Rationale and methods for a multicenter clinical trial assessing exercise and intensive vascular risk reduction in preventing dementia (rrAD Study)

Abstract

Alzheimer’s Disease (AD) is an age-related disease with modifiable risk factors such as hypertension, hypercholesterolemia, obesity, and physical inactivity influencing the onset and progression. There is however, no direct evidence that reducing these risk factors prevents or slows AD. The Risk Reduction for Alzheimer’s Disease (rrAD) trial is designed to study the independent and combined effects of intensive pharmacological control of blood pressure and cholesterol and exercise training on neurocognitive function. Six hundred and forty cognitively normal older adults age 60 to 85 years with hypertension and increased risk for dementia will be enrolled. Participants are randomized into one of four intervention group for two years: usual care, Intensive Reduction of Vascular Risk factors (IRVR) with blood pressure and cholesterol reduction, exercise training (EX), and IRVR+EX. Neurocognitive function is measured at baseline, 6, 12, 18, and 24 months; brain MRIs are obtained at baseline and 24 months. We hypothesize that both IRVR and EX will improve global cognitive function, while IRVR+EX will provide a greater benefit than either IRVR or EX alone. We also hypothesize that IRVR and EX will slow brain atrophy, improve brain structural and functional connectivity, and improve brain perfusion. Finally, we will explore the mechanisms by which study interventions impact neurocognition and brain. If rrAD interventions are shown to be safe, practical, and successful, our study will have a significant impact on reducing the risks of AD in older adults.

Antihypertensive agents in Alzheimer’s disease: beyond vascular protection

“…We did not find published clinical studies on ARBs in AD, underlining the gap between a wealth of encouraging preclinical data and the paucity of clinical trials in AD. Few clinical trials are ongoing [67,68], using mostly telmisartan and losartan, with an estimated study completion in 2021.…”

Evaluation of noise regression techniques in resting-state fMRI studies using data of 434 older adults

“…Risk Reduction for Alzheimer’s Disease (rrAD) is a multi-center clinical trial (NCT02913664) designed to assess the effects of aerobic exercise and pharmacological interventions on cognitive function in older hypertensive adults (60–85) who are at a higher risk of developing Alzheimer’s Disease and related dementias (ADRD) ( Szabo-Reed et al, 2019 ). As part of the neuroimaging protocol, resting-state fMRI (rs-fMRI) was obtained at baseline and again after 2 years of intervention.…”

A review of the mechanisms underlying selected comorbidities in Alzheimer’s disease

“…This trial will evaluate the independent and cumulative effects of these pharmacological agents upon blood pressure, cholesterol control, and exercise training on neurocognitive function. The results of this clinical trial may have a significant impact on AD risk reduction [ 95 ].…”