Isabel J Sible1, Daniel A Nation2,3. 1. Department of Psychology, University of Southern California, Los Angeles (I.J.S.). 2. Institute for Memory Impairments and Neurological Disorders (D.A.N.), University of California Irvine. 3. Department of Psychological Science (D.A.N.), University of California Irvine.
Abstract
BACKGROUND: Elevated blood pressure variability (BPV) is predictive of dementia, independent of average blood pressure levels, but neuropathological mechanisms remain unclear. We examined whether BPV in older adults is related to tau accumulation in brain regions vulnerable to Alzheimer disease and whether relationships are modified by apoϵ4 carrier status. METHODS: Two hundred eighty-six Alzheimer's Disease Neuroimaging Initiative participants without history of dementia underwent 3 to 4 blood pressure measurements over 12 months and ≥1 tau positron emission tomography thereafter. BPV was calculated as variability independent of mean. Each scan determined tau burden (standardized uptake value ratio) for a temporal meta-region of interest, including burden from entorhinal cortex, amygdala, parahippocampus, fusiform, inferior temporal, and middle temporal. Bayesian linear growth modeling examined the role of BPV, apolipoprotein ϵ4 carrier status, and time on regional tau accumulation after controlling for several variables, including baseline hypertension. RESULTS: Elevated BPV was related to tau accumulation at follow-up in a temporal meta-region, independent of average blood pressure levels (ß, 0.89 [95% credible interval, 0.86-0.92]) and especially in entorhinal cortex (ß, 2.57 [95% credible interval, 2.15-2.99]). Apoϵ4 carriers with elevated BPV had the fastest tau accumulation at follow-up (ß, 1.73 [95% credible interval, 0.47-3.03]). CONCLUSIONS: BPV is related to tau accumulation in brain regions vulnerable to Alzheimer disease, independent of average blood pressure. APOEϵ4 modified this relationship. Bidirectionality of findings is possible. BPV may represent a marker of vascular dysfunction related to early-stage tau pathology contributing to Alzheimer disease.
BACKGROUND: Elevated blood pressure variability (BPV) is predictive of dementia, independent of average blood pressure levels, but neuropathological mechanisms remain unclear. We examined whether BPV in older adults is related to tau accumulation in brain regions vulnerable to Alzheimer disease and whether relationships are modified by apoϵ4 carrier status. METHODS: Two hundred eighty-six Alzheimer's Disease Neuroimaging Initiative participants without history of dementia underwent 3 to 4 blood pressure measurements over 12 months and ≥1 tau positron emission tomography thereafter. BPV was calculated as variability independent of mean. Each scan determined tau burden (standardized uptake value ratio) for a temporal meta-region of interest, including burden from entorhinal cortex, amygdala, parahippocampus, fusiform, inferior temporal, and middle temporal. Bayesian linear growth modeling examined the role of BPV, apolipoprotein ϵ4 carrier status, and time on regional tau accumulation after controlling for several variables, including baseline hypertension. RESULTS: Elevated BPV was related to tau accumulation at follow-up in a temporal meta-region, independent of average blood pressure levels (ß, 0.89 [95% credible interval, 0.86-0.92]) and especially in entorhinal cortex (ß, 2.57 [95% credible interval, 2.15-2.99]). Apoϵ4 carriers with elevated BPV had the fastest tau accumulation at follow-up (ß, 1.73 [95% credible interval, 0.47-3.03]). CONCLUSIONS: BPV is related to tau accumulation in brain regions vulnerable to Alzheimer disease, independent of average blood pressure. APOEϵ4 modified this relationship. Bidirectionality of findings is possible. BPV may represent a marker of vascular dysfunction related to early-stage tau pathology contributing to Alzheimer disease.
Entities:
Keywords:
Alzheimer disease; aging; blood pressure; dementia; tau protein
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