Visit-to-Visit Blood Pressure Variability and CSF Alzheimer Disease Biomarkers in Cognitively Unimpaired and Mildly Impaired Older Adults - PubMed (original) (raw)

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

Isabel J Sible et al. Neurology. 2022.

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 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 to 4 blood pressure measurements over a 12-month period and ≥1 lumbar puncture for evaluation of CSF phosphorylated tau, total tau, and β-amyloid 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: Four hundred sixty-six participants (mean 76.7 [SD 7.1] years of age) were included in the study. Elevated blood pressure variability was associated with increased CSF phosphorylated tau (β = 0.81 [95% CI 0.74, 0.97]), increased total tau (β = 0.98 [95% CI 0.71, 1.31]), and decreased β-amyloid levels (β = -1.52 [95% CI -3.55, -0.34]) at follow-up. APOE ε4 carriers with elevated blood pressure variability had the fastest increase in phosphorylated tau levels (β = 9.03 [95% CI 1.67, 16.36]). Blood pressure variability was not significantly related to total tau or β-amyloid levels over time according to APOE ε4 carrier status.

Discussion: Older adults with elevated blood pressure variability exhibit increased CSF phosphorylated tau, increased total tau, and decreased β-amyloid over time, suggesting that blood pressure variability may correlate with alterations in Alzheimer disease biomarkers. Findings warrant further study of the relationship between blood pressure variability and the development of Alzheimer disease. APOE ε4 carrier status moderated relationships between blood pressure variability and CSF phosphorylated tau but not total tau or β-amyloid, consistent with other studies relating hemodynamic factors to tau changes.

PubMed Disclaimer

Figures

Figure 1. BPV and CSF AD Biomarker Level Change in Cognitively Unimpaired or Mildly Impaired Older Adults

Conditional effects of the interaction of blood pressure (BP) variability (BPV) by time on (A) CSF phosphorylated tau (Ptau) levels, (B) CSF total tau levels, and (C) CSF β-amyloid (Aβ) levels in cognitively unimpaired or mildly impaired older adults. Model adjusted for age at CSF sample collection, sex, APOE ε4 carrier status, baseline Mini-Mental State Examination score, years of education, average BP, baseline hypertension, vascular risk, and antihypertensive medication use. AD = Alzheimer disease.

Figure 2. BPV and CSF AD Biomarker Level Change in Cognitively Unimpaired or Mildly Impaired Older Adults Based on APOE ε4 Carrier Status

Conditional effects of the interaction of blood pressure (BP) variability (BPV) by APOE ε4 carrier status by time on CSF phosphorylated tau (Ptau) levels in cognitively unimpaired or mildly impaired older adults. Model adjusted for age at CSF sample collection, sex, APOE ε4 carrier status, baseline Mini-Mental State Examination score, years of education, average BP, baseline hypertension, vascular risk, and antihypertensive medication use. AD = Alzheimer disease.

References

1. Zlokovic BV. Neurovascular pathways to neurodegeneration in Alzheimer's disease and other disorders. Nat Rev Neurosci. 2011;12:723-738. -PMC -PubMed
1. Barnes DE, Yaffe K. The projected effect of risk factor reduction on Alzheimer's disease prevalence. Lancet Neurol. 2011;10:819-828. -PMC -PubMed
1. Yaffe K. Prevention of cognitive impairment with intensive systolic blood pressure control. JAMA. 2019;321(6):548-549. -PubMed
1. Ding J, Davis-Plourde KL, Sedaghat S, et al. Antihypertensive medications and risk for incident dementia and Alzheimer's disease: a meta-analysis of individual participant data from prospective cohort studies. Lancet Neurol. 2020;19:61-70. -PMC -PubMed
1. Wright JT, Wright JT, Williamson JD, et al. A randomized trial of intensive versus standard blood-pressure control. N Engl J Med. 2015;373(22):2103-2116. -PMC -PubMed

Visit-to-Visit Blood Pressure Variability and CSF Alzheimer Disease Biomarkers in Cognitively Unimpaired and Mildly Impaired Older Adults - PubMed (original) (raw)