APOE-ε4 associates with hippocampal volume, learning, and memory across the spectrum of Alzheimer's disease and dementia with Lewy bodies

Saeed, Usman and Mirza, Saira S. and MacIntosh, Bradley J. and Herrmann, Nathan and Keith, Julia and Ramirez, Joel and Nestor, Sean M. and Yu, Qinggang and Knight, Jo and Swardfager, Walter and Potkin, Steven G. and Rogaeva, Ekaterina and George-Hyslop, Peter St. and Black, Sandra E. and Masellis, Mario (2018) APOE-ε4 associates with hippocampal volume, learning, and memory across the spectrum of Alzheimer's disease and dementia with Lewy bodies. Alzheimer's and Dementia, 14 (9). pp. 1137-1147. ISSN 1552-5260

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Introduction Although the apolipoprotein E ε4-allele (APOE-ε4) is a susceptibility factor for Alzheimer's disease (AD) and dementia with Lewy bodies (DLB), its relationship with imaging and cognitive measures across the AD/DLB spectrum remains unexplored. Methods We studied 298 patients (AD = 250, DLB = 48; 38 autopsy confirmed; NCT01800214) using neuropsychological testing, volumetric magnetic resonance imaging, and APOE genotyping to investigate the association of APOE-ε4 with hippocampal volume and learning/memory phenotypes, irrespective of diagnosis. Results Across the AD/DLB spectrum: (1) hippocampal volumes were smaller with increasing APOE-ε4 dosage (no genotype × diagnosis interaction observed), (2) learning performance as assessed by total recall scores was associated with hippocampal volumes only among APOE-ε4 carriers, and (3) APOE-ε4 carriers performed worse on long-delay free word recall. Discussion These findings provide evidence that APOE-ε4 is linked to hippocampal atrophy and learning/memory phenotypes across the AD/DLB spectrum, which could be useful as biomarkers of disease progression in therapeutic trials of mixed disease.

Item Type:
Journal Article
Journal or Publication Title:
Alzheimer's and Dementia
Additional Information:
This is the author’s version of a work that was accepted for publication in Alzheimer's & Dementia. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Alzheimer's & Dementia, 14, 9, 2018 DOI: 10.1016/j.jalz.2018.04.005
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Deposited On:
30 May 2018 09:52
Last Modified:
31 Aug 2022 00:07