Semantic loss marks early Alzheimer's disease-related neurodegeneration in older adults without dementia
MEMENTO cohort Study Group
(2020) Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring, volume 12, issue 1, pp. 1 - 14
(Article)
Abstract
Objective: To assess progression of semantic loss in early stages of cognitive decline using semantic and letter fluency performance, and its relation with Alzheimer's disease (AD)-specific neurodegeneration using longitudinal multimodal neuroimaging measures. Methods: Change in verbal fluency was analyzed among 2261 non-demented individuals with a follow-up diagnosis of no mild
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cognitive impairment (MCI), amnestic MCI (aMCI), non-amnestic MCI (naMCI), or incident dementia, using linear mixed models across 4 years of follow-up, and relations with magnetic resonance imaging (MRI; n = 1536) and 18F-fluorodeoxyglucose brain positron emission tomography (18F-FDG-PET) imaging (n = 756) using linear regression models across 2 years of follow-up. Results: Semantic fluency declined-fastest in those at higher risk for AD (apolipoprotein E [APOE] e4 carriers, Clinical Dementia Rating score of .5, aMCI, or incident dementia)-while letter fluency did not except for those with incident dementia. Lower baseline semantic fluency was associated with an increase in white matter hyperintensities and total mean cortical thinning over time, and regionally with less hippocampal volume as well as more cortical thinning and reduced 18F-FDG-PET uptake in the inferior parietal lobule, entorhinal cortex, isthmus cingulate, and precuneus-posterior cingulate area. In contrast, baseline letter fluency was not associated with change in total nor regional neurodegeneration. Whole-brain neurodegeneration over time was associated with faster decline in both fluencies, while AD-specific regions were associated with a faster rate of decline in semantic but not letter fluency. Interpretation: This study provides strong evidence of distinctive degeneration of semantic abilities early on in relation to both cognitive decline and AD-specific neurodegeneration.
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Keywords: Alzheimer's disease, MCI, amnestic, biomarkers, category fluency, cognitive aging, cohort studies, letter fluency, neuroimaging, semantic fluency, verbal fluency, Clinical Neurology, Psychiatry and Mental health
ISSN: 2352-8729
Publisher: John Wiley & Sons, Ltd.
Note: Funding Information: The MEMENTO cohort is funded by the Fondation Plan Alzheimer (Alzheimer Plan 2008‐2012), and the French Ministry of Research (MESRI, DGRI) through the Plan Maladies Neurodégénératives (2014‐2019). This work was also supported by CIC 1401‐EC, Bordeaux University Hospital (CHU Bordeaux, sponsor of the cohort), Inserm, and the University of Bordeaux, as well as an Alzheimer Nederland Fellowship to J.M.J. Vonk (WE.15‐2018‐05) and a ZonMw NWO Veni grant to J.M.J. Vonk (project number 09150161810017). This work was undertaken using resources on the Dementias Platform UK (DPUK) Data Portal; the Medical Research Council supports DPUK through grant MR/L023784/2. Funding Information: The MEMENTO cohort is funded by the Fondation Plan Alzheimer (Alzheimer Plan 2008-2012), and the French Ministry of Research (MESRI, DGRI) through the Plan Maladies Neurod?g?n?ratives (2014-2019). This work was also supported by CIC 1401-EC, Bordeaux University Hospital (CHU Bordeaux, sponsor of the cohort), Inserm, and the University of Bordeaux, as well as an Alzheimer Nederland Fellowship to J.M.J. Vonk (WE.15-2018-05) and a ZonMw NWO Veni grant to J.M.J. Vonk (project number 09150161810017). This work was undertaken using resources on the Dementias Platform UK (DPUK) Data Portal; the Medical Research Council supports DPUK through grant MR/L023784/2. Publisher Copyright: © 2020 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals LLC on behalf of Alzheimer's Association Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
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