APOE and hypertensive disorder: Finally, we examined the interaction between modifiable risk factors and APOE4 on midlife SVD—considering that the combination of modifiable risk factors (e.g. hypertension) and APOE4 relates to increased risk of SVD in elderly participants [16, 17], we hypothesised that the effect of modifiable risk on SVD burden would be similarly amplified in middle-aged APOE4 carriers.