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Effects of Aerobic Exercise on Mild Cognitive Impairment: A Controlled Trial
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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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Exercise and Hippocampal Memory Systems
Voss, M. W., Soto, C., Yoo, S., Sodoma, M., Vivar, C., & van Praag, H. (2019) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2019.01.006 · Cited by 235
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Brown, B. M., Peiffer, J. J., Taddei, K., Lui, J. K., Laws, S. M., Gupta, V. B., Taddei, T., Ward, V. K., Rodrigues, M. A., Burnham, S., et al. (2013) · Molecular Psychiatry · doi:10.1038/mp.2012.107 · Cited by 235
Targeting Neuroinflammation to Treat Alzheimer’s Disease
Ardura-Fabregat, A., Boddeke, E., Boza‐Serrano, A., Brioschi, S., Castro‐Gomez, S., Ceyzériat, K., Dansokho, C., Dierkes, T., Gelders, G., Heneka, M. T., et al. (2017) · CNS Drugs · doi:10.1007/s40263-017-0483-3 · Cited by 241
Phase I/II randomized trial of aerobic exercise in Parkinson disease in a community setting
Uc, E. Y., Doerschug, K. C., Magnotta, V., Dawson, J. D., Thomsen, T. R., Kline, J. N., Rizzo, M., Newman, S. R., Mehta, S., Grabowski, T. J., et al. (2014) · Neurology · doi:10.1212/wnl.0000000000000644 · Cited by 230
Song, D., & Yu, D. S. F. (2019) · International Journal of Nursing Studies · doi:10.1016/j.ijnurstu.2019.02.019 · Cited by 252
Treatment for mild cognitive impairment: systematic review
Cooper, C., Li, R., Lyketsos, C. G., & Livingston, G. (2013) · The British Journal of Psychiatry · doi:10.1192/bjp.bp.113.127811 · Cited by 229
Brown, B. M., Peiffer, J. J., & Martins, R. N. (2012) · Molecular Psychiatry · doi:10.1038/mp.2012.162 · Cited by 239
Sáez de Asteasu, M. L., Martínez-Velilla, N., Zambom-Ferraresi, F., Casas-Herrero, Á., & Izquierdo, M. (2017) · Ageing Research Reviews · doi:10.1016/j.arr.2017.05.007 · Cited by 215
Safiri, S., Jolfayi, A. G., Fazlollahi, A., Morsali, S., Sarkesh, A., Sorkhabi, A. D., Golabi, B., Aletaha, R., Asghari, K. M., Hamidi, S., et al. (2024) · Frontiers in Medicine · doi:10.3389/fmed.2024.1474043 · Cited by 273
Rodakowski, J., Saghafi, E., Butters, M. A., & Skidmore, E. R. (2015) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2015.06.003 · Cited by 212
“Author (year) Intervention Primary outcomes Secondary outcomes Statistically significant between group findings Baker et al. (2010) 2 groups: (1) High intensity aerobic exercise intervention group (2) Stretching control group Symbol-Digit Modalities, Verbal Fluency, Stroop, Trail Making B, Task…”
BackgroundInfluentialStröhle, A., Schmidt, D. K., Schultz, F., Fricke, N., Staden, T., Hellweg, R., Priller, J., Rapp, M. A., & Rieckmann, N. (2015) · American Journal of Geriatric Psychiatry · doi:10.1016/j.jagp.2015.07.007 · Cited by 228
“…p<.01 Test for Overall Effect: Z=4.69, p<.01 −0.50 0.50 1.50 Favours Control − Favours Exercise Scherder et al. 2005 v.Uffelen et al. 2008 (walking) Lautenschlager et al. 2008 Baker et al. 2010 Varela et al. 2011 (60% HRR) Suzuki et al. 2013 15 77 48 19 16 47 15 75 52 10 15 45 2.88% 0.05 [ −0.43…”
InfluentialTsukamoto, H., Suga, T., Takenaka, S., Tanaka, D., Takeuchi, T., Hamaoka, T., Isaka, T., & Hashimoto, T. (2015) · Physiology & Behavior · doi:10.1016/j.physbeh.2015.12.021 · Cited by 234
Modifiable Risk Factors for Alzheimer’s Disease
Edwards III, G. A., Gamez, N., Escobedo Jr., G., Calderon, O., & Moreno-Gonzalez, I. (2019) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2019.00146 · Cited by 253
“Some other studies have also found that aerobic exercise is able to improve memory performance and cognitive function in aging, MCI, and AD patients (Baker et al., 2010; Vidoni et al., 2012; Morris et al., 2017).”
