Effect Modifiers of the Association of Blood Pressure With Brain Amyloid and Tau Pathology.

Background and objectives: Hypertension is an important modifiable risk factor of Alzheimer disease (AD), but previous studies reported heterogeneous associations of late-life blood pressure (BP) with brain amyloid and tau pathologies. We investigated how the associations of BP with brain amyloid and tau vary by APOE ε4 carriership, age, cerebrovascular burden, and cognitive status.

Methods: We performed analyses among participants with postmortem neuropathology measurements (2005-June 2022) from the National Alzheimer's Coordinating Center. The average systolic BP (SBP) of the first 3 annual visits was the primary exposure, and baseline hypertension status was the secondary exposure. Brain AD pathologies were assessed using Thal and Braak staging. Potential modifiers included APOE ε4 carriership, age, stroke history, and cognitive status. Multinomial logistic regressions with interaction terms were used to test effect modification, adjusting for age, sex, APOE ε4 carriership, education, antihypertensive medication use, and years to death.

Results: Among 2,094 participants (baseline age: 75 ± 9.5 years; 51.4% women), the association of higher SBP with higher amyloid and tau burdens varied by stroke history and cognitive status while the effect modification by age or APOE ε4 carriership was less consistent. More pronounced associations of SBP with higher amyloid and tau burdens were observed in those with dementia (vs without dementia) and those with a history of stroke (vs without stroke) (All p interaction<0.05). The odds ratios (ORs) per 10-mm Hg increase in SBP in the stroke vs nonstroke subgroup were 1.58 (95% CI 1.04-2.41) vs 1.14 (1.03-1.27) for amyloid and 1.54 (1.00-2.36) vs 1.04 (0.96-1.12) for tau. When comparing dementia with cognitively normal subgroups, ORs were 1.39 (1.17-1.64) vs 1.12 (0.96-1.31) for amyloid and 1.24 (1.08-1.42) vs 0.98 (0.85-1.14) for tau. Similar findings were observed for baseline hypertension status.

Discussion: Preexisting cerebrovascular burden and cognitive status might interact with elevated SBP in their association with higher brain amyloid and tau, which could help identify high-risk subgroups for BP management and AD prevention. These heterogeneous association patterns need to be confirmed in longitudinal studies with in vivo AD pathology assessments.