Stephen Rao, PhD

"Our understanding is, is that we’re probably not going to be able to get everyone to exercise, but we may be able to understand the mechanisms in which exercise prevents Alzheimer disease. Perhaps that could be used to create some type of pharmacological intervention, for example.”

The recently initiated CYCLE-AD trial (NCT04748861), led by 2 researchers from Cleveland Clinic, will represent the first randomized controlled trial to explore if a long-term exercise intervention program can alter the progression of late-onset Alzheimer disease (AD) in sedentary, high-risk individuals.

One of those principal investigators, Stephen Rao, PhD, previously conducted an 18-month observational study that found AD-related progression, as measured by memory testing and hippocampal volume, was slower in genetically high-risk individuals who exercise regularly. Additionally, the data suggested that beginning a physical activity regimen as early as possible, specifically before substantial hippocampal volume or functional activity loss occurs, can help maximize the effect of the activity.

According to Rao, the results of the study were “interesting” but needed further validation and a more expanded look at the mechanism of why exercise is neuroprotective. Jay Alberts, PhD, co-principal of CYCLE-AD also noted that challenges for the 2 include finding out how much activity makes a difference for altering the progression of AD, as well as devising a widely available program that’s interesting enough for people to consistently engage in during their senior years.

Rao discussed his recently conducted research, some of the biggest takeaways, and how it played a role in the creation of the CYCLE-AD trial.

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The director of the Schey Center for Cognitive Neuroimaging at Cleveland Clinic shared the next steps in building on previous research that links exercise with a reduced Alzheimer disease risk.

Next Steps in Understanding Role of Exercise in Alzheimer Risk: Stephen Rao, PhD

"If we can delay the onset by just 5 years, we can cut the number of people who have Alzheimer’s in half. If we delay it by 10 years, we can basically wipe out the disease. Prevention is sometimes the better way the go than treating someone who already has the disease and then try to reverse the effects.”

Cleveland Clinic was recently awarded a $6.7 million grant to evaluate if high-intensity exercise, using the home-based indoor cycling Peleton bike, can prevent the development of Alzheimer disease (AD). The 5-year study, led by Stephen Rao, PhD, and Jay Alberts, PhD, will assess the effect of this intervention in slowing disease progression in healthy older people at high genetic risk for developing the disease.

If successful, the trial has the potential to provide a scalable, low-cost intervention capable of substantially reducing healthcare costs by modifying the trajectory of the disease. The effects that exercise has on cognition and potentially lowering the risk of AD has been previously observed, but not in this same capacity. A total of 150 healthy, sedentary individuals between ages 65 and 80 years who carry the apolipoprotein E epsilon (APOE4) allele will be enrolled in the study.

Rao, director of the Schey Center for Cogntive Neuroimaging at Cleveland Clinic, and Alberts, The Edward F. and Barbara A. Bell Family Endowed Chair at the Cleveland Clinic Lerner Research Institute, sat down to discuss their study. In this interview, they provide a background of how the study will be conducted, how it differs from other previous exercise-based research projects, and the long-term goals they are looking to complete.

A duo of researchers from Cleveland Clinic outlined their new 5-year study that tests home-based intervention in high-risk individuals for Alzheimer disease.

Stephen Rao, PhD

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Next Steps in Understanding Role of Exercise in Alzheimer Risk: Stephen Rao, PhD

Assessing High-Intensity Exercise to Prevent Alzheimer Disease: Stephen Rao, PhD; Jay Alberts, PhD