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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In a Netherlands study, 800 μg daily oral folic acid for 3 years in 818 participants significantly improved cognitive domains that decline with age.
“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]
The Abstract (Participants) describes 33 adults with mild cognitive impairment, and the Abstract (Design) describes a six-month trial; the Methods (Procedure) identifies aerobic exercise and stretching groups. Our copy does not report the claimed Netherlands folic-acid study or its cognitive results (searched: 800 μg, 818 participants, folic acid, Netherlands). (LLM, conf=0.78)
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Wilkinson, C. W., Petrie, E. C., Murray, S., Colasurdo, E. A., Raskind, M. A., & Peskind, E. R. (2001) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.86.2.7232 · Cited by 99 · see citing works
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Elevated urinary free cortisol in patients with dementia
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Prevention of CIND by physical activity: Different impact on VCI-ND compared with MCI
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Human Glucocorticoid Feedback Inhibition Is Reduced in Older Individuals: Evening Study
Wilkinson, C. W. (2001) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.86.2.545 · Cited by 76 · see citing works
Self-citationThe Aging of Executive Functions
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“In humans, results of crosssectional(24) and prospective(25) brain imaging studies suggest that increased aerobic fitness in cognitively healthy older adults is associated with reduced age-related atrophy and increased perfusion in regions that support executive control and memory processes, yet are most vulnerable to…”
Lexical and semantic fluency discrepancy scores in aMCI and early Alzheimer's disease
Lonie, J. A., Herrmann, L. L., Tierney, K. M., Donaghey, C. L., O’Carroll, R. E., Lee, A., & Ebmeier, K. P. (2008) · Journal of Neuropsychology · doi:10.1348/174866408x289935 · Cited by 62 · cited 4× · see citing works
“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.”
InfluentialTraustadóttir, T., Bosch, P. R., Cantu, T., & Matt, K. S. (2004) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2003-031713 · Cited by 54 · see citing works
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“Although cortisol typically rises following an acute bout of exercise, chronic exposure to exercise and consequent improvement in aerobic fitness reduces acute HPA axis reactivity.(55,56) In older adults, cortisol levels are elevated relative to younger adults,(57,58) and this age effect is almost 3 times greater for…”
Mattson, M. P. (2002) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(02)00032-5 · Cited by 48 · see citing works
High plasma levels of cortisol in patients with senile dementia of the Alzheimer's type.
Masugi, F., Ogihara, T., Sakaguchi, K., Otsuka, A., Tsuchiya, Y., Morimoto, S., Kumahara, Y., Saeki, S., & Nishide, M. (1989) · PubMed · Cited by 48 · see citing works
The impact of age, weight and gender on BDNF levels in human platelets and plasma
Lommatzsch, M. (2004) · Neurobiology of Aging · doi:10.1016/s0197-4580(04)00107-1 · Cited by 39 · see citing works
Peskind, E. R., Raskind, M. A., Wingerson, D. K., Pascualy, M., Thal, L. J., Dobie, D. J., & Wilkinson, C. W. (1996) · Biological Psychiatry · doi:10.1016/0006-3223(95)00318-5 · Cited by 37 · cited 1× · see citing works
“Hypothalamic-pituitary-adrenal axis overactivity may ultimately compromise brain resilience to stress, increasing vulnerability to neurodegeneration.(57,66,72-74) Neurodegenerative disease has been linked to changes in growth factors such as BDNF.”
Self-citationExercise, Aging, and Cognition: Healthy Body, Healthy Mind?
Rogers, W. A., & Fisk, A. D. (2001) · CRC Press eBooks · doi:10.1201/b12459-12 · Cited by 37 · see citing works
A computer-assisted cognitive test battery for aged monkeys
Buccafusco, J. J., Terry, A. V., & Murdoch, P. B. (2002) · Journal of Molecular Neuroscience · doi:10.1007/s12031-002-0030-6 · Cited by 29 · see citing works
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Self-citationDeuster, P. A. (1998) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.83.9.3332 · Cited by 24 · see citing works
Exercise assessment of arthritic and elderly individuals
Hagberg, J. M. (1994) · Baillière s Clinical Rheumatology · doi:10.1016/s0950-3579(05)80223-7 · Cited by 23 · see citing works
Increased CSF cortisol in AD is a function of APOE genotype
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Cardiorespiratory fitness and brain atrophy in early Alzheimer disease
Talbott, J. A. (2009) · Yearbook of Psychiatry and Applied Mental Health · doi:10.1016/s0084-3970(08)79065-0 · Cited by 8 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
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 · see citing works
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 · see citing works
“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 · see citing works
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 · see citing works
“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 · see citing works
Nagamatsu, L. S., Chan, A., Davis, J. C., Beattie, B. L., Graf, P., Voss, M. W., Sharma, D., & Liu-Ambrose, T. Y. L. (2013) · Journal of Aging Research · doi:10.1155/2013/861893 · Cited by 1,090 · see citing works
“Furthermore, emerging evidence also suggests that exercise training has cognitive benefits for seniors with MCI.”
