that AD is more prevalent in women, and converging lines of evidence from brain imaging, post-mortem analyses, hormone therapy and genetics suggesting that AD affects men and women differently. We provide an overview of evidence attesting to the poorer cognitive profiles in women than in men at the same stage of AD. Indeed, men significantly outperform women in several cognitive domains, including: Language and semantic abilities, visuospatial abilities and episodic memory. These differences do not appear to be attributable to any differences in age, education, or dementia severity. Reasons posited for this female disadvantage include a reduction of estrogen in postmenopausal women, greater cognitive reserve in men, and the influence of the apolipoprotein E ε4 allele. Assessment of cognitive abilities contributes to the diagnosis of the condition and thus, it is crucial to identify the role of sex differences if potentially more accurate diagnoses and treatments are to emerge.
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Cortical thinning of parahippocampal subregions in very early Alzheimer's disease. Neurobiol Aging 2016; 38:188-196. [DOI: 10.1016/j.neurobiolaging.2015.11.001] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2015] [Revised: 11/02/2015] [Accepted: 11/03/2015] [Indexed: 11/20/2022]
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Preliminary Validation of a Questionnaire Covering Risk Factors for Impaired Driving Skills in Elderly Patients. Geriatrics (Basel) 2016; 1:geriatrics1010005. [PMID: 31022801 PMCID: PMC6371095 DOI: 10.3390/geriatrics1010005] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2015] [Revised: 12/07/2015] [Accepted: 12/16/2015] [Indexed: 11/17/2022] Open
Abstract
Due to rather unspecific statutory regulations in Germany, particularly for patients with neurodegenerative disorders, many seniors still drive despite severe driving-related cognitive deficits. An accurate assessment of driving fitness requires immense financial, personnel and temporal resources which go beyond daily clinical routines. In cooperation with a working group from Switzerland, we therefore developed the questionnaire Safety Advice For Elderly drivers (SAFE), an economic instrument covering different risk factors for driving safety. The main aim of the current work was a first validation of the SAFE. Twenty-two driving seniors performed the Corporal A, a test battery permitted by law to assess driving-related cognitive functions. Based upon the Corporal results and the percentile rank 16 criterion, participants were divided into cognitively impaired and unimpaired drivers. Moreover, participants were assessed using the SAFE and an extensive neuropsychological test battery. The results revealed high sensitivity and specifity scores for the SAFE suggesting that the SAFE may be a valuable and economical instrument to quantify and document individual risk factors for driving safety and to differentiate between impaired and unimpaired drivers. Notably, the results must be replicated in future studies including a larger sample, different clinical subgroups, and a practical driving lesson.
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Giebel CM, Challis D, Montaldi D. Understanding the cognitive underpinnings of functional impairments in early dementia: a review. Aging Ment Health 2015; 19:859-75. [PMID: 25632849 DOI: 10.1080/13607863.2014.1003282] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
Abstract
OBJECTIVES Early dementia is marked by cognitive and functional impairments, and although studies indicate an association between these, detailed analyses exploring this relationship are rare. It is crucial to understand how specific cognitive deficits underlie functional deficits to develop successful cognitive interventions. This paper reviews the evidence of impairment in everyday functioning and in working, long-term and prospective memory in early dementia. Findings are evaluated with respect to the relationship between cognitive and functional impairments. METHODS From the literature searches, 17 studies on everyday functioning and 40 studies on memory were obtained. Studies were only included if patients had an official diagnosis and were in the early stages of dementia. RESULTS Complex instrumental activities of daily living were subject to greater impairment than basic activities of daily living. In particular, early dementia patients struggle with finance tasks; a deficit linked to impaired working memory. Regarding cognition, long-term memory is the earliest form of memory to decline as is well recognised. Evidence also indicates deficits in working and prospective memory, with inconsistent evidence about impairments of the former. A major limitation of the literature is a lack of studies assessing individual everyday activities and the associated error patterns that might occur. CONCLUSION This review critically assesses the status of translational research for everyday activities in early dementia, an area with critical implications for cognitive-based rehabilitation. Further research is required into the detailed assessment of individual everyday activity and specific memory deficits, in order to effectively map cognitive functions onto functional performance.
