|
1
|
Duong MT, Das SR, Khandelwal P, Lyu X, Xie L, McGrew E, Dehghani N, McMillan CT, Lee EB, Shaw LM, Yushkevich PA, Wolk DA, Nasrallah IM. Hypometabolic mismatch with atrophy and tau pathology in mixed Alzheimer's and Lewy body disease. Brain 2025; 148:1577-1587. [PMID: 39573823 PMCID: PMC12073973 DOI: 10.1093/brain/awae352] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2024] [Revised: 08/27/2024] [Accepted: 10/10/2024] [Indexed: 01/19/2025] Open
Abstract
Polypathology is a major driver of heterogeneity in the clinical presentation and extent of neurodegeneration (N) in patients with Alzheimer's disease (AD). Beyond amyloid (A) and tau (T) pathologies, over half of patients with AD have concomitant pathology such as α-synuclein (S) in mixed AD with Lewy body disease (LBD). Patients with multiple aetiology dementia such as AD + LBD have faster progression and potentially differential responses to targeted treatments, although the diagnosis of AD + LBD can be challenging given the overlapping clinical and imaging features. Development and validation of improved in vivo biomarkers are required to study relationships between N and S and identify imaging patterns reflecting mixed AD + LBD pathologies. We hypothesized that individual proteinopathies, such as T and S, are associated with commensurate levels of N. Thus, we assessed biomarkers of A, T, N and S with PET, MRI and CSF seeding amplification assay (SAA) data to determine molecular presentations of mixed A+S+ versus A+S- cognitively impaired patients from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Strikingly, A+S+ patients had parieto-occipital 18F-fluorodeoxyglucose hypometabolism (a measure of N) disproportionate to the degree of regional atrophy or T burden, highlighting worse hypometabolism associated with S+ status on SAA. Following up on this hypometabolic mismatch with CSF metabolite and proteome analyses, we found that A+S+ patients exhibited lower CSF levels of dopamine metabolites and synaptic markers like neuronal pentraxin-2 (NPTX2), suggesting that altered neurotransmission and neuron integrity contribute to this dissociation between metabolic PET and MRI. Potential confounders exist when studying relations between N, AD and LBD pathologies, including neuroinflammation and other non-Alzheimer's pathologies in mixed dementia, although our findings imply posterior hypometabolic mismatch is related more to S than vascular or TDP-43 pathology. Overall, A+S+ patients had posterior mismatch with excessive 18F-fluorodeoxyglucose hypometabolism relative to atrophy or T load, possibly reflecting impaired neuronal integrity. Further research must disentangle the impact of multiple proteinopathies and clinicopathologic factors on hypometabolism and atrophy. Cumulatively, patients with mixed AD + LBD aetiologies harbour a unique metabolic PET mismatch signature.
Collapse
Affiliation(s)
- Michael Tran Duong
- Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
- Department of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, PA 19104, USA
| | - Sandhitsu R Das
- Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
- Alzheimer’s Disease Research Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
| | - Pulkit Khandelwal
- Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
- Department of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, PA 19104, USA
| | - Xueying Lyu
- Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
- Department of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, PA 19104, USA
| | - Long Xie
- Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
- Department of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, PA 19104, USA
| | - Emily McGrew
- Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
| | - Nadia Dehghani
- Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
| | - Corey T McMillan
- Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
- Alzheimer’s Disease Research Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
| | - Edward B Lee
- Alzheimer’s Disease Research Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
- Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
| | - Leslie M Shaw
- Alzheimer’s Disease Research Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
- Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
| | - Paul A Yushkevich
- Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
- Department of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, PA 19104, USA
- Alzheimer’s Disease Research Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
| | - David A Wolk
- Department of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, PA 19104, USA
- Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
- Alzheimer’s Disease Research Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
| | - Ilya M Nasrallah
- Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
- Department of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, PA 19104, USA
- Alzheimer’s Disease Research Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
| |
Collapse
|
|
2
|
Bendella Z, Purrer V, Haase R, Zülow S, Kindler C, Borger V, Banat M, Dorn F, Wüllner U, Radbruch A, Schmeel FC. Brain and Ventricle Volume Alterations in Idiopathic Normal Pressure Hydrocephalus Determined by Artificial Intelligence-Based MRI Volumetry. Diagnostics (Basel) 2024; 14:1422. [PMID: 39001312 PMCID: PMC11241572 DOI: 10.3390/diagnostics14131422] [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: 05/28/2024] [Revised: 06/25/2024] [Accepted: 06/29/2024] [Indexed: 07/16/2024] Open
Abstract
The aim of this study was to employ artificial intelligence (AI)-based magnetic resonance imaging (MRI) brain volumetry to potentially distinguish between idiopathic normal pressure hydrocephalus (iNPH), Alzheimer's disease (AD), and age- and sex-matched healthy controls (CG) by evaluating cortical, subcortical, and ventricular volumes. Additionally, correlations between the measured brain and ventricle volumes and two established semi-quantitative radiologic markers for iNPH were examined. An IRB-approved retrospective analysis was conducted on 123 age- and sex-matched subjects (41 iNPH, 41 AD, and 41 controls), with all of the iNPH patients undergoing routine clinical brain MRI prior to ventriculoperitoneal shunt implantation. Automated AI-based determination of different cortical and subcortical brain and ventricular volumes in mL, as well as calculation of population-based normalized percentiles according to an embedded database, was performed; the CE-certified software mdbrain v4.4.1 or above was used with a standardized T1-weighted 3D magnetization-prepared rapid gradient echo (MPRAGE) sequence. Measured brain volumes and percentiles were analyzed for between-group differences and correlated with semi-quantitative measurements of the Evans' index and corpus callosal angle: iNPH patients exhibited ventricular enlargement and changes in gray and white matter compared to AD patients and controls, with the most significant differences observed in total ventricular volume (+67%) and the lateral (+68%), third (+38%), and fourth (+31%) ventricles compared to controls. Global ventriculomegaly and marked white matter reduction with concomitant preservation of gray matter compared to AD and CG were characteristic of iNPH, whereas global and frontoparietally accentuated gray matter reductions were characteristic of AD. Evans' index and corpus callosal angle differed significantly between the three groups and moderately correlated with the lateral ventricular volumes in iNPH patients [Evans' index (r > 0.83, p ≤ 0.001), corpus callosal angle (r < -0.74, p ≤ 0.001)]. AI-based MRI volumetry in iNPH patients revealed global ventricular enlargement and focal brain atrophy, which, in contrast to healthy controls and AD patients, primarily involved the supratentorial white matter and was marked temporomesially and in the midbrain, while largely preserving gray matter. Integrating AI volumetry in conjunction with traditional radiologic measures could enhance iNPH identification and differentiation, potentially improving patient management and therapy response assessment.
Collapse
Affiliation(s)
- Zeynep Bendella
- Department of Neuroradiology, Faculty of Medicine, University Hospital Bonn, Rheinische Friedrich-Wilhelms-Universität Bonn, 53127 Bonn, Germany; (Z.B.); (R.H.); (S.Z.); (F.D.); (A.R.)
- German Center of Neurodegenerative Diseases (DZNE), 53127 Bonn, Germany; (V.P.); (C.K.); (U.W.)
| | - Veronika Purrer
- German Center of Neurodegenerative Diseases (DZNE), 53127 Bonn, Germany; (V.P.); (C.K.); (U.W.)
- Department of Neurodegenerative Diseases, University Hospital Bonn, Rheinische Friedrich-Wilhelms-Universität Bonn, 53127 Bonn, Germany
| | - Robert Haase
- Department of Neuroradiology, Faculty of Medicine, University Hospital Bonn, Rheinische Friedrich-Wilhelms-Universität Bonn, 53127 Bonn, Germany; (Z.B.); (R.H.); (S.Z.); (F.D.); (A.R.)
- German Center of Neurodegenerative Diseases (DZNE), 53127 Bonn, Germany; (V.P.); (C.K.); (U.W.)
| | - Stefan Zülow
- Department of Neuroradiology, Faculty of Medicine, University Hospital Bonn, Rheinische Friedrich-Wilhelms-Universität Bonn, 53127 Bonn, Germany; (Z.B.); (R.H.); (S.Z.); (F.D.); (A.R.)
| | - Christine Kindler
- German Center of Neurodegenerative Diseases (DZNE), 53127 Bonn, Germany; (V.P.); (C.K.); (U.W.)
- Department of Neurodegenerative Diseases, University Hospital Bonn, Rheinische Friedrich-Wilhelms-Universität Bonn, 53127 Bonn, Germany
| | - Valerie Borger
- Department of Neurosurgery, University Hospital Bonn, Rheinische Friedrich-Wilhelms-Universität Bonn, 53127 Bonn, Germany; (V.B.); (M.B.)
| | - Mohammed Banat
- Department of Neurosurgery, University Hospital Bonn, Rheinische Friedrich-Wilhelms-Universität Bonn, 53127 Bonn, Germany; (V.B.); (M.B.)
| | - Franziska Dorn
- Department of Neuroradiology, Faculty of Medicine, University Hospital Bonn, Rheinische Friedrich-Wilhelms-Universität Bonn, 53127 Bonn, Germany; (Z.B.); (R.H.); (S.Z.); (F.D.); (A.R.)
| | - Ullrich Wüllner
- German Center of Neurodegenerative Diseases (DZNE), 53127 Bonn, Germany; (V.P.); (C.K.); (U.W.)
- Department of Neurodegenerative Diseases, University Hospital Bonn, Rheinische Friedrich-Wilhelms-Universität Bonn, 53127 Bonn, Germany
| | - Alexander Radbruch
- Department of Neuroradiology, Faculty of Medicine, University Hospital Bonn, Rheinische Friedrich-Wilhelms-Universität Bonn, 53127 Bonn, Germany; (Z.B.); (R.H.); (S.Z.); (F.D.); (A.R.)
- German Center of Neurodegenerative Diseases (DZNE), 53127 Bonn, Germany; (V.P.); (C.K.); (U.W.)
| | - Frederic Carsten Schmeel
- Department of Neuroradiology, Faculty of Medicine, University Hospital Bonn, Rheinische Friedrich-Wilhelms-Universität Bonn, 53127 Bonn, Germany; (Z.B.); (R.H.); (S.Z.); (F.D.); (A.R.)
- German Center of Neurodegenerative Diseases (DZNE), 53127 Bonn, Germany; (V.P.); (C.K.); (U.W.)
| |
Collapse
|
|
3
|
Iannaccone S, Houdayer E, Spina A, Nocera G, Alemanno F. Quantitative EEG for early differential diagnosis of dementia with Lewy bodies. Front Psychol 2023; 14:1150540. [PMID: 37151310 PMCID: PMC10157484 DOI: 10.3389/fpsyg.2023.1150540] [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: 01/25/2023] [Accepted: 03/31/2023] [Indexed: 05/09/2023] Open
Abstract
Introduction Differentiating between the two most common forms of dementia, Alzheimer's dementia and dementia with Lewy bodies (DLB) remains difficult and requires the use of invasive, expensive, and resource-intensive techniques. We aimed to investigate the sensitivity and specificity of electroencephalography quantified using the statistical pattern recognition method (qEEG-SPR) for identifying dementia and DLB. Methods Thirty-two outpatients and 16 controls underwent clinical assessment (by two blinded neurologists), EEG recording, and a 6-month follow-up clinical assessment. EEG data were processed using a qEEG-SPR protocol to derive a Dementia Index (positive or negative) and DLB index (positive or negative) for each participant which was compared against the diagnosis given at clinical assessment. Confusion matrices were used to calculate sensitivity, specificity, and predictive values for identifying dementia and DLB specifically. Results Clinical assessment identified 30 cases of dementia, 2 of which were diagnosed clinically with possible DLB, 14 with probable DLB and DLB was excluded in 14 patients. qEEG-SPR confirmed the dementia diagnosis in 26 out of the 32 patients and led to 6.3% of false positives (FP) and 9.4% of false negatives (FN). qEEG-SPR was used to provide a DLB diagnosis among patients who received a positive or inconclusive result of Dementia index and led to 13.6% of FP and 13.6% of FN. Confusion matrices indicated a sensitivity of 80%, a specificity of 89%, a positive predictive value of 92%, a negative predictive value of 72%, and an accuracy of 83% to diagnose dementia. The DLB index showed a sensitivity of 60%, a specificity of 90%, a positive predictive value of 75%, a negative predictive value of 81%, and an accuracy of 75%. Neuropsychological scores did not differ significantly between DLB and non- DLB patients. Head trauma or story of stroke were identified as possible causes of FP results for DLB diagnosis. Conclusion qEEG-SPR is a sensitive and specific tool for diagnosing dementia and differentiating DLB from other forms of dementia in the initial state. This non-invasive, low-cost, and environmentally friendly method is a promising diagnostic tool for dementia diagnosis which could be implemented in local care settings.