BackgroundInfluentialBridging animal and human models of exercise-induced brain plasticity
Voss, M. W., Vivar, C., Kramer, A. F., & van Praag, H. (2013) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2013.08.001 · Cited by 1,030 · see citing works
Exercise-linked FNDC5/irisin rescues synaptic plasticity and memory defects in Alzheimer’s models
Lourenco, M. V., Frozza, R. L., de Freitas, G. B., Zhang, H., Kincheski, G. C., Ribeiro, F. C., Gonçalves, R. A., Clarke, J. R., Beckman, D., Staniszewski, A., et al. (2019) · Nature Medicine · doi:10.1038/s41591-018-0275-4 · Cited by 935 · see citing works
A meta-analytic review of the effects of exercise on brain-derived neurotrophic factor
Szuhany, K. L., Bugatti, M., & Otto, M. W. (2015) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2014.10.003 · Cited by 909 · see citing works
Bherer, L., Erickson, K. I., & Liu-Ambrose, T. (2013) · Journal of Aging Research · doi:10.1155/2013/657508 · Cited by 899 · see citing works
“A recent randomized clinical study evaluated the impact of a six-month aerobic exercise intervention in individuals with mild cognitive impairment [81].”
BackgroundKnaepen, K., Goekint, M., Heyman, E. M., & Meeusen, R. (2010) · Sports Medicine · doi:10.2165/11534530-000000000-00000 · Cited by 882 · see citing works
Physical Exercise as a Preventive or Disease-Modifying Treatment of Dementia and Brain Aging
Ahlskog, J. E., Geda, Y. E., Graff-Radford, N. R., & Petersen, R. C. (2011) · Mayo Clinic Proceedings · doi:10.4065/mcp.2011.0252 · Cited by 885 · see citing works
Baker, L. D., Cross, D. J., Minoshima, S., Belongia, D., Watson, G. S., & Craft, S. (2011) · Archives of Neurology · doi:10.1001/archneurol.2010.225 · Cited by 639 · see citing works
Self-citationThe Influence of Exercise on Cognitive Abilities
Gómez‐Pinilla, F., & Hillman, C. H. (2012) · Comprehensive physiology · doi:10.1002/cphy.c110063 · Cited by 683 · see citing works
Kapogiannis, D., & Mattson, M. P. (2011) · The Lancet Neurology · doi:10.1016/s1474-4422(10)70277-5 · Cited by 594 · see citing works
Physical exercise in the prevention and treatment of Alzheimer's disease
la Rosa, A. D., González, G. O., Arc‐Chagnaud, C., Millán-Domingo, F., Salvador‐Pascual, A., García-Lucerga, C., Blasco-Lafarga, C., García-Domínguez, E., Carretero, A., Correas, Á. G., et al. (2020) · Journal of sport and health science/Journal of Sport and Health Science · doi:10.1016/j.jshs.2020.01.004 · Cited by 601 · see citing works
“128 Among neurotrophins, BDNF has been extensively studied, and its relationship with exercise and cognitive function has been widely established.(32,50,129) 135 The brain synthesizes about 75% of BDNF under normal conditions.”
BackgroundResultErickson, K. I., Miller, D. L., & Roecklein, K. A. (2011) · The Neuroscientist · doi:10.1177/1073858410397054 · Cited by 550 · see citing works
State of the science on mild cognitive impairment (MCI)
Anderson, N. D. (2019) · CNS Spectrums · doi:10.1017/s1092852918001347 · Cited by 547 · see citing works
Hippocampal insulin resistance and cognitive dysfunction
Biessels, G. J., & Reagan, L. P. (2015) · Nature reviews. Neuroscience · doi:10.1038/nrn4019 · Cited by 536 · see citing works
High Cortisol and the Risk of Dementia and Alzheimer’s Disease: A Review of the Literature
Ouanes, S., & Popp, J. (2019) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2019.00043 · Cited by 474 · see citing works
Physical exercise and cognitive performance in the elderly: Current perspectives.