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Affiliation(s)
- Clarissa M Giebel
- a School of Psychological Sciences , The University of Manchester , Manchester , UK
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Abstract
Symbols and signs have been suggested to improve the orientation of patients suffering from Alzheimer disease (AD). However, there are hardly any studies that confirm whether AD patients benefit from signs or symbols and which symbol characteristics might improve or impede their symbol comprehension. To address these issues, 30 AD patients and 30 matched healthy controls performed a symbol processing task (SPT) with 4 different item categories. A repeated-measures analysis of variance was run to identify impact of different item categories on performance accuracy in both the experimental groups. Moreover, SPT scores were correlated with neuropsychological test scores in a broad range of other cognitive domains. Finally, diagnostic accuracy of the SPT was calculated by a receiver-operating characteristic curve analysis. Results revealed a global symbol processing dysfunction in AD that was associated with semantic memory and executive deficits. Moreover, AD patients showed a disproportional performance decline at SPT items with visual distraction. Finally, the SPT total score showed high sensitivity and specificity in differentiating between AD patients and healthy controls. The present findings suggest that specific symbol features impede symbol processing in AD and argue for a diagnostic benefit of the SPT in neuropsychological assessment.
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Histologic validation of locus coeruleus MRI contrast in post-mortem tissue. Neuroimage 2015; 113:235-45. [PMID: 25791783 DOI: 10.1016/j.neuroimage.2015.03.020] [Citation(s) in RCA: 156] [Impact Index Per Article: 15.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2014] [Revised: 01/27/2015] [Accepted: 03/09/2015] [Indexed: 11/22/2022] Open
Abstract
The locus coeruleus (LC) noradrenergic system regulates arousal and modulates attention through its extensive projections across the brain. LC dysfunction has been implicated in a broad range of neurodevelopmental, neurodegenerative and psychiatric disorders, as well as in the cognitive changes observed during normal aging. Magnetic resonance imaging (MRI) has been used to characterize the human LC (elevated contrast relative to surrounding structures), but there is limited understanding of the factors underlying putative LC contrast that are critical to successful biomarker development and confidence in localizing nucleus LC. We used ultra-high-field 7 T magnetic resonance imaging (MRI) to acquire T1-weighted microscopy resolution images (78 μm in-plane resolution) of the LC from post-mortem tissue samples. Histological analyses were performed to characterize the distribution of tyrosine hydroxylase (TH) and neuromelanin in the scanned tissue, which allowed for direct comparison with MR microscopy images. Our results indicate that LC-MRI contrast corresponds to the location of neuromelanin cells in LC; these also correspond to norepinephrine neurons. Thus, neuromelanin appears to serve as a natural contrast agent for nucleus LC that can be used to localize nucleus LC and may have the potential to characterize neurodegenerative disease.
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Lin CH, Chen PK, Chang YC, Chuo LJ, Chen YS, Tsai GE, Lane HY. Benzoate, a D-amino acid oxidase inhibitor, for the treatment of early-phase Alzheimer disease: a randomized, double-blind, placebo-controlled trial. Biol Psychiatry 2014; 75:678-685. [PMID: 24074637 DOI: 10.1016/j.biopsych.2013.08.010] [Citation(s) in RCA: 95] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2013] [Revised: 07/25/2013] [Accepted: 08/05/2013] [Indexed: 01/25/2023]
Abstract
BACKGROUND N-methyl-D-aspartate receptor (NMDAR)-mediated neurotransmission is vital for learning and memory. Hypofunction of NMDAR has been reported to play a role in the pathophysiology of Alzheimer disease (AD), particularly in the early phase. Enhancing NMDAR activation might be a novel treatment approach. One of the methods to enhance NMDAR activity is to raise the levels of NMDA coagonists by blocking their metabolism. This study examined the efficacy and safety of sodium benzoate, a D-amino acid oxidase inhibitor, for the treatment of amnestic mild cognitive impairment and mild AD. METHODS We conducted a randomized, double-blind, placebo-controlled trial in four major medical centers in Taiwan. Sixty patients with amnestic mild cognitive impairment or mild AD were treated with 250-750 mg/day of sodium benzoate or placebo for 24 weeks. Alzheimer's Disease Assessment Scale-cognitive subscale (the primary outcome) and global function (assessed by Clinician Interview Based Impression of Change plus Caregiver Input) were measured every 8 weeks. Additional cognition composite was measured at baseline and endpoint. RESULTS Sodium benzoate produced a better improvement than placebo in Alzheimer's Disease Assessment Scale-cognitive subscale (p = .0021, .0116, and .0031 at week 16, week 24, and endpoint, respectively), additional cognition composite (p = .007 at endpoint) and Clinician Interview Based Impression of Change plus Caregiver Input (p = .015, .016, and .012 at week 16, week 24, and endpoint, respectively). Sodium benzoate was well-tolerated without evident side-effects. CONCLUSIONS Sodium benzoate substantially improved cognitive and overall functions in patients with early-phase AD. The preliminary results show promise for D-amino acid oxidase inhibition as a novel approach for early dementing processes.