Collapse
Affiliation(s)
- Sandro Iannaccone
- Department of Rehabilitation and Functional Recovery, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Elise Houdayer
- Department of Rehabilitation and Functional Recovery, IRCCS San Raffaele Scientific Institute, Milan, Italy
- *Correspondence: Elise Houdayer,
| | - Alfio Spina
- Department of Neurosurgery and Gamma Knife Radiosurgery, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Gianluca Nocera
- Department of Neurosurgery and Gamma Knife Radiosurgery, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Federica Alemanno
- Department of Rehabilitation and Functional Recovery, IRCCS San Raffaele Scientific Institute, Milan, Italy
| |
Collapse
|
|
4
|
Niu J, Zhang J, Yan J, Xu Z, Fang X, You J, Liu Z, Wu W, Li T. Neural Dysconnectivity in the Hippocampus Correlates With White Matter Lesions and Cognitive Measures in Patients With Coronary Artery Disease. Front Aging Neurosci 2022; 14:786253. [PMID: 35832064 PMCID: PMC9271740 DOI: 10.3389/fnagi.2022.786253] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2021] [Accepted: 05/26/2022] [Indexed: 11/13/2022] Open
Abstract
PurposeRecent neuroimaging reports have shown the microstructural changes in coronary artery disease (CAD) and its correlation with cognitive dysfunction while little is known about the functional characteristics of CAD. We hypothesize that functional characteristics may give clues to underlying pathology in CAD and its link with cognitive dysfunction. Degree centrality (DC), a graph-based assessment of network organization was performed to explore the neural connectivity changes in CAD patients compared with healthy controls and their correlation with cognitive measures.MethodsThirty CAD patients and 36 healthy controls were included in our study. All participants underwent functional magnetic resonance imaging (fMRI) of the brain. We performed DC analysis to identify voxels that showed changes in whole-brain functional connectivity with other voxels. DC was measured by the fMRI graph method and comparisons between the two groups were done. All participants underwent neuropsychological assessment (Montreal Cognitive Assessment, MoCA and Mini-Mental State Examination, MMSE).ResultsOur data analysis included 30 CAD patients (59.90 ± 7.53 years) and 36 HCs (61.61 ± 6.19 years). CAD patients showed a greater prevalence of white matter lesions using the Fazekas score than healthy controls (P < 0.001). Importantly, CAD patients showed significantly lower (P < 0.001) MoCA and MMSE scores compared with healthy controls. CAD patients showed significantly decreased DC value (P < 0.001) in the right hippocampus (hippocampus_R), right lingual gyrus (lingual_R), and significantly increased DC value (P < 0.001) in the left middle frontal gyrus (Frontal_Mid_L) when compared with healthy controls respectively. DC value in the hippocampus_R significantly correlated (P < 0.00) with MMSE and MoCA scores in CAD patients. Fazekas scores in CAD patients showed a significant correlation (P < 0.001) with the DC value in the hippocampus_R.ConclusionThese findings suggest that reduced cerebral neural connectivity in CAD may contribute to their cognitive impairment and white matter microstructural damage.
Collapse
|
|
5
|
Ma WY, Tian MJ, Yao Q, Li Q, Tang FY, Xiao CY, Shi JP, Chen J. Neuroimaging alterations in dementia with Lewy bodies and neuroimaging differences between dementia with Lewy bodies and Alzheimer's disease: An activation likelihood estimation meta-analysis. CNS Neurosci Ther 2021; 28:183-205. [PMID: 34873859 PMCID: PMC8739049 DOI: 10.1111/cns.13775] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2020] [Revised: 11/07/2021] [Accepted: 11/21/2021] [Indexed: 12/11/2022] Open
Abstract
Aims The aim of this study was to identify brain regions with local, structural, and functional abnormalities in dementia with Lewy bodies (DLB) and uncover the differences between DLB and Alzheimer's disease (AD). The neural networks involved in the identified abnormal brain regions were further described. Methods PubMed, Web of Science, OVID, Science Direct, and Cochrane Library databases were used to identify neuroimaging studies that included DLB versus healthy controls (HCs) or DLB versus AD. The coordinate‐based meta‐analysis and functional meta‐analytic connectivity modeling were performed using the activation likelihood estimation algorithm. Results Eleven structural studies and fourteen functional studies were included in this quantitative meta‐analysis. DLB patients showed a dysfunction in the bilateral inferior parietal lobule and right lingual gyrus compared with HC patients. DLB patients showed a relative preservation of the medial temporal lobe and a tendency of lower metabolism in the right lingual gyrus compared with AD. The frontal‐parietal, salience, and visual networks were all abnormally co‐activated in DLB, but the default mode network remained normally co‐activated compared with AD. Conclusions The convergence of local brain regions and co‐activation neural networks might be potential specific imaging markers in the diagnosis of DLB. This might provide a pathway for the neural regulation in DLB patients, and it might contribute to the development of specific interventions for DLB and AD.
Collapse
Affiliation(s)
- Wen-Ying Ma
- Department of Neurology, Affiliated Nanjing Brain Hospital, Nanjing Medical University, Nanjing, Jiangsu, China
| | - Min-Jie Tian
- Department of Neurology, Affiliated Nanjing Brain Hospital, Nanjing Medical University, Nanjing, Jiangsu, China
| | - Qun Yao
- Department of Neurology, Affiliated Nanjing Brain Hospital, Nanjing Medical University, Nanjing, Jiangsu, China
| | - Qian Li
- Department of Neurology, Affiliated Nanjing Brain Hospital, Nanjing Medical University, Nanjing, Jiangsu, China
| | - Fan-Yu Tang
- Department of Neurology, Affiliated Nanjing Brain Hospital, Nanjing Medical University, Nanjing, Jiangsu, China
| | - Chao-Yong Xiao
- Department of Radiology, Affiliated Nanjing Brain Hospital, Nanjing Medical University, Nanjing, Jiangsu, China
| | - Jing-Ping Shi
- Department of Neurology, Affiliated Nanjing Brain Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.,Institute of Brain Functional Imaging, Affiliated Nanjing Brain Hospital, Nanjing Medical University, Nanjing, Jiangsu, China
| | - Jiu Chen
- Institute of Neuropsychiatry, Affiliated Nanjing Brain Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.,Institute of Brain Functional Imaging, Affiliated Nanjing Brain Hospital, Nanjing Medical University, Nanjing, Jiangsu, China
| |
Collapse
|
|
6
|
Added value of semiquantitative analysis of brain FDG-PET for the differentiation between MCI-Lewy bodies and MCI due to Alzheimer's disease. Eur J Nucl Med Mol Imaging 2021; 49:1263-1274. [PMID: 34651219 DOI: 10.1007/s00259-021-05568-w] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2021] [Accepted: 09/17/2021] [Indexed: 01/13/2023]
Abstract
PURPOSE FDG-PET is an established supportive biomarker in dementia with Lewy bodies (DLB), but its diagnostic accuracy is unknown at the mild cognitive impairment (MCI-LB) stage when the typical metabolic pattern may be difficultly recognized at the individual level. Semiquantitative analysis of scans could enhance accuracy especially in less skilled readers, but its added role with respect to visual assessment in MCI-LB is still unknown. METHODS We assessed the diagnostic accuracy of visual assessment of FDG-PET by six expert readers, blind to diagnosis, in discriminating two matched groups of patients (40 with prodromal AD (MCI-AD) and 39 with MCI-LB), both confirmed by in vivo biomarkers. Readers were provided in a stepwise fashion with (i) maps obtained by the univariate single-subject voxel-based analysis (VBA) with respect to a control group of 40 age- and sex-matched healthy subjects, and (ii) individual odds ratio (OR) plots obtained by the volumetric regions of interest (VROI) semiquantitative analysis of the two main hypometabolic clusters deriving from the comparison of MCI-AD and MCI-LB groups in the two directions, respectively. RESULTS Mean diagnostic accuracy of visual assessment was 76.8 ± 5.0% and did not significantly benefit from adding the univariate VBA map reading (77.4 ± 8.3%) whereas VROI-derived OR plot reading significantly increased both accuracy (89.7 ± 2.3%) and inter-rater reliability (ICC 0.97 [0.96-0.98]), regardless of the readers' expertise. CONCLUSION Conventional visual reading of FDG-PET is moderately accurate in distinguishing between MCI-LB and MCI-AD, and is not significantly improved by univariate single-subject VBA but by a VROI analysis built on macro-regions, allowing for high accuracy independent of reader skills.
Collapse
|
|
7
|
Ishii K, Yamada T, Hanaoka K, Kaida H, Miyazaki K, Ueda M, Hanada K, Saigoh K, Sauerbeck J, Rominger A, Bartenstein P, Kimura Y. Regional gray matter-dedicated SUVR with 3D-MRI detects positive amyloid deposits in equivocal amyloid PET images. Ann Nucl Med 2020; 34:856-863. [DOI: 10.1007/s12149-020-01513-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2020] [Accepted: 08/18/2020] [Indexed: 11/24/2022]
|
|
8
|
Evaluating 2-[ 18F]FDG-PET in differential diagnosis of dementia using a data-driven decision model. NEUROIMAGE-CLINICAL 2020; 27:102267. [PMID: 32417727 PMCID: PMC7229490 DOI: 10.1016/j.nicl.2020.102267] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/13/2020] [Revised: 04/06/2020] [Accepted: 04/08/2020] [Indexed: 12/14/2022]
Abstract
Addition of 2-[18F]FDG-PET to common diagnostic tests improved the accuracy for DLB and FTD. Two new 2-[18F]FDG-PET biomarkers demonstrated specific disease patterns for DLB and FTD. Different combinations of diagnostic tests were valuable for each subtype of dementia. 2-[18F]fluoro-2-deoxy-d-glucose positron emission tomography (2-[18F]FDG-PET) has an emerging supportive role in dementia diagnostic as distinctive metabolic patterns are specific for Alzheimer's disease (AD), dementia with Lewy bodies (DLB) and frontotemporal dementia (FTD). Previous studies have demonstrated that a data-driven decision model based on the disease state index (DSI) classifier supports clinicians in the differential diagnosis of dementia by using different combinations of diagnostic tests and biomarkers. Until now, this model has not included 2-[18F]FDG-PET data. The objective of the study was to evaluate 2-[18F]FDG-PET biomarkers combined with commonly used diagnostic tests in the differential diagnosis of dementia using the DSI classifier. We included data from 259 subjects diagnosed with AD, DLB, FTD, vascular dementia (VaD), and subjective cognitive decline from two independent study cohorts. We also evaluated three 2-[18F]FDG-PET biomarkers (anterior vs. posterior index (API-PET), occipital vs. temporal index, and cingulate island sign) to improve the classification accuracy for both FTD and DLB. We found that the addition of 2-[18F]FDG-PET biomarkers to cognitive tests, CSF and MRI biomarkers considerably improved the classification accuracy for all pairwise comparisons of DLB (balanced accuracies: DLB vs. AD from 64% to 77%; DLB vs. FTD from 71% to 92%; and DLB vs. VaD from 71% to 84%). The two 2-[18F]FDG-PET biomarkers, API-PET and occipital vs. temporal index, improved the accuracy for FTD and DLB, especially as compared to AD. Moreover, different combinations of diagnostic tests were valuable to differentiate specific subtypes of dementia. In conclusion, this study demonstrated that the addition of 2-[18F]FDG-PET to commonly used diagnostic tests provided complementary information that may help clinicians in diagnosing patients, particularly for differentiating between patients with FTD, DLB, and AD.
Collapse
|
|
9
|
Role of [18F]-FDG PET in patients with atypical parkinsonism associated with dementia. Clin Transl Imaging 2020. [DOI: 10.1007/s40336-020-00360-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
|
|
10
|
Iizuka T, Kameyama M. Spatial metabolic profiles to discriminate dementia with Lewy bodies from Alzheimer disease. J Neurol 2020; 267:1960-1969. [PMID: 32170446 DOI: 10.1007/s00415-020-09790-8] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2020] [Revised: 03/05/2020] [Accepted: 03/09/2020] [Indexed: 11/26/2022]
Abstract
BACKGROUND To differentiate dementia with Lewy bodies (DLB) from Alzheimer disease (AD) using a single imaging modality is challenging, because of their common hypometabolic findings. Scaled subprofile modeling/principal component analysis (SSM/PCA), an unsupervised artificial intelligence, has the potential to offer an alternative to image analysis. OBJECTIVE We aimed to produce spatial metabolic profiles to discriminate DLB from AD and to identify the characteristics of the profiles. METHODS Fifty individuals each with DLB, AD, and normal cognition (NL) underwent 18F-FDG-PET and MRI. The spatial metabolic profile to differentiate DLB from AD (DLB-AD discrimination profile) was determined using SSM/PCA with tenfold cross validation. For comparison, we also produced disease-related profiles that can discriminate AD and DLB from NL (AD- and DLB-related profiles, respectively). RESULTS The DLB-AD discrimination profile significantly differentiated DLB from AD with comparable accuracy to that of discriminating DLB and AD from NL. The AD- and DLB-related profiles comprised metabolic imaging features typical of each pathology. In contrast, the DLB-AD discrimination profile emphasized preservation in the posterior cingulate cortex (cingulate island sign) and medial temporal lobe, and occipital hypometabolism. Common hypometabolic findings between DLB and AD were less noticeable in the profile. The DLB-related profile significantly correlated with cognitive function and three core features of DLB, whereas the DLB-AD discrimination profile did not. CONCLUSIONS Spatial metabolic profile that could discriminate DLB from AD emphasized different imaging features and eliminated common findings between DLB and AD. Neither cognitive function nor core features were associated with the profile.