Kirk-Sanchez, N., & McGough, E. (2013) · Clinical Interventions in Aging · doi:10.2147/cia.s39506 · Cited by 465 · see citing works
Exergaming and Older Adult Cognition
Anderson-Hanley, C., Arciero, P. J., Brickman, A. M., Nimon, J. P., Okuma, N., Westen, S. C., Merz, M. E., Pence, B. D., Woods, J. A., Kramer, A. F., et al. (2012) · American Journal of Preventive Medicine · doi:10.1016/j.amepre.2011.10.016 · Cited by 464 · see citing works
“Further, evidence is accumulating that cognitive benefıts may be achieved by way of improved neuronal functions, including neurogenesis, shown by concomitant structural and functional changes in the brain, impacts on biomarkers of Alzheimer’s disease,(18,19) and increases in brain-derived neurotrophic growth factor (B…”
BackgroundDoes vigorous exercise have a neuroprotective effect in Parkinson disease?
Ahlskog, J. E. (2011) · Neurology · doi:10.1212/wnl.0b013e318225ab66 · Cited by 463 · see citing works
Brain metabolic dysfunction at the core of Alzheimer's disease
de la Monte, S. M., & Tong, M. (2014) · Biochemical Pharmacology · doi:10.1016/j.bcp.2013.12.012 · Cited by 462 · see citing works
“In humans, weight loss sufficient to reduce peripheral insulin resistance improves cognitive performance [122, 123] and enhances neuropsychiatric function [124], and reductions in metabolic indices through Mediterranean diet adherence lowers the risk for AD [125].”
BackgroundBrain Insulin Resistance and Deficiency as Therapeutic Targets in Alzheimers Disease
de la Monte, S. M. (2012) · Current Alzheimer Research · doi:10.2174/156720512799015037 · Cited by 446 · see citing works
“Aging is by far the most significant risk factor for AD [434, 436, 465-470] and AD is mediated in large measure by brain insulin resistance and impaired energy metabolism [7, 8].”
BackgroundBarha, C. K., Davis, J. C., Falck, R. S., Nagamatsu, L. S., & Liu-Ambrose, T. (2017) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2017.04.002 · Cited by 432 · see citing works
“We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), CINAHL, and PsychInfo databases to identify all RCTs studying the effects of exercise on cognition.”
InfluentialFiatarone Singh, M. A., Gates, N., Saigal, N., Wilson, G. C., Meiklejohn, J., Brodaty, H., Wen, W., Singh, N., Baune, B. T., Suo, C., et al. (2014) · Journal of the American Medical Directors Association · doi:10.1016/j.jamda.2014.09.010 · Cited by 424 · see citing works
Santos, C. Y., Snyder, P. J., Wu, W., Zhang, M., Echeverria, A., & Alber, J. (2017) · Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring · doi:10.1016/j.dadm.2017.01.005 · Cited by 431 · see citing works
Environment and Brain Plasticity: Towards an Endogenous Pharmacotherapy
Sale, A., Berardi, N., & Maffei, L. (2014) · Physiological Reviews · doi:10.1152/physrev.00036.2012 · Cited by 402 · see citing works
Lin, J. S., O’Connor, E., Rossom, R. C., Perdue, L. A., & Eckstrom, E. (2013) · Annals of Internal Medicine · doi:10.7326/0003-4819-159-9-201311050-00730 · Cited by 412 · see citing works
The Role of the Built Environment in Healthy Aging
Kerr, J., Rosenberg, D. E., & Frank, L. D. (2012) · Journal of Planning Literature · doi:10.1177/0885412211415283 · Cited by 393 · see citing works
“There is also growing evidence that physical activity can improve cognitive function among healthy older adults (Angevaren et al. 2008) as well as those with mild cognitive impairment (Baker et al. 2010; Angevaran et al. 2008).”
