Neurovascular Changes During Midlife Hypertension and Alzheimer’s Disease

The goal of this project is to study the structural and functional neurovascular changes during the progression of Alzheimer’s disease and how hypertension alters these dynamics throughout midlife.

Midlife hypertension is an increasingly important risk factor for Alzheimer’s disease and related dementias. We will investigate how hypertension affects the progression of Alzheimer’s disease from a blood flow, cognitive, and pathological perspective through midlife. We will test if anti-hypertensive medication can slow the progression of Alzheimer’s disease and improve cognitive function.

This work is innovative because it will employ multiscale approaches to investigate the longitudinal impact of angiotensin II (ATII)-induced hypertension during midlife on structural and functional changes to the blood-brain barrier (BBB), cerebral blood flow, and Alzheimer’s disease (AD) progression. Furthermore, BBB-crossing angiotensin receptor blockers (ARBs), such as telmisartan, are shown to slow cognitive decline. This research will study the effects of telmisartan, which is currently in phase 1 and 2 clinical trials for AD, on neurovascular alterations during AD.

Upon completion of this study, the general public can benefit from results that determine if commonly prescribed blood-brain barrier (BBB) crossing angiotensin receptor blockers (ARBs) improve cognition, slow Alzheimer’s disease pathogenesis, and preserve neurovascular changes during midlife hypertension. From a research perspective, more clinically translatable studies from midlife into late-life can be designed to help determine therapeutic time windows that rescue cognitive decline and ameliorate vascular and Alzheimer’s disease pathological alterations.