APOE ɛ4 Carriers Show Delayed Recovery of Verbal Memory and Smaller Entorhinal Volume in the First Year After Ischemic Stroke

J Alzheimers Dis. 2019;71(1):245-259. doi: 10.3233/JAD-190566.


Background: The apolipoprotein E (APOE) gene ɛ4 allele is a risk factor for Alzheimer's disease and cardiovascular disease. However, its relationship with cognition and brain volume after stroke is not clear.

Objective: We compared cognition and medial temporal lobe volumes in APOEɛ4 carriers and non-carriers in the first year after ischemic stroke.

Methods: We sampled 20 APOEɛ4 carriers and 20 non-carriers from a larger cohort of 135 ischemic stroke participants in the longitudinal CANVAS study. Participants were matched on a range of demographic and stroke characteristics. We used linear mixed-effect models to compare cognitive domain z-scores (attention, processing speed, executive function, verbal and visual memory, language, visuospatial function) and regional medial temporal lobe volumes (hippocampal, entorhinal cortex) between groups at each time-point (3, 12-months post-stroke), and within groups across time-points. APOE gene single nucleotide polymorphisms (SNPs; rs7412, rs429358) were genotyped on venous blood.

Results: APOEɛ4 carriers and non-carriers did not differ on any demographic, clinical, or stroke variable. Carriers performed worse than non-carriers in verbal memory at 3 months post-stroke (p = 0.046), but were better in executive function at 12 months (p = 0.035). Carriers demonstrated a significant improvement in verbal memory (p = 0.012) and executive function (p = 0.015) between time-points. Non-carriers demonstrated a significant improvement in visual memory (p = 0.0005). Carriers had smaller bilateral entorhinal cortex volumes (p < 0.05), and larger right sided and contralesional hippocampal volumes, at both time-points (p < 0.05).

Conclusion: APOE ɛ4 is associated with delayed recovery of verbal memory function and reduced entorhinal cortex volumes in the first year after ischemic stroke.

Keywords: Apolipoproteins E; hippocampus; magnetic resonance imaging; memory; stroke.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Apolipoprotein E4 / genetics*
  • Brain Ischemia / complications*
  • Brain Ischemia / pathology
  • Brain Ischemia / psychology
  • Case-Control Studies
  • Entorhinal Cortex / diagnostic imaging
  • Entorhinal Cortex / pathology*
  • Female
  • Heterozygote
  • Humans
  • Longitudinal Studies
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Neuroimaging
  • Organ Size
  • Prospective Studies
  • Recovery of Function
  • Stroke / complications*
  • Stroke / pathology
  • Stroke / psychology
  • Verbal Learning*


  • Apolipoprotein E4