BackgroundSelf-citationHuang, X., Zhao, X., Li, B., Cai, Y., Zhang, S., Wan, Q., & Yu, F. (2021) · Journal of sport and health science/Journal of Sport and Health Science · doi:10.1016/j.jshs.2021.05.003 · Cited by 393 · see citing works
“We also planned to perform subgroup analyses by gender and severity of cognitive impairment, given that these 2 variables might affect the participants’ responses to exercise interventions.(33,44) However, during the process of data extraction we found that most of the studies did not report cognition outcomes separat…”
MethodNagamatsu, L. S. (2012) · Archives of Internal Medicine · doi:10.1001/archinternmed.2012.379 · Cited by 385 · see citing works
“Both aerobic training (AT) and resistance training (RT) enhance cognitive performance and functional plasticity in healthy, community-dwelling seniors(3-5) and those with mild cognitive impairment.(6) However, to our knowledge, no intervention study has compared the efficacy of both types of exercise on cognitive func…”
BackgroundSuzuki, T., Shimada, H., Makizako, H., Doi, T., Yoshida, D., Ito, K., Shimokata, H., Washimi, Y., Endo, H., & Kato, T. (2013) · PLoS ONE · doi:10.1371/journal.pone.0061483 · Cited by 390 · see citing works
“[4,5,6,7,8] To our knowledge, this is the first study to demonstrate an improvement in logical memory following multicomponent exercise training among older adults with aMCI.”
BackgroundResultInfluentialPhysical Activity and Cognitive Vitality
Prakash, R. S., Voss, M. W., Erickson, K. I., & Kramer, A. F. (2015) · Annual Review of Psychology · doi:10.1146/annurev-psych-010814-015249 · Cited by 376 · see citing works
“…effect of aerobic exercise training on cognitive function in an MCI population that is either low in self-reported activity before the intervention (Baker et al. 2010, Gates et al. 2013, Nagamatsu et al. 2013) or relatively active at baseline (Lautenschlager et al. 2008, van Uffelen et al. 2008).”
Backgroundten Brinke, L. F., Bolandzadeh, N., Nagamatsu, L. S., Hsu, C. L., Davis, J. C., Miran-Khan, K., & Liu-Ambrose, T. (2015) · British Journal of Sports Medicine · doi:10.1136/bjsports-2013-093184 · Cited by 380 · see citing works
The Mental Activity and eXercise (MAX) Trial
Barnes, D. E., Santos‐Modesitt, W., Poelke, G., Kramer, A. F., Castro, C. M., Middleton, L. E., & Yaffe, K. S. (2013) · JAMA Internal Medicine · doi:10.1001/jamainternmed.2013.189 · Cited by 376 · see citing works
Hoffmann, K., Sobol, N. A., Frederiksen, K. S., Beyer, N., Vogel, A., Vestergaard, K., Brændgaard, H., Gottrup, H., Lolk, A., Wermuth, L., et al. (2016) · Journal of Alzheimer s Disease · doi:10.3233/jad-150817 · Cited by 356 · see citing works
“Further, some studies in patients with AD or MCI have relied on unsupervised, caregiver supervised, or partly unsupervised exercise [8, 10, 11].”
BackgroundInfluentialGates, N., Fiatarone Singh, M. A., Sachdev, P. S., & Valenzuela, M. (2013) · The American Journal of Geriatric Psychiatry · doi:10.1016/j.jagp.2013.02.018 · Cited by 355 · see citing works
“Am J Geriatr Psychiatry 21:11, November 2013 Data from nonsignificant findings were not always provided.(26) General cognitive function was measured using MMSE,(24,25,27,29,31,34) ADASCog,(29,37) and CAMCOG,(30) and fluid intelligence with subtests of the WAIS-R.”
MethodMang, C. S., Campbell, K. L., Ross, C. J., & Boyd, L. A. (2013) · Physical Therapy · doi:10.2522/ptj.20130053 · Cited by 352 · see citing works
Dinoff, A., Herrmann, N., Swardfager, W., Liu, C. S., Sherman, C., Chan, S. W., & Lanctôt, K. L. (2016) · PLoS ONE · doi:10.1371/journal.pone.0163037 · Cited by 343 · see citing works
Aerobic exercise for Alzheimer's disease: A randomized controlled pilot trial
Morris, J. K., Vidoni, E. D., Johnson, D. K., Sciver, A. R. V., Mahnken, J. D., Honea, R. A., Wilkins, H., Brooks, W. M., Billinger, S. A., Swerdlow, R. H., et al. (2017) · PLoS ONE · doi:10.1371/journal.pone.0170547 · Cited by 331 · see citing works
Coelho, F. G. D. M., Gobbi, S., Andreatto, C. A. A., Corazza, D. I., Pedroso, R. V., & Santos-Galduróz, R. F. (2013) · Archives of Gerontology and Geriatrics · doi:10.1016/j.archger.2012.06.003 · Cited by 327 · see citing works
Jackson, J. C., Ely, E. W., Morey, M. C., Anderson, V. M., Denne, L. B., Clune, J., Siebert, C. S., Archer, K. R., Torres, R., Janz, D., et al. (2012) · Critical Care Medicine · doi:10.1097/ccm.0b013e3182373115 · Cited by 318 · see citing works
“The benefits of vigorous physical exercise on cognitive functioning have been widely demonstrated in the context of randomized controlled trials with other populations (70, 71).”
