Aerobic exercise improves hippocampal blood flow for hypertensive Apolipoprotein E4 carriers.

Cerebrovascular dysfunction likely contributes causally to Alzheimer's disease (AD). The strongest genetic risk factor for late-onset AD, (), may act synergistically with vascular risk to cause dementia. Therefore, interventions that improve vascular health, such as exercise, may be particularly beneficial for carriers. We assigned cognitively normal adults (65-87 years) to an aerobic exercise intervention or education only. Arterial spin labeling MRI measured hippocampal blood flow (HBF) before and after the 52-week intervention. We selected participants with hypertension at enrollment (n = 44). For carriers, change in HBF (ΔHBF) was significantly ( = 0.006) higher for participants in the exercise intervention (4.09 mL/100g/min) than the control group (-2.08 mL/100g/min). There was no difference in ΔHBF between the control (-0.32 mL/100g/min) and exercise (-0.54 mL/100g/min) groups for non-carriers (p = 0.918). Additionally, a multiple regression showed an interaction between change in systolic blood pressure (ΔSBP) and carrier status on ΔHBF ( = 0.035), with reductions in SBP increasing HBF for carriers only. Aerobic exercise improved HBF for hypertensive carriers only. Additionally, only carriers exhibited an inverse relationship between ΔSBP and ΔHBF. This suggests exercise interventions, particularly those that lower SBP, may be beneficial for individuals at highest genetic risk of AD.: .