Hostname: page-component-797576ffbb-6mkhv Total loading time: 0 Render date: 2023-12-08T12:44:22.337Z Has data issue: false Feature Flags: { "corePageComponentGetUserInfoFromSharedSession": true, "coreDisableEcommerce": false, "useRatesEcommerce": true } hasContentIssue false

Physical activity and risk of neurodegenerative disease: a systematic review of prospective evidence

Published online by Cambridge University Press:  23 June 2008

M. Hamer*
Psychobiology Group, Department of Epidemiology and Public Health, University College London, UK
Y. Chida
Psychobiology Group, Department of Epidemiology and Public Health, University College London, UK
*Address for correspondence: M. Hamer, Ph.D., Department of Epidemiology and Public Health, University College London, 1–19 Torrington Place, London WC1E 6BT, UK. (Email:



The association between physical activity and risk of neurodegenerative diseases is not well established. We therefore aimed to quantify this association using meta-analytical techniques.


We searched Medline, the Cochrane Database of Systematic Reviews and Web of Science databases from 1990 to 2007 for prospective epidemiological studies of physical activity and incident dementia, Alzheimer's and Parkinson's disease. We excluded studies of physical activity and cognitive decline without diagnosis of a neurodegenerative disease. Information on study design, participant characteristics, measurement of exposure and outcome variables, adjustment for potential confounding, and estimates of associations was abstracted independently by the two investigators.


We included 16 prospective studies in the overall analysis, which incorporated 163797 non-demented participants at baseline with 3219 cases at follow-up. We calculated pooled relative risk (RR) using a random effects model. The RR of dementia in the highest physical activity category compared with the lowest was 0.72 [95% confidence interval (CI) 0.60–0.86, p<0.001], for Alzheimer's, 0.55 (95% CI 0.36–0.84, p=0.006), and for Parkinson's 0.82 (95% CI 0.57–1.18, p=0.28).


Our results suggest that physical activity is inversely associated with risk of dementia. Future studies should examine the optimal dose of physical activity to induce protection, which presently remains unclear.

Review Article
Copyright © 2008 Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)


