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

Article type: Research Article

Authors: Werden, Emilio^{a; *} | Khlif, Mohamed Salah^a | Bird, Laura J.^a | Cumming, Toby^a | Bradshaw, Jennifer^b | Khan, Wasim^a | Pase, Matthew^a | Restrepo, Carolina^a | Veldsman, Michele^c | Egorova, Natalia^{a; d} | Patel, Sheila K.^a | Gottlieb, Elie^a | Brodtmann, Amy^{a; b; e}

Affiliations: [a] The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, Australia | [b] Austin Health, Heidelberg, Melbourne, VIC, Australia | [c] Department of Experimental Psychology, University of Oxford, Oxford, UK | [d] Melbourne School of Psychological Sciences, University of Melbourne, Melbourne, Australia | [e] Eastern Clinical Research Unit, Box Hill Hospital, Melbourne, VIC, Australia

Correspondence: [*] Correspondence to: Emilio Werden, PhD, The Florey Institute of Neuroscience and Mental Health, Melbourne Brain Centre, 245 Burgundy St, Heidelberg, Victoria 3084, Australia. Tel.: +61 3 9035 7275; E-mail: ewerden@florey.edu.au.

Abstract: 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 APOE ɛ4 carriers and non-carriers in the first year after ischemic stroke. Methods:We sampled 20 APOE ɛ4 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:APOE ɛ4 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

DOI: 10.3233/JAD-190566

Journal: Journal of Alzheimer's Disease, vol. 71, no. 1, pp. 245-259, 2019