Collapse
Affiliation(s)
- Tomomichi Iizuka
- Center for Dementia, Fukujuji Hospital, Japan Anti-Tuberculosis Association, Kiyose, 204-8522, Japan.
| | - Masashi Kameyama
- Department of Diagnostic Radiology, Tokyo Metropolitan Geriatric Hospital, Tokyo, 173-0015, Japan
- Division of Nuclear Medicine, Department of Radiology, School of Medicine, Keio University, Tokyo, 160-8582, Japan
| |
Collapse
|
|
11
|
Patterson L, Firbank MJ, Colloby SJ, Attems J, Thomas AJ, Morris CM. Neuropathological Changes in Dementia With Lewy Bodies and the Cingulate Island Sign. J Neuropathol Exp Neurol 2019; 78:717-724. [PMID: 31271438 PMCID: PMC6640897 DOI: 10.1093/jnen/nlz047] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
The cingulate island sign (CIS) refers to the relative sparing of metabolism in the posterior cingulate cortex (PCC) and represents an important biomarker in distinguishing dementia with Lewy bodies (DLB) from Alzheimer disease (AD). The underlying basis of the CIS is unknown; therefore, our aim was to investigate which neurodegenerative changes underpin the formation of CIS. Using quantitative neuropathology, α-synuclein, phosphorylated Tau, and amyloid-β pathology was assessed in 12 DLB, 9 AD and 6 age-matched control patients in the anterior cingulate (ACC), midcingulate, PCC, precuneus/cuneus and parahippocampal gyrus. All participants had undergone 99mTc-hexamethylpropyleneamine oxime (HMPAO) single-photon emission computed tomography imaging during life to define the presence or absence of CIS. In the DLB group, no significant correlations were observed between CIS ratios and neurodegenerative pathology in PCC. In DLB, however, the ACC showed lower HMPAO uptake, as well as significantly higher α-synuclein and amyloid-β burden compared with PCC, possibly underlying the relative preservation of perfusion in PCC when compared with ACC. Our findings suggest that neurodegenerative pathology does not directly correlate with the CIS in DLB, and other metabolic or pathological changes are therefore more likely to be relevant for the development of the CIS.
Collapse
Affiliation(s)
- Lina Patterson
- Alzheimer’s Society Doctoral Training Centre, Newcastle University, Newcastle upon Tyne, UK
| | - Michael J Firbank
- Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK
| | - Sean J Colloby
- Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK
| | - Johannes Attems
- Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK
- Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
| | - Alan J Thomas
- Alzheimer’s Society Doctoral Training Centre, Newcastle University, Newcastle upon Tyne, UK
- Gateshead Health NHS Foundation Trust, Queen Elizabeth Hospital, Gateshead, Tyne and Wear, UK
| | - Christopher M Morris
- NIHR Biomedical Research Centre Newcastle, Newcastle University, Newcastle upon Tyne, UK
| |
Collapse
|
|
12
|
Sala A, Caminiti SP, Iaccarino L, Beretta L, Iannaccone S, Magnani G, Padovani A, Ferini-Strambi L, Perani D. Vulnerability of multiple large-scale brain networks in dementia with Lewy bodies. Hum Brain Mapp 2019; 40:4537-4550. [PMID: 31322307 DOI: 10.1002/hbm.24719] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2019] [Revised: 06/01/2019] [Accepted: 06/19/2019] [Indexed: 01/08/2023] Open
Abstract
Aberrations of large-scale brain networks are found in the majority of neurodegenerative disorders. The brain connectivity alterations underlying dementia with Lewy bodies (DLB) remain, however, still elusive, with contrasting results possibly due to the pathological and clinical heterogeneity characterizing this disorder. Here, we provide a molecular assessment of brain network alterations, based on cerebral metabolic measurements as proxies of synaptic activity and density, in a large cohort of DLB patients (N = 72). We applied a seed-based interregional correlation analysis approach (p < .01, false discovery rate corrected) to evaluate large-scale resting-state networks' integrity and their interactions. We found both local and long-distance metabolic connectivity alterations, affecting the posterior cortical networks, that is, primary visual and the posterior default mode network, as well as the limbic and attention networks, suggesting a widespread derangement of the brain connectome. Notably, patients with the lowest visual and attention cognitive scores showed the most severe connectivity derangement in regions of the primary visual network. In addition, network-level alterations were differentially associated with the core clinical manifestations, namely, hallucinations with more severe metabolic dysfunction of the attention and visual networks, and rapid eye movement sleep behavior disorder with alterations of connectivity of attention and subcortical networks. These multiple network-level vulnerabilities may modulate the core clinical and cognitive features of DLB and suggest that DLB should be considered as a complex multinetwork disorder.
Collapse
Affiliation(s)
- Arianna Sala
- Vita-Salute San Raffaele University, Milan, Italy.,In Vivo Human Molecular and Structural Neuroimaging Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Silvia Paola Caminiti
- Vita-Salute San Raffaele University, Milan, Italy.,In Vivo Human Molecular and Structural Neuroimaging Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Leonardo Iaccarino
- Vita-Salute San Raffaele University, Milan, Italy.,In Vivo Human Molecular and Structural Neuroimaging Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Luca Beretta
- In Vivo Human Molecular and Structural Neuroimaging Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Sandro Iannaccone
- Clinical Neuroscience Department, San Raffaele Turro Hospital, Milan, Italy
| | - Giuseppe Magnani
- Department of Neurology, IRCCS San Raffaele Hospital, Milan, Italy
| | - Alessandro Padovani
- Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy
| | - Luigi Ferini-Strambi
- Vita-Salute San Raffaele University, Milan, Italy.,Department of Clinical Neurosciences, San Raffaele Scientific Institute, Neurology, Sleep Disorders Center, Milan, Italy
| | - Daniela Perani
- Vita-Salute San Raffaele University, Milan, Italy.,In Vivo Human Molecular and Structural Neuroimaging Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.,Nuclear Medicine Unit, IRCCS San Raffaele Hospital, Milan, Italy
| |
Collapse
|
|
13
|
Balážová Z, Nováková M, Minsterová A, Rektorová I. Structural and Functional Magnetic Resonance Imaging of Dementia With Lewy Bodies. INTERNATIONAL REVIEW OF NEUROBIOLOGY 2018; 144:95-141. [PMID: 30638458 DOI: 10.1016/bs.irn.2018.10.005] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Dementia with Lewy bodies (DLB) is the second most common cause of neurodegenerative dementia after Alzheimer's disease (AD). Although diagnosis may be challenging, there is increasing evidence that the use of biomarkers according to 2017 revised criteria for diagnosis and management of dementia with Lewy bodies can increase diagnostic accuracy. Apart from nuclear medicine techniques, various magnetic resonance imaging (MRI) techniques have been utilized in attempt to enhance diagnostic accuracy. This chapter reviews structural, functional and diffusion MRI studies in DLB cohorts being compared to healthy controls, AD or dementia in Parkinson's disease (PDD). We also included relatively new MRI methods that may have potential to identify early DLB subjects and aim at examining brain iron and neuromelanin.
Collapse
Affiliation(s)
- Zuzana Balážová
- Applied Neuroscience Research Group, Central European Institute of Technology, CEITEC MU, Masaryk University, Brno, Czech Republic; Department of Radiology and Nuclear Medicine, University Hospital Brno, Faculty of Medicine, Brno, Czech Republic
| | - Marie Nováková
- Applied Neuroscience Research Group, Central European Institute of Technology, CEITEC MU, Masaryk University, Brno, Czech Republic
| | - Alžběta Minsterová
- Applied Neuroscience Research Group, Central European Institute of Technology, CEITEC MU, Masaryk University, Brno, Czech Republic
| | - Irena Rektorová
- Applied Neuroscience Research Group, Central European Institute of Technology, CEITEC MU, Masaryk University, Brno, Czech Republic; St. Anne's University Hospital and Faculty of Medicine, Masaryk University, Brno, Czech Republic.
| |
Collapse
|
|
14
|
Nobili F, Arbizu J, Bouwman F, Drzezga A, Agosta F, Nestor P, Walker Z, Boccardi M. European Association of Nuclear Medicine and European Academy of Neurology recommendations for the use of brain 18 F-fluorodeoxyglucose positron emission tomography in neurodegenerative cognitive impairment and dementia: Delphi consensus. Eur J Neurol 2018; 25:1201-1217. [PMID: 29932266 DOI: 10.1111/ene.13728] [Citation(s) in RCA: 142] [Impact Index Per Article: 20.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2018] [Accepted: 06/20/2018] [Indexed: 12/17/2022]
Abstract
BACKGROUND AND PURPOSE Recommendations for using fluorodeoxyglucose positron emission tomography (FDG-PET) to support the diagnosis of dementing neurodegenerative disorders are sparse and poorly structured. METHODS Twenty-one questions on diagnostic issues and on semi-automated analysis to assist visual reading were defined. Literature was reviewed to assess study design, risk of bias, inconsistency, imprecision, indirectness and effect size. Critical outcomes were sensitivity, specificity, accuracy, positive/negative predictive value, area under the receiver operating characteristic curve, and positive/negative likelihood ratio of FDG-PET in detecting the target conditions. Using the Delphi method, an expert panel voted for/against the use of FDG-PET based on published evidence and expert opinion. RESULTS Of the 1435 papers, 58 papers provided proper quantitative assessment of test performance. The panel agreed on recommending FDG-PET for 14 questions: diagnosing mild cognitive impairment due to Alzheimer's disease (AD), frontotemporal lobar degeneration (FTLD) or dementia with Lewy bodies (DLB); diagnosing atypical AD and pseudo-dementia; differentiating between AD and DLB, FTLD or vascular dementia, between DLB and FTLD, and between Parkinson's disease and progressive supranuclear palsy; suggesting underlying pathophysiology in corticobasal degeneration and progressive primary aphasia, and cortical dysfunction in Parkinson's disease; using semi-automated assessment to assist visual reading. Panellists did not support FDG-PET use for pre-clinical stages of neurodegenerative disorders, for amyotrophic lateral sclerosis and Huntington disease diagnoses, and for amyotrophic lateral sclerosis or Huntington-disease-related cognitive decline. CONCLUSIONS Despite limited formal evidence, panellists deemed FDG-PET useful in the early and differential diagnosis of the main neurodegenerative disorders, and semi-automated assessment helpful to assist visual reading. These decisions are proposed as interim recommendations.
Collapse
Affiliation(s)
- F Nobili
- Department of Neuroscience (DINOGMI), University of Genoa and Polyclinic San Martino Hospital, Genoa, Italy
| | - J Arbizu
- Department of Nuclear Medicine, Clinica Universidad de Navarra, University of Navarra, Pamplona, Spain
| | - F Bouwman
- Department of Neurology and Alzheimer Center, Amsterdam Neuroscience, VU University Medical Center, Amsterdam, The Netherlands
| | - A Drzezga
- Department of Nuclear Medicine, University Hospital of Cologne, University of Cologne and German Center for Neurodegenerative Diseases (DZNE), Cologne, Germany
| | - F Agosta
- Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy
| | - P Nestor
- German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany
| | - Z Walker
- Division of Psychiatry, Essex Partnership University NHS Foundation Trust, University College London, London, UK
| | - M Boccardi
- Department of Psychiatry, Laboratoire du Neuroimagerie du Vieillissement (LANVIE), University of Geneva, Geneva, Switzerland
| | | |
Collapse
|
|
15
|
Clinical utility of FDG-PET for the differential diagnosis among the main forms of dementia. Eur J Nucl Med Mol Imaging 2018; 45:1509-1525. [PMID: 29736698 DOI: 10.1007/s00259-018-4035-y] [Citation(s) in RCA: 73] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2018] [Accepted: 04/18/2018] [Indexed: 12/14/2022]
Abstract
AIM To assess the clinical utility of FDG-PET as a diagnostic aid for differentiating Alzheimer's disease (AD; both typical and atypical forms), dementia with Lewy bodies (DLB), frontotemporal lobar degeneration (FTLD), vascular dementia (VaD) and non-degenerative pseudodementia. METHODS A comprehensive literature search was conducted using the PICO model to extract evidence from relevant studies. An expert panel then voted on six different diagnostic scenarios using the Delphi method. RESULTS The level of empirical study evidence for the use of FDG-PET was considered good for the discrimination of DLB and AD; fair for discriminating FTLD from AD; poor for atypical AD; and lacking for discriminating DLB from FTLD, AD from VaD, and for pseudodementia. Delphi voting led to consensus in all scenarios within two iterations. Panellists supported the use of FDG-PET for all PICOs-including those where study evidence was poor or lacking-based on its negative predictive value and on the assistance it provides when typical patterns of hypometabolism for a given diagnosis are observed. CONCLUSION Although there is an overall lack of evidence on which to base strong recommendations, it was generally concluded that FDG-PET has a diagnostic role in all scenarios. Prospective studies targeting diagnostically uncertain patients for assessing the added value of FDG-PET would be highly desirable.
