Visit‐to‐visit blood pressure variability and medial temporal perfusion in APOE e4 homozygotes

Abstract

AbstractBackgroundBlood pressure variability (BPV), independent of traditionally studied/targeted average blood pressure levels, is an emerging risk factor for cognitive impairment and Alzheimer’s dementia, possibly through links with cerebrovascular disease. Recent studies suggest vulnerability of the medial temporal lobes to tau accumulation and atrophy among individuals with elevated BPV, especially older APOE e4 carriers. Increased BPV has also been linked with lower cerebral blood flow (CBF) and perfusion decline in medial temporal regions, but it remains unclear how BPV and APOE e4 may interact to influence CBF. The aim of the current study was to determine whether the relationship between BPV and medial temporal lobe CBF varies by APOE e4 dose in older adults without dementia.Method105 older adults without dementia from the Alzheimer’s Disease Neuroimaging Initiative underwent 3‐4 blood pressure measurements between study baseline and 12‐months follow‐up and arterial spin labeling (ASL)‐MRI at 12‐months follow‐up or later (range: 0 – 84 months). Visit‐to‐visit BPV was calculated as variability independent of mean. CBF was determined for medial temporal regions (residualized by precentral [reference region] CBF), including hippocampus, parahippocampal gyrus, and entorhinal cortex. Venipuncture determined APOE e4 allele count (0 alleles: n = 71; 1 allele: n = 28; 2 alleles: n = 6). Multiple linear regression examined the interaction of BPV x APOE e4 dose on medial temporal CBF, controlling for age, sex, race/ethnicity, antihypertensive use, mean blood pressure, and cerebral metabolism (FDG‐PET).ResultElevated BPV was associated with lower CBF in entorhinal cortex (ß = ‐.96 [‐1.62, ‐.31]; p = .005) and parahippocampal gyrus (ß = ‐.63 [‐1.26, ‐.0002]; p = .049) in individuals with 2 APOE e4 alleles, whereas BPV was not significantly associated with CBF in these regions in individuals with 0 or 1 APOE e4 alleles (p’s > = .08). There was no significant interaction of BPV x APOE e4 dose on hippocampal CBF.ConclusionHigher BPV is associated with lower medial temporal CBF in APOE e4/e4 carriers, suggesting BPV may be an understudied vascular risk factor for those at greatest genetic risk for Alzheimer’s disease, with potential therapeutic implications.