Blood pressure variability and medial temporal atrophy in apolipoprotein epsilon 4 carriers

摘要

Blood pressure variability is an emerging risk factor for dementia but relationships with markers of neurodegeneration and Alzheimer's disease risk are understudied. We investigated blood pressure variability over one year and follow-up medial temporal brain volume change in apolipoprotein epsilon 4 carriers and non-carriers, and in those with and without Alzheimer's disease biomarker abnormality. 1051 Alzheimer's Disease Neuroimaging Initiative participants without history of dementia or stroke underwent 3-4 blood pressure measurements over 12 months and >= 1 MRI thereafter. A subset (n = 252) underwent lumbar puncture to determine Alzheimer's disease cerebral spinal fluid amyloid-beta and phosphorylated tau biomarker abnormality. Blood pressure variability over 12 months was calculated as variability independent of mean. Longitudinal hippocampal and entorhinal cortex volume data were extracted from serial brain MRI scans obtained after the final blood pressure measurement. Apolipoprotein epsilon 4 carrier status was defined as at least one epsilon 4 allele. Bayesian growth modelling revealed a significant interaction of blood pressure variability by epsilon 4 by time on hippocampal (ss: -2.61 [95% credible interval -3.02, -2.12]) and entorhinal cortex (ss: -1.47 [95% credible interval -1.71, -1.17]) volume decline. A similar pattern emerged in subsets with Alzheimer's disease pathophysiology (i.e., abnormal levels of both amyloid-beta and phosphorylated tau). Findings suggest that elevated blood pressure variability is related to medial temporal volume loss specifically in epsilon 4 carriers, and in those with Alzheimer's disease biomarker abnormality. Findings could implicate blood pressure variability in medial temporal neurodegeneration observed in older epsilon 4 carriers and those with prodromal Alzheimer's disease.