Collapse
|
|
16
|
Yao X, Yan J, Risacher S, Moore J, Saykin A, Shen L. NETWORK-BASED GENOME WIDE STUDY OF HIPPOCAMPAL IMAGING PHENOTYPE IN ALZHEIMER'S DISEASE TO IDENTIFY FUNCTIONAL INTERACTION MODULES. PROCEEDINGS OF THE ... IEEE INTERNATIONAL CONFERENCE ON ACOUSTICS, SPEECH, AND SIGNAL PROCESSING. ICASSP (CONFERENCE) 2017; 2017:6170-6174. [PMID: 28989328 DOI: 10.1109/icassp.2017.7953342] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Abstract
Identification of functional modules from biological network is a promising approach to enhance the statistical power of genome-wide association study (GWAS) and improve biological interpretation for complex diseases. The precise functions of genes are highly relevant to tissue context, while a majority of module identification studies are based on tissue-free biological networks that lacks phenotypic specificity. In this study, we propose a module identification method that maps the GWAS results of an imaging phenotype onto the corresponding tissue-specific functional interaction network by applying a machine learning framework. Ridge regression and support vector machine (SVM) models are constructed to re-prioritize GWAS results, followed by exploring hippocampus-relevant modules based on top predictions using GWAS top findings. We also propose a GWAS top-neighbor-based module identification approach and compare it with Ridge and SVM based approaches. Modules conserving both tissue specificity and GWAS discoveries are identified, showing the promise of the proposal method for providing insight into the mechanism of complex diseases.
Collapse
Affiliation(s)
- Xiaohui Yao
- Radiology and Imaging Sciences, Indiana University, Indianapolis, IN, 46202, USA.,Informatics and Computing, Indiana University, Indianapolis, IN, 46202, USA
| | - Jingwen Yan
- Radiology and Imaging Sciences, Indiana University, Indianapolis, IN, 46202, USA.,Informatics and Computing, Indiana University, Indianapolis, IN, 46202, USA
| | - Shannon Risacher
- Radiology and Imaging Sciences, Indiana University, Indianapolis, IN, 46202, USA
| | - Jason Moore
- Biomedical Informatics, University of Pennsylvania, Philadelphia, PA, 19104, USA
| | - Andrew Saykin
- Radiology and Imaging Sciences, Indiana University, Indianapolis, IN, 46202, USA
| | - Li Shen
- Radiology and Imaging Sciences, Indiana University, Indianapolis, IN, 46202, USA.,Informatics and Computing, Indiana University, Indianapolis, IN, 46202, USA
| |
Collapse
|
|
17
|
The value of whole-brain CT perfusion imaging and CT angiography using a 320-slice CT scanner in the diagnosis of MCI and AD patients. Eur Radiol 2017; 27:4756-4766. [PMID: 28577254 DOI: 10.1007/s00330-017-4865-1] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2016] [Revised: 03/31/2017] [Accepted: 04/20/2017] [Indexed: 02/01/2023]
Abstract
OBJECTIVES To validate the value of whole-brain computed tomography perfusion (CTP) and CT angiography (CTA) in the diagnosis of mild cognitive impairment (MCI) and Alzheimer's disease (AD). METHODS Whole-brain CTP and four-dimensional CT angiography (4D-CTA) images were acquired in 30 MCI, 35 mild AD patients, 35 moderate AD patients, 30 severe AD patients and 50 normal controls (NC). Cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), time to peak (TTP), and correlation between CTP and 4D-CTA were analysed. RESULTS Elevated CBF in the left frontal and temporal cortex was found in MCI compared with the NC group. However, TTP was increased in the left hippocampus in mild AD patients compared with NC. In moderate and severe AD patients, hypoperfusion was found in multiple brain areas compared with NC. Finally, we found that the extent of arterial stenosis was negatively correlated with CBF in partial cerebral cortex and hippocampus, and positively correlated with TTP in these areas of AD and MCI patients. CONCLUSIONS Our findings suggest that whole-brain CTP and 4D-CTA could serve as a diagnostic modality in distinguishing MCI and AD, and predicting conversion from MCI based on TTP of left hippocampus. KEY POINTS • Whole-brain perfusion using the full 160-mm width of 320 detector rows • Provide clinical experience of 320-row CT in cerebrovascular disorders of Alzheimer's disease • Initial combined 4D CTA-CTP data analysed perfusion and correlated with CT angiography • Whole-brain CTP and 4D-CTA have high value for monitoring MCI to AD progression • TTP in the left hippocampus may predict the transition from MCI to AD.
Collapse
|
|
18
|
Kim J, Cho SG, Song M, Kang SR, Kwon SY, Choi KH, Choi SM, Kim BC, Song HC. Usefulness of 3-dimensional stereotactic surface projection FDG PET images for the diagnosis of dementia. Medicine (Baltimore) 2016; 95:e5622. [PMID: 27930593 PMCID: PMC5266065 DOI: 10.1097/md.0000000000005622] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
To compare diagnostic performance and confidence of a standard visual reading and combined 3-dimensional stereotactic surface projection (3D-SSP) results to discriminate between Alzheimer disease (AD)/mild cognitive impairment (MCI), dementia with Lewy bodies (DLB), and frontotemporal dementia (FTD).[F]fluorodeoxyglucose (FDG) PET brain images were obtained from 120 patients (64 AD/MCI, 38 DLB, and 18 FTD) who were clinically confirmed over 2 years follow-up. Three nuclear medicine physicians performed the diagnosis and rated diagnostic confidence twice; once by standard visual methods, and once by adding of 3D-SSP. Diagnostic performance and confidence were compared between the 2 methods.3D-SSP showed higher sensitivity, specificity, accuracy, positive, and negative predictive values to discriminate different types of dementia compared with the visual method alone, except for AD/MCI specificity and FTD sensitivity. Correction of misdiagnosis after adding 3D-SSP images was greatest for AD/MCI (56%), followed by DLB (13%) and FTD (11%). Diagnostic confidence also increased in DLB (visual: 3.2; 3D-SSP: 4.1; P < 0.001), followed by AD/MCI (visual: 3.1; 3D-SSP: 3.8; P = 0.002) and FTD (visual: 3.5; 3D-SSP: 4.2; P = 0.022). Overall, 154/360 (43%) cases had a corrected misdiagnosis or improved diagnostic confidence for the correct diagnosis.The addition of 3D-SSP images to visual analysis helped to discriminate different types of dementia in FDG PET scans, by correcting misdiagnoses and enhancing diagnostic confidence in the correct diagnosis. Improvement of diagnostic accuracy and confidence by 3D-SSP images might help to determine the cause of dementia and appropriate treatment.
Collapse
Affiliation(s)
| | | | | | | | | | - Kang-Ho Choi
- Department of Neurology, Chonnam National University Hospital, Donggu, Gwangju, Republic of Korea
| | - Seong-Min Choi
- Department of Neurology, Chonnam National University Hospital, Donggu, Gwangju, Republic of Korea
| | - Byeong-Chae Kim
- Department of Neurology, Chonnam National University Hospital, Donggu, Gwangju, Republic of Korea
| | | |
Collapse
|
|
19
|
Pagani M, Giuliani A, Öberg J, Chincarini A, Morbelli S, Brugnolo A, Arnaldi D, Picco A, Bauckneht M, Buschiazzo A, Sambuceti G, Nobili F. Predicting the transition from normal aging to Alzheimer's disease: A statistical mechanistic evaluation of FDG-PET data. Neuroimage 2016; 141:282-290. [PMID: 27453158 DOI: 10.1016/j.neuroimage.2016.07.043] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2016] [Revised: 06/28/2016] [Accepted: 07/20/2016] [Indexed: 12/13/2022] Open
|
|
20
|
Roquet D, Sourty M, Botzung A, Armspach JP, Blanc F. Brain perfusion in dementia with Lewy bodies and Alzheimer's disease: an arterial spin labeling MRI study on prodromal and mild dementia stages. ALZHEIMERS RESEARCH & THERAPY 2016; 8:29. [PMID: 27401267 PMCID: PMC4940880 DOI: 10.1186/s13195-016-0196-8] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/14/2016] [Accepted: 06/06/2016] [Indexed: 01/29/2023]
Abstract
Background We aimed to describe specific changes in brain perfusion in patients with dementia with Lewy bodies (DLB) at both the prodromal (also called mild cognitive impairment) and mild dementia stages, relative to patients with Alzheimer’s disease (AD) and controls. Methods Altogether, 96 participants in five groups (prodromal DLB, prodromal AD, DLB with mild dementia, AD with mild dementia, and healthy elderly controls) took part in an arterial spin labeling MRI study. Three analyses were performed: a global perfusion value comparison, a voxel-wise analysis of both absolute and relative perfusion, and a linear discriminant analysis. These were used to assess the global decrease in perfusion, regional changes, and the sensitivity and specificity of these changes. Results Patterns of perfusion in DLB differed from AD and controls in both the prodromal stage and dementia, DLB having more deficits in frontal, insular, and temporal cortices whereas AD showed reduced perfusion in parietal and parietotemporal cortices. Decreases but also increases of perfusion in DLB relative to controls were observed in both absolute and relative measurements. All these regional changes of perfusion classified DLB patients with respect to either healthy controls or AD with sensitivity from 87 to 100 % and specificity from 90 to 96 % depending on the stage of the disease. Conclusions Our results are consistent with previous studies. We extend the scope of those studies by integrating prodromal DLB patients and by describing both hypo- and hyperperfusion in DLB. While decreases in perfusion may relate to functional impairments, increases might suggest a functional compensation of some brain areas. Electronic supplementary material The online version of this article (doi:10.1186/s13195-016-0196-8) contains supplementary material, which is available to authorized users.
Collapse
Affiliation(s)
- Daniel Roquet
- ICube laboratory, University of Strasbourg, CNRS, FMTS(Fédération de Médecine Translationnelle de Strasbourg), ICube - IPB, Faculté de Médecine, 4 rue Kirschleger, Strasbourg, 67085, France.
| | - Marion Sourty
- ICube laboratory, University of Strasbourg, CNRS, FMTS(Fédération de Médecine Translationnelle de Strasbourg), ICube - IPB, Faculté de Médecine, 4 rue Kirschleger, Strasbourg, 67085, France
| | - Anne Botzung
- ICube laboratory, University of Strasbourg, CNRS, FMTS(Fédération de Médecine Translationnelle de Strasbourg), ICube - IPB, Faculté de Médecine, 4 rue Kirschleger, Strasbourg, 67085, France.,University Hospital of Strasbourg, CMRR (Memory Resources and Research Centre), Strasbourg, France
| | - Jean-Paul Armspach
- ICube laboratory, University of Strasbourg, CNRS, FMTS(Fédération de Médecine Translationnelle de Strasbourg), ICube - IPB, Faculté de Médecine, 4 rue Kirschleger, Strasbourg, 67085, France
| | - Frédéric Blanc
- ICube laboratory, University of Strasbourg, CNRS, FMTS(Fédération de Médecine Translationnelle de Strasbourg), ICube - IPB, Faculté de Médecine, 4 rue Kirschleger, Strasbourg, 67085, France.,University Hospital of Strasbourg, CMRR (Memory Resources and Research Centre), Strasbourg, France
| |
Collapse
|
|
21
|
Narayanan L, Murray AD. What can imaging tell us about cognitive impairment and dementia? World J Radiol 2016; 8:240-254. [PMID: 27029053 PMCID: PMC4807333 DOI: 10.4329/wjr.v8.i3.240] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/24/2015] [Revised: 11/28/2015] [Accepted: 01/07/2016] [Indexed: 02/06/2023] Open
Abstract
Dementia is a contemporary global health issue with far reaching consequences, not only for affected individuals and their families, but for national and global socio-economic conditions. The hallmark feature of dementia is that of irreversible cognitive decline, usually affecting memory, and impaired activities of daily living. Advances in healthcare worldwide have facilitated longer life spans, increasing the risks of developing cognitive decline and dementia in late life. Dementia remains a clinical diagnosis. The role of structural and molecular neuroimaging in patients with dementia is primarily supportive role rather than diagnostic, American and European guidelines recommending imaging to exclude treatable causes of dementia, such as tumor, hydrocephalus or intracranial haemorrhage, but also to distinguish between different dementia subtypes, the commonest of which is Alzheimer’s disease. However, this depends on the availability of these imaging techniques at individual centres. Advanced magnetic resonance imaging (MRI) techniques, such as functional connectivity MRI, diffusion tensor imaging and magnetic resonance spectroscopy, and molecular imaging techniques, such as 18F fluoro-deoxy glucose positron emission tomography (PET), amyloid PET, tau PET, are currently within the realm of dementia research but are available for clinical use. Increasingly the research focus is on earlier identification of at risk preclinical individuals, for example due to family history. Intervention at the preclinical stages before irreversible brain damage occurs is currently the best hope of reducing the impact of dementia.