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Affiliation(s)
- Chieh-Hsin Lin
- Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan; Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Ping-Kun Chen
- Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan; Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan; Department of Neurology, Lin-Shin Hospital, Taichung, Taiwan
| | - Yue-Cune Chang
- Department of Mathematics, Tamkang University, Taipei, Taiwan
| | - Liang-Jen Chuo
- Department of Psychiatry, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Yan-Syun Chen
- Department of Mathematics, Tamkang University, Taipei, Taiwan; Department of Psychiatry, China Medical University Hospital, Taichung, Taiwan
| | - Guochuan E Tsai
- Department of Psychiatry, Harbor-UCLA Medical Center, Torrance, California
| | - Hsien-Yuan Lane
- Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan; Department of Psychiatry, China Medical University Hospital, Taichung, Taiwan.
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Mura T, Proust-Lima C, Jacqmin-Gadda H, Akbaraly T, Touchon J, Dubois B, Berr C. Measuring cognitive change in subjects with prodromal Alzheimer's disease. J Neurol Neurosurg Psychiatry 2014; 85:363-70. [PMID: 23840054 PMCID: PMC5225268 DOI: 10.1136/jnnp-2013-305078] [Citation(s) in RCA: 47] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
OBJECTIVE To investigate the sensitivity of a large set of neuropsychological tests to detect cognitive changes due to prodromal Alzheimer's disease(AD); to compare their metrological properties in order to select a restricted number of these tests for the longitudinal follow-up of subjects with prodromal AD. PARTICIPANTS 212 patients with mild cognitive impairment were tested at baseline by a standardised neuropsychological battery, which included: the Free and Cued Selective Reminding test (FCSRT), the Benton Visual Retention test, the Deno100, verbal fluency, a serial digit learning test, the double task of Baddeley, the Wechsler Adult Intelligence Scale (WAIS) similarities, the Trail-Making Test and the WAIS digit symbol test. Patients were monitored every 6 months for up to 3 years in order to identify those who converted to AD (retrospectively classified as prodromal AD). Statistical analyses were performed using a nonlinear multivariate mixed model involving a latent process. This model assumes that the psychometric tests are nonlinear transformations of a common latent cognitive process, and it captures the metrological properties of tests. RESULTS 57 patients converted to AD. The most sensitive tests in the detection of cognitive changes due to prodromal AD were the FCSRT, the semantic verbal fluency and the Deno100. Some tests exhibited a higher sensitivity to cognitive changes for subjects with high levels of cognition, such as the free recall, delayed free recall scores of the FCSRT and the semantic verbal fluency, whereas others showed a higher sensitivity at low levels of cognition, such as the total recall score of the FCSRT. CONCLUSIONS Tests used for the follow-up of prodromal AD subjects should be chosen among those that actually decline in this stage of the disease and should be selected according to the subject's initial scores.
