National Institutes of Health Awards Cleveland Clinic $6.7 Million Grant to Evaluate Impact of High-Intensity Exercise in Preventing Alzheimer’s Disease

New five-year study tests home-based intervention in high-risk individuals

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The National Institutes of Health has awarded Cleveland Clinic a $6.7 million grant to evaluate if high-intensity exercise can prevent development of Alzheimer’s disease. The five-year study will assess the effect of home-based indoor cycling in slowing disease progression in healthy older people at high genetic risk for developing the disease.

This represents the first randomized control trial to explore if a long-term exercise intervention program can alter progression of late-onset Alzheimer’s disease in sedentary, high-risk individuals. 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 study, named CYCLE-AD (Cycling to Cease or Limit the Effects of Alzheimer’s Disease), is led by co-principal investigators Stephen Rao, Ph.D., of the Cleveland Clinic Lou Ruvo Center for Brain Health – Cleveland, and Jay Alberts, Ph.D., of the Cleveland Clinic Lerner Research Institute’s Department of Biomedical Engineering.

“Slowing progression can make a significant difference in the quality of life of patients and their families,” Rao said. “As Alzheimer’s disease predominately affects the elderly, postponing symptoms for five years would cut the national burden of disease in half, and delaying onset for 10 years would nearly eliminate it.”

The study aims to enroll 150 healthy, sedentary individuals between ages 65 and 80 years who are carriers of the apolipoprotein E epsilon 4 (APOE ɛ4) allele, the most important known genetic risk factor for late-onset Alzheimer’s disease. Study participants will be randomized to either the home-based internet-connected cycling program or unmonitored usual activity. Individuals in the exercise group will undergo high-intensity interval training three times a week for 18 months using the Peloton® home cycling system.

Subjects will be assessed at study entry and at 18 months with comprehensive cognitive testing and imaging. Of particular interest is the hippocampus, a brain region critical to healthy episodic memory function and one of the first regions to show changes associated with Alzheimer’s disease.

Alberts and Rao are inventors of technology used in this study that Cleveland Clinic licensed to Qr8 Health Inc. Cleveland Clinic, Alberts and Rao have equity interests in and rights to royalties from Qr8 and serve as consultants to the company.

Prior to this grant, Rao’s research team conducted an 18-month observational study that found that Alzheimer’s disease-related progression, as measured by memory testing and hippocampal volume, can be slowed in genetically high-risk individuals who exercise regularly.

Alberts is also leading a study investigating the effects of a cycling program on patients with Parkinson’s disease. Earlier findings from his group indicated that the intervention leads to significant motor and cognitive benefits.

“Exercise appears to have a powerful effect on cognition,” said Alberts, who is also vice chair of innovation in Cleveland Clinic’s Neurological Institute. “Our challenges are to find out how much activity makes a difference for altering the progression of Alzheimer’s disease and to devise a widely available program that’s interesting enough for people to consistently engage in during their senior years.”

The home cycling system has interactive capabilities and the ability to track performance gains. It also measures program compliance and exercise parameter data (mean resistance, cadence, heart rate and total output), which can be collected and tracked remotely by the investigators.

CYCLE-AD is further distinguished by two other aspects of its study design:

  • Potential advantages of high-intensity interval training. Frequent modulation of exercise intensity is believed to combat boredom and increase exercise efficiency. Some evidence suggests it also leads to better cognitive improvement compared with a continuous exercise level.
  • Scalability to a large population. The program will be applicable to any indoor cycle, as cycling courses can be streamed online. “Once we know the appropriate level of exercise to make a difference, a similar home exercise program can be rapidly recommended to a large population,” said Alberts. “A low-cost, effective intervention that does not involve pharmaceuticals would be most welcome to stave off Alzheimer’s disease in high-risk individuals.”

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Cleveland Clinic is a nonprofit multispecialty academic medical center that integrates clinical and hospital care with research and education. Located in Cleveland, Ohio, it was founded in 1921 by four renowned physicians with a vision of providing outstanding patient care based upon the principles of cooperation, compassion and innovation. Cleveland Clinic has pioneered many medical breakthroughs, including coronary artery bypass surgery and the first face transplant in the United States. U.S. News & World Report consistently names Cleveland Clinic as one of the nation’s best hospitals in its annual “America’s Best Hospitals” survey. Among Cleveland Clinic’s 72,500 employees worldwide are more than 5,050 salaried physicians and researchers, and 17,800 registered nurses and advanced practice providers, representing 140 medical specialties and subspecialties. Cleveland Clinic is a 6,500-bed health system that includes a 173-acre main campus near downtown Cleveland, 21 hospitals, more than 220 outpatient facilities, including locations in northeast Ohio; southeast Florida; Las Vegas, Nevada; Toronto, Canada; Abu Dhabi, UAE; and London, England. In 2021, there were 10.2 million total outpatient visits, 304,000 hospital admissions and observations, and 259,000 surgical cases throughout Cleveland Clinic’s health system. Patients came for treatment from every state and 185 countries. Visit us at Follow us at News and resources available at

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