APOE-epsilon 4 associates with hippocampal volume, learning, and memory across the spectrum of Alzheimer's disease and dementia with Lewy bodies

Introduction: Although the apolipoprotein E epsilon 4-allele (APOE-epsilon 4) 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-epsilon 4 with hippocampal volume and learning/memory phenotypes, irrespective of diagnosis. Results: Across the AD/DLB spectrum: (1) hippocampal volumes were smaller with increasing APOE-epsilon 4 dosage (no genotype X diagnosis interaction observed), (2) learning performance as assessed by total recall scores was associated with hippocampal volumes only among APOE-epsilon 4 carriers, and (3) APOE-epsilon 4 carriers performed worse on long-delay free word recall. Discussion: These findings provide evidence that APOE-epsilon 4 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. (C) 2018 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.