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

Donald M Lyall, Simon Cox, Laura M Lyall, Carlos A. Celis-morales, Breda Cullen, Daniel F. Mackay, Joey Ward, Rona J. Strawbridge, Andrew McIntosh, Naveed A. Sattar, Daniel J Smith, Jonathan Cavanagh, Ian Deary, Jill P. Pell

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Apolipoprotein (APOE) e4 genotype is an accepted risk factor for accelerated cognitive ageing 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=8,395 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 ageing.
Original languageEnglish
JournalBrain imaging and behavior
Early online date22 Mar 2019
Publication statusE-pub ahead of print - 22 Mar 2019

Keywords / Materials (for Non-textual outputs)

  • aging
  • epidemiology
  • genetic association studies
  • MRI


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