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Affiliation(s)
- Thibault Mura
- Neuropsychiatrie : recherche épidémiologique et clinique
Université Montpellier 1Institut National de la Santé et de la Recherche MédicaleHôpital La Colombière 39 avenue Charles Flahault BP 34493 -Pav 42 Calixte Cavalier 34093 Montpellier Cedex
- Département d'Information Médicale
Centre Hospitalier Régional Universitaire [Montpellier]34093 Montpellier
- CIC - Montpellier
Institut National de la Santé et de la Recherche MédicaleUniversité Montpellier 1Hopital Saint-Eloi Montpellier 80 avenue Augustin Fliche 34295 Montpellier Cedex 5
- * Correspondence should be addressed to Thibault Mura
| | - Cécile Proust-Lima
- Epidémiologie et Biostatistique [Bordeaux]
Université Bordeaux Segalen - Bordeaux 2Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)Institut National de la Santé et de la Recherche Médicale146 rue Léo-Saignat 33076 Bordeaux
| | - Hélène Jacqmin-Gadda
- Epidémiologie et Biostatistique [Bordeaux]
Université Bordeaux Segalen - Bordeaux 2Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)Institut National de la Santé et de la Recherche Médicale146 rue Léo-Saignat 33076 Bordeaux
| | - Tasnime Akbaraly
- Neuropsychiatrie : recherche épidémiologique et clinique
Université Montpellier 1Institut National de la Santé et de la Recherche MédicaleHôpital La Colombière 39 avenue Charles Flahault BP 34493 -Pav 42 Calixte Cavalier 34093 Montpellier Cedex
- Department of Epidemiology and Public Health
University College of London [London]1-19 Torrington Place London WC1E 6BT
| | - Jacques Touchon
- Neuropsychiatrie : recherche épidémiologique et clinique
Université Montpellier 1Institut National de la Santé et de la Recherche MédicaleHôpital La Colombière 39 avenue Charles Flahault BP 34493 -Pav 42 Calixte Cavalier 34093 Montpellier Cedex
- Centre Mémoire Recherche Ressources MPL
Centre Hospitalier Régional Universitaire [Montpellier]Hôpital Gui de Chauliac, CHU de Montpellier, 34025 Montpellier Cedex 5
| | - Bruno Dubois
- CRICM, Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière
Université Pierre et Marie Curie - Paris 6Institut National de la Santé et de la Recherche MédicaleCentre National de la Recherche ScientifiqueGH Pitié-Salpêtrière 47 boulevard de l'Hôpital 75651 Paris Cedex 13
| | - Claudine Berr
- Neuropsychiatrie : recherche épidémiologique et clinique
Université Montpellier 1Institut National de la Santé et de la Recherche MédicaleHôpital La Colombière 39 avenue Charles Flahault BP 34493 -Pav 42 Calixte Cavalier 34093 Montpellier Cedex
- Centre Mémoire Recherche Ressources MPL
Centre Hospitalier Régional Universitaire [Montpellier]Hôpital Gui de Chauliac, CHU de Montpellier, 34025 Montpellier Cedex 5
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Bioactive metabolites from macrofungi: ethnopharmacology, biological activities and chemistry. FUNGAL DIVERS 2013. [DOI: 10.1007/s13225-013-0265-2] [Citation(s) in RCA: 66] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
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Gildengers AG, Chisholm D, Butters MA, Anderson SJ, Begley A, Holm M, Rogers JC, Reynolds CF, Mulsant BH. Two-year course of cognitive function and instrumental activities of daily living in older adults with bipolar disorder: evidence for neuroprogression? Psychol Med 2013; 43:801-11. [PMID: 22846332 PMCID: PMC3593938 DOI: 10.1017/s0033291712001614] [Citation(s) in RCA: 58] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND While bipolar disorder (BD) is a leading cause of disability, and an important contributor to disability in BD is cognitive impairment, there is little systematic research on the longitudinal course of cognitive function and instrumental activities of daily living (IADLs) in late-life. In this report, we characterize the 2-year course of cognitive function and IADLs in older adults with BD. Method We recruited non-demented individuals 50 years and older with BD I or BD II (n = 47) from out-patient clinics or treatment studies at the University of Pittsburgh. Comparator subjects ('controls') were 22 individuals of comparable age and education with no psychiatric or neurologic history, but similar levels of cardiovascular disease. We assessed cognitive function and IADLs at baseline, 1- and 2-year time-points. The neuropsychological evaluation comprised 21 well-established and validated tests assessing multiple cognitive domains. We assessed IADLs using a criterion-referenced, performance-based instrument. We employed repeated-measures mixed-effects linear models to examine trajectory of cognitive function. We employed non-parametric tests for analysis of IADLs. RESULTS The BD group displayed worse cognitive function in all domains and worse IADL performance than the comparator group at baseline and over follow-up. Global cognitive function and IADLs were correlated at all time-points. The BD group did not exhibit accelerated cognitive decline over 2 years. CONCLUSIONS Over 2 years, cognitive impairment and associated functional disability of older adults with BD appear to be due to long-standing neuroprogressive processes compounded by normal cognitive aging rather than accelerated cognitive loss in old age.
