Visit-to-visit Blood Pressure Variability and Regional Cerebral Perfusion Decline in Older Adults

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.

Visit-to-Visit Blood Pressure Variability and Longitudinal Tau Accumulation in Older Adults

“…Study limitations include the fact that some aspects of BP collection were not explicitly standardized across sites and may have been collected by individuals who did not have expertise in diagnosing hypertension. BPV was determined from 3 to 4 BP measurements, consistent with other studies of visit-to-visit BPV in ADNI, 33,36 but additional BP measurements may improve measurement of BPV. 69 Antihypertensive treatment initiation, discontinuation, or dosage change over the course of BP measurements were not addressed.…”

“…Baseline clinical evaluation identified participants to be cognitively normal or MCI, as described elsewhere, 33,36 and all participants were confirmed to be without history of dementia or stroke. Briefly, a clinical diagnosis of MCI was given if the following criteria were met: 37 subjective memory complaint; Mini-Mental State Exam scores between 24 and 30 (inclusive); global Clinical Dementia Rating scale score of 0.5; scores on delayed recall of Story A of the Wechsler Memory Scale–Revised Logical Memory II subtest that are below expected performance based on years of education; general presentation that would disqualify for a diagnosis of AD.…”

“…Baseline clinical evaluation identified participants to be cognitively normal or MCI, as described elsewhere, 33,36 and all participants were confirmed to be without history of dementia or stroke. Briefly, a clinical diagnosis of MCI was given if the following criteria were met: 37 Clinical/Pathophysiological Implications?…”

“…Recent interest in BP variability (BPV) over months to years (eg, visit-to-visit BPV) has emerged as a vascular risk factor for cerebrovascular disease and cognitive decline, independent of average BP levels. [22][23][24][25][26][27][28][29][30] Consistent evidence suggests elevated BPV is related both to cerebrovascular disease [25][26][27]31,32 and cerebral perfusion decline, 33 particularly within brain regions vulnerable to early-stage AD. However, it remains unclear whether increased BPV may convey risk for dementia purely through its association with cerebrovascular disease or whether BPV is also linked to AD biomarker abnormality.…”

Visit‐to‐visit office blood pressure variability revisited in SPRINT

“…In the SPRINT, 6 this concept would also apply for the relationship between VVV and prognosis specifically in the hypertensives with higher FRS (Figure 1). The novel contribution of SHATS is its synergistic consideration of VVV and hemodynamic stress in relation to vascular disease, because exaggerated VVV might be reciprocally associated with TODs involving the brain (cerebral small “strain” vessel disease, 19 cerebral hypoperfusion, 20 cognitive dysfunction, 21 and Alzheimer's disease 22–25 ) and heart (coronary artery remodeling, 7,26 left ventricular remodeling, 25 increased NT‐proBNP, 26 and HF 27 ).…”