Clinical Trial

. 2025 Apr;21(4):e14586.

doi: 10.1002/alz.14586.

Effects of exercise on cognition and Alzheimer's biomarkers in a randomized controlled trial of adults with mild cognitive impairment: The EXERT study

Laura D Baker^{1

2}, Judy A Pa^{3

4}, Jeffrey A Katula⁵, Vahan Aslanyan⁶, David P Salmon^{3

4}, Diane M Jacobs^{3

4}, Elizabeth A Chmelo¹, Heather Hodge⁷, Rosemary Morrison^{3

4}, Genevieve Matthews^{3

4}, James Brewer^{3

4}, Youngkyoo Jung⁸, Robert A Rissman⁹, Curtis Taylor^{3

4}, Gabriel C Léger^{3

4}, Karen Messer^{10

11}, A Carol Evans^{3

4}, Ozioma C Okonkwo¹², Aladdin H Shadyab^{10

13}, Jingjing Zou^{3

10

11

13}, Sheila Jin^{3

4}, Ronald G Thomas^{3

10}, Jin Zhang¹¹, Andrea Z La Croix¹⁰, Carl W Cotman^{14

15}, Howard H Feldman^{3

4}; EXERT Study Group

Affiliations

¹ Department of Internal Medicine-Geriatrics, Wake Forest University School of Medicine, Winston Salem, North Carolina, USA.
² Departments of Social Science & Health Policy, and Epidemiology, Division of Public Health Sciences, Wake Forest University Health Sciences, Winston Salem, North Carolina, USA.
³ Alzheimer's Disease Cooperative Study, University of California, La Jolla, California, USA.
⁴ Department of Neurosciences, University of California, La Jolla, California, USA.
⁵ Department of Health and Exercise Science, Wake Forest University, Winston Salem, North Carolina, USA.
⁶ Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
⁷ YMCA of the USA, Chicago, Illinois, USA.
⁸ Department of Radiology, Medical Physics, University of California Davis Health, Davis, California, USA.
⁹ Department of Physiology and Neurosciences, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
¹⁰ Herbert Wertheim School of Public Health and Human Longevity Science, University of California San Diego, La Jolla, California, USA.
¹¹ Moors Cancer Center, University of California San Diego, La Jolla, California, USA.
¹² Department of Medicine, Division of Geriatrics and Gerontology, University of Wisconsin-Madison, Madison, Wisconsin, USA.
¹³ Department of Medicine, Division of Geriatrics, Gerontology, and Palliative Care, University of California San Diego, La Jolla, California, USA.
¹⁴ Shiley-Marcos Alzheimer's Disease Research Center, University of California San Diego, La Jolla, California, USA.
¹⁵ Department of Neurobiology and Behavior; Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, California, USA.

PMID: 40271888
PMCID: PMC12019696
DOI: 10.1002/alz.14586

Clinical Trial

Effects of exercise on cognition and Alzheimer's biomarkers in a randomized controlled trial of adults with mild cognitive impairment: The EXERT study

Laura D Baker et al. Alzheimers Dement. 2025 Apr.

. 2025 Apr;21(4):e14586.

doi: 10.1002/alz.14586.

Authors

Affiliations

¹ Department of Internal Medicine-Geriatrics, Wake Forest University School of Medicine, Winston Salem, North Carolina, USA.
² Departments of Social Science & Health Policy, and Epidemiology, Division of Public Health Sciences, Wake Forest University Health Sciences, Winston Salem, North Carolina, USA.
³ Alzheimer's Disease Cooperative Study, University of California, La Jolla, California, USA.
⁴ Department of Neurosciences, University of California, La Jolla, California, USA.
⁵ Department of Health and Exercise Science, Wake Forest University, Winston Salem, North Carolina, USA.
⁶ Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
⁷ YMCA of the USA, Chicago, Illinois, USA.
⁸ Department of Radiology, Medical Physics, University of California Davis Health, Davis, California, USA.
⁹ Department of Physiology and Neurosciences, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
¹⁰ Herbert Wertheim School of Public Health and Human Longevity Science, University of California San Diego, La Jolla, California, USA.
¹¹ Moors Cancer Center, University of California San Diego, La Jolla, California, USA.
¹² Department of Medicine, Division of Geriatrics and Gerontology, University of Wisconsin-Madison, Madison, Wisconsin, USA.
¹³ Department of Medicine, Division of Geriatrics, Gerontology, and Palliative Care, University of California San Diego, La Jolla, California, USA.
¹⁴ Shiley-Marcos Alzheimer's Disease Research Center, University of California San Diego, La Jolla, California, USA.
¹⁵ Department of Neurobiology and Behavior; Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, California, USA.

PMID: 40271888
PMCID: PMC12019696
DOI: 10.1002/alz.14586

Abstract

Introduction: The EXERT study (Exercise in Adults with Mild Memory Problems) was a Phase 3, multicenter, randomized controlled trial that examined effects of exercise on cognition and other measures of brain health in sedentary older adults with amnestic mild cognitive impairment (MCI).