BackgroundCoelho, F. G. D. M., Vital, T. M., Stein, A. M., Arantes, F. J., Rueda, A. V., Camarini, R., Teodorov, E., & Santos-Galduróz, R. F. (2014) · Journal of Alzheimer's Disease · doi:10.3233/jad-131073 · Cited by 203
Huckans, M. S., Hutson, L., Twamley, E. W., Jak, A. J., Kaye, J. A., & Storzbach, D. M. (2013) · Neuropsychology Review · doi:10.1007/s11065-013-9230-9 · Cited by 219
“…the efficacy of cognitive rehabilitation therapies for mild cognitive impairment (MCI) Study RCT CCT LFS PTX D Objective cognitive performance Self-report measures A/I M EF GC SCC DF QOL PS O ST LT ST LT ST LT ST LT ST LT ST LT ST LT ST LT ST LT Focused lifestyle interventions Baker et al. 2010 – –”
InfluentialBiazus-Sehn, L. F., Schuch, F. B., Firth, J., & Stigger, F. D. S. (2020) · Archives of Gerontology and Geriatrics · doi:10.1016/j.archger.2020.104048 · Cited by 194
Best, J. R., Chiu, B. K., Liang Hsu, C., Nagamatsu, L. S., & Liu-Ambrose, T. (2015) · Journal of the International Neuropsychological Society · doi:10.1017/s1355617715000673 · Cited by 201
“Related to this concern, future research should directly compare the effects of RT betweenmen and women, especially given that the physiological adaptations to exercise might be sex specific (Baker et al., 2010).”
BackgroundInfluentialCurrent treatment options for Alzheimer’s disease and Parkinson’s disease dementia
Y.Y. Szeto, J., & J.G. Lewis, S. (2016) · Current Neuropharmacology · doi:10.2174/1570159x14666151208112754 · Cited by 198
“While Galantamine has been reported to be ineffective in improving cognitive performance (i.e. attention, executive functioning, memory, and visuospatial performance) in non-demented PD patients [57], Donepezil and Rivastigmine have showed significant effect and a trend effect respectively for improvements on global m…”
BackgroundInfluentialBenefits of exercise training on cerebrovascular and cognitive function in ageing
Bliss, E., Wong, R. H. X., Howe, P. R. C., & Mills, D. E. (2020) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x20957807 · Cited by 226
It Is Not About the Bike, It Is About the Pedaling: Forced Exercise and Parkinson's Disease
Alberts, J. L., Linder, S. M., Penko, A. L., Lowe, M. J., & Phillips, M. (2011) · Exercise and Sport Sciences Reviews · doi:10.1097/jes.0b013e31822cc71a · Cited by 192
Effect of lifestyle activities on alzheimer disease biomarkers and cognition
Vemuri, P., Lesnick, T. G., Przybelski, S. A., Knopman, D. S., Roberts, R. O., Lowe, V. J., Kantarci, K., Senjem, M. L., Gunter, J. L., Boeve, B. F., et al. (2012) · Annals of Neurology · doi:10.1002/ana.23665 · Cited by 193
A ketogenic drink improves cognition in mild cognitive impairment: Results of a 6‐month RCT
Fortier, M., Castellano, C., St‐Pierre, V., Myette‐Côté, É., Langlois, F., Roy, M., Morin, M., Bocti, C., Fülöp, T., Godin, J., et al. (2020) · Alzheimer s & Dementia · doi:10.1002/alz.12206 · Cited by 190
Low‐intensity daily walking activity is associated with hippocampal volume in older adults
Varma, V. R., Chuang, Y., Harris, G. C., Tan, E. J., & Carlson, M. C. (2015) · Hippocampus · doi:10.1002/hipo.22397 · Cited by 188
“…findings are consistent with a meta-analysis showing that physical activity may be more cognitively beneficial for women (Colcombe and Kramer, 2003) as well as the results of a number of randomized-clinical trials of exercise (van Uffelen et al., 2008; Baker et al., 2010; Vaughan et al., 2012).”
