Cited by 1,171Dementia and Cognitive Impairment ResearchPhysical Activity and HealthAlzheimer's disease research and treatments

The DOI matches its Crossref record; 88 of the 89 references it cites were found in a registry or an index.

Effects of Aerobic Exercise on Mild Cognitive Impairment: A Controlled Trial

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Baker, Laura D., Frank, Laura L., Foster-Schubert, Karen, Green, Pattie S., Wilkinson, Charles W., McTiernan, Anne, Plymate, Stephen R., Fishel, Mark A., Watson, G. Stennis, Cholerton, Brenna A., Duncan, Glen E., Mehta, Pankaj D., Craft, Suzanne·2010·Archives of Neurology

DOI 10.1001/archneurol.2009.307PMC PMC3056436

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Abstract

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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Homeostasis model assessment: insulin resistance and ?-cell function from fasting plasma glucose and insulin concentrations in man
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Influential

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“Physical exercise has been positioned as a pill to boost cognitive and executive functions in mild cognitive impairment [39,40]; nonetheless, the underlying mechanisms of cognitive impairment in post-COVID-19 patients are unclear [41], although it seems that neuroinflammation is one of the determining factors.”
Background
A Randomized Controlled Clinical Trial of the Seattle Protocol for Activity in Older Adults
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“(4) found that aerobic exercise reduced selective attention deficits caused by mild cognitive impairment, although stretching did not.”
Background
Physical activity and beta-amyloid pathology in Alzheimer's disease
Ebrahimi, K., Majdi, A., Baghaiee, B., Hosseini, S. H., & Sadigh‐Eteghad, S. (2017) · EXCLI journal · doi:10.17179/excli2017-475 · Cited by 42
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“Conversely, a high-intensity AET program showed the sex-speciﬁc beneﬁts for improving executive function in amnestic MCI patients [38], suggesting that high intensity AET aiming to increase VO 2peak may improve cognitive performance in MCI patients.”
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“The primary outcome measure is ST, which we selected because 1) previous studies using exercise training showed that exercise training can improve executive functions [45,46], 2) ST is a task that is often used to measure executive functions [47,48], and 3) ST has been standardized, with high reliability and validity…”
Method
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Anstey, K. J., Eramudugolla, R., Hosking, D. E., Lautenschlager, N. T., & Dixon, R. A. (2015) · The Journal of Prevention of Alzheimer s Disease · doi:10.14283/jpad.2015.75 · Cited by 40
“Some studies have reported significant benefits in the cognitive domains of attention, executive functions and memory (31, 32); however, other reports did not demonstrate such benefits (33).”
Result
Improved Functional Performance in Individuals With Dementia After a Moderate-Intensity Home-Based Exercise Program: A Randomized Controlled Trial
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“, 2010), physical exercise (Baker et al., 2010; Yaffe et al., 2001), and nutritional modifications (Naismith et al.”
Background
The effect of exercise intervention on cognitive performance in persons at risk of, or with, dementia: A systematic review and meta-analysis
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“Furthermore, a comprehensive exercise program for fall prevention typically requires more than 1h to complete (Hauer et al., 2012; Baker et al., 2010).”
Background
Effectiveness of a Personalized Brain-Computer Interface System for Cognitive Training in Healthy Elderly: A Randomized Controlled Trial
Yeo, S. N., Lee, T.-S. W., Sng, W. T., Heo, M. Q., Bautista, D., Cheung, Y. B., Zhang, H., Wang, C., Chin, Z. Y., Feng, L., et al. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-180450 · Cited by 40
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“Second, intervention studies in mild cognitive impairment [5] and AD [6–9] indicate that physical exercise improves cognitive function and other symptoms of AD.”
Background
Association of Cognitive Impairment With Treatment and Outcomes in Older Myocardial Infarction Patients: A Report From the NCDR Chest Pain–MI Registry
