High-Intensity Exercise for Alzheimer's Disease

(CYCLE-AD Trial)

Overseen By Andrea Rohr, BS

Age: 65+

Sex: Any

Trial Phase: Academic

Sponsor: The Cleveland Clinic

Must not be taking: Alzheimer's medications

Disqualifiers: Neurologic disease, Uncontrolled illness, Schizophrenia, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 18

Duration: 18 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether high-intensity indoor cycling (IC) can slow or delay brain changes associated with Alzheimer's disease in individuals with the APOE ε4 genotype. The researchers aim to determine if this exercise can transform Alzheimer's treatment, enhance life quality, and reduce healthcare costs. Participants will either engage in regular high-intensity cycling at home or maintain their usual physical activity. Those who have exercised less than three times a week at a moderate to vigorous level and have no cognitive impairments might be suitable candidates. Participants must have a stationary bike at home and internet access to track their cycling activity. As an unphased trial, this study offers participants the opportunity to contribute to groundbreaking research that could redefine Alzheimer's treatment.

Will I have to stop taking my current medications?

The trial requires that participants do not currently use Alzheimer's disease medications, including cholinesterase inhibitors and memantine. Other medications are not specifically mentioned, so it's best to discuss your current medications with the study doctor.

What prior data suggests that high-intensity exercise is safe for Alzheimer's patients?

Research has shown that high-intensity exercise, such as indoor cycling, is usually well-tolerated. Studies have found that regular cycling is linked to a 19% lower risk of all types of dementia and a 22% lower risk of Alzheimer's disease, suggesting that biking might be both safe and beneficial.

One previous study demonstrated that a six-month aerobic exercise program greatly improved overall brain function in participants. This finding indicates that exercise can be a safe way to support brain health, even for those at risk for Alzheimer's.

The CYCLE-AD trial involves high-intensity indoor cycling, which requires exercising at 60-90% of maximum heart rate. While intense, such exercise is generally considered safe for most people. However, it is always important to pay attention to one's body and consult a healthcare provider before starting a new exercise routine. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Most treatments for Alzheimer's disease focus on medications that aim to slow cognitive decline or manage symptoms. However, indoor cycling is unique because it leverages high-intensity interval training (HIIT) to potentially improve cognitive function through physical exercise. This approach is exciting because it integrates a commercially available system like Peloton® to make high-intensity exercise more accessible, offering a non-pharmacological option that could complement existing therapies. Researchers are curious about whether this method can enhance brain health by increasing blood flow and stimulating neuroplasticity in ways that medications alone may not achieve.

What evidence suggests that high-intensity exercise is effective for Alzheimer's?

Studies have shown that high-intensity exercise can improve brain health. Research indicates that working out enhances memory, focus, sleep, and overall brain function. In this trial, participants will engage in high-intensity interval training through indoor cycling, which might help slow the progression of Alzheimer's disease. Early findings suggest that cycling regularly for 18 months could delay Alzheimer's symptoms in people with a genetic risk. Staying active and cycling may help keep the mind sharp for longer. ^{1 3 5 6 7}

Who Is on the Research Team?

Jay L Alberts, PhD

Principal Investigator

The Cleveland Clinic

Stephen Rao, PhD

Principal Investigator

The Cleveland Clinic

Are You a Good Fit for This Trial?

The CYCLE-AD trial is for healthy elders aged 65-80 with no cognitive impairment, carrying the APOE ε4 gene. Participants should be inactive (exercising less than three times a week), fluent in English, able to use a Peloton bike safely, and have in-home Wi-Fi. They must not have severe medical conditions or plan extensive travel during the study.

Inclusion Criteria

You need Wi-Fi at home to use the Peloton exercise system.

I do not plan to travel for more than 2 weeks during the study.

I can safely get on and off a stationary bike by myself.

Exclusion Criteria

You are too heavy for your height, have metal objects in your body, are pregnant, or have a fear of being in small, enclosed spaces.

You have a history of a certain type of mini-stroke or a high score on a scale that measures the risk of having a stroke.