Collapse
|
|
22
|
Koikkalainen J, Rhodius-Meester H, Tolonen A, Barkhof F, Tijms B, Lemstra AW, Tong T, Guerrero R, Schuh A, Ledig C, Rueckert D, Soininen H, Remes AM, Waldemar G, Hasselbalch S, Mecocci P, van der Flier W, Lötjönen J. Differential diagnosis of neurodegenerative diseases using structural MRI data. NEUROIMAGE-CLINICAL 2016; 11:435-449. [PMID: 27104138 PMCID: PMC4827727 DOI: 10.1016/j.nicl.2016.02.019] [Citation(s) in RCA: 123] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/02/2015] [Revised: 02/02/2016] [Accepted: 02/29/2016] [Indexed: 01/11/2023]
Abstract
Different neurodegenerative diseases can cause memory disorders and other cognitive impairments. The early detection and the stratification of patients according to the underlying disease are essential for an efficient approach to this healthcare challenge. This emphasizes the importance of differential diagnostics. Most studies compare patients and controls, or Alzheimer's disease with one other type of dementia. Such a bilateral comparison does not resemble clinical practice, where a clinician is faced with a number of different possible types of dementia. Here we studied which features in structural magnetic resonance imaging (MRI) scans could best distinguish four types of dementia, Alzheimer's disease, frontotemporal dementia, vascular dementia, and dementia with Lewy bodies, and control subjects. We extracted an extensive set of features quantifying volumetric and morphometric characteristics from T1 images, and vascular characteristics from FLAIR images. Classification was performed using a multi-class classifier based on Disease State Index methodology. The classifier provided continuous probability indices for each disease to support clinical decision making. A dataset of 504 individuals was used for evaluation. The cross-validated classification accuracy was 70.6% and balanced accuracy was 69.1% for the five disease groups using only automatically determined MRI features. Vascular dementia patients could be detected with high sensitivity (96%) using features from FLAIR images. Controls (sensitivity 82%) and Alzheimer's disease patients (sensitivity 74%) could be accurately classified using T1-based features, whereas the most difficult group was the dementia with Lewy bodies (sensitivity 32%). These results were notable better than the classification accuracies obtained with visual MRI ratings (accuracy 44.6%, balanced accuracy 51.6%). Different quantification methods provided complementary information, and consequently, the best results were obtained by utilizing several quantification methods. The results prove that automatic quantification methods and computerized decision support methods are feasible for clinical practice and provide comprehensive information that may help clinicians in the diagnosis making.
Differential diagnostics of dementias was studied using structural MRI data. 504 patients with both T1 and FLAIR MRIs from five patient classes were evaluated. Different fully automatic quantification methods were compared and combined. Classification accuracy of 70.6% was obtained for 5-class classification problem. Combination of several quantification methods was needed for optimal accuracy.
Collapse
Affiliation(s)
- Juha Koikkalainen
- VTT Technical Research Centre of Finland, Tampere, Finland; Combinostics Ltd., Tampere, Finland.
| | - Hanneke Rhodius-Meester
- Alzheimer Center, Department of Neurology, VU University Medical Centre, Neuroscience Campus Amsterdam, Amsterdam, The Netherlands
| | - Antti Tolonen
- VTT Technical Research Centre of Finland, Tampere, Finland
| | - Frederik Barkhof
- Department of Radiology and Nuclear Medicine, VU University Medical Centre, Neuroscience Campus Amsterdam, Amsterdam, The Netherlands
| | - Betty Tijms
- Alzheimer Center, Department of Neurology, VU University Medical Centre, Neuroscience Campus Amsterdam, Amsterdam, The Netherlands
| | - Afina W Lemstra
- Alzheimer Center, Department of Neurology, VU University Medical Centre, Neuroscience Campus Amsterdam, Amsterdam, The Netherlands
| | - Tong Tong
- Department of Computing, Imperial College London, London, UK
| | | | - Andreas Schuh
- Department of Computing, Imperial College London, London, UK
| | - Christian Ledig
- Department of Computing, Imperial College London, London, UK
| | - Daniel Rueckert
- Department of Computing, Imperial College London, London, UK
| | - Hilkka Soininen
- Department of Neurology, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland
| | - Anne M Remes
- Department of Neurology, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland
| | - Gunhild Waldemar
- Department of Neurology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
| | - Steen Hasselbalch
- Department of Neurology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
| | - Patrizia Mecocci
- Section of Gerontology and Geriatrics, University of Perugia, Perugia, Italy
| | - Wiesje van der Flier
- Alzheimer Center, Department of Neurology, VU University Medical Centre, Neuroscience Campus Amsterdam, Amsterdam, The Netherlands; Department of Epidemiology and Biostatistics, VU University Medical Centre, Neuroscience Campus Amsterdam, Amsterdam, The Netherlands
| | - Jyrki Lötjönen
- VTT Technical Research Centre of Finland, Tampere, Finland; Combinostics Ltd., Tampere, Finland
| |
Collapse
|
|
23
|
Landy KM, Salmon DP, Galasko D, Filoteo JV, Festa EK, Heindel WC, Hansen LA, Hamilton JM. Motion discrimination in dementia with Lewy bodies and Alzheimer disease. Neurology 2015; 85:1376-82. [PMID: 26400581 DOI: 10.1212/wnl.0000000000002028] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2013] [Accepted: 06/25/2015] [Indexed: 11/15/2022] Open
Abstract
OBJECTIVE Visual processing abilities of patients with dementia with Lewy bodies (DLB) or Alzheimer disease (AD) dementia were assessed psychophysically using a simple horizontal motion discrimination task that engages the dorsal visual processing stream. METHODS Participants included patients with mild dementia with DLB, AD dementia or Parkinson disease (PD) with dementia (PDD), without dementia with PD, and normal controls. Participants indicated the left or right direction of coherently moving dots that were embedded within dynamic visual noise provided by randomly moving dots. The proportion of coherently moving dots was increased or decreased across trials to determine a threshold at which participants could correctly indicate their direction with greater than 80% accuracy. RESULTS Motion discrimination thresholds of patients with DLB and PDD were comparable and significantly higher (i.e., worse) than those of patients with AD dementia. The thresholds of patients with AD dementia and patients with PD were normal. These results were confirmed in subgroups of patients with DLB/PDD and AD dementia with autopsy-confirmed disease. A motion discrimination threshold greater than 0.23 distinguished between DLB/PDD and AD dementia with 67% sensitivity and 85% specificity. CONCLUSIONS Differential deficits in detecting direction of simple horizontal motion suggest that dorsal processing stream dysfunction is greater in DLB and PDD than in AD dementia. Therefore, impaired performance on simple visual motion discrimination tasks that specifically engage occipitoparietal brain regions suggests the presence of Lewy body pathology.
Collapse
Affiliation(s)
- Kelly M Landy
- From the Departments of Neurosciences (K.M.L., D.P.S., D.G., L.A.H., J.M.H.), Psychiatry (J.V.F.), and Pathology (L.A.H.), University of California, San Diego, La Jolla; the Departments of Neurology (D.G.) and Psychology Services (J.V.F.), Veterans Affairs San Diego Healthcare System, La Jolla, CA; and the Department of Cognitive, Linguistic and Psychological Sciences (E.K.F., W.C.H.), Brown University, Providence, RI
| | - David P Salmon
- From the Departments of Neurosciences (K.M.L., D.P.S., D.G., L.A.H., J.M.H.), Psychiatry (J.V.F.), and Pathology (L.A.H.), University of California, San Diego, La Jolla; the Departments of Neurology (D.G.) and Psychology Services (J.V.F.), Veterans Affairs San Diego Healthcare System, La Jolla, CA; and the Department of Cognitive, Linguistic and Psychological Sciences (E.K.F., W.C.H.), Brown University, Providence, RI.
| | - Douglas Galasko
- From the Departments of Neurosciences (K.M.L., D.P.S., D.G., L.A.H., J.M.H.), Psychiatry (J.V.F.), and Pathology (L.A.H.), University of California, San Diego, La Jolla; the Departments of Neurology (D.G.) and Psychology Services (J.V.F.), Veterans Affairs San Diego Healthcare System, La Jolla, CA; and the Department of Cognitive, Linguistic and Psychological Sciences (E.K.F., W.C.H.), Brown University, Providence, RI
| | - J Vincent Filoteo
- From the Departments of Neurosciences (K.M.L., D.P.S., D.G., L.A.H., J.M.H.), Psychiatry (J.V.F.), and Pathology (L.A.H.), University of California, San Diego, La Jolla; the Departments of Neurology (D.G.) and Psychology Services (J.V.F.), Veterans Affairs San Diego Healthcare System, La Jolla, CA; and the Department of Cognitive, Linguistic and Psychological Sciences (E.K.F., W.C.H.), Brown University, Providence, RI
| | - Elena K Festa
- From the Departments of Neurosciences (K.M.L., D.P.S., D.G., L.A.H., J.M.H.), Psychiatry (J.V.F.), and Pathology (L.A.H.), University of California, San Diego, La Jolla; the Departments of Neurology (D.G.) and Psychology Services (J.V.F.), Veterans Affairs San Diego Healthcare System, La Jolla, CA; and the Department of Cognitive, Linguistic and Psychological Sciences (E.K.F., W.C.H.), Brown University, Providence, RI
| | - William C Heindel
- From the Departments of Neurosciences (K.M.L., D.P.S., D.G., L.A.H., J.M.H.), Psychiatry (J.V.F.), and Pathology (L.A.H.), University of California, San Diego, La Jolla; the Departments of Neurology (D.G.) and Psychology Services (J.V.F.), Veterans Affairs San Diego Healthcare System, La Jolla, CA; and the Department of Cognitive, Linguistic and Psychological Sciences (E.K.F., W.C.H.), Brown University, Providence, RI
| | - Lawrence A Hansen
- From the Departments of Neurosciences (K.M.L., D.P.S., D.G., L.A.H., J.M.H.), Psychiatry (J.V.F.), and Pathology (L.A.H.), University of California, San Diego, La Jolla; the Departments of Neurology (D.G.) and Psychology Services (J.V.F.), Veterans Affairs San Diego Healthcare System, La Jolla, CA; and the Department of Cognitive, Linguistic and Psychological Sciences (E.K.F., W.C.H.), Brown University, Providence, RI
| | - Joanne M Hamilton
- From the Departments of Neurosciences (K.M.L., D.P.S., D.G., L.A.H., J.M.H.), Psychiatry (J.V.F.), and Pathology (L.A.H.), University of California, San Diego, La Jolla; the Departments of Neurology (D.G.) and Psychology Services (J.V.F.), Veterans Affairs San Diego Healthcare System, La Jolla, CA; and the Department of Cognitive, Linguistic and Psychological Sciences (E.K.F., W.C.H.), Brown University, Providence, RI
| |
Collapse
|
|
24
|
Landy KM, Salmon DP, Filoteo JV, Heindel WC, Galasko D, Hamilton JM. Visual search in Dementia with Lewy Bodies and Alzheimer's disease. Cortex 2015; 73:228-39. [PMID: 26476402 DOI: 10.1016/j.cortex.2015.08.020] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2014] [Revised: 08/03/2015] [Accepted: 08/31/2015] [Indexed: 11/30/2022]
Abstract
Visual search is an aspect of visual cognition that may be more impaired in Dementia with Lewy Bodies (DLB) than Alzheimer's disease (AD). To assess this possibility, the present study compared patients with DLB (n = 17), AD (n = 30), or Parkinson's disease with dementia (PDD; n = 10) to non-demented patients with PD (n = 18) and normal control (NC) participants (n = 13) on single-feature and feature-conjunction visual search tasks. In the single-feature task participants had to determine if a target stimulus (i.e., a black dot) was present among 3, 6, or 12 distractor stimuli (i.e., white dots) that differed in one salient feature. In the feature-conjunction task participants had to determine if a target stimulus (i.e., a black circle) was present among 3, 6, or 12 distractor stimuli (i.e., white dots and black squares) that shared either of the target's salient features. Results showed that target detection time in the single-feature task was not influenced by the number of distractors (i.e., "pop-out" effect) for any of the groups. In contrast, target detection time increased as the number of distractors increased in the feature-conjunction task for all groups, but more so for patients with AD or DLB than for any of the other groups. These results suggest that the single-feature search "pop-out" effect is preserved in DLB and AD patients, whereas ability to perform the feature-conjunction search is impaired. This pattern of preserved single-feature search with impaired feature-conjunction search is consistent with a deficit in feature binding that may be mediated by abnormalities in networks involving the dorsal occipito-parietal cortex.
