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

150 Participants Needed

Trial Summary

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 data supports the effectiveness of the treatment Indoor Cycling (IC), High-Intensity Interval Training (HIIT), Stationary Cycling, Home-Based Cycling, Peloton Cycling for Alzheimer's Disease?

Research suggests that exercise, including cycling, may help improve daily life activities, mental health, and physical fitness in people with Alzheimer's disease. While specific data on cycling is limited, general exercise has shown benefits in flexibility, balance, and some cognitive functions. ^{1 2 3 4 5}

Is high-intensity exercise safe for people with Alzheimer's disease?

Exercise, including aerobic training, is generally safe for older adults with Alzheimer's disease, with studies showing it can improve fitness and cognitive function. It has fewer side effects and better adherence compared to medications. ^{1 3 6 7 8}

How does the treatment of high-intensity exercise differ from other treatments for Alzheimer's disease?

High-intensity exercise, like indoor cycling, is unique because it focuses on improving brain health through physical activity, which can enhance blood flow to the brain and support brain cell growth, unlike medications that often have mixed effectiveness and more side effects. ^{1 3 4 7 9}

What is the purpose of this trial?

The overall goal of the CYCLE-AD trial is to determine the role of long-term, high intensity exercise in slowing or delaying the onset of cognitive and AD-related brain changes in e4 carriers. Successful translation and demonstration of the effectiveness of a scalable home-based exercise intervention capable of slowing or delaying disease onset will transform AD treatment, improve patient outcomes and quality of life, and reduce health care costs.

Research Team

Jay L Alberts, PhD

Principal Investigator

The Cleveland Clinic

Stephen Rao, PhD

Principal Investigator

The Cleveland Clinic

Eligibility Criteria

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

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.

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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 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]

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Aerobic training for older men with Alzheimer's disease: individual examples of progression. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Effects of physical activity training in patients with Alzheimer's dementia: results of a pilot RCT study. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Home-based multimodal exercise program in older people with Alzheimer disease: Randomized controlled trial protocol. [2021]

4. Netherlands pubmed.ncbi.nlm.nih.gov

The effect of physical exercise on cerebral blood flow in Alzheimer's disease. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

What are the Benefits of Exercise for Alzheimer's Disease? A Systematic Review of the Past 10 Years. [2018]

6. United States pubmed.ncbi.nlm.nih.gov

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

7. United States pubmed.ncbi.nlm.nih.gov

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

8. United States pubmed.ncbi.nlm.nih.gov

Relationship between physical activity, cognition, and Alzheimer pathology in autosomal dominant Alzheimer's disease. [2021]

9. Germany 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. [2023]