Abstract
Background: Blood pressure variability has been linked to dementia risk, independent of average blood pressure levels. It has been hypothesized that dysregulated blood pressure may challenge autoregulatory mechanisms and risk cerebral hypoperfusion. The current study examined whether visit-to-visit blood pressure variability over one year is related to concurrent regional cerebral perfusion decline over the same period in older adults.Methods: Sixty-three older adults without history of dementia or stroke underwent repeated blood pressure measurement and arterial spin-labelling magnetic resonance imaging over the same one year period. Fluorodeoxyglucose-positron emission tomography determined cerebral metabolism at baseline. A subset underwent lumbar puncture to detect cerebral spinal fluid amyloid-beta (n=18) and phosphorylated tau (n=21) abnormalities. Visit-to-visit blood pressure variability and change in regional cerebral perfusion were both calculated over 12 months. Multiple linear regression examined relationships between blood pressure variability and change in regional perfusion after controlling for age, sex, average blood pressure, antihypertensive medication use and cerebral metabolism. Exploratory analyses were repeated in participant subsets with abnormal cerebral spinal fluid amyloid-beta and phosphorylated tau.Results: Elevated blood pressure variability was related to perfusion decline in medial orbitofrontal cortex (ß = -.36; p = .008), hippocampus (ß = -.37; p = .005), entorhinal cortex (ß = -.48; p < .001), precuneus (ß = -.31; p = .02), inferior parietal cortex (ß = -.44; p < .001) and inferior temporal cortex (ß = -.46; p < .001). Elevated blood pressure variability was similarly related to perfusion decline in some regions among participant subsets showing abnormal cerebral spinal fluid amyloid-beta and phosphorylated tau.Conclusions: Older adults with elevated visit-to-visit blood pressure variability exhibit concurrent regional cerebral perfusion decline in areas vulnerable to cerebrovascular dysfunction in Alzheimer’s disease, independent of cerebral hypometabolism. Similar findings are observed in exploratory analyses of older adults with Alzheimer’s disease biomarker abnormalities. The study is limited by the small sample size, particularly the subset of participants with Alzheimer’s disease biomarker abnormalities. Findings may have therapeutic implications, given that certain antihypertensive medications have differential effects on variability of blood pressure independent of average levels.
Indomethacin markedly blunts cerebral perfusion and reactivity, with little cognitive consequence in healthy young and older adults
