Abstract 105: Potential Effect Modifiers In The Relationship Between Late-life Systolic Blood Pressure And Alzheimer’s Neuropathology

Abstract

Mixed evidence exists on the relationship between late-life blood pressure (BP) and Alzheimer’s disease (AD) pathology such as amyloid and tau deposition in the brain, possibly partly due to heterogeneous effects across population subgroups. Utilizing data from the National Alzheimer’s Coordinating Center longitudinal dataset, we investigated to what extent age (<65 yrs, 65-74 yrs, >74 yrs), APOE genotype, stroke history, and baseline cognitive status modified the association between systolic BP (SBP) at baseline and amyloid and tau neuropathology in 3165 older adults (mean [SD] age=74 [9.8] yrs, women 47.4% [1501 of 3165]). Amyloid pathology was assessed by Thal staging, diffuse plaque, neuritic plaque and tau pathology was assessed by Braak staging at brain autopsy. Effect modification was assessed by stratified analyses and interaction analyses in multinomial logistic regression with adjustment for age at first visit, sex, APOE genotype, education years and antihypertensive medications use. We observed that both APOE e4 carriership (interaction p-value = 0.03) and stroke history (interaction p-value = 0.03) statistically modified the association of SBP with amyloid pathology, whereas baseline cognitive status modified the association with both amyloid and tau pathology (interaction p-value <0.001). The SBP-amyloid association appears to be pronounced in older age group (65-74 group: OR=1.19 [CI:1.05-1.35], >74 group: OR=1.12 [CI:1.02-1.23]), APOE e4 carriers (OR=1.17[CI:1.02-1.34]), and those with stroke history (OR=1.69 [CI:1.20-2.38]) and participants with dementia at baseline (OR=1.16 [CI:1.05-1.27]), whereas SBP-tauopathy association was only found in APOE e4 carriers (OR=1.25[CI:1.05-1.48]), participants without stroke history (OR=1.12[CI:1.01-1.24]), and participants with normal cognitive function at baseline (OR=1.67[CI:1.24-2.24]). Our study suggests that the relationship between SBP and amyloid and tau pathology may vary across subgroups based on age, APOE genotype, cerebrovascular burden, and stage of cognitive impairment. The underlying mechanisms warrant further investigation to inform precision blood pressure control for the prevention of dementia.