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“In a recent report, elderly adults with MCI performed aerobic exercise four times per week during 6 months meaningfully increased executive function (heart rate reserve was 75% to 85%) [33].”
Background
Effects of exercise on cognition and Alzheimer's biomarkers in a randomized controlled trial of adults with mild cognitive impairment: The EXERT study
Baker, L. D., Pa, J., Katula, J. A., Aslanyan, V., Salmon, D. P., Jacobs, D. M., Chmelo, E. A., Hodge, H., Morrison, R. H., Matthews, G., et al. (2025) · Alzheimer s & Dementia · doi:10.1002/alz.14586 · Cited by 41
“26,31,33,40,49,50 Thetrialwaspoweredtoconservativelyaccom-modate20%attrition.”
Self-citation
Rationale for Combined Exercise and Cognition-Focused Interventions to Improve Functional Independence in People with Dementia
Thom, J. M., & Clare, L. (2010) · Gerontology · doi:10.1159/000322198 · Cited by 36
Effects of Metabolic Syndrome on Cognitive Performance of Adults During Exercise
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“In addition to direct physical and physiological effects, exercise has been shown to have positive effects on cognitive processing, memory and other neurobehavioral symptoms in multiple populations (Colcombe and Kramer 2003; Baker et al. 2010; Tanaka et al. 2009; Carruthers et al. 2014).”
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Townsend, L. K., MacPherson, R. E. K., & Wright, D. C. (2021) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgab333 · Cited by 36
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“Considering the greater prevalence of AD and faster progression from MCI to AD in women (Podcasy and Epperson, 2016), potential gender differences have been investigated by Baker et al. (2010).”
Risks and Benefits of Clinical Diagnosis Around the Time of Dementia Onset
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“For example, increased physical activity can decrease depression and reduce behavioral disturbances (Teri et al., 2003) and may slow cognitive decline (Baker et al., 2010), while behavioral therapy has been shown to significantly increase quality of life (Teri et al., 2005).”
Background
Guiding Research and Practice: A Conceptual Model for Aerobic Exercise Training in Alzheimer’s Disease
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“Cognitive improvement was also observed in older adults with mild cognitive impairment who participated in aerobic exercise training.(25) The evidence above collectively suggests that aerobic exercise training could probably benefit older adults with AD via both the physiologic cardiorespiratory fitness and the neurop…”
Background
High Cardiorespiratory Fitness Is Negatively Associated with Daily Cortisol Output in Healthy Aging Men
Lucertini, F., Ponzio, E., Palma, M. D., Galati, C., Federici, A., Barbadoro, P., D’Errico, M. M., Prospero, E., Ambrogini, P., Cuppini, R., et al. (2015) · PLoS ONE · doi:10.1371/journal.pone.0141970 · Cited by 36
“After a 6-month aerobic training program, a reduction in serum cortisol levels was described in older women, but not in men [31].”
BackgroundInfluential
Effect of Interval and Continuous Aerobic Training on Basal Serum and Plasma Brain-Derived Neurotrophic Factor Values in Seniors: A Systematic Review of Intervention Studies
Enette, L., Vogel, T., Fanon, J. L., & Lang, P. O. (2017) · Rejuvenation Research · doi:10.1089/rej.2016.1886 · Cited by 36
“15,43–50 The studies enrolled people with mild cognitive impairment (MCI), 39,41,44,50 depressive symptoms according to the assessment with the Geriatric Depressive Scale (but not formally depressed), 47 PD, 38,40 glucose intolerance, 43 or simply healthy individuals 15,42,45,46,48,49 When 13/14…”
Influential
The association between physical activity and cognition in men with and without HIV infection
Monroe, A. K., Zhang, L., Jacobson, L. P., Plankey, M. W., Brown, T. T., Miller, E. N., Martin, E. M., Becker, J. T., Levine, A. M., Ragin, A. B., et al. (2017) · HIV Medicine · doi:10.1111/hiv.12490 · Cited by 36
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Aerobic exercise improves hippocampal blood flow for hypertensive Apolipoprotein E4 carriers
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“In a randomized-controlled intervention (Baker et al., 2010), high intensity exercise (experimental group, n = 19) was compared to stretching (control group, n = 10) with respect to pre- to postcognitive performance and several biomarkers.”