Collapse
Affiliation(s)
- Kelly M Landy
- Department of Neurosciences, University of California, San Diego, CA, United States
| | - David P Salmon
- Department of Neurosciences, University of California, San Diego, CA, United States.
| | - J Vincent Filoteo
- Department of Psychiatry, University of California, San Diego, CA, United States; Psychology Service, Veterans Affairs San Diego Healthcare System, CA, United States
| | - William C Heindel
- Department of Cognitive, Linguistic, and Psychological Sciences, Brown University, Providence, RI, United States
| | - Douglas Galasko
- Department of Neurosciences, University of California, San Diego, CA, United States; Neurology Service, Veterans Affairs San Diego Healthcare System, CA, United States
| | - Joanne M Hamilton
- Department of Neurosciences, University of California, San Diego, CA, United States
| |
Collapse
|
|
25
|
Haight TJ, Bryan RN, Erus G, Davatzikos C, Jacobs DR, D'Esposito M, Lewis CE, Launer LJ. Vascular risk factors, cerebrovascular reactivity, and the default-mode brain network. Neuroimage 2015; 115:7-16. [PMID: 25917517 PMCID: PMC4469180 DOI: 10.1016/j.neuroimage.2015.04.039] [Citation(s) in RCA: 56] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2015] [Revised: 04/14/2015] [Accepted: 04/19/2015] [Indexed: 01/12/2023] Open
Abstract
Cumulating evidence from epidemiologic studies implicates cardiovascular health and cerebrovascular function in several brain diseases in late life. We examined vascular risk factors with respect to a cerebrovascular measure of brain functioning in subjects in mid-life, which could represent a marker of brain changes in later life. Breath-hold functional MRI (fMRI) was performed in 541 women and men (mean age 50.4 years) from the Coronary Artery Risk Development in Young Adults (CARDIA) Brain MRI sub-study. Cerebrovascular reactivity (CVR) was quantified as percentage change in blood-oxygen level dependent (BOLD) signal in activated voxels, which was mapped to a common brain template and log-transformed. Mean CVR was calculated for anatomic regions underlying the default-mode network (DMN) - a network implicated in AD and other brain disorders - in addition to areas considered to be relatively spared in the disease (e.g. occipital lobe), which were utilized as reference regions. Mean CVR was significantly reduced in the posterior cingulate/precuneus (β=-0.063, 95% CI: -0.106, -0.020), anterior cingulate (β=-0.055, 95% CI: -0.101, -0.010), and medial frontal lobe (β=-0.050, 95% CI: -0.092, -0.008) relative to mean CVR in the occipital lobe, after adjustment for age, sex, race, education, and smoking status, in subjects with pre-hypertension/hypertension compared to normotensive subjects. By contrast, mean CVR was lower, but not significantly, in the inferior parietal lobe (β=-0.024, 95% CI: -0.062, 0.014) and the hippocampus (β=-0.006, 95% CI: -0.062, 0.050) relative to mean CVR in the occipital lobe. Similar results were observed in subjects with diabetes and dyslipidemia compared to those without these conditions, though the differences were non-significant. Reduced CVR may represent diminished vascular functionality for the DMN for individuals with prehypertension/hypertension in mid-life, and may serve as a preclinical marker for brain dysfunction in later life.
Collapse
Affiliation(s)
- Thaddeus J Haight
- Laboratory of Epidemiology and Population Sciences, National Institute on Aging, 7201 Wisconsin Avenue, Room 3C309, Bethesda, MD 20814, USA.
| | - R Nick Bryan
- Department of Radiology, University of Pennsylvania, 3600 Market St., Philadelphia, PA 19104, USA
| | - Guray Erus
- Department of Radiology, University of Pennsylvania, 3600 Market St., Philadelphia, PA 19104, USA
| | - Christos Davatzikos
- Department of Radiology, University of Pennsylvania, 3600 Market St., Philadelphia, PA 19104, USA
| | - David R Jacobs
- Division of Epidemiology and Community Health, University of Minnesota, 1300 S. 2nd Street, Suite 300, Minneapolis, MN, USA
| | - Mark D'Esposito
- Helen Wills Neuroscience Institute, University of California-Berkeley, 132 Barker Hall, Berkeley, CA, USA
| | - Cora E Lewis
- Department of Medicine, Division of Preventive Medicine, University of Alabama, Medical Towers 614, 1717 11th Avenue South, Birmingham, AL, USA
| | - Lenore J Launer
- Laboratory of Epidemiology and Population Sciences, National Institute on Aging, 7201 Wisconsin Avenue, Room 3C309, Bethesda, MD 20814, USA
| |
Collapse
|
|
26
|
Chiba Y, Fujishiro H, Ota K, Kasanuki K, Arai H, Hirayasu Y, Sato K, Iseki E. Clinical profiles of dementia with Lewy bodies with and without Alzheimer's disease-like hypometabolism. Int J Geriatr Psychiatry 2015; 30:316-23. [PMID: 24839913 DOI: 10.1002/gps.4144] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2013] [Accepted: 04/23/2014] [Indexed: 12/19/2022]
Abstract
OBJECTIVES It is well known that Alzheimer's disease (AD)-type pathology is commonly present in dementia with Lewy bodies (DLB) brains and that the degree of AD-type pathology has an influence on the clinical characteristics of DLB. Although significant hypometabolism in the temporoparietal/precuneus on [(18)F]fluoro-d-glucose ((18)F-FDG) positron emission tomography (PET) scans is considered to support a diagnosis of AD, some DLB patients also exhibit this metabolic pattern. The clinical significance of the metabolic pattern on DLB remains unknown. METHODS Twenty-three DLB patients, 10 AD patients, and 11 controls underwent (18)F-FDG PET scans. According to the degree of hypometabolism in the parietal/precuneus regions, representing the AD-like metabolic pattern, 12 patients were placed in the DLB-AD(+) group and 11 patients were placed in the DLB-AD(-) group. The demographics and clinical variables were compared among the four groups. RESULTS In addition to the parietal/precuneus regions, the DLB-AD(+) group exhibited significantly greater posterior cingulate hypometabolism than the DLB-AD(-) group, although occipital metabolism did not differ. The prevalence of visual hallucinations and extracampine hallucinations, and the Bender-Gestalt test score were significantly higher in the DLB-AD(+) group than the DLB-AD(-) group, although there were no differences in the demographics and other examined clinical variables between the two DLB groups. These clinical differences were absent in the DLB-AD(-) group, AD group, and controls. CONCLUSIONS Parietal/precuneus hypometabolism may be associated with clinical characteristics in DLB patients. Further multiple imaging modalities that are sensitive to AD-type pathology are needed to reveal the neurobiological basis of the AD-like metabolic pattern.
Collapse
Affiliation(s)
- Yuhei Chiba
- PET/CT Dementia Research Center, Juntendo Tokyo Koto Geriatric Medical Center, Juntendo University School of Medicine, Tokyo, Japan; Department of Psychiatry, Juntendo University School of Medicine, Tokyo, Japan; Department of Psychiatry, Yokohama City University School of Medicine, Kanagawa, Japan
| | | | | | | | | | | | | | | |
Collapse
|
|
27
|
Abstract
OBJECTIVE We review the role of brain FDG PET in the diagnosis of Alzheimer disease, frontotemporal dementia, dementia with Lewy bodies, and vascular dementia. Characteristic spatial patterns of brain metabolism on FDG PET can help differentiate various subtypes of dementia. CONCLUSION In patients with different subtypes of dementia, FDG PET/CT shows distinct spatial patterns of metabolism in the brain and can help clinicians to make a reasonably accurate and early diagnosis for appropriate management or prognosis.
Collapse
|
|
28
|
Deep Brain Stimulation Influences Brain Structure in Alzheimer's Disease. Brain Stimul 2014; 8:645-54. [PMID: 25814404 DOI: 10.1016/j.brs.2014.11.020] [Citation(s) in RCA: 137] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2014] [Revised: 11/25/2014] [Accepted: 11/29/2014] [Indexed: 12/25/2022] Open
Abstract
BACKGROUND Deep Brain Stimulation (DBS) is thought to improve the symptoms of selected neurological disorders by modulating activity within dysfunctional brain circuits. To date, there is no evidence that DBS counteracts progressive neurodegeneration in any particular disorder. OBJECTIVE/HYPOTHESIS We hypothesized that DBS applied to the fornix in patients with Alzheimer's Disease (AD) could have an effect on brain structure. METHODS In six AD patients receiving fornix DBS, we used structural MRI to assess one-year change in hippocampal, fornix, and mammillary body volume. We also used deformation-based morphometry to identify whole-brain structural changes. We correlated volumetric changes to hippocampal glucose metabolism. We also compared volumetric changes to those in an age-, sex-, and severity-matched group of AD patients (n = 25) not receiving DBS. RESULTS We observed bilateral hippocampal volume increases in the two patients with the best clinical response to fornix DBS. In one patient, hippocampal volume was preserved three years after diagnosis. Overall, mean hippocampal atrophy was significantly slower in the DBS group compared to the matched AD group, and no matched AD patients demonstrated bilateral hippocampal enlargement. Across DBS patients, hippocampal volume change correlated strongly with hippocampal metabolism and with volume change in the fornix and mammillary bodies, suggesting a circuit-wide effect of stimulation. Deformation-based morphometry in DBS patients revealed local volume expansions in several regions typically atrophied in AD. CONCLUSION We present the first in-human evidence that, in addition to modulating neural circuit activity, DBS may influence the natural course of brain atrophy in a neurodegenerative disease.
Collapse
|
|
29
|
Narayanan L, Murray AD. What is the role of neuroimaging in dementia? A review. IMAGING 2014. [DOI: 10.1259/img.20120015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
|
|
30
|
Ito K, Shimano Y, Imabayashi E, Nakata Y, Omachi Y, Sato N, Arima K, Matsuda H. Concordance between (99m)Tc-ECD SPECT and 18F-FDG PET interpretations in patients with cognitive disorders diagnosed according to NIA-AA criteria. Int J Geriatr Psychiatry 2014; 29:1079-86. [PMID: 24687634 DOI: 10.1002/gps.4102] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2013] [Revised: 02/16/2014] [Accepted: 02/20/2014] [Indexed: 12/12/2022]
Abstract
OBJECTIVES The purpose of this study was to clarify the concordance of diagnostic abilities and interobserver agreement between 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) and brain perfusion single photon-emission computed tomography (SPECT) in patients with Alzheimer's disease (AD) who were diagnosed according to the research criteria of the National Institute of Aging-Alzheimer's Association Workshop. METHODS Fifty-five patients with "AD and mild cognitive impairment (MCI)" (n = 40) and "non-AD" (n = 15) were evaluated with 18F-FDG PET and (99m)Tc-ethyl cysteinate dimer (ECD) SPECT during an 8-week period. Three radiologists independently graded the regional uptake in the frontal, temporal, parietal, and occipital lobes as well as the precuneus/posterior cingulate cortex in both images. Kappa values were used to determine the interobserver reliability regarding regional uptake. RESULTS The regions with better interobserver reliability between 18F-FDG PET and (99m)Tc-ECD SPECT were the frontal, parietal, and temporal lobes. The (99m)Tc-ECD SPECT agreement in the occipital lobes was not significant. The frontal, temporal, and parietal lobes showed good correlations between 18F-FDG PET and (99m)Tc-ECD SPECT in the degree of uptake, but the occipital lobe and precuneus/posterior cingulate cortex did not show good correlations. The diagnostic accuracy rates of "AD and MCI" ranged from 60% to 70% in both of the techniques. CONCLUSIONS The degree of uptake on 18F-FDG PET and (99m)Tc-ECD SPECT showed significant correlations in the frontal, temporal, and parietal lobes. The diagnostic abilities of 18F-FDG PET and (99m)Tc-ECD SPECT for "AD and MCI," when diagnosed according to the National Institute of Aging-Alzheimer's Association Workshop criteria, were nearly identical.
Collapse
Affiliation(s)
- Kimiteru Ito
- Department of Diagnostic Radiology, Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, Tokyo, Japan
| | | | | | | | | | | | | | | |
Collapse
|
|
31
|
Binnewijzend MAA, Kuijer JPA, van der Flier WM, Benedictus MR, Möller CM, Pijnenburg YAL, Lemstra AW, Prins ND, Wattjes MP, van Berckel BNM, Scheltens P, Barkhof F. Distinct perfusion patterns in Alzheimer’s disease, frontotemporal dementia and dementia with Lewy bodies. Eur Radiol 2014; 24:2326-33. [DOI: 10.1007/s00330-014-3172-3] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2013] [Revised: 03/10/2014] [Accepted: 04/01/2014] [Indexed: 10/25/2022]
|
|
32
|
Zhong J, Pan P, Dai Z, Shi H. Voxelwise meta-analysis of gray matter abnormalities in dementia with Lewy bodies. Eur J Radiol 2014; 83:1870-4. [PMID: 25043498 DOI: 10.1016/j.ejrad.2014.06.014] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2014] [Accepted: 06/19/2014] [Indexed: 11/16/2022]
Abstract
BACKGROUND Increasing neuroimaging studies have revealed brain gray matter (GM) atrophy by voxel-based morphometry (VBM) studies in patients with dementia with Lewy bodies (DLB) relative to healthy controls. However, the spatial localization of GM abnormalities reported in the existing studies is heterogeneous. Here, we aimed to investigate concurrence across VBM studies to help clarify the structural abnormalities underpinning this condition. METHODS A systematic search for VBM studies of DLB patients and healthy controls published in PubMed database from January 2000 to March 2014 was conducted. A quantitative meta-analysis of whole-brain VBM studies in DLB patients and healthy controls was performed by means of Anisotropic Effect Size version of Signed Differential Mapping (AES-SDM) software package. RESULTS Seven studies comprising 218 DLB patients and 219 healthy controls were included in the present study. Compared to healthy subjects, the patients group showed consistent decreased GM in right lateral temporal/insular cortex and left lenticular nucleus/insular cortex. The results remained largely unchanged in the following jackknife sensitivity analyses. Meta-regression analysis indicated an increased probability of finding brain atrophy in left superior temporal gyrus in patients with lower MMSE scores. CONCLUSIONS The present meta-analysis quantitatively demonstrates a characteristic pattern of GM alternations that contributed to the understanding of pathophysiology underlying DLB. Future studies will benefit from employing meta-analytical comparisons to other dementia subtypes with solid evidence to extend these findings.
