Visit-to-Visit Blood Pressure Variability and CSF Alzheimer Disease Biomarkers in Cognitively Unimpaired and Mildly Impaired Older Adults

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.

Blood pressure variability and plasma Alzheimer’s disease biomarkers in older adults

“…Findings suggest elevated BPV over a period of a few minutes is associated with plasma AD biomarker levels in a sample of community-dwelling older adults, independent of average BP levels. Results are consistent with growing evidence that BPV may be a useful marker of vascular dysfunction related to AD [5][6][7][8][9][10]15,[19][20][21][24][25][26][27][28] . Findings add to previous studies on BPV using CSF 21 and PET 20 AD biomarkers.…”

“…Emerging evidence suggests elevated BPV over the longer term (e.g., over months to years or "visit-to-visit" BPV) and shorter term (e.g., over minutes, days) is associated with cognitive impairment and decline 8 , incidence and progression of dementia, including AD and vascular dementia 7,[9][10][11][12] , cerebrovascular disease [13][14][15] , stroke 16,17 , and AD pathology 18 , independent of average BP levels 8 . Further evidence indicates these relationships may be especially pronounced in individuals at increased genetic risk for AD through the apolipoprotein (APOE) e4 allele [19][20][21] .…”

“…There are several methods available to measure these hallmark AD biomarkers: cerebrospinal fluid (CSF), positron emission tomography (PET), post-mortem evaluation, and most recently, plasma from blood samples. Growing evidence suggests elevated BPV is associated with CSF 21 , PET 20 , and postmortem markers 15,18 of AD pathology. However, relationships with the newer plasma markers are unknown and could represent a less invasive and lower cost method to characterize AD biomarkers.…”

“…However, relationships with the newer plasma markers are unknown and could represent a less invasive and lower cost method to characterize AD biomarkers. Additionally, the majority of studies on BPV and markers of AD have used visit-to-visit measures of BPV 15,18,20,21 , and relationships with continuous, acute BPV are understudied. The…”

Thyroid-stimulating hormone and the risk of Alzheimer's disease: an ADNI cohort study

“…Assessment of covariates APOE allele status was tested using DNA extracted from peripheral blood cells by quantitative polymerase chain reaction assays (TaqMan; Qiagen) [15]. Sitting blood pressure was measured in the same arm using the same calibrated mercury sphygmomanometer and blood pressure cuff with the participants keeping calm at baseline [17]. History of diabetes or hyperlipidemia was de ned by the medical recording at baseline.…”