Method
Effects of Virtual Reality Physical and Cognitive Training Intervention On Cognitive Abilities of Elders with Mild Cognitive Impairment
Baldimtsi, E. N., Mouzakidis, C., Karathanasi, E. M., Verykouki, E., Hassandra, M., Galanis, E., Hatzigeorgiadis, A., Γούδας, Μ., Zikas, P., Evangelou, G., et al. (2023) · Journal of Alzheimer s Disease Reports · doi:10.3233/adr-230099 · Cited by 36
“…like global cognition, logical memory, inhibitory control, attention, and executive functions, like Symbol Digit tests, Verbal Fluency, and Stroop [17, 19–23]—motor abilities, quality of life and reductions in psychological symptoms, like depression and anxiety in older adults with MCI [24].”
Method
Long-term proteasomal inhibition in transgenic mice by UBB+1 expression results in dysfunction of central respiration control reminiscent of brainstem neuropathology in Alzheimer patients
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Perneczky, R. (2019) · Phlebolymphology · doi:10.31887/dcns.2019.21.1/rperneczky2 · Cited by 40
Acute exercise increases circulating IGF-1 in Alzheimer’s disease patients, but not in older adults without dementia
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“Previous research has shown minor improvements, as a function of participation in physical activity and exercise, in cognitive and brain health in older adults [3, 4].”
Background
Physical Exercise Improves Cognitive Function in Older Adults with Stage 3–4 Chronic Kidney Disease: A Randomized Controlled Trial
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Modulating heart rate oscillation affects plasma amyloid beta and tau levels in younger and older adults
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A Cluster Randomized Controlled Trial of Nonpharmacological Interventions for Old-Old Subjects with a Clinical Dementia Rating of 0.5: The Kurihara Project
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Exercise improves cognitive function in aging patients.
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Current and Emerging Therapies for Alzheimer’s Disease
Nygaard, H. B. (2013) · Clinical Therapeutics · doi:10.1016/j.clinthera.2013.09.009 · Cited by 32
Aerobic Exercise in People with Multiple Sclerosis
Swank, C., Thompson, M. E., & Medley, A. (2013) · International Journal of MS Care · doi:10.7224/1537-2073.2012-037 · Cited by 32
Exercise Training on Locomotion in Patients with Alzheimer’s Disease: A Feasibility Study
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“One study evaluated the effect of a moderate-intensity exercise program in patients with mild cognitive impairment (Baker et al., 2010), but it is not known whether a similar program is feasible in patients with AD.”
Background
Limited Health Literacy and Decline in Executive Function in Older Adults
Sequeira, S., Eggermont, L. H. P., Silliman, R. A., Bickmore, T., Henault, L. E., Winter, M. R., Nelson, K. P., & Paasche‐Orlow, M. K. (2013) · Journal of Health Communication · doi:10.1080/10810730.2013.825673 · Cited by 34
Exercise Increases the Dynamics of Diurnal Cortisol Secretion and Executive Function in People With Amnestic Mild Cognitive Impairment
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Physical Activity in Midlife is not Associated with Cognitive Health in Later Life Among Cognitively Normal Older Adults
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“Several trials reporting a relationship between improved physical activity and slower cognitive decline broke randomization or reported positive results for a post-priori subgroup [8, 44].”
Effects of Aerobic and Resistance Exercise Interventions on Cognitive and Physiologic Adaptations for Older Adults with Mild Cognitive Impairment: A Systematic Review and Meta-Analysis of Randomized Control Trials
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“Baker (2010) [11] RCT: Aerobic exercise (n = 19) vs.”
Neurocognitive Plasticity Is Associated with Cardiorespiratory Fitness Following Physical Exercise in Older Adults with Amnestic Mild Cognitive Impairment
Yogev‐Seligmann, G., Eisenstein, T., Ash, E. L., Giladi, N., Sharon, H., Nachman, S., Bregman, N., Kodesh, E., Hendler, T., & Lerner, Y. (2021) · Journal of Alzheimer s Disease · doi:10.3233/jad-201429 · Cited by 36