You have had problems with drinking too much alcohol or using drugs in the past 2 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants engage in high-intensity interval training (HIIT) using the Peloton® cycling system or continue their habitual physical activity for 18 months

18 months

Regular home-based sessions, with assessments at study entry and 18 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, including cognitive testing and brain MR imaging

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Indoor Cycling (IC)

Trial Overview This trial tests if long-term high-intensity indoor cycling can slow down or delay Alzheimer's-related brain changes in e4 carriers. It involves using a home-based Peloton exercise program to see if it can improve patient outcomes and reduce healthcare costs related to Alzheimer's Disease.

How Is the Trial Designed?

Group I: Indoor Cycling (IC) Experimental Treatment 1 Intervention

Participants will engage in high-intensity interval training (HIIT; 60-90% of heart rate reserve) in their home via the commercially available Peloton® cycling system or 2) 3x/week (minimum 90 minutes/week) for 18 months.

Group II: Usual and Customary Care (UCC) Active Control 1 Intervention

Participants engage in their habitual level of physical activity.

Who Is Running the Clinical Trial?

The Cleveland Clinic

Lead Sponsor

Trials

1,072

Recruited

1,377,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

University of Maryland, College Park

Collaborator

Trials

163

Recruited

46,800+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

Published Research Related to This Trial

Moderate-intensity intermittent exercise (MIIE) significantly prevents memory impairment and neuronal loss in a rat model of Alzheimer's dementia induced by trimethyltin (TMT), as shown by improved performance in the Morris water maze test and preservation of hippocampal neurons.

MIIE also reduced levels of Alzheimer's disease markers, such as phosphorylated tau and presenilin-1, while enhancing anti-inflammatory markers like interleukin-10, suggesting a protective mechanism against neuroinflammation and degeneration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Moderate-intensity intermittent exercise prevents memory deficit, hippocampal neuron loss, and elevated level of Alzheimer's dementia markers in the hippocampus of trimethyltin-induced rats. Nurmasitoh, T., Sari, DCR., Susilowati, R.[2023]

A 12-week home-based physical activity program for 30 patients with Alzheimer's disease helped maintain their ability to perform daily activities, while the control group showed a decline in performance over the same period.

The intervention also led to improvements in cognitive functions, such as semantic word fluency and reaction time, and helped stabilize caregiver burden, suggesting that physical activity can be beneficial for both patients and their caregivers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of physical activity training in patients with Alzheimer's dementia: results of a pilot RCT study. Holthoff, VA., Marschner, K., Scharf, M., et al.[2022]

A review of 14 studies on exercise and Alzheimer's disease found that exercise can significantly improve daily functioning and performance in patients, enhancing their ability to carry out daily activities.

Exercise also positively impacts neuropsychiatric symptoms and various cognitive functions, including sustained attention and visual memory, suggesting it may be a valuable intervention for managing Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

What are the Benefits of Exercise for Alzheimer's Disease? A Systematic Review of the Past 10 Years. Hernández, SS., Sandreschi, PF., da Silva, FC., et al.[2018]

In a study of 372 individuals with genetically driven early-onset Alzheimer's disease, those who engaged in high levels of physical activity showed significantly better cognitive and functional performance compared to low exercisers.

High physical activity was associated with less Alzheimer's-related pathology in cerebrospinal fluid and a delay in the onset of very mild dementia by approximately 15 years, highlighting the potential protective effects of exercise against cognitive decline in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relationship between physical activity, cognition, and Alzheimer pathology in autosomal dominant Alzheimer's disease. Müller, S., Preische, O., Sohrabi, HR., et al.[2021]

A 2-month aerobic training program showed that older men with moderate Alzheimer's disease (AD) can improve their cardiorespiratory fitness, while those with severe AD may not benefit as much, indicating variability in response to exercise.

The study suggests that a longer duration of aerobic training, such as 6 months, may be more effective for improving fitness in older adults with AD, highlighting the need for tailored exercise programs based on individual fitness levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aerobic training for older men with Alzheimer's disease: individual examples of progression. Yu, F., Leon, AS., Bliss, D., et al.[2021]

A home-based multimodal exercise program for 40 older adults with mild to moderate Alzheimer's disease is expected to improve muscle strength, balance, cognition, and overall functioning after 16 weeks of training.