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Affiliation(s)
- A. G. Gildengers
- University of Pittsburgh School of Medicine, Department of Psychiatry, Pittsburgh, PA, USA
| | - D. Chisholm
- University of Pittsburgh School of Rehabilitation Sciences, Department of Occupational Therapy, Pittsburgh, PA, USA
| | - M. A. Butters
- University of Pittsburgh School of Medicine, Department of Psychiatry, Pittsburgh, PA, USA
| | - S. J. Anderson
- University of Pittsburgh Graduate School of Public Health, Department of Biostatistics, Pittsburgh, PA, USA
| | - A. Begley
- University of Pittsburgh School of Medicine, Department of Psychiatry, Pittsburgh, PA, USA
| | - M. Holm
- University of Pittsburgh School of Rehabilitation Sciences, Department of Occupational Therapy, Pittsburgh, PA, USA
| | - J. C. Rogers
- University of Pittsburgh School of Rehabilitation Sciences, Department of Occupational Therapy, Pittsburgh, PA, USA
| | - C. F. Reynolds
- University of Pittsburgh School of Medicine, Department of Psychiatry, Pittsburgh, PA, USA
| | - B. H. Mulsant
- Centre for Addiction and Mental Health and the University of Toronto, Department of Psychiatry, Toronto, ON, Canada
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Jain S, Yoon SY, Zhu L, Brodbeck J, Dai J, Walker D, Huang Y. Arf4 determines dentate gyrus-mediated pattern separation by regulating dendritic spine development. PLoS One 2012; 7:e46340. [PMID: 23050017 PMCID: PMC3457985 DOI: 10.1371/journal.pone.0046340] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2012] [Accepted: 08/29/2012] [Indexed: 11/18/2022] Open
Abstract
The ability to distinguish between similar experiences is a critical feature of episodic memory and is primarily regulated by the dentate gyrus (DG) region of the hippocampus. However, the molecular mechanisms underlying such pattern separation tasks are poorly understood. We report a novel role for the small GTPase ADP ribosylation factor 4 (Arf4) in controlling pattern separation by regulating dendritic spine development. Arf4(+/-) mice at 4-5 months of age display severe impairments in a pattern separation task, as well as significant dendritic spine loss and smaller miniature excitatory post-synaptic currents (mEPSCs) in granule cells of the DG. Arf4 knockdown also decreases spine density in primary neurons, whereas Arf4 overexpression promotes spine development. A constitutively active form of Arf4, Arf4-Q71L, promotes spine density to an even greater extent than wildtype Arf4, whereas the inactive Arf4-T31N mutant does not increase spine density relative to controls. Arf4's effects on spine development are regulated by ASAP1, a GTPase-activating protein that modulates Arf4 GTPase activity. ASAP1 overexpression decreases spine density, and this effect is partially rescued by concomitant overexpression of wildtype Arf4 or Arf4-Q71L. In addition, Arf4 overexpression rescues spine loss in primary neurons from an Alzheimer's disease-related apolipoprotein (apo) E4 mouse model. Our findings suggest that Arf4 is a critical modulator of DG-mediated pattern separation by regulating dendritic spine development.
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Affiliation(s)
- Sachi Jain
- Gladstone Institute of Neurological Disease, San Francisco, California, United States of America
- Biomedical Sciences Graduate Program, University of California San Francisco, San Francisco, California, United States of America
| | - Seo Yeon Yoon
- Gladstone Institute of Neurological Disease, San Francisco, California, United States of America
| | - Lei Zhu
- Gladstone Institute of Neurological Disease, San Francisco, California, United States of America
| | - Jens Brodbeck
- Gladstone Institute of Neurological Disease, San Francisco, California, United States of America
| | - Jessica Dai
- Gladstone Institute of Neurological Disease, San Francisco, California, United States of America
| | - David Walker
- Gladstone Institute of Neurological Disease, San Francisco, California, United States of America
- Gladstone Institute of Cardiovascular Disease, San Francisco, California, United States of America
| | - Yadong Huang
- Gladstone Institute of Neurological Disease, San Francisco, California, United States of America
- Gladstone Institute of Cardiovascular Disease, San Francisco, California, United States of America
- Biomedical Sciences Graduate Program, University of California San Francisco, San Francisco, California, United States of America
- Department of Neurology, University of California San Francisco, San Francisco, California, United States of America
- Department of Pathology, University of California San Francisco, San Francisco, California, United States of America
- * E-mail:
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