Collapse
Affiliation(s)
- JianGuo Zhong
- Department of Neurology, Affiliated Yancheng Hospital of Southeast University, Yancheng, PR China
| | - PingLei Pan
- Department of Neurology, Affiliated Yancheng Hospital of Southeast University, Yancheng, PR China
| | - ZhenYu Dai
- Department of Radiology, Affiliated Yancheng Hospital of Southeast University, Yancheng, PR China
| | - HaiCun Shi
- Department of Neurology, Affiliated Yancheng Hospital of Southeast University, Yancheng, PR China.
| |
Collapse
|
|
33
|
Valkanova V, Ebmeier KP. Neuroimaging in dementia. Maturitas 2014; 79:202-8. [PMID: 24685291 DOI: 10.1016/j.maturitas.2014.02.016] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2014] [Revised: 02/25/2014] [Accepted: 02/28/2014] [Indexed: 10/25/2022]
Abstract
Over the last few years, advances in neuroimaging have generated biomarkers, which increase diagnostic certainty, provide valuable information about prognosis, and suggest a particular pathology underlying the clinical dementia syndrome. We aim to review the evidence for use of already established imaging modalities, along with selected techniques that have a great potential to guide clinical decisions in the future. We discuss structural, functional and molecular imaging, focusing on the most common dementias: Alzheimer's disease, fronto-temporal dementia, dementia with Lewy bodies and vascular dementia. Finally, we stress the importance of conducting research using representative cohorts and in a naturalistic set up, in order to build a strong evidence base for translating imaging methods for a National Health Service. If we assess a broad range of patients referred to memory clinic with a variety of imaging modalities, we will make a step towards accumulating robust evidence and ultimately closing the gap between the dramatic advances in neurosciences and meaningful clinical applications for the maximum benefit of our patients.
Collapse
Affiliation(s)
- Vyara Valkanova
- Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford OX3 7JX, UK
| | - Klaus P Ebmeier
- Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford OX3 7JX, UK.
| |
Collapse
|
|
34
|
|
|
35
|
Ishii K, Soma T, Shimada K, Oda H, Terashima A, Kawasaki R. Automatic volumetry of the cerebrospinal fluid space in idiopathic normal pressure hydrocephalus. Dement Geriatr Cogn Dis Extra 2013; 3:489-96. [PMID: 24516417 PMCID: PMC3919424 DOI: 10.1159/000357329] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
Abstract
Objectives To measure the cerebrospinal fluid (CSF) space volume in idiopathic normal pressure hydrocephalus (INPH), we developed a software that allows us to automatically measure the regional CSF space and compared the volumes of the ventricle systems (VS), Sylvian fissures (SF) and sulci at high convexity and midline (SHM) among INPH patients, Alzheimer's disease (AD) patients and healthy volunteers (HVs). Methods Fifteen INPH patients, 15 AD patients and 15 HVs were retrospectively selected for this study. 3D-T1 MR images were obtained. We improved upon an automatic gray matter volume system to measure CSF spaces, adopting new regions for the template of INPH-characteristic CSF spaces and measured them. The VS, SF and SHM volumes were calculated relative to the intracranial volume. Results The relative SHM volume of the INPH group (0.0237 ± 0.0064) was the smallest among the 3 groups (AD: 0.0477 ± 0.0109, HV: 0.0542 ± 0.0045). The VS (0.0499 ± 0.0135) and SF (0.0187 ± 0.0037) volumes of the INPH group were significantly larger than those of the AD (VS: 0.0311 ± 0.0075, SF: 0.0146 ± 0.0026) and HV groups (VS: 0.0167 ± 0.0065, SF: 0.0111 ± 0.017). Conclusion Automatic volume measurement can be used to delineate the characteristic changes in CSF space in patients with INPH and is useful in the diagnosis of INPH.
Collapse
Affiliation(s)
- Kazunari Ishii
- Department of Radiology, Kinki University Faculty of Medicine, Osakasayama, Tokyo, Japan ; Department of Radiology, Hyogo Brain and Heart Center, Himeji, Tokyo, Japan
| | - Tsutomu Soma
- Department of Radiology, The University of Tokyo, Tokyo, Japan ; Software Development Group, FUJIFILM RI Pharma Co. Ltd., Tokyo, Japan
| | - Kenichi Shimada
- Institute for Aging Brain and Cognitive Disorders, Hyogo Brain and Heart Center, Himeji, Tokyo, Japan
| | - Haruhiko Oda
- Institute for Aging Brain and Cognitive Disorders, Hyogo Brain and Heart Center, Himeji, Tokyo, Japan
| | - Akira Terashima
- Institute for Aging Brain and Cognitive Disorders, Hyogo Brain and Heart Center, Himeji, Tokyo, Japan
| | - Ryota Kawasaki
- Department of Radiology, Hyogo Brain and Heart Center, Himeji, Tokyo, Japan
| |
Collapse
|
|
36
|
|
|
37
|
Lebouvier T, Delrieu J, Evain S, Pallardy A, Sauvaget A, Letournel F, Chevrier R, Lepetit M, Vercelletto M, Boutoleau-Bretonnière C, Derkinderen P. [Dementia: Where are the Lewy bodies?]. Rev Neurol (Paris) 2013; 169:844-57. [PMID: 24103321 DOI: 10.1016/j.neurol.2013.05.004] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2012] [Revised: 05/28/2013] [Accepted: 05/28/2013] [Indexed: 11/25/2022]
Abstract
Dementia with Lewy bodies (DLB) is the second cause of degenerative dementia in autopsy studies. In clinical pratice however, the prevalence of DLB is much lower with important intercenter variations. Among the reasons for this low sensitivity of DLB diagnosis are (1) the imprecision and subjectivity of the diagnostic criteria; (2) the underestimation of non-motor symptoms (REM-sleep behavior disorder, dysautonomia, anosmia); mostly (3) the nearly constant association of Lewy bodies with Alzheimer's disease pathology, which dominates the clinical phenotype. With the avenue of targeted therapies against the protein agregates, new clinical scales able to apprehend the coexistence of Lewy pathology in Alzheimer's disease are expected.
Collapse
Affiliation(s)
- T Lebouvier
- CMRR des Pays de Loire, hôpital Laënnec, CHU de Nantes, boulevard Professeur-Jacques-Monod, 44800 Saint-Herblain, France.
| | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
38
|
AutoSPET: an SPM plugin to automatize neuroimages PET analysis. Interdiscip Sci 2013; 5:225-32. [PMID: 24307413 DOI: 10.1007/s12539-013-0169-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2013] [Revised: 03/30/2013] [Accepted: 06/12/2013] [Indexed: 10/25/2022]
Abstract
Neuroimaging analysis supports clinicians in the diagnosis of neurological diseases by extracting information from digital images. Due to the large number of images generated by new devices (e.g. PET ones), there is a lot of effort in defining computer-based tools to analyze and classify (brain) radiological images. Statistical tools, such as SPM (for Statistical Parametric Mapping), are largely used by physicians for image analysis. Nevertheless, large datasets analysis requires repetitive steps, due to the lack of automatic procedures. E.g. SPM requires human intervention during long and complex steps.We here present a tool, called AutoSPET (for Automatic SPM analysis for PET images), which allows to perform SPM analyses on large sets of PET images. It works as a meta-component orchestrating interactions with SPM, Matlab and with SPM plugins via a unified user interface. AutoSPET has been tested with real clinical datasets and it is publicly available as an official SPM plugin on the SPM website.
Collapse
|
|
39
|
Abstract
There is increasing use of neuroimaging modalities, including PET, for diagnosing dementia. For example, FDG-PET demonstrates hypometabolic regions in the posterior cingulate gyri, precuneus, and parietotemporal association cortices, while amyloid PET indicates amyloid deposition in Alzheimer disease and mild cognitive impairment due to Alzheimer disease. Furthermore, the use of combination PET with structural MR imaging can improve the diagnostic accuracy of dementia. In other neurodegenerative dementias, each disease exhibits a specific metabolic reduction pattern. In dementia with Lewy bodies, occipital glucose metabolism is decreased, while in frontotemporal dementia, frontal and anterior temporal metabolism is predominantly decreased. These FDG-PET findings and positive or negative amyloid deposits are important biomarkers for various neurodegenerative dementias.
Collapse
Affiliation(s)
- K Ishii
- From the Neurocognitive Disorders Center, Kinki University Hospital, Osaka, Japan.
| |
Collapse
|
|
40
|
Yamane T, Ikari Y, Nishio T, Ishii K, Ishii K, Kato T, Ito K, Silverman DHS, Senda M, Asada T, Arai H, Sugishita M, Iwatsubo T. Visual-statistical interpretation of (18)F-FDG-PET images for characteristic Alzheimer patterns in a multicenter study: inter-rater concordance and relationship to automated quantitative evaluation. AJNR Am J Neuroradiol 2013; 35:244-9. [PMID: 23907243 DOI: 10.3174/ajnr.a3665] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Abstract
BACKGROUND AND PURPOSE The role of (18)F-FDG-PET in the diagnosis of Alzheimer disease is increasing and should be validated. The aim of this study was to assess the inter-rater variability in the interpretation of (18)F-FDG-PET images obtained in the Japanese Alzheimer's Disease Neuroimaging Initiative, a multicenter clinical research project. MATERIALS AND METHODS This study analyzed 274 (18)F-FDG-PET scans (67 mild Alzheimer disease, 100 mild cognitive impairment, and 107 normal cognitive) as baseline scans for the Japanese Alzheimer's Disease Neuroimaging Initiative, which were acquired with various types of PET or PET/CT scanners in 23 facilities. Three independent raters interpreted all PET images by using a combined visual-statistical method. The images were classified into 7 (FDG-7) patterns by the criteria of Silverman et al and further into 2 (FDG-2) patterns. RESULTS Agreement among the 7 visual-statistical categories by at least 2 of the 3 readers occurred in >94% of cases for all groups: Alzheimer disease, mild cognitive impairment, and normal cognitive. Perfect matches by all 3 raters were observed for 62% of the cases by FDG-7 and 76 by FDG-2. Inter-rater concordance was moderate by FDG-7 (κ = 0.57) and substantial in FDG-2 (κ = 0.67) on average. The FDG-PET score, an automated quantitative index developed by Herholz et al, increased as the number of raters who voted for the AD pattern increased (ρ = 0.59, P < .0001), and the FDG-PET score decreased as those for normal pattern increased (ρ = -0.64, P < .0001). CONCLUSIONS Inter-rater agreement was moderate to substantial for the combined visual-statistical interpretation of (18)F-FDG-PET and was also significantly associated with automated quantitative assessment.
Collapse
Affiliation(s)
- T Yamane
- From the Division of Molecular Imaging (T.Y., Y.I., T.N., M. Senda), Institute of Biomedical Research and Innovation, Kobe, Japan
| | | | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
41
|
Nakatsuka T, Imabayashi E, Matsuda H, Sakakibara R, Inaoka T, Terada H. Discrimination of dementia with Lewy bodies from Alzheimer's disease using voxel-based morphometry of white matter by statistical parametric mapping 8 plus diffeomorphic anatomic registration through exponentiated Lie algebra. Neuroradiology 2013; 55:559-66. [PMID: 23322456 PMCID: PMC3659278 DOI: 10.1007/s00234-013-1138-9] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2012] [Accepted: 01/04/2013] [Indexed: 01/08/2023]
Abstract
Introduction The purpose of this study was to identify brain atrophy specific for dementia with Lewy bodies (DLB) and to evaluate the discriminatory performance of this specific atrophy between DLB and Alzheimer’s disease (AD). Methods We retrospectively reviewed 60 DLB and 30 AD patients who had undergone 3D T1-weighted MRI. We randomly divided the DLB patients into two equal groups (A and B). First, we obtained a target volume of interest (VOI) for DLB-specific atrophy using correlation analysis of the percentage rate of significant whole white matter (WM) atrophy calculated using the Voxel-based Specific Regional Analysis System for Alzheimer’s Disease (VSRAD) based on statistical parametric mapping 8 (SPM8) plus diffeomorphic anatomic registration through exponentiated Lie algebra, with segmented WM images in group A. We then evaluated the usefulness of this target VOI for discriminating the remaining 30 DLB patients in group B from the 30 AD patients. Z score values in this target VOI obtained from VSRAD were used as the determinant in receiver operating characteristic (ROC) analysis. Results Specific target VOIs for DLB were determined in the right-side dominant dorsal midbrain, right-side dominant dorsal pons, and bilateral cerebellum. ROC analysis revealed that the target VOI limited to the midbrain exhibited the highest area under the ROC curves of 0.75. Conclusions DLB patients showed specific atrophy in the midbrain, pons, and cerebellum. Midbrain atrophy demonstrated the highest power for discriminating DLB and AD. This approach may be useful for determining the contributions of DLB and AD pathologies to the dementia syndrome.
