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

Alzheimers Dement. 2018 Sep;14(9):1137-1147. doi: 10.1016/j.jalz.2018.04.005. Epub 2018 May 18.


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.

Keywords: APOE; Alzheimer's disease; Dementia with Lewy bodies; Endophenotype; Hippocampus; Learning; MRI; Memory.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease / diagnostic imaging
  • Alzheimer Disease / genetics*
  • Alzheimer Disease / psychology
  • Apolipoprotein E4 / genetics*
  • Endophenotypes
  • Female
  • Genetic Predisposition to Disease
  • Heterozygote
  • Hippocampus / diagnostic imaging*
  • Hippocampus / pathology
  • Humans
  • Learning*
  • Lewy Body Disease / diagnostic imaging
  • Lewy Body Disease / genetics*
  • Lewy Body Disease / psychology
  • Magnetic Resonance Imaging
  • Male
  • Neuropsychological Tests
  • Organ Size


  • Apolipoprotein E4

Associated data

  • ClinicalTrials.gov/NCT01800214