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Effects of Aerobic Exercise on Mild Cognitive Impairment: A Controlled Trial
Open accessAbstract
OBJECTIVES: To examine the effects of aerobic exercise on cognition and other biomarkers associated with Alzheimer disease pathology for older adults with mild cognitive impairment, and assess the role of sex as a predictor of response. DESIGN: Six-month, randomized, controlled, clinical trial. SETTING: Veterans Affairs Puget Sound Health Care System clinical research unit. PARTICIPANTS: Thirty-three adults (17 women) with amnestic mild cognitive impairment ranging in age from 55 to 85 years (mean age, 70 years). Intervention Participants were randomized either to a high-intensity aerobic exercise or stretching control group. The aerobic group exercised under the supervision of a fitness trainer at 75% to 85% of heart rate reserve for 45 to 60 min/d, 4 d/wk for 6 months. The control group carried out supervised stretching activities according to the same schedule but maintained their heart rate at or below 50% of their heart rate reserve. Before and after the study, glucometabolic and treadmill tests were performed and fat distribution was assessed using dual-energy x-ray absorptiometry. At baseline, month 3, and month 6, blood was collected for assay and cognitive tests were administered. MAIN OUTCOME MEASURES: Performance measures on Symbol-Digit Modalities, Verbal Fluency, Stroop, Trails B, Task Switching, Story Recall, and List Learning. Fasting plasma levels of insulin, cortisol, brain-derived neurotrophic factor, insulinlike growth factor-I, and beta-amyloids 40 and 42. RESULTS: Six months of high-intensity aerobic exercise had sex-specific effects on cognition, glucose metabolism, and hypothalamic-pituitary-adrenal axis and trophic activity despite comparable gains in cardiorespiratory fitness and body fat reduction. For women, aerobic exercise improved performance on multiple tests of executive function, increased glucose disposal during the metabolic clamp, and reduced fasting plasma levels of insulin, cortisol, and brain-derived neurotrophic factor. For men, aerobic exercise increased plasma levels of insulinlike growth factor I and had a favorable effect only on Trails B performance. CONCLUSIONS: This study provides support, using rigorous controlled methodology, for a potent nonpharmacologic intervention that improves executive control processes for older women at high risk of cognitive decline. Moreover, our results suggest that a sex bias in cognitive response may relate to sex-based differences in glucometabolic and hypothalamic-pituitary-adrenal axis responses to aerobic exercise.
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“However, in another study from The Netherlands, supplementation with 800 μg daily of oral folic acid for 3 years in 818 participants significantly improved domains of cognitive function that tend to decline with age.477”
From Vascular Contributions to Cognitive Impairment and Dementia: A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association (2011) · cites this paper as [477]
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Mild cognitive impairment as a diagnostic entity
Petersen, R. C. (2004) · Journal of Internal Medicine · doi:10.1111/j.1365-2796.2004.01388.x · Cited by 7,864
Glucose clamp technique: a method for quantifying insulin secretion and resistance.
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Exercise builds brain health: key roles of growth factor cascades and inflammation
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Aerobic Exercise Training Increases Brain Volume in Aging Humans
Colcombe, S. J., Erickson, K. I., Scalf, P. E., Kim, J. S., Prakash, R., McAuley, E., Elavsky, S., Marquez, D. X., Hu, L., & Kramer, A. F. (2006) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/61.11.1166 · Cited by 2,134
Exercise enhances learning and hippocampal neurogenesis in aged mice
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“on memory have been reported in a few clinical trials,(20,21) although most support for a memory benefit comes from animal research.(8,11,22,23) In humans, results of crosssectional(24) and prospective(25) brain imaging studies suggest that increased aerobic fitness in cognitively healthy older adults is associated wi…”
Lautenschlager, N. T., Cox, K. L., Flicker, L., Foster, J. K., van Bockxmeer, F. M., Xiao, J., Greenop, K. R., & Almeida, O. P. (2008) · JAMA · doi:10.1001/jama.300.9.1027 · Cited by 1,637 · cited 1×
“In a recent exercise trial for older memory-impaired adults, Lautenschlager et al found benefits for memory and language but not executive function.(20) However, in their study subjects were not sedentary at study entry and sexspecific effects were not examined.”
