This finding aligned with previous research showing the influence of the e4 allele on smaller hippocampus volumes.34 A positive relationship between APOE e4 and WMH was also found, being consistent with previous research in an earlier sub-sample of UK Biobank imaging cohort (N= 8395).14 In a systematic analysis of APOE e4 genotype versus blood biomarkers in UK Biobank, Ferguson et al. 35 reported a predominantly cardiometabolic influence of APOE e4 genotype on UK Biobank participants without dementia (N=∼502k), which aligns with this WMH observation. This evidence concerns the gene APOE and dementia.