Abstract
Hypertension in midlife is associated with increased dementia risk, yet its relationship with early pathological changes of Alzheimer’s disease and related dementias (ADRD) remains unclear. Unlike office blood pressure (BP), 24-h ambulatory BP (ABPM) may better reflect cardiovascular risk, but associations between 24-h BP measures with ADRD biomarkers are unknown. This cross-sectional study examined associations between BP and cerebrospinal fluid biomarkers of ADRD in mid-to-late life. Dementia-free participants ( n = 77; mean age = 67 [SD, 6]; 39% women) from the community-based Brain and Cognitive Health (BACH) cohort underwent office and 24-h ABPM assessments to calculate mean BP, nocturnal dipping, blood pressure variability (BPV, coefficient of variation) across 24-h, awake and asleep periods. Participants also completed a lumbar puncture to assess ADRD biomarkers: Aβ42/Aβ40 ratio, phosphorylated tau at threonine 217 (pTau217), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL). Linear regression models examined associations between BP and ADRD biomarkers, adjusting for age, sex, BMI, smoking, anti-hypertensive medication use, and APOE ε4 status. Higher 24-h and awake mean BP were associated with higher GFAP (24-h: per 1-SD unit increase, β = 1606.6 pg/mL, p = .03; awake: β = 1668.pg/mL, p = .03) and NfL (24-h: β = 172.3 pg/mL, p = .03; awake: β = 162.3 pg/mL, p = .04) levels. Elevated asleep BPV was associated with higher Aβ42/Aβ40 ratio ( β = 0.01, p = .01). No, other clear associations were identified for the other BP metrics ( p > .05 for all). Findings indicate that elevated BP is associated with neuronal injury and astrocytic reactivity, suggesting possible pathways through which BP may relate to neurodegenerative processes, independent of overt amyloid or tau.