Association between APOE e4 and white matter hyperintensity volume, but not total brain volume or white matter integrity
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ORIGINAL RESEARCH
Association between APOE e4 and white matter hyperintensity volume, but not total brain volume or white matter integrity Donald M. Lyall 1 & Simon R. Cox 2 & Laura M. Lyall 1 & Carlos Celis-Morales 3 & Breda Cullen 1 & Daniel F. Mackay 1 & Joey Ward 1 & Rona J. Strawbridge 1,4 & Andrew M. McIntosh 2 & Naveed Sattar 3 & Daniel J. Smith 1 & Jonathan Cavanagh 1 & Ian J. Deary 2 & Jill P. Pell 1
# The Author(s) 2019
Abstract 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. Keywords Aging . APOE . Epidemiology . Genetic association studies . MRI
Introduction
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11682-019-00069-9) contains supplementary material, which is available to authorized users. * Donald M. Lyall [email protected] * Simon R. Cox [email protected] 1
Institute of Health & Wellbeing, University of Glasgow, 1 Lilybank Gardens, G12 8RZ, Glasgow, Scotland, UK
2
Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Scotland, UK
3
Institute of Cardiovascular and Medical Sciences, University of Glasgow, Scotland, UK
4
Department of Medicine Solna, Karolinska Institute, Stockholm, Sweden
Variation at the APOE genetic locus is an established risk factor for Alzheimer’s disease (AD) (Lutz et al. 2010), and cognitive decline in domains of memory, information processing speed and overall cognitive function (‘g’) (Wisdom et al. 2011). The e4 allele, which typically has a frequency of around 15% in Caucasian/European populations (Eisenberg et
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