APOE genotype and blood pressure influence global and regional cerebral blood flow in older adults post‐high lipid feeding

Abstract

AbstractBackgroundBoth hypertension and the E4 allele of the APOE gene are known risk factors for Alzheimer’s disease (AD). We investigated the influence of these factors on global cerebral blood flow (CBF) and four prespecified areas (angular gyrus, hippocampus, posterior cingulate, temporal lobe) using arterial spin labeling (ASL) MRI both in fasting state and after ingestion of a high fat drink.MethodAfter fasting, 29 older adults (age 66.8 ± 4.1) underwent baseline and 1, 2, 3‐hour ASL MRI after ingestion of 1/2 cup heavy cream with comparable total and saturated fat to a high fat breakfast. We used pCASL MRI with background suppression to measure CBF in ml/100g/min. Imaging parameters were in accordance with the recommendations of ISMRM: label duration = 1.8 s, postlabeling delay = 2 s, labeling offset = 25‐30 mm, slices = 20, resolution = 3.5×3.5×5 mm3, SENSE‐factor = 2, TR/TE= 5000/18 ms. Finally, we acquired a reference scan (M0, 1 minute) identical to above scan but with TR = 10,000 ms and no labeling or background suppression. Statistical analyses included repeated measures ANOVA as well as cross‐sectional multiple regressions with robust estimators adjusting for age, E4 status, BMI, heart rate, systolic and diastolic blood pressure (DBP).ResultGlobal CBF decreased at 1‐, 2‐, and 3‐hours post‐lipid drink, compared to time 0 (RM ANOVA F=5.57, p=0.002). These findings were recapitulated in the posterior cingulate (F=3, p=0.036) and hippocampus (F=3.3, p= 0.025); this difference was not seen in the temporal lobe or angular gyrus. E4 genotype was significantly associated with lower global CBF at hour 2 and in three areas examined (Table). Additionally, higher DBP was associated with lower CBF globally and in all four areas (Table).ConclusionCBF decreased in response to lipid ingestion, both globally and in regions known to be important in AD, and this was exaggerated in individuals with the E4+ genotype and with elevated DBP. Further examination of E4 and blood pressure interactions are ongoing, as well as how these findings relate to cognitive performance.