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. 2020 Aug 5;12(1):e12066.
doi: 10.1002/dad2.12066. eCollection 2020.

Semantic loss marks early Alzheimer's disease-related neurodegeneration in older adults without dementia

Jet M J Vonk  1   2 , Vincent Bouteloup  3   4 , Jean-François Mangin  5   6 , Bruno Dubois  7 , Frédéric Blanc  8 , Audrey Gabelle  9   10 , Mathieu Ceccaldi  11 , Cédric Annweiler  12   13   14   15   16 , Pierre Krolak-Salmon  17 , Catherine Belin  18 , Thérèse Rivasseau-Jonveaux  19 , Adrien Julian  20 , François Sellal  21   22 , Eloi Magnin  23   24 , Marie Chupin  5 , Marie-Odile Habert  5   25   26 , Geneviève Chêne  3   4 , Carole Dufouil  3   4 ; MEMENTO cohort Study Group
Affiliations

Semantic loss marks early Alzheimer's disease-related neurodegeneration in older adults without dementia

Jet M J Vonk et al. Alzheimers Dement (Amst). .

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 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.

Keywords: Alzheimer's disease; MCI; amnestic; biomarkers; category fluency; cognitive aging; cohort studies; letter fluency; neuroimaging; semantic fluency; verbal fluency.

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Conflict of interest statement

The authors have no relevant conflicts of interest or financial or other nonprofessional benefits to disclose that could bias the authors in the conduct of the reported work.

Figures

FIGURE 1
FIGURE 1
Trajectories of semantic and letter fluency across diagnosis at follow‐up, including 95% confidence interval bands
FIGURE 2
FIGURE 2
Trajectories of semantic and letter fluency across strata of apolipoprotein E e4 status and baseline Clinical Dementia Rating score, including 95% confidence interval bands
FIGURE 3
FIGURE 3
Relationships of baseline performance in semantic and letter fluency with neurodegeneration
See this image and copyright information in PMC

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