Methods: Participants were randomized to moderate-high intensity aerobic training (AX) or low-intensity stretching/balance/range of motion (SBR) for 18 months. Exercise was supervised for the first 12 months. Assessments were administered at baseline and every 6 months. The primary outcome was a global cognitive composite.

Results: A total of 296 participants were enrolled, and intervention adherence was high (supervised session attendance: AX = 81%, SBR = 87%). Intervention effects on cognition did not differ for AX and SBR (regression = -0.078, standard error [SE] = 0.074; p = 0.3). Notably, there was no 12 month cognition decline for either group, and mean 12 month hippocampal volume loss for both groups was low at 0.51%.

Discussion: Exercise intensity did not differentially affect cognitive trajectory. Intervention delivery was successful (high adherence) and cognition remained stable over 12 months for both MCI groups, an association that warrants further study.

Highlights: Exercise in Adults with Mild Memory Problems (EXERT) was a large multisite randomized controlled trial of moderate-high intensity aerobic training versus lower-intensity flexibility and balance exercise in sedentary older adults with amnestic mild cognitive impairment (MCI). A sensitive and validated measure of global cognitive function, the Alzheimer's Disease Assessment Scale-Cognition supplemented with tests of executive function (ADAS-Cog-Exec), was used to assess intervention efficacy with 12 months of supervised exercise. There was no intervention group difference on the 12-month cognitive trajectory of the ADAS-Cog-Exec. Intervention delivery was successful (high adherence), and cognition remained stable over 12 months for both exercise groups. Regular supported moderate-high or lower-intensity exercise may stall decline in adults with amnestic MCI, but further investigation is needed.

Keywords: Alzheimer's; brain MRI; clinical trial; cognition; exercise; mild cognitive impairment; multisite; nonpharmacological intervention.

PubMed Disclaimer

Conflict of interest statement

Feldman receives grant funding from the National Institute on Aging (U19AG010483‐22), from Biohaven Pharmaceuticals, Vivoryon (Probiodrug), and LuMind Foundation; service agreements for consulting activities with LuMind, Axon Neuroscience, Novo Nordisk, Arrowhead Pharmaceuticals, Roche/Genentech Pharmaceuticals (DMC/DSMB), Tau Consortium (SAB), and Janssen Research & Development (DSMB); support for travel from Novo Nordisk, Royal Society of Canada, Translating Research in Elder Care (TREC), Association for Frontotemporal Dementia (AFTD), and Rainwater Charitable Foundation; and a philanthropic donation for the Epstein Family Alzheimer Research Collaboration. No personal funds have been received for these activities. Feldman personally receives royalties for patent: Feldman HH (filed November 26, 2008). Detecting and Treating Dementia Serial Number 12/3‐2691 U.S. Patent No. PCT/US2007/07008. Washington, DC: U.S. Patent and Trademark Office. For other authors, there are no conflicts to report for this work. Author disclosures are available in the Supporting Information.

Figures

**FIGURE 1**
Study design and intervention oversight.

**FIGURE 2**
Consolidated Standards of Reporting Trials (CONSORT) flow diagram.

**FIGURE 3**
Intervention adherence by exercise session attendance (A), supervised exercise mean peak heart rate by anti‐hypertensive medication use (B)*, and supervised exercise mean peak rating of perceived exertion by anti‐hypertensive medication use (C)*.

**FIGURE 4**
Mean change across months 6 and 12 relative to baseline on the ADAS‐Cog‐Exec Global Cognitive Composite Score*.

See this image and copyright information in PMC

References

1. Prince M, Wimo A, Guerchet M, Ali GC, Wu Y. The Global Impact of Dementia: an Analysis of Prevalence, Incidence, Cost and Trends. Alzheimer's Disease International; 2015.
1. Petersen RC, Thomas RG, Grundman M, et al. Vitamin E and donepezil for the treatment of mild cognitive impairment. N Engl J Med. 2005;352(23):2379‐2388. - PubMed
1. Winblad B, Gauthier S, Scinto L, et al. Safety and efficacy of galantamine in subjects with mild cognitive impairment. Neurology. 2008;70(22):2024‐2035. - PubMed
1. Sims JR, Zimmer JA, Evans CD, et al. Donanemab in early symptomatic Alzheimer disease: the TRAILBLAZER‐ALZ 2 randomized clinical trial. JAMA. 2023;330(6):512‐527. - PMC - PubMed
1. van Dyck CH, Swanson CJ, Aisen P, et al. Lecanemab in early Alzheimer's disease. N Engl J Med. 2023;388(1):9‐21. - PubMed

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Effects of exercise on cognition and Alzheimer's biomarkers in a randomized controlled trial of adults with mild cognitive impairment: The EXERT study

Affiliations

Effects of exercise on cognition and Alzheimer's biomarkers in a randomized controlled trial of adults with mild cognitive impairment: The EXERT study

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Medical