BackgroundCognitive symptoms of Alzheimer’s disease: clinical management and prevention
Joe, E., & Ringman, J. M. (2019) · BMJ · doi:10.1136/bmj.l6217 · Cited by 324 · see citing works
Sanders, L. M. J., Hortobágyi, T., Gemert, S. L. B., van der Zee, E. A., & van Heuvelen, M. J. G. (2019) · PLoS ONE · doi:10.1371/journal.pone.0210036 · Cited by 319 · see citing works
“Differences in inclusion criteria yielded variations in the baseline levels of physical activity (PA) of the participants: in four studies [49,51,52,82] only sedentary participants were included, whereas the other studies did not focus on Dose-response effects of exercise on cognition in old adults with and without co…”
BackgroundScreening for Cognitive Impairment in Older Adults
Patnode, C. D., Perdue, L. A., Rossom, R. C., Rushkin, M. C., Redmond, N., Thomas, R. G., & Lin, J. S. (2020) · JAMA · doi:10.1001/jama.2019.22258 · Cited by 310 · see citing works
BDNF mediates improvements in executive function following a 1-year exercise intervention.
Leckie, R. L., Oberlin, L. E., Voss, M. W., Prakash, R. S., Szabo-Reed, A., Chaddock-Heyman, L., Phillips, S. M., Gothe, N. P., Mailey, E., Vieira-Potter, V. J., et al. (2014) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2014.00985 · Cited by 307 · see citing works
“However, more chronic and longer-term exercise programs have not reliably demonstrated increases in BDNF levels (Baker et al., 2010; Erickson et al., 2011; Ruscheweyh et al., 2011).”
BackgroundLeisure activities, cognition and dementia
Wang, H.-X., Xu, W., & Pei, J.-J. (2012) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2011.09.002 · Cited by 289 · see citing works
Baker, L. D., Frank, L. L., Foster‐Schubert, K. E., Green, P. S., Wilkinson, C. W., McTiernan, A., Cholerton, B., Plymate, S. R., Fishel, M. A., Watson, G. S., et al. (2010) · Journal of Alzheimer s Disease · doi:10.3233/jad-2010-100768 · Cited by 293 · see citing works
Self-citationZheng, G., Xia, R., Zhou, W., Tao, J., & Chen, L. (2016) · British Journal of Sports Medicine · doi:10.1136/bjsports-2015-095699 · Cited by 292 · see citing works
Exercise counteracts declining hippocampal function in aging and Alzheimer's disease
Intlekofer, K. A., & Cotman, C. W. (2012) · Neurobiology of Disease · doi:10.1016/j.nbd.2012.06.011 · Cited by 286 · see citing works
“IGF-1 can be boosted by exercise (Baker et al., 2010), particularly in the form of strength training (Vale et al., 2009).”
BackgroundExercise, cognitive function, and aging
Barnes, J. N. (2015) · AJP Advances in Physiology Education · doi:10.1152/advan.00101.2014 · Cited by 291 · see citing works
“(5) enrolled MCI patients into a 6-mo trial of either stretching or aerobic exercise.”