ResultAnderson‐Hanley, C., Barcelos, N. M., Zimmerman, E. A., Gillen, R. W., Dunnam, M., Cohen, B. D., Yerokhin, V., Miller, K. E., Hayes, D. J., Arciero, P. J., et al. (2018) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2018.00076 · Cited by 194
“…including exercise, to improve cognitive function and decrease risk of progression to dementia among individuals with MCI (e.g., Kramer et al., 1999; Colcombe and Kramer, 2003; Studenski et al., 2006; Angevaren et al., 2008; Baker et al., 2010; Geda et al., 2010; Martin et al., 2011).”
BackgroundNutrition and neurodegeneration: epidemiological evidence and challenges for future research
Guyonnet, S., Secher, M., & Vellas, B. J. (2013) · British Journal of Clinical Pharmacology · doi:10.1111/bcp.12058 · Cited by 186
Neuroimmunological effects of physical exercise in depression
Eyre, H. A., & Baune, B. T. (2011) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2011.09.015 · Cited by 201
“Exercise is also found to be beneficial in the treatment and prevention of cognitive disorders (Alzheimer’s disease and mild cognitive impairment), Parkinson’s disease, bipolar disorder, schizophrenia and anxiety disorder (Ng et al., 2007; Baker et al., 2010; Gorczynski and Faulkner, 2010; Radak et al., 2010; Gleeson…”
BackgroundPeng, L., Xu, L., & Ouyang, W. (2013) · PLoS ONE · doi:10.1371/journal.pone.0079624 · Cited by 188
Kennedy, G., Hardman, R. J., Macpherson, H., Scholey, A. B., & Pipingas, A. (2016) · Journal of Alzheimer s Disease · doi:10.3233/jad-160665 · Cited by 199
“However, while one study, which involved six months of regular high intensity exercise, found improvements in insulin sensitivity [245], the other study used a less vigorous intervention of tai-chi over only 12 weeks and found no such improvement [246].”
Rizzo, L. B., Costa, L. G., Mansur, R. B., Swardfager, W., Belangero, S. I., Grassi-Oliveira, R., McIntyre, R. S., Bauer, M. E., & Brietzke, E. (2014) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2014.02.004 · Cited by 183
Dose-Response of Aerobic Exercise on Cognition: A Community-Based, Pilot Randomized Controlled Trial
Vidoni, E. D., Johnson, D. K., Morris, J. K., Sciver, A. R. V., Greer, C. S., Billinger, S. A., Donnelly, J. E., & Burns, J. M. (2015) · PLoS ONE · doi:10.1371/journal.pone.0131647 · Cited by 196
Wells, R. E., Yeh, G. Y., Kerr, C. E., Wolkin, J. R., Davis, R. B., Tan, Y. H. V., Spaeth, R. B., Wall, R. B., Walsh, J. N., Kaptchuk, T. J., et al. (2013) · Neuroscience Letters · doi:10.1016/j.neulet.2013.10.001 · Cited by 179
Cognitive Aging and the Promise of Physical Activity
Erickson, K. I., Donofry, S. D., Sewell, K. R., Brown, B. M., & Stillman, C. M. (2022) · Annual Review of Clinical Psychology · doi:10.1146/annurev-clinpsy-072720-014213 · Cited by 195
Novelty Interventions to Enhance Broad Cognitive Abilities and Prevent Dementia
Fissler, P., Küster, O. C., Schlee, W., & Kolassa, I. (2013) · Progress in brain research · doi:10.1016/b978-0-444-63327-9.00017-5 · Cited by 192
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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