Blood pressure and risk of incident Alzheimer's disease dementia by antihypertensive medications and APOE ε4 allele

ObjectiveTo examine the association of blood pressure (BP) with incident Alzheimer's disease (AD) dementia. MethodsThis work is based on a longitudinal, cohort study of 18 years, the Chicago Health and Aging Project (CHAP) performed in 2,137 participants (55% black) with systolic BP measured around 8.1 years before incident AD dementia. ResultsThe association of BP with risk of AD dementia was U-shaped, with the lowest risks of AD dementia near the center of the systolic BP (SBP) and diastolic BP (DBP) distributions, and modestly elevated risk at lower BPs, and greater risk at higher BPs. The degree of U-shape and the range of lowest risk (threshold ranges) varied with antihypertensive medication use and presence of the APOE epsilon 4 allele. The U-shape was most prominent for the subgroup not taking antihypertensive medications and having an APOE epsilon 4 allele. At higher BPs, those having the APOE epsilon 4 allele and not receiving antihypertensive medication were at greater risk of AD dementia than other groups: The risk of incident AD dementia increased by 100% (relative risk [RR]=2.00; 95% confidence interval [CI]=1.70, 2.31) for every 10mm Hg increase in SBP above 140mm Hg. For DBP, the risk of incident of AD dementia increased by 57% (RR=1.57; 95% CI=1.33, 1.86) for every 5mm Hg increase in DBP above 76mm Hg. InterpretationThe BP risk of AD dementia association is U-shaped, with elevated risk at lower and higher BPs. People having the APOE epsilon 4 allele and not receiving antihypertensive medication with higher BPs have notably elevated risk of AD dementia. Ann Neurol 2018;83:935-944