Abstract
Background and Objectives: Blood pressure variability is an emerging risk factor for cognitive decline and dementia, but mechanisms remain unclear. The current study examined whether visit-to-visit blood pressure variability is related to CSF Alzheimer’s disease biomarker levels over time, and whether associations differed by APOE ϵ4 carrier status.
Methods: In this retrospective analysis of a prospective cohort study, cognitively unimpaired or mildly impaired older adults from the Alzheimer’s Disease Neuroimaging Initiative underwent 3-4 blood pressure measurements over a 12-month period and ≥ 1 lumbar puncture for the evaluation of CSF phosphorylated tau, total tau, and amyloid-beta levels at follow-up (6-108 months later). APOE ϵ4 carriers were defined as having ≥ 1 ϵ4 allele. Visit-to-visit blood pressure variability was determined over 12 months as variability independent of mean. Only CSF samples collected after the final blood pressure measurement were analyzed. Bayesian linear growth modeling investigated the role of blood pressure variability, APOE ϵ4, and the passage of time on CSF biomarker levels after controlling for several variables, including average blood pressure and baseline hypertension.
Results: 466 participants (mean 76.7 (7.1 SD) years of age) were included in the study. Elevated blood pressure variability was associated with increased CSF phosphorylated tau (ß: .81 [95% CI .74, .97]), increased total tau (ß: .98 [95% CI .71, 1.31]), and decreased amyloid-beta levels (ß: -1.52 [95% CI -3.55, -.34]) at follow-up. APOE ϵ4 carriers with elevated blood pressure variability had the fastest increase in phosphorylated tau levels (ß: 9.03 [95% CI 1.67, 16.36]). Blood pressure variability was not significantly related to total tau or amyloid-beta levels over time based on APOE ϵ4 carrier status.
Discussion: Older adults with elevated blood pressure variability exhibit increased CSF phosphorylated tau, increased total tau, and decreased amyloid-beta over time, suggesting blood pressure variability may correlate with alterations in Alzheimer’s disease biomarkers. Findings warrant further study of the relationship between blood pressure variability and the development of Alzheimer’s disease. APOE ϵ4 carrier status moderated relationships between blood pressure variability and CSF phosphorylated tau but total tau or not amyloid-beta, consistent with other studies relating hemodynamic factors to tau changes.
- Received September 13, 2021.
- Accepted in final form February 16, 2022.
- Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
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