Physical activity and risk of cognitive impairment and dementia in elderly persons
Laurin, D., Verreault, R., Lindsay, J., MacPherson, K., & Rockwood, K. (2001) · Archives of Neurology · doi:10.1001/archneur.58.3.498 · Cited by 1,561 · cited 4×
“80 Interventions such as aerobic exercise that can markedly alter HPA axis activity 61,81 may have the potential to confer clinically meaningful cognitive benefits, particularly for older women at elevated risk of AD.”
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Gorelick, P. B., Scuteri, A., Black, S. E., DeCarli, C., Greenberg, S. M., Iadecola, C., Launer, L. J., Laurent, S., Lopez, O. L., Nyenhuis, D., et al. (2011) · Stroke · doi:10.1161/str.0b013e3182299496 · Cited by 3,811
Exercise as medicine - evidence for prescribing exercise as therapy in 26 different chronic diseases
Pedersen, B. K., & Saltin, B. (2015) · Scandinavian Journal of Medicine & Science in Sports · doi:10.1111/sms.12581 · Cited by 3,514
“The effect was twice as strong for women as for men (Baker et al., 2010).”
BackgroundMethodDefeating Alzheimer's disease and other dementias: a priority for European science and society
Winblad, B., Amouyel, P., Andrieu, S., Ballard, C., Brayne, C., Brodaty, H., Cedazo-Minguez, A., Dubois, B., Edvardsson, D., Feldman, H., et al. (2016) · The Lancet Neurology · doi:10.1016/s1474-4422(16)00062-4 · Cited by 1,676
Miranda, M., Morici, J. F., Zanoni, M. B., & Bekinschtein, P. (2019) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2019.00363 · Cited by 1,416
“In the same manner, changes in BDNF levels induced pharmacologically or by aerobic exercise are related to better cognitive function and diminished synaptic dysfunction both in humans at risk of developing AD and in animal models of AD (Baker et al., 2010; Intlekofer and Cotman, 2013).”
BackgroundThe Diagnosis and Management of Mild Cognitive Impairment: A Clinical Review
Langa, K. M., & Levine, D. A. (2014) · JAMA · doi:10.1001/jama.2014.13806 · Cited by 1,337
Metadata
- Authors
- Baker, L. D., Frank, L. L., Foster-Schubert, K., Green, P. S., Wilkinson, C. W., McTiernan, A., Plymate, S. R., Fishel, M. A., Watson, G. S., Cholerton, B. A., Duncan, G. E., Mehta, P. D., & Craft, S.
- Affiliations
- University of Washington (US)
- Washington State University Spokane (US)
- ORCID
- Venue
- Archives of Neurology
- Publisher
- American Medical Association (AMA)
- Published
- 2010-01-01
- Volume
- 67
- Issue
- 1
- Pages
- 71-9
- ISSN
- 0003-9942 (ISSN-L)
- PMC
- PMC3056436
- OpenAlex
- W2005355670
- Cited by
- 1,171
- References
- 89
- Citations by year
- 2026: 37 · 2025: 64 · 2024: 57 · 2023: 70 · 2022: 56 · 2021: 75 · 2020: 75 · 2019: 94 · 2018: 70 · 2017: 96 · 2016: 70 · 2015: 80 · 2014: 75 · 2013: 89 · 2012: 70
- FWCI
- 53.93
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Archives of Neurology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- ResearchWorks at the University of Washington (University of Washington) (submittedVersion)
- Funders
- U.S. Department of Veterans Affairs
- Alzheimer's Association
- National Institutes of Health (UL1TR000423, 5kl2rr025015-02)
- National Center for Research Resources (KL2-RR025015)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Physical Activity and Health
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Keywords
- aerobic exercise, mild cognitive impairment, amnestic mild cognitive impairment, Alzheimer's disease, sex differences, executive function, glucose metabolism, hypothalamic-pituitary-adrenal axis, cortisol, insulin, brain-derived neurotrophic factor, insulin-like growth factor I, amyloid-beta, older adults, non-pharmacological treatment, cognitive decline
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Cognition Disorders, Energy Metabolism, Exercise Test, Exercise Therapy, Female, Glucose, Heart Rate, Humans, Male, Middle Aged, Neuropsychological Tests, Physical Fitness, Exercise, Absorptiometry, Photon, Treatment Outcome, Outcome Assessment, Health Care, Exercise Tolerance, Body Fat Distribution
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