Does association between APOE e4 genotype and brain structure increase with older age in UK Biobank? (N = 1,217)

The apolipoprotein e (APOE) e4 genotype is a known risk factor for cognitive decline and dementia, though the differences in brain anatomy which underpin this are unclear. The deleterious effects of this genotype on brain... [ view full abstract ]

The apolipoprotein e (APOE) e4 genotype is a known risk factor for cognitive decline and dementia, though the differences in brain anatomy which underpin this are unclear. The deleterious effects of this genotype on brain structure may increase in magnitude with increasing age. Structural magnetic resonance imaging of the brain, and genetic data, both from the general-population UK Biobank cohort (N=1,217) were used to test for association between APOE e4 allele presence (vs. absence) and brain structural imaging phenotypes, and to test whether there was significant interaction with cross-sectional age (at time of imaging). There was evidence of significant interaction between APOE e4 allele presence and increasing age on reduced white matter tract integrity, using tract fractional anisotropy as a proxy; where increased age was associated with less healthy white matter, and possessing an e4 allele exaggerated that association. These findings survived adjustments for age and sex, Townsend social deprivation scores, and cardiometabolic diseases, however did not survive false discovery rate correction. There were no interactions between e4 genotype and increasing age on: hippocampal volumes, total grey matter, or total white matter volume. Associations between APOE genotype and white matter integrity may be partly dependent on age at assessment, where there may be a modestly greater effect of e4 allele presence (vs. e4 absence) in older people. This may explain equivocal findings across different participant samples.