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

Amanda N. Szabo-Reed, Eric Vidoni, Ellen F. Binder, Jeffrey Burns, C. Munro Cullum, William P. Gahan, Aditi Gupta, Linda S. Hynan, Diana R. Kerwin, Heidi Rossetti, Ann M. Stowe, Wanpen Vongpatanasin, David C. Zhu, Rong Zhang, Jeffrey N. Keller

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


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.

Original languageEnglish
Pages (from-to)44-54
Number of pages11
JournalContemporary Clinical Trials
StatePublished - Apr 2019

Bibliographical note

Funding Information:
This study was supported by the National Institutes of Health grant R01-AG49749 and KL2TR002367 .

Publisher Copyright:
© 2019


  • Alzheimer's disease
  • Brain structure
  • Cognition
  • Exercise
  • Reduction of vascular risk factors

ASJC Scopus subject areas

  • Pharmacology (medical)


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