Collapse
Affiliation(s)
- Tomoya Nakatsuka
- Department of Radiology, Toho University Sakura Medical Center, 564-1, Shimoshizu, Sakura, Chiba 285-8741, Japan.
| | | | | | | | | | | |
Collapse
|
|
42
|
Multivariate classification of patients with Alzheimer's and dementia with Lewy bodies using high-dimensional cortical thickness measurements: an MRI surface-based morphometric study. J Neurol 2012; 260:1104-15. [PMID: 23224109 DOI: 10.1007/s00415-012-6768-z] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2012] [Revised: 11/13/2012] [Accepted: 11/15/2012] [Indexed: 10/27/2022]
Abstract
CONTEXT Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) are the most common neurodegenerative dementia types. It is important to differentiate between them because of the differences in prognosis and treatment approaches. OBJECTIVE Investigate if sparse partial least squares (SPLS) classification of cortical thickness measurements could differentiate between AD and DLB. METHODS Two independent cohorts without MR-protocol alignment in Norway and Slovenia with 97 AD and DLB subjects were enrolled. Cortical thickness measurements acquired with Freesurfer were used in subsequent SPLS classification runs. The cohorts were analyzed separately and afterwards combined. The models were trained with leave-one-out cross validation and test datasets where used when available. To study the impact of MR-protocol alignment, the classifiers were additionally tested on sets drawn exclusively from the independent cohorts. RESULTS The obtained sensitivity/specificity/AUC values were 94.4/88.89/0.978 and 88.2/94.1/0.969 in the Norwegian and Slovenian cohorts, respectively. Both cohorts showed AD-associated pattern of thinning in mid-anterior temporal, occipital and subgenual cingulate cortex, whereas the pattern supportive for DLB included thinning in dorsal cingulate, posterior temporal and lateral orbitofrontal regions. When combining the cohorts, sensitivity/specificity/AUC were 82.1/85.7/0.948 for the training and 77.8/75/0.731 for the testing datasets with the same pattern-of-difference. The models tested on datasets drawn exclusively from the independent cohorts did not produce adequate accuracy. CONCLUSION SPLS classification of cortical thickness is a good method for differentiating between AD and DLB, relatively stable even for mixed data, but not when tested on completely independent data drawn from different cohorts (without MR-protocol alignment).
Collapse
|
|
43
|
Abstract
Brain imaging has progressed from exclusion of rare treatable mass lesions to a specific antemortem diagnosis. MR imaging-derived hippocampal atrophy and WMH are regarded as imaging biomarkers of AD and CVD respectively. Abnormal FP-CIT SPECT or cardiac iodobenzamide SPECT is a useful supportive imaging feature in the diagnosis of DLB. Frontal and/or anterior temporal atrophy and anterior defects on molecular imaging with FDG-PET or perfusion SPECT are characteristic of FTDs. Whole-body FDG-PET may be helpful in patients with rapidly progressing "autoimmune dementias," and FLAIR and DWI are indicated in suspected CJD. A major role of imaging is in the development of new drugs and less costly biomarkers.
Collapse
Affiliation(s)
- A D Murray
- Aberdeen Biomedical Imaging Centre, Division of Applied Medicine, University of Aberdeen, Aberdeen, UK.
| |
Collapse
|
|
44
|
Filippi M, Agosta F, Barkhof F, Dubois B, Fox NC, Frisoni GB, Jack CR, Johannsen P, Miller BL, Nestor PJ, Scheltens P, Sorbi S, Teipel S, Thompson PM, Wahlund LO. EFNS task force: the use of neuroimaging in the diagnosis of dementia. Eur J Neurol 2012; 19:e131-40, 1487-501. [DOI: 10.1111/j.1468-1331.2012.03859.x] [Citation(s) in RCA: 91] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2012] [Accepted: 07/18/2012] [Indexed: 01/18/2023]
Affiliation(s)
- M. Filippi
- Neuroimaging Research Unit; Division of Neuroscience; Institute of Experimental Neurology; San Raffaele Scientific Institute; Vita-Salute San Raffaele University; Milan Italy
| | - F. Agosta
- Neuroimaging Research Unit; Division of Neuroscience; Institute of Experimental Neurology; San Raffaele Scientific Institute; Vita-Salute San Raffaele University; Milan Italy
| | - F. Barkhof
- Department of Radiology; VU University Medical Center; Amsterdam The Netherlands
| | - B. Dubois
- Centre de Recherche de l'Institut du Cerveau et de la Moelle Epinière; Université Pierre et Marie Curie; Paris France
| | - N. C. Fox
- Dementia Research Centre; Institute of Neurology; University College London; London UK
| | - G. B. Frisoni
- IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli di Brescia; Brescia Italy
| | - C. R. Jack
- Department of Radiology; Mayo Clinic and Foundation; Rochester MN USA
| | - P. Johannsen
- Memory Clinic; Rigshospitalet; Copenhagen University Hospital; Copenhagen Denmark
| | - B. L. Miller
- Memory and Aging Center; University of California; San Francisco CA USA
| | - P. J. Nestor
- Department of Clinical Neuroscience; University of Cambridge; Cambridge UK
| | - P. Scheltens
- Department of Neurology and Alzheimer Center; VU University Medical Center; Amsterdam The Netherlands
| | - S. Sorbi
- Department of Neurological and Psychiatric Sciences; Azienda Ospedaliero-Universitaria di Careggi; Florence Italy
| | - S. Teipel
- Department of Psychiatry; University of Rostock, and German Center for Neuro-degenerative Diseases (DZNE); Rostock Germany
| | - P. M. Thompson
- Department of Neurology; David Geffen School of Medicine at the University of California Los Angeles; Los Angeles CA USA
| | - L.-O. Wahlund
- Division of Clinical Geriatrics; Department of Neurobiology; Karolinska Institute; Stockholm Sweden
| |
Collapse
|
|
45
|
Standley K, Brock C, Hoffmann M. Advances in functional neuroimaging in dementias and potential pitfalls. Neurol Int 2012; 4:e7. [PMID: 22593811 PMCID: PMC3349962 DOI: 10.4081/ni.2012.e7] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2011] [Accepted: 02/23/2012] [Indexed: 11/23/2022] Open
Abstract
Neuroimaging is continuously advancing at a rapid rate and has progressed from excluding relatively uncommon secondary causes (stroke, tumor) to assisting with early diagnosis and subtype of dementia. Structural imaging has given way to functional, metabolic and receptor imaging.
Collapse
|
|
46
|
Cognitive and Behavioral Neurology. Neurology 2012. [DOI: 10.1007/978-0-387-88555-1_8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
|
|
47
|
Shine JM, Halliday GM, Naismith SL, Lewis SJG. Visual misperceptions and hallucinations in Parkinson's disease: dysfunction of attentional control networks? Mov Disord 2011; 26:2154-9. [PMID: 21953814 DOI: 10.1002/mds.23896] [Citation(s) in RCA: 139] [Impact Index Per Article: 9.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2011] [Revised: 06/28/2011] [Accepted: 07/05/2011] [Indexed: 12/15/2022] Open
Abstract
Visual misperceptions and hallucinations are a major cause of distress in patients with Parkinson's disease (PD), particularly in the advanced stages of the condition. Recent work has provided a framework for understanding the pathogenesis of these symptoms, implicating impairments from the retina to the integration of external information with preformed internal images. In this article, we propose a novel hypothesis that attempts to explain the presence of visual misperceptions and hallucinations in PD through the aberrant coordination of complimentary yet competing neural networks. We propose that hallucinations in PD reflect the relative inability to recruit activation in the dorsal attention network in the presence of an ambiguous percept, leading to overreliance on default mode network processing and salience arising from the ventral attention network. This inability is proposed to stem from improper function across cortical and subcortical structures secondary to the presence of Lewy body pathology. This hypothesis may be empirically tested by the use of targeted cognitive paradigms. In turn, this may assist our understanding of the pathophysiological mechanisms and cognitive processes contributing to visual misperceptions and hallucinations and ultimately may inform more effective treatment strategies for this troubling symptom.
Collapse
Affiliation(s)
- James M Shine
- Ageing Brain Centre, Brain and Mind Research Institute, the University of Sydney, Sydney, NSW, Australia
| | | | | | | |
Collapse
|
|
48
|
Abstract
Clinical use of positron emission tomography (PET) is now well established in neurodegenerative disorders, especially in the diagnosis of dementia. Measurement of cerebral glucose metabolism is of significant value, and it facilitates early diagnosis, appropriate differential diagnosis, and the evaluation of drug treatment in patients with dementia. In addition, tracers offer new perspectives for studying the neuropathology of underlying dementia, such as the accumulation of amyloid proteins, tau-proteins, or the presence of neuroinflammation. Finally, PET tracer studies of different neurotransmitter systems in dementia may not only increase the understanding of pathophysiologic mechanisms of the different disorders, but also improve diagnostic accuracy. In conclusion, PET imaging with different tracers offers reliable biomarkers in dementia, which can assist clinicians in the diagnosis of different dementing disorders, especially in the situation of overlapping phenotypes.
Collapse
Affiliation(s)
- Valentina Berti
- Department of Clinical Pathophysiology, Nuclear Medicine Unit, University of Florence, Florence, Italy.
| | | | | |
Collapse
|
|
49
|
Galvin JE, Price JL, Yan Z, Morris JC, Sheline YI. Resting bold fMRI differentiates dementia with Lewy bodies vs Alzheimer disease. Neurology 2011; 76:1797-803. [PMID: 21525427 DOI: 10.1212/wnl.0b013e31821ccc83] [Citation(s) in RCA: 103] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
OBJECTIVE Clinicopathologic phenotypes of dementia with Lewy bodies (DLB) and Alzheimer disease (AD) often overlap, making discrimination difficult. We performed resting state blood oxygen level-dependent (BOLD) functional connectivity MRI (fcMRI) to determine whether there were differences between AD and DLB. METHODS Participants (n = 88) enrolled in a longitudinal study of memory and aging underwent 3-T fcMRI. Clinical diagnoses of probable DLB (n = 15) were made according to published criteria. Cognitively normal control participants (n = 38) were selected for the absence of cerebral amyloid burden as imaged with Pittsburgh compound B (PiB). Probable AD cases (n = 35) met published criteria and had appreciable amyloid deposits with PiB imaging. Functional images were collected using a gradient spin-echo sequence sensitive to BOLD contrast (T2* weighting). Correlation maps selected a seed region in the combined bilateral precuneus. RESULTS Participants with DLB had a functional connectivity pattern for the precuneus seed region that was distinct from AD; both the DLB and AD groups had functional connectivity patterns that differed from the cognitively normal group. In the DLB group, we found increased connectivity between the precuneus and regions in the dorsal attention network and the putamen. In contrast, we found decreased connectivity between the precuneus and other task-negative default regions and visual cortices. There was also a reversal of connectivity in the right hippocampus. CONCLUSIONS Changes in functional connectivity in DLB indicate patterns of activation that are distinct from those seen in AD and may improve discrimination of DLB from AD and cognitively normal individuals. Since patterns of connectivity differ between AD and DLB groups, measurements of BOLD functional connectivity can shed further light on neuroanatomic connections that distinguish DLB from AD.
Collapse
Affiliation(s)
- J E Galvin
- Center of Excellence on Brain Aging, New York University Langone School of Medicine, 145 East 32nd St, Second Floor, New York, NY 10016, USA.
| | | | | | | | | |
Collapse
|
|
50
|
Fong TG, Inouye SK, Dai W, Press DZ, Alsop DC. Association cortex hypoperfusion in mild dementia with Lewy bodies: a potential indicator of cholinergic dysfunction? Brain Imaging Behav 2011; 5:25-35. [PMID: 20924800 PMCID: PMC3122107 DOI: 10.1007/s11682-010-9108-x] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
Dementia with Lewy bodies (DLB) is often associated with occipital hypometabolism or hypoperfusion, as well as deficits in cholinergic neurotransmission. In this study, 11 mild DLB, 16 mild AD and 16 age-matched controls underwent arterial spin-labeled perfusion MRI (ASL-pMRI) and neuropsychological testing. Patterns of cerebral blood flow (CBF) and cognitive performance were compared. In addition, combined ASL-pMRI and ChEI drug challenge (pharmacologic MRI) was tested as a probe of cholinergic function in 4 of the DLB participants. Frontal and parieto-occipital hypoperfusion was observed in both DLB and AD but was more pronounced in DLB. Following ChEI treatment, perfusion increased in temporal and parieto-occipital cortex, and cognitive performance improved on a verbal fluency task. If confirmed in a larger study, these results provide further evidence for brain cholinergic dysfunction in DLB pathophysiology, and use of pharmacologic MRI as an in vivo measure of cholinergic function.
Collapse
Affiliation(s)
- Tamara G Fong
- Aging Brain Center, Institute for Aging Research, Hebrew SeniorLife, 1200 Centre Street, Boston, MA 02131, USA.
| | | | | | | | | |
Collapse
|