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News — Researchers at University of California San Diego and Wake Forest University have found that both low and moderate-high intensity exercise could be valuable tools in the fight against Alzheimer’s. The new research, published as two papers in Alzheimer’s and Dementia: The Journal of the Alzheimer’s Association, describes the results of the EXERT study (Exercise in Adults with Mild Memory Problems), a multi-site clinical trial of lower or moderate-high intensity exercise in sedentary older adults with amnestic mild cognitive impairment, a major risk factor for Alzheimer’s dementia. The researchers also compared their results to an existing dataset of comparable individuals who only received usual care, such as regular check-ups with health care providers and medication management.

The researchers found:

• In EXERT participants, cognitive function remained stable over 12 months in both low and moderate-high intensity exercise groups.
• Both forms of exercise were associated with significantly less cognitive decline over 12 months when compared to individuals who were not involved in the exercise study.
• Both EXERT exercise groups tended to show less brain volume loss over 12 months, including in the prefrontal cortex.

Individuals with amnestic mild cognitive impairment, a condition characterized by memory complaints and objective memory decline, are at high risk of developing Alzheimer’s dementia, with approximately 16% of people with this condition progressing to Alzheimer’s each year.

“This is a critical time to intervene in this population, because they don’t have dementia yet, but are at a very high risk,” said Aladdin Shadyab, Ph.D., M.P.H., lead author of one of the new papers and associate professor at the UC San Diego Herbert Wertheim School of Public Health and Human Longevity Science and School of Medicine. “Together, these findings show us that even low intensity exercise may slow cognitive decline in at-risk older adults.”

While previous studies have suggested that exercise may be beneficial for cognitive health, the evidence has been mixed, and large, well-designed studies are needed to fully understand the potential benefits of exercise for older adults with mild cognitive impairment. The EXERT study, coordinated by the Alzheimer’s Disease Cooperative Study (ADCS) at UC San Diego, in partnership with Wake Forest University School of Medicine, fills this gap.

“EXERT was one of the first large clinical trials of exercise that partnered with the YMCA and its trainers to bring the intervention closer to home for research participants,” said Howard Feldman, M.D., ADCS director. “This approach brings us one step closer to its implementation in the community.”

The ADCS was formed in 1991 under a cooperative agreement between the National Institute on Aging and UC San Diego and is one of the key initiatives for Alzheimer’s research supported by the federal government, addressing treatments for both cognitive and behavioral symptoms of Alzheimer’s.

“There’s an urgent need to identify effective and feasible ways to prevent and treat Alzheimer’s dementia, and UC San Diego has been a leader in this field for many years,” added Feldman, who is also a professor in the Department of Neurosciences at UC San Diego School of Medicine.

EXERT included nearly 300 sedentary older adults with mild cognitive impairment who were randomly assigned to either moderate-high intensity aerobic training or lower-intensity stretching, balance and range of motion activities. Participants completed their assigned exercise 3-4 times per week for 12 months under the supervision of a YMCA trainer, and the study also included regular assessments of cognitive function and brain volume.

“EXERT is a landmark study because it’s the largest rigorous trial of exercise ever conducted in adults with mild cognitive impairment,” said Laura Baker, Ph.D., principal investigator of the EXERT study and professor of gerontology and geriatric medicine at Wake Forest University School of Medicine. “Exercise has well-documented benefits to nearly every aspect of human health, but we’re still unlocking the full potential of exercise as medicine for older adults with memory problems.

Though the researchers expected to see further cognitive decline in EXERT participants, they actually found that cognitive function remained stable for both exercise groups over the course of the study. This suggests that both lower and higher intensity exercise could slow cognitive decline. Another possible explanation for the results is that participating in research itself, regardless of the treatment, may offer protection against cognitive decline due to the intellectual and social stimulation involved.

Overall, the findings of both studies taken together suggest that exercise may be a promising, safe, and feasible strategy to promote brain health and prevent continued cognitive decline for older adults with mild cognitive impairment.

“While there’s still a lot to learn, these findings show that regular intensity exercise, even at low intensity, could go a long way toward helping older adults slow or delay cognitive decline, and this is promising news for those who are at high risk for dementia,” added Shadyab.

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Link to the main EXERT findings:

Additional co-authors of main EXERT findings include Judy A. Pa, David P. Salmon, Diane M. Jacobs, Rosemary Morrison, Genevieve Matthews, James Brewer, Curtis Taylor, Gabriel C. Léger, Karen Messer, A. Carol Evans, Jingjing Zou, Sheila Jin, Ronald G. Thomas, Jin Zhang, Andrea Z. La Croix and Carl W. Cotman at UC San Diego, Jeffrey A. Katula and Elizabeth A. Chmelo at Wake Forest University, Heather Hodge at YMCA of the USA, Youngkyoo Jung at UC Davis Health, and Robert A. Rissman at University of Southern California.

The EXERT study was supported through the National Institutes of Health/National Institute on Aging (U19AG010483-25 and AG058644) and by the Brain Research Foundation (BRF ECD-2014-01).

Disclosures: 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.

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Link to the second study:

Additional co-authors of the additional study include Diane M. Jacobs, David P. Salmon, Rosemary Morrison, Shelia Jin, Ronald G. Thomas, Andrea Z. LaCroix, Judy Pa and Carl W. Cotman at UC San Diego, Vahan Aslanyan at University of Southern California and Jeffrey A. Katula at Wake Forest University.

Disclosures: Howard Feldman receives grant funding from the National Institute on Aging (U19AG010483), from Biohaven Pharmaceuticals, Vivoryon (Probiodrug), Allyx Therapeutics, and LuMind Foundation; service agreements for consulting activities with LuMind, Axon Neuroscience, Novo Nordisk, Biosplice Therapeutics, Arrowhead Pharmaceuticals, Roche/Genentech Pharmaceuticals (DMC/DSMB), Tau Consortium (SAB), 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. Feldman also receives royalties for patent: Feldman HH (filed November 26, 2008). Detecting and Treating Dementia Serial Number 12/3- 2691 US Patent No. PCT/US2007/07008. Washington, DC: U.S. Patent and Trademark Office. Baker reports grant funding from NIH (U19 AG010483, AG062689, AG066910, U19 AG063744, P30AG049638- 01A1, HL 133684-01A1, AG064440, U24 AG057437) and Alzheimer’s Association (POINTER-19-611541), honoraria from Washington State University and National Academy of Neuropsychology, payments from Alzheimer’s Association and Oregon State University for invited speakerships, and participation in the Data Safety Monitoring Board for the Alzheimer Center at Washington State University. Katula reports funding from NIH (U19 AG010483) and Alzheimer’s Association, and participation in the Data Safety Monitoring Board for South Asians Active Together (SAATH) study. Morrison reports funding from NIA (U19 AG010483). LaCroix reports NIA funding from ADCS. Shadyab reports funding from NIH/NIA (U19 AG010483). Jacobs reports funding from NIH/NIA, Biohaven Pharmaceuticals, Vivoryon Therapeutics, and the Epstein Family Alzheimer Research Collaboration.