Wednesday, January 28, 2026 1/28/2026

CYCLE-AD: Randomized Controlled Trial to Assess the Efficacy of Indoor Cycling in Slowing Disease Progression in Healthy Older Persons at Genetic Risk for Alzheimers Disease

Award Number: R01AG070736
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 01/15/2021
PERIOD OF PERFORMANCE END DATE: 12/31/2026

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CYCLE-AD: Randomized Controlled Trial to Assess the Efficacy of Indoor Cycling in Slowing Disease Progression in Healthy Older Persons at Genetic Risk for Alzheimers Disease - PROJECT SUMMARY/ABSTRACT The apolipoprotein E epsilon 4 (APOE 4) allele is the most important genetic risk factor for late onset Alzheimer's disease (AD). A recent review by the World Health Organization highlighted the potential protective role of physical activity and exercise against cognitive decline, all-cause dementia, AD, and vascular dementia in healthy individuals. In an 18-month longitudinal observational study, we showed that sedentary 4 carriers experience significant declines in episodic memory and hippocampal volume compared to 4 carriers who engaged in moderate PA. Importantly, among 4 non-carriers, no significant longitudinal changes in cognition and brain imaging were observed whether the non-carriers were sedentary or engaged in moderate PA, suggesting that PA has a specific neuroprotective role in delaying the progression of AD in 4 carriers. Based on our results, a pragmatic, randomized controlled trial with blinded clinical and imaging outcomes is proposed to determine the impact of a home based, high intensity exercise intervention in healthy, cognitively intact 4 carriers between the ages of 65 and 80 years. The CYCLE-AD (CYcling to Cease or Limit the Effects of Alzheimer's Disease) trial will recruit otherwise healthy sedentary carriers randomized to one of two groups (n=75 each): 1) an Indoor Cycling (IC) group that participates in high-intensity interval training (HIIT; 60-90% of heart rate reserve) in their home via the commercially available Peloton® cycling system or 2) a Usual and Customary Care (UCC) group, in which participants engage in their habitual level of PA. We hypothesize that an 18-month high-intensity aerobic exercise regimen will slow AD-related disease progression in sedentary elders at genetic risk for AD. Participants in the intervention group will engage in exercise 3x/week (minimum 90 minutes/week) for 18 months. Primary outcome measures, obtained at study entry and at 18 months, will include comprehensive cognitive testing and brain MR imaging to assess disease progression and a comprehensive PA/fitness assessment to measure the degree of change in physical fitness due to high intensity aerobic exercise. 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 4 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.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $0 )
2026	2025	CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE OF CASE WESTERN RESERVE UNIVERSITY	9500 EUCLID AVE.	CLEVELAND	OH	44195	CUYAHOGA	USA	Aging Research	000	5	10/13/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $1,476,501 )
2025	2025	CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE OF CASE WESTERN RESERVE UNIVERSITY	9500 EUCLID AVE.	CLEVELAND	OH	44195	CUYAHOGA	USA	Aging Research	001	5	8/12/2025	NON-COMPETING CONTINUATION	$120,530
2025	2025	CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE OF CASE WESTERN RESERVE UNIVERSITY	9500 EUCLID AVE.	CLEVELAND	OH	44195	CUYAHOGA	USA	Aging Research	000	5	1/8/2025	NON-COMPETING CONTINUATION	$1,355,971
														Subtotal = $1,476,501

Issue Date FY: 2024 ( Subtotal = $1,641,747 )
2024	2024	CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE OF CASE WESTERN RESERVE UNIVERSITY	9500 EUCLID AVE.	CLEVELAND	OH	44195	CUYAHOGA	USA	Aging Research	001	4	5/24/2024	NON-COMPETING CONTINUATION	$126,497
2024	2024	CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE OF CASE WESTERN RESERVE UNIVERSITY	9500 EUCLID AVE.	CLEVELAND	OH	44195	CUYAHOGA	USA	Aging Research	002	4	8/27/2024	SUPPLEMENT FOR EXPANSION	$376,774
2024	2024	CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE OF CASE WESTERN RESERVE UNIVERSITY	9500 EUCLID AVE.	CLEVELAND	OH	44195	CUYAHOGA	USA	Aging Research	000	4	1/9/2024	NON-COMPETING CONTINUATION	$1,138,476
														Subtotal = $1,641,747

Issue Date FY: 2023 ( Subtotal = $1,544,290 )
2023	2023	CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE/CWRU	9500 EUCLID AVE	CLEVELAND	OH	44195	CUYAHOGA	USA	Aging Research	000	3	1/23/2023	NON-COMPETING CONTINUATION	$1,544,290
														Subtotal = $1,544,290

Issue Date FY: 2022 ( Subtotal = $1,423,624 )
2022	2022	CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE/CWRU	9500 EUCLID AVE	CLEVELAND	OH	44195	CUYAHOGA	USA	Aging Research	002	2	7/1/2022	NON-COMPETING CONTINUATION	$0
2022	2022	CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE/CWRU	9500 EUCLID AVE	CLEVELAND	OH	44195	CUYAHOGA	USA	Aging Research	000	2	12/17/2021	NON-COMPETING CONTINUATION	$1,281,262
2022	2022	CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE/CWRU	9500 EUCLID AVE	CLEVELAND	OH	44195	CUYAHOGA	USA	Aging Research	001	2	4/26/2022	NON-COMPETING CONTINUATION	$142,362
														Subtotal = $1,423,624

Issue Date FY: 2021 ( Subtotal = $1,303,339 )
2021	2021	CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE/CWRU	9500 EUCLID AVE	CLEVELAND	OH	44195	CUYAHOGA	USA	Aging Research	002	1	7/6/2021	NEW	$0
2021	2021	CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE/CWRU	9500 EUCLID AVE	CLEVELAND	OH	44195	CUYAHOGA	USA	Aging Research	001	1	2/8/2021	NEW	$0
2021	2021	CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE/CWRU	9500 EUCLID AVE	CLEVELAND	OH	44195	CUYAHOGA	USA	Aging Research	000	1	1/14/2021	NEW	$1,303,339
														Subtotal = $1,303,339

Grand Total All Awards = $7,389,501

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CYCLE-AD: Randomized Controlled Trial to Assess the Efficacy of Indoor Cycling in Slowing Disease Progression in Healthy Older Persons at Genetic Risk for Alzheimers Disease

Award Number: R01AG070736

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 01/15/2021

PERIOD OF PERFORMANCE END DATE: 12/31/2026

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

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Award Information

CYCLE-AD: Randomized Controlled Trial to Assess the Efficacy of Indoor Cycling in Slowing Disease Progression in Healthy Older Persons at Genetic Risk for Alzheimers Disease

Award Number: R01AG070736

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 01/15/2021

PERIOD OF PERFORMANCE END DATE: 12/31/2026

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer

CYCLE-AD: Randomized Controlled Trial to Assess the Efficacy of Indoor Cycling in Slowing Disease Progression in Healthy Older Persons at Genetic Risk for Alzheimers Disease