BackgroundThe Lifestyle Interventions and Independence for Elders Study: Design and Methods
Fielding, R. A., Rejeski, W. J., Blair, S. N., Church, T. S., Espeland, M. A., Gill, T. M., Guralnik, J. M., Hsu, F.-C., Katula, J. A., King, A. C., et al. (2011) · The Journals of Gerontology Series A · doi:10.1093/gerona/glr123 · Cited by 278 · see citing works
Physical activity and cognitive function in individuals over 60 years of age: a systematic review
Parimon, T., Cusack, B. J., Rea, I. M., & Carvalho, A. (2014) · Clinical Interventions in Aging · doi:10.2147/cia.s55520 · Cited by 276 · see citing works
Blood-brain barrier permeability and physical exercise
Małkiewicz, M. A., Szarmach, A., Sabisz, A., Cubała, W. J., Szurowska, E., & Winklewski, P. J. (2019) · Journal of Neuroinflammation · doi:10.1186/s12974-019-1403-x · Cited by 276 · see citing works
Öhman, H., Savikko, N. M., Strandberg, T. E., & Pitkälä, K. H. (2014) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000365388 · Cited by 271 · see citing works
de la Monte, S. M. (2012) · Drugs · doi:10.2165/11597760-000000000-00000 · Cited by 265 · see citing works
“benefits in vigorous aerobic exercise for improving cognitive performance in individuals withMCI.([176])”
BackgroundJuster, R.-P., Bizik, G., Picard, M., Arsenault-Lapierre, G., Sindi, S., Trepanier, L., Marin, M.-F., Wan, N., Sekerovic, Z., Lord, C., et al. (2011) · Development and Psychopathology · doi:10.1017/s0954579411000289 · Cited by 268 · see citing works
“…with increased neurogenesis (Olson, Eadie, Ernst, & Christie, 2006), larger HV, and improved memory performance (Erickson et al., 2009), as well as enhanced executive functioning (Baker et al., 2010; Colcombe, Kramer, McAuley, Erickson, & Scalf, 2004; Etgen et al., 2010; Kramer et al., 1999).”
BackgroundLam, F. M. H., Huang, M., Liao, L.-R., Chung, R. C. K., Kwok, T. C. Y., & Pang, M. Y. C. (2017) · Journal of physiotherapy · doi:10.1016/j.jphys.2017.12.001 · Cited by 266 · see citing works
Chen, F., Etnier, J. L., Chan, K., Chiu, P.-K., Hung, T.-M., & Chang, Y. (2020) · Sports Medicine · doi:10.1007/s40279-020-01292-x · Cited by 259 · see citing works
Physical Exercise Protects Against Alzheimer's Disease in 3xTg-AD Mice
García‐Mesa, Y., López, J. C., Giménez‐Llort, L., Revilla, S., Guerra, R., Gruart, A., LaFerla, F. M., Cristòfol, R. M., Delgado-Garcia, J. M., & Sanfeliu, C. (2011) · Journal of Alzheimer s Disease · doi:10.3233/jad-2011-101635 · Cited by 253 · see citing works
“These effects are gender-specific even though both men and women are responsive to training [13].”
BackgroundSuzuki, T., Shimada, H., Makizako, H., Doi, T., Yoshida, D., Tsutsumimoto, K., Anan, Y., Uemura, K., Lee, S., & Park, H. (2012) · BMC Neurology · doi:10.1186/1471-2377-12-128 · Cited by 252 · see citing works
“reported that high intensity aerobic exercise increased VFT scores in older women with MCI [16].”
BackgroundInfluentialSong, D., Yu, D. S. F., Li, P. W. C., & Lei, Y. (2018) · International Journal of Nursing Studies · doi:10.1016/j.ijnurstu.2018.01.002 · Cited by 244 · see citing works
Cognitive intervention in amnestic Mild Cognitive Impairment: A systematic review
Simon, S. S., Yokomizo, J. E., & Bottino, C. M. C. (2012) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2012.01.007 · Cited by 245 · see citing works
Halperin, J. M., & Healey, D. M. (2011) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2010.07.006 · Cited by 237 · see citing works
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 · see citing works
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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 · see citing works
Targeting Neuroinflammation to Treat Alzheimer’s Disease
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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 · see citing works
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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 · see citing works
Brown, B. M., Peiffer, J. J., & Martins, R. N. (2012) · Molecular Psychiatry · doi:10.1038/mp.2012.162 · Cited by 228 · see citing works
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 · see citing works
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 242 · see citing works
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 · see citing works
“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 212 · see citing works
“…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 216 · see citing works
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 · see citing works
“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).”
BackgroundHuckans, 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 202 · see citing works
“…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 – –”
InfluentialCoelho, 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 · see citing works
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“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).”
BackgroundInfluentialBiazus-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 · see citing works
Current 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 · see citing works
“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 207 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
“…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 188 · see citing works
“…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
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Neuroimmunological effects of physical exercise in depression
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“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…”
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“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].”
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Dose-Response of Aerobic Exercise on Cognition: A Community-Based, Pilot Randomized Controlled Trial
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Cognitive Aging and the Promise of Physical Activity
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Fissler, P., Küster, O., Schlee, W., & Kolassa, I. (2013) · Progress in Brain Research · doi:10.1016/b978-0-444-63327-9.00017-5 · Cited by 160 · see citing works
- 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 › Physiology › Physical Activity and Health
- Health Sciences › Medicine › Physiology › 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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