The study aims to provide a foundation for future clinical interventions and health promotion strategies tailored for older individuals with Alzheimer's, highlighting the potential benefits of at-home exercise for this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Home-based multimodal exercise program in older people with Alzheimer disease: Randomized controlled trial protocol. Cezar, NOC., Ansai, JH., de Andrade, LP.[2021]

In a study involving 51 patients with mild to moderate Alzheimer's disease, 16 weeks of moderate-to-high intensity aerobic exercise did not lead to consistent improvements in overall or regional cerebral blood flow.

The results suggest that this duration and intensity of exercise may not be enough to significantly impact cerebral blood flow in Alzheimer's patients, indicating a need for further research on exercise interventions in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of physical exercise on cerebral blood flow in Alzheimer's disease. van der Kleij, LA., Petersen, ET., Siebner, HR., et al.[2021]

Individuals at risk for Alzheimer's disease (AD) engage in significantly more sedentary behavior (494.9 minutes/day) and less moderate-to-vigorous physical activity (MVPA) (22.4 minutes/day) compared to those not at risk (477.9 minutes/day and 24.3 minutes/day, respectively).

This study, which analyzed data from 3015 participants, highlights a concerning trend where adults at risk for AD, including minorities, are less active and more sedentary, potentially increasing their risk for developing the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Need for Increased Promotion of Physical Activity Among Adults at Risk for Alzheimer's Disease: A Brief Report. Loprinzi, PD.[2022]

Exercise can be an effective treatment for Alzheimer's disease (AD), showing improvements in cognitive function, reduced neuropsychiatric symptoms, and slower decline in daily activities, making it a valuable intervention alongside traditional medications.

Physical inactivity is a major preventable risk factor for developing AD, and higher levels of physical activity are linked to a lower risk of disease, highlighting the importance of exercise in both prevention and treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alzheimer's Disease and Exercise: A Literature Review. Cass, SP.[2017]

Citations

1. newsroom.clevelandclinic.org newsroom.clevelandclinic.org/2021/01/28/national-institutes-of-health-awards-cleveland-clinic-6-7-million-grant-to-evaluate-impact-of-high-intensity-exercise-in-preventing-alzheimers-disease

National Institutes of Health Awards ... The five-year study will assess the effect of home-based indoor cycling in slowing disease progression in healthy older people at high genetic ...

2. consultqd.clevelandclinic.org consultqd.clevelandclinic.org/cycle-ad-trial-high-intensity-exercise-to-stave-off-alzheimers-disease

CYCLE-AD Trial: High-Intensity Exercise to Stave Off ... A new randomized trial aims to show whether 18 months of high-intensity indoor cycling delays disease onset among cognitively normal older ...

3. onepeloton.com onepeloton.com/blog/exercise-and-brain-health

Exercise and Brain Health New research reveals that working out contributes to improvements in memory, focus, sleep and overall cognitive function. Here's how.

4. trialx.com trialx.com/clinical-trials/listings/260234/cycle-ad-cycling-to-cease-or-limit-the-effects-of-alzheimers-disease/

CYCLE-AD (CYcling to Cease or Limit the Effects of ... Investigators hypothesize that an 18-month high-intensity aerobic exercise regimen will slow AD-related disease progression in sedentary elders at genetic risk ...

5. trial.medpath.com trial.medpath.com/clinical-trial/5d6143ec6fb8a8f6/cycle-ad-randomized-controlled-trial

CYCLE-AD (CYcling to Cease or Limit the Effects of Alzheimer's ... Investigators hypothesize that an 18-month high-intensity aerobic exercise regimen will slow AD-related disease progression in sedentary elders at genetic risk ...

6. cnn.com cnn.com/2025/09/20/health/cycling-lower-dementia-risk-study-wellness

Cycling linked with lower dementia risk, study finds Riding a bike is associated with a 19% lower risk of all-cause dementia and a 22% lower risk of Alzheimer's disease, compared with taking ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8075384/

Cognitive Effects of Aerobic Exercise in Alzheimer's Disease Our primary finding indicates that a 6-month aerobic exercise intervention significantly reduced the decline in global cognition in comparison ...