Systolic Blood Pressure Is Associated with Increased Brain Amyloid Load in Mild Cognitively Impaired Participants: Alzheimer's Disease Neuroimaging Initiatives Study

Abstract

Background: Cardiovascular disease (CVD), including elevated blood pressure (BP), is known to promote Alzheimer's disease (AD) risk. Although brain amyloid load is a recognized hallmark of pre-symptomatic AD, its relationship to increased BP is less known. The objective of this study was to examine the relationship of BP to brain estimates of amyloid-β (Aβ) and standard uptake ratio (SUVr). We hypothesized that increased BP is associated with increased SUVr. Methods: Using data from the Alzheimer's Disease Neuroimaging Initiative (ADNI), we stratified BP according to the Seventh Joint National Committee (JNC) on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure Classification (JNC VII). Florbetapir (AV-45) SUVr was derived from the averaged frontal, anterior cingulate, precuneus, and parietal cortex relative to the cerebellum. A linear mixed-effects model enabled the elucidation of amyloid SUVr relationships to BP. The model discounted the effects of demographics, biologics, and diagnosis at baseline within APOE genotype groups. The least squares means procedure was used to estimate the fixed-effect means. All analyses were performed using the Statistical Analysis System (SAS). Results: In non-ϵ4 carrier MCI subjects, escalating JNC categories of BP was associated with increasing mean SUVr using JNC-4 as a reference point (low-normal (JNC1) p = 0.018; normal (JNC-1) p = 0.039; JNC-2 p = 0.018 and JNC-3 p = 0.04). A significantly higher brain SUVr was associated with increasing BP despite adjustment for demographics and biological variables in non-ϵ4 carriers but not in ϵ4-carriers. This observation supports the view that CVD risk may promote increased brain amyloid load, and potentially, amyloid-mediated cognitive decline. Conclusion: Increasing levels of JNC classification of BP is dynamically associated with significant changes in brain amyloid burden in non-ϵ4 carriers but not in ϵ4-carrier MCI subjects. Though not statistically significant, amyloid burden tended to decrease with increasing BP in ϵ4 homozygote, perhaps motivated by increased vascular resistance and the need for higher brain perfusion pressure.