We aimed to explore whether the relationships of blood pressures (BPs) with Alzheimer’s disease (AD) endophenotypes varied by usage of antihypertensive drugs (AHDs).

A total of 765 non-demented older adults (mean age: 74.4 years; female: 43.1%) with a self-reported history of hypertension were followed for 6 years. Multiple linear regression and linear-mixed effect models were used to investigate the interaction effects of five categories of AHDs (angiotensin-converting enzyme inhibitors [ACEI], angiotensin II receptor blockers [ARBs], β-blocker, calcium channel blockers [CCB], diuretic) with BPs (systolic blood pressure [SBP], diastolic blood pressure [DBP], and pulse pressure [PP]) on AD core pathology and neurodegenerative markers.

After Bonferroni correction, significant interaction effects of BPs with AHDs were observed. Elevated SBP or PP in late-life was associated with higher levels of cerebral Aβ burden (diuretic alone/β-blocker × SBP), higher levels of CSF tau proteins (diuretic × SBP/PR ARBs/CCB × SBP), and lower volume of entorhinal region (β-blocker × SBP, diuretic × PP) only among hypertensive patients who received no antihypertensive treatments, while these associations became compromised or null for users of specific AHDs except for ACEI. Compared to taking other classes of AHDs, elevated SBP in late-life was associated with lower cerebral Aβ burden in diuretic users (padjusted = 0.08) and was associated with higher CSF tau proteins in ACEI alone users (padjusted = 0.03). Longitudinal data validated the above-mentioned interaction effects on changes of cerebral Aβ burden (padjusted < 0.05), CSF tau proteins (padjusted < 0.10), and brain atrophy (padjusted < 0.05).

The relationships of late-life BP with AD pathology and neurodegeneration could be modified by antihypertensive treatments and varied by AHD classification. These findings provide preliminary evidence for tailored BP management strategy for preventing AD among late-life hypertensive adults.