Association between APOE e4 and white matter hyperintensity volume, but not total brain volume or white matter integrity

Lyall, D. M. et al. (2020) Association between APOE e4 and white matter hyperintensity volume, but not total brain volume or white matter integrity. Brain Imaging and Behavior, 14(5), pp. 1468-1476. (doi: 10.1007/s11682-019-00069-9) (PMID:30903549) (PMCID:PMC7572345)

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Apolipoprotein (APOE) e4 genotype is an accepted risk factor for accelerated cognitive aging and dementia, though its neurostructural substrates are unclear. The deleterious effects of this genotype on brain structure may increase in magnitude into older age. This study aimed to investigate in UK Biobank the association between APOE e4 allele presence vs. absence and brain imaging variables that have been associated with worse cognitive abilities; and whether this association varies by cross-sectional age. We used brain magnetic resonance imaging (MRI) and genetic data from a general-population cohort: the UK Biobank (N = 8395 after exclusions). We adjusted for the covariates of age in years, sex, Townsend social deprivation scores, smoking history and cardiometabolic diseases. There was a statistically significant association between APOE e4 genotype and increased (i.e. worse) white matter (WM) hyperintensity volumes (standardised beta = 0.088, 95% confidence intervals = 0.036 to 0.139, P = 0.001), a marker of poorer cerebrovascular health. There were no associations with left or right hippocampal, total grey matter (GM) or WM volumes, or WM tract integrity indexed by fractional anisotropy (FA) and mean diffusivity (MD). There were no statistically significant interactions with age. Future research in UK Biobank utilising intermediate phenotypes and longitudinal imaging hold significant promise for this area, particularly pertaining to APOE e4’s potential link with cerebrovascular contributions to cognitive aging.

Item Type:Articles
Additional Information:UK Biobank was established by the Wellcome Trust medical charity, Medical Research Council (MRC), Department of Health, Scottish Government and the Northwest Regional Development Agency. It has also had funding from the Welsh Assembly Government and the British Heart Foundation. Cox is supported by grants from the MRC (MR/M013111/1 and MR/R024065/1) and US National Institutes of Health (National Institute on Aging; 1R01AG054628-01A1) and the work was undertaken within the University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology (, part of the cross council Lifelong Health and Wellbeing Initiative (G0700704/84698 and MR/K026992/1). Smith is supported by an MRC Mental Health Data Pathfinder Award (MC_PC_17217). Funding from the Biotechnology and Biological Sciences Research Council (BBSRC), Engineering and Physical Sciences Research Council (EPSRC), Economic and Social Research Council (ESRC) and MRC is gratefully acknowledged.
Glasgow Author(s) Enlighten ID:Smith, Professor Daniel and Cullen, Dr Breda and Mackay, Professor Daniel and Lyall, Dr Laura and Cavanagh, Professor Jonathan and Ward, Dr Joey and Celis, Dr Carlos and Pell, Professor Jill and Sattar, Professor Naveed and Strawbridge, Dr Rona and Lyall, Dr Donald
Authors: Lyall, D. M., Cox, S. R., Lyall, L. M., Celis Morales, C., Cullen, B., Mackay, D. F., Ward, J., Strawbridge, R., McIntosh, A. M., Sattar, N., Smith, D., Cavanagh, J., Deary, I. J., and Pell, J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > Mental Health and Wellbeing
College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > Public Health
Journal Name:Brain Imaging and Behavior
ISSN (Online):1931-7565
Published Online:22 March 2019
Copyright Holders:Copyright © 2019 The Authors
First Published:First published Brain Imaging and Behavior 14(5): 1468-1476
Publisher Policy:Reproduced under a Creative Commons license

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
3029570Mental Health Data PathfinderDaniel SmithMedical Research Council (MRC)MC_PC_17217HW - Mental Health and Wellbeing