Abstract
BACKGROUND AND OBJECTIVES
Blood pressure (BP) fluctuates across the 24-hour period. High 24-hour BP variability (BPV) is associated with cardiovascular disease risk, yet its relevance for brain health is unclear. We aimed to examine associations between 24-hour BPV, cognition, and multimodal MRI markers of brain health, and whether these were modified by APOE ε4 status.
METHODS
In a cross-sectional study, dementia-free participants aged 55-80, from the community-based Brain and Cognitive Health (BACH) study in Melbourne, Australia, completed 24-hour ambulatory BP monitoring (ABPM) and hospital-based assessments: office BP, blood collection, neuropsychological testing, and brain MRI. ABPM variables included mean BP and coefficient of variation for 24-hour, awake, and asleep periods. Composites for global cognition and executive function were calculated. MRI markers included white matter hyperintensities (WMHs), brain volumetrics, cerebral blood flow, white matter free water, diffusion along the perivascular space, and blood-brain barrier water exchange rate. The primary outcomes were global cognition and WMH. We sought to partially replicate associations between ABPM and cognition in the HYpertension and gut PERmeability (HYPER) study, where cognition was assessed with the digital NIH Toolbox. Linear regressions were adjusted for demographic and vascular risk factors, with coefficients representing SD change in outcome per SD increase in exposure.
RESULTS
In the BACH study (mean age = 67 years; 51% female; n = 225), higher 24-hour and awake BPV were associated with poorer global cognition (24-hour BPV: β = -0.152, 95% CI 0.278 to -0.027; awake BPV: -0.158, 95% CI -0.285 to -0.031) and executive function (24-hour BPV: β = -0.174, 95% CI-0.299 to -0.049; awake BPV: β = -0.168, 95% CI -0.294 to -0.042). BPV negatively associated with BBB k w (β = -0.180, 95% CI-0.314 to -0.045, n = 213). Mean 24-hour BP, positively associated with WMH burden (β = 0.182, 95% CI 0.047-0.316, n = 217). The 24-hour BPV positively associated with WMH volume among APOE ε4 carriers only. In HYPER (27-73 years, median age = 63 years; 50% female; n = 76), asleep BPV was negatively associated with fluid cognition (β = -0.211, 95% CI -0.382 to -0.040).
DISCUSSION
Higher BPV was associated with poorer global cognition and executive functioning, and compromised blood-brain barrier integrity, with additional associations evident only among APOE ε4 carriers. Elevated BPV may be a risk factor for accelerated brain aging, particularly in APOE ε4 carriers.