Antemortem visit‐to‐visit blood pressure variability predicts cerebrovascular lesion burden in autopsy‐confirmed Alzheimer’s disease

Abstract

Blood pressure variability is a risk factor for stroke, cognitive impairment and Alzheimer's dementia, but the underlying neuropathological mechanisms remain understudied. Large blood pressure fluctuations may stress arterial walls and promote vascular-endothelial injury, increasing risk for cerebrovascular disease. Several studies link elevated blood pressure variability to MRI-based markers of cerebrovascular lesions, but less is known about relationships with specific cerebrovascular or Alzheimer's pathologies at autopsy. The aim of the current study was to determine whether antemortem blood pressure variability predicts cerebrovascular and Alzheimer's pathology in autopsy-confirmed Alzheimer's disease. 513 older adults from the National Alzheimer's Coordinating Center study underwent repeated annual blood pressure measurement and were confirmed to have Alzheimer's disease at postmortem evaluation. Visit-to-visit blood pressure variability was calculated over a 3-4 year follow-up period. Multiple linear regression examined relationships between blood pressure variability and an index of overall cerebrovascular lesion burden and Braak & Braak stage. Ordinal logistic regression examined relationships with other specific cerebrovascular and Alzheimer's neuropathological features. All analyses covaried for age, sex, years of education, body mass index, Mini Mental State Examination score, years from first blood pressure measurement to death, antihypertensive medication use and average blood pressure. Elevated blood pressure variability predicted increased postmortem cerebrovascular lesion burden (ß = .26 [.11, .42]; p = .001; R2 = .12). Increased blood pressure variability predicted specific cerebrovascular lesion severity, including atherosclerosis in the Circle of Willis (OR = 1.21 [1.02, 1.43]; p = .03) and cerebral arteriolosclerosis (OR = 1.30 [1.06, 1.61]; p = .01). No significant relationships were observed between blood pressure variability and Alzheimer's disease pathological findings, including Braak & Braak stage, neuritic plaques or diffuse plaques. Findings suggest that elevated blood pressure variability is related to postmortem cerebrovascular lesion burden in autopsy-confirmed Alzheimer's disease, independent of average blood pressure and Alzheimer's disease neuropathology. Blood pressure fluctuation may selectively promote atherosclerotic and arteriolosclerotic brain lesions with potential implications for cognitive impairment and dementia.