“Several studies that examined the effect of exercise interventions in aMCI [32–37] demonstrated improvement in cognitive performance.”
Longitudinal Associations between the Neighborhood Built Environment and Cognition in US Older Adults: The Multi-Ethnic Study of Atherosclerosis
Besser, L. M., Chang, L., Hirsch, J. A., Rodrı́guez, D. A., Renne, J. L., Rapp, S. R., Fitzpatrick, A. L., Heckbert, S. R., Kaufman, J. D., & Hughes, T. M. (2021) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph18157973 · Cited by 31
“Despite finding that PA was not a mediator, other studies found that it was associated with processing speed and mediated BE-cognition associations [22,41].”
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Cardiorespiratory Response to Exercise Testing in Individuals With Alzheimer's Disease
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The Role of Physical Fitness in the Neurocognitive Performance of Task Switching in Older Persons with Mild Cognitive Impairment
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“Recently, Baker et al. [48] examined the effects of aerobic exercise on aMCI, and found that six months of high-intensity (75–85% of heart rate reserve) exercise intervention had sex-speciﬁc effects on cognition.”
Influential
Disease-modifying therapies for Alzheimer’s disease: Clinical trial progress and opportunity
Zhang, Y., Chen, J., Li, Y., Jiao, B., & Luo, S. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102595 · Cited by 34
Development of an exercise intervention to improve cognition in people with mild to moderate dementia: Dementia And Physical Activity (DAPA) Trial, registration ISRCTN32612072
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Physical activity, body composition and general health status of physically active students of the University of the Third Age (U3A)
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“The effect of physical activity level in older adults on selective cognitive functions, especially executive-control processes, was confirmed also in longitudinal (Baker et al., 2010; Lindwall et al., 2012) and meta-analytical studies (Bherer, Erickson, & Liu-Ambrose, 2013; Colcombe & Kramer, 2003), although these res…”
Background
Walking With Meaning
McDuff, J., & Phinney, A. (2015) · Global Qualitative Nursing Research · doi:10.1177/2333393615605116 · Cited by 30
“More recent research suggests that this may also hold true for those with neurocognitive deficits who are at increased risk for developing dementia (Baker et al., 2010; Lautenschlager et al., 2008; Nagamatsu, Handy, Hsu, Voss, & Liu-Ambrose, 2012).”
Background
Effect of physical exercise on cognitive function and brain measures after chemotherapy in patients with breast cancer (PAM study): protocol of a randomised controlled trial
Witlox, L., Schagen, S. B., de Ruiter, M. B., Geerlings, M. I., Peeters, P. H. M., Koevoets, E. W., van der Wall, E., Stuiver, M. M., Sonke, G. S., Velthuis, M. J., et al. (2019) · BMJ Open · doi:10.1136/bmjopen-2018-028117 · Cited by 31
Effects of Aerobic Training on Cognition and Brain Glucose Metabolism in Subjects with Mild Cognitive Impairment
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“Because some evidence exists indicating that women may achieve greater cognitive benefits from PE than men[14], thegeneralizabilityofourresultsmaybecompromised.”
Effect of Baduanjin exercise on cognitive function in older adults with mild cognitive impairment: study protocol for a randomised controlled trial
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Rehabilitation of patients with glioma
Vargo, M. M., Henriksson, R., & Salander, P. (2016) · Handbook of clinical neurology · doi:10.1016/b978-0-12-802997-8.00017-7 · Cited by 30
Bénéfices de l’activité physique en endurance chez les seniors âgés de 70 ans ou plus : une revue systématique
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Exercise-Induced Neuroplasticity: Adaptive Mechanisms and Preventive Potential in Neurodegenerative Disorders
Mansoor, M. A., Ibrahim, A., Hamide, A., Tran, T., Candreva, E., & Baltaji, J. (2025) · Physiologia · doi:10.3390/physiologia5020013 · Cited by 38
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Changing Perspectives on Alzheimer's Disease: Thinking Outside the Amyloid Box
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“DISCLOSURE STATEMENT Authors’ disclosures available”
