Late-life blood pressure association with cerebrovascular and Alzheimer disease pathology

Abstract

Objective: To examine associations of average and change in late-life blood pressure (BP) with cerebrovascular and Alzheimer disease (AD) neuropathology in a large group of decedents followed longitudinally in vivo.

Methods: This clinical-pathologic study was derived from prospective, community-based cohort studies of aging with similar design and data collection. Measurements of systolic BP (SBP) and diastolic BP (DBP) were obtained annually (mean follow-up 8 years, SD = 4.8). Postmortem neuropathologic evaluations documented diseases of aging. Using regression analyses, we examined associations of average and decline in late-life SBP, and separately in DBP, with neuropathology.

Results: In 1,288 persons (mean age at death = 88.6 years; 65% women), the mean standardized person-specific SBP across the study was 134 (SD = 13) and DBP was 71 (SD = 8) mm Hg. The odds of brain infarcts were increased for participants with a higher mean SBP. Specifically, a person with a 1 SD SBP above the mean (147 vs 134 mm Hg) would have a 46% increased odds of having one or more infarcts, and an increased odds of gross infarct (46%) and microinfarct (36%). Furthermore, a more rapidly declining SBP slope over time increased the odds of one or more infarcts. Mean DBP, not slope, was related to brain infarcts. AD pathology analyses showed an association of a higher mean SBP with higher number of tangles (p = 0.038) but not plaques or other pathology (all p > 0.06). Changes in BP were not significantly related to AD pathology.

Conclusions: Higher average late-life SBP and DBP, and independently a faster decline in SBP, are associated with increasing number of brain infarcts, including gross and microinfarcts. We found some evidence for a relation of SBP with AD, specifically tangles. Both average and decline in BP are related to brain disease.

Figure 1. Relation of mean and slope of blood pressure with brain infarcts

Horizontal dashed line represents an odds ratio of 1. (A) Associations between the mean and declining slope of systolic blood pressure with each of the infarct outcomes (categorized as one, and more than one, compared to the reference of none), including any infarcts, gross infarcts and microinfarcts, and cortical and subcortical infarcts. (B) Associations for diastolic blood pressure with the same infarct outcomes.

Figure 2. Relation of mean and slope of blood pressure with brain infarcts, according to age

(A) SBP. (B) DBP. The estimated odds of any infarct, and respective 95% confidence interval, for an increase of 1 SD above the mean SBP (or DBP), or 1-unit-faster decline in the slope of SBP (or DBP), on a participant with a mean age of 89 years (center), a participant 1 SD younger than the mean age or 82 years old (left portion of figure), and a participant 1 SD older than the mean age or 95 years old (right portion of figure). DBP = diastolic blood pressure; SBP = systolic blood pressure.