Angiotensin II Blood Levels Are Associated with Smaller Hippocampal and Cortical Volumes in Cognitively Normal Older Adults

Background: There is emerging evidence about possible involvement of the renin-Angiotensin system (RAS) in the pathogenesis of Alzheimer's disease (AD) and decline of cognitive function. However, little is known about associations with brain biomarkers. Objective: Our study aimed to examine associations between blood ACE-1 and ANG II levels and brain MRI based volumes in non-demented participants, and whether these associations were mediated by blood pressure. Methods: This cross-sectional study was conducted in 34 older participants from the Baltimore Experience Corps Trial (BECT) Brain Health Sub-study (BHS). Blood ANGII and ACE-1 levels were measured by ELISA and brain MRI volumes were generated using FreeSurfer 6.0. Multiple linear regression analysis, adjusting for intracranial volume and confounders, was used to determine associations between log transformed ANGII and ACE-1 levels and MRI volumes (mm³). Results: Participants were predominantly female (76%), African-American (94%), with mean age of 66.9 and education of 14.4 years. In the fully adjusted model we observed significant inverse associations between log ANGII levels and total grey matter (β=Angiotensin II associated with smaller hippocampus14,935.50, ±7,444.83, p=0.05), total hippocampus (β=-129.97, ±105.27, p=0.03), rostral middle frontal (β=-1580.40, ±584.74, p=0.02), and supramarginal parietal (β=-978.90, ±365.54, p=0.02) volumes. There were no associations between ANGII levels and total white matter or entorhinal cortex volumes, or ACE-1 levels and any brain volumes. Conclusion: We observed that increased blood ANGII levels were associated with lower total grey matter, hippocampal, rostral middle frontal, and supramarginal parietal volumes, which are associated with cognitive domains that decline in preclinical AD.