Effects of low and moderate acute resistance exercise on executive function in community-living older adults.
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The Impact of the Six Pillars of Lifestyle Medicine on Brain Health
Jaqua, E. E., Biddy, E., Moore, C., & Browne, G. (2023) · Cureus · doi:10.7759/cureus.34605 · Cited by 35
“The exercise intensity was also studied and demonstrated a positive correlation with extraneous physical activity and increased blood flow to the brain, improving executive function, increasing brain size, and decreasing the risk of neurocognitive decline [1,17].”
Background
Ethical considerations of biomarker use in neurodegenerative diseases--a case study of Alzheimer's disease.
Prvulovic, D., & Hampel, H. (2011) · Progress in neurobiology · doi:10.1016/j.pneurobio.2011.11.009 · Cited by 37
“), interventional application of aerobic physical activity has been suggested to modestly modulate cognitive impairments in MCI subjects and may thus represent a promising secondary prevention strategy (Baker et al., 2010).”
Background
Cognitive response to estradiol in postmenopausal women is modified by high cortisol
Baker, L. D., Asthana, S., Cholerton, B., Wilkinson, C. W., Plymate, S. R., Green, P. S., Merriam, G. R., Fishel, M. A., Watson, G. S., Cherrier, M. M., et al. (2011) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2011.07.002 · Cited by 28
Self-citation
Does physical activity influence semantic memory activation in amnestic mild cognitive impairment?
Smith, J. C., Nielson, K. A., Woodard, J. L., Seidenberg, M., Verber, M., Durgerian, S., Antuono, P., Butts, A. M., Hantke, N. C., Lancaster, M. A., et al. (2011) · Psychiatry Research Neuroimaging · doi:10.1016/j.pscychresns.2011.04.001 · Cited by 29
“…neuropsychological test performance in healthy older adults (Lautenschlager et al., 2008), improves semantic memory retrieval in aMCI patients (Baker et al., 2010), and is associated with greater semantic memory-related brain activation in healthy older adults, particularly in those carrying…”
BackgroundInfluential
Effect of physical exercise on brain and lipid metabolism in mouse models of multiple sclerosis
Houdebine, L., Gallelli, C. A., Rastelli, M., Sampathkumar, N. K., & Grenier, J. (2017) · Chemistry and Physics of Lipids · doi:10.1016/j.chemphyslip.2017.06.002 · Cited by 29
A Remote Intervention to Prevent or Delay Cognitive Impairment in Older Adults: Design, Recruitment, and Baseline Characteristics of the Virtual Cognitive Health (VC Health) Study
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“However, the response of BDNF to exercise might differ between genders [39], and circulating BDNF levels might be greater after aerobic exercise, rather than muscle strengthening, in men [40].”
Background
Development and Delivery of a Physical Activity Intervention for People With Huntington Disease
Quinn, L., Trubey, R., Gobat, N., Dawes, H., Edwards, R. T., Jones, C., Townson, J. K., Drew, C. J. G., Kelson, M. J., Poile, V., et al. (2016) · Neurology Report · doi:10.1097/npt.0000000000000119 · Cited by 28
“The workbook is structured into 5 distinct sections: (1) Exercise-Who Me?; (2) HD Experiences in Increasing Physical Activity; (3) Goals; (4) My Physical Activity Plan; and (5) Recording Progress.”
Does the diurnal cycle of cortisol explain the relationship between physical performance and cognitive function in older adults?
Dijckmans, B., Tortosa‐Martínez, J., Pertegáz, N. C. I., González-Caballero, G., Martínez-Pelegrin, B., Manchado, C., Cortell-Tormo, J. M., Chulvi‐Medrano, I., & Clow, A. (2017) · European Review of Aging and Physical Activity · doi:10.1186/s11556-017-0175-5 · Cited by 28
“[26] analyzed cortisol using a one time-point measurement (ranging from 8:00 to 10:00), without controlling for time of awakening, which again might not be the most accurate measure.”
BackgroundMethod

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: Baker, Laura D.
Wilkinson, Charles W.
McTiernan, Anne
Plymate, Stephen R.
Cholerton, Brenna A.
Duncan, Glen E.
Mehta, Pankaj D.
Craft, Suzanne
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)
DOI: 10.1001/archneurol.2009.307
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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Effects of Aerobic Exercise on Mild Cognitive Impairment: A Controlled Trial

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