Abbott, RD, White, LR, Ross, GW, Masaki, KH, Curb, JD, Petrovitch, H (2004). Walking and dementia in physically capable elderly men. Journal of the American Medical Association 292, 14471453.Google Scholar
Adlard, PA, Perreau, VM, Pop, V, Cotman, CW (2005). Voluntary exercise decreases amyloid load in a transgenic model of Alzheimer's disease. Journal of Neuroscience 25, 42174221.Google Scholar
Albert, MS, Jones, K, Savage, CR, Berkman, L, Seeman, T, Blazer, D, Rowe, JW (1995). Predictors of cognitive change in older persons: MacArthur studies of successful aging. Psychology and Aging 10, 578589.Google Scholar
Begg, CB, Berlin, JA (1989). Publication bias and dissemination of clinical research. Journal of the National Cancer Institute 81, 107115.Google Scholar
Broe, GA, Creasey, H, Jorm, AF, Bennett, HP, Casey, B, Waite, LM, Grayson, DA, Cullen, J (1998). Health habits and risk of cognitive impairment and dementia in old age: a prospective study on the effects of exercise, smoking and alcohol consumption. Australian and New Zealand Journal of Public Health 22, 621623.Google Scholar
Carmelli, D, Swan, GE, Reed, T, Miller, BL, DeCarli, C (1999). Midlife cardiovascular risk factors and brain morphology in identical older male twins. Neurology 52, 11191124.Google Scholar
Chen, H, Zhang, SM, Schwarzschild, MA, Hernan, MA, Ascherio, A (2005). Physical activity and the risk of Parkinson disease. Neurology 64, 664669.Google Scholar
Colcombe, S, Kramer, AF (2003). Fitness effects on the cognitive function of older adults: a meta-analytic study. Psychological Science 14, 125130.Google Scholar
Cotman, CW, Berchtold, NC (2002). Exercise: a behavioral intervention to enhance brain health and plasticity. Trends in Neurosciences 25, 295301.Google Scholar
Cotman, CW, Berchtold, NC, Christie, L-A (2007). Exercise builds brain health: key roles of growth factor cascades and inflammation. Trends in Neurosciences 30, 464472.Google Scholar
Day, DS (2008). Exercise physiologists talk about sex differences. Medicine and Science in Sports and Exercise 40, 646647.Google Scholar
Dersimonian, R, Laird, N (1986). Meta-analysis in clinical trials. Controlled Clinical Trials 7, 177188.Google Scholar
Fabrigoule, C, Letenneur, L, Dartigues, JF, Zarrouk, M, Commenges, D, Barberger-Gateau, P (1995). Social and leisure activities and risk of dementia: a prospective longitudinal study. Journal of the American Geriatrics Society 43, 485490.Google Scholar
Farris, W, Mansourian, S, Chang, Y, Lindsley, L, Eckman, EA, Frosch, MP, Eckman, CB, Tanzi, RE, Selkoe, DJ, Guenette, S (2003). Insulin-degrading enzyme regulates the levels of insulin, amyloid beta-protein, and the beta-amyloid precursor protein intracellular domain in vivo. Proceedings of the National Academy of Sciences USA 100, 41624167.Google Scholar
Ho, SC, Woo, J, Sham, A, Chan, SG, Yu, AL (2001). A 3-year follow-up study of social, lifestyle and health predictors of cognitive impairment in a Chinese older cohort. International Journal of Epidemiology 30, 13891396.Google Scholar
Kivipelto, M, Ngandu, T, Fratiglioni, L, Viitanen, M, Kareholt, I, Winblad, B, Helkala, EL, Tuomilehto, J, Soininen, H, Nissinen, A (2005). Obesity and vascular risk factors at midlife and the risk of dementia and Alzheimer disease. Archives of Neurology 62, 15561560.Google Scholar
Kramer, AF, Colcombe, SJ, McAuley, E, Scalf, PE, Erickson, KI (2005). Fitness, aging and neurocognitive function. Neurobiology of Aging 26 (Suppl. 1), 124127.Google Scholar
Larson, EB, Wang, L, Bowen, JD, McCormick, WC, Teri, L, Crane, P, Kukull, W (2006). Exercise is associated with reduced risk for incident dementia among persons 65 years of age and older. Annals of Internal Medicine 144, 7381.Google Scholar
Laurin, D, Verreault, R, Lindsay, J, MacPherson, K, Rockwood, K (2001). Physical activity and risk of cognitive impairment and dementia in elderly persons. Archives of Neurology 58, 498504.Google Scholar
Lazarov, O, Robinson, J, Tang, YP, Hairston, IS, Korade-Mirnics, Z, Lee, VM, Hersh, LB, Sapolsky, RM, Mirnics, K, Sisodia, SS (2005). Environmental enrichment reduces Abeta levels and amyloid deposition in transgenic mice. Cell 120, 701713.Google Scholar
Linn, RT, Wolf, PA, Bachman, DL, Knoefel, JE, Cobb, JL, Belanger, AJ, Kaplan, EF, D'Agostino, RB (1995). The ‘preclinical phase’ of probable Alzheimer's disease. A 13-year prospective study of the Framingham cohort. Archives of Neurology 52, 485490.Google Scholar
Logroscino, G, Sesso, HD, Paffenbarger, RS Jr., Lee, IM (2006). Physical activity and risk of Parkinson's disease: a prospective cohort study. Journal of Neurology, Neurosurgery and Psychiatry 77, 13181322.Google Scholar
Lytle, ME, Vander Bilt, J, Pandav, RS, Dodge, HH, Ganguli, M (2004). Exercise level and cognitive decline: the MoVIES project. Alzheimer Disease and Associated Disorders 18, 5764.Google Scholar
Marks, BL, Madden, DJ, Bucur, B, Provenzale, JM, White, LE, Cabeza, R, Huettel, SA (2007). Role of aerobic fitness and aging on cerebral white matter integrity. Annals of the New York Academy of Sciences 1097, 171174.Google Scholar
Masui, K (ed.) (2003). Meta-analysis Software User's Guide. Shinko-Koueki Medical Press: Tokyo, pp. 91121.Google Scholar
O'Donovan, G, Biddle, S, Blazevich, A, Boreham, C, Cooper, A, Crank, H, Ekelund, U, Fox, K, Gately, P, Gill, J, Hamer, M, McDermott, I, Murphy, M, Mutrie, N, Reilly, J, Riddoch, C, Saxton, J, Stamatakis, E (in press). Physical activity in the prevention of chronic diseases: the consensus statement of the British Association of Sports and Exercise Sciences. Journal of Sport Sciences.Google Scholar
Podewils, LJ, Guallar, E, Beauchamp, N, Lyketsos, CG, Kuller, LH, Scheltens, P (2007). Physical activity and white matter lesion progression: assessment using MRI. Neurology 68, 1223–126.Google Scholar
Podewils, LJ, Guallar, E, Kuller, LH, Fried, LP, Lopez, OL, Carlson, M, Lyketsos, CG (2005). Physical activity, APOE genotype, and dementia risk: findings from the Cardiovascular Health Cognition Study. American Journal of Epidemiology 161, 639651.Google Scholar
Richards, M, Hardy, R, Wadsworth, ME (2003). Does active leisure protect cognition? Evidence from a national birth cohort. Social Science and Medicine 56, 785792.Google Scholar
Rosendorff, C, Beeri, MS, Silverman, JM (2007). Cardiovascular risk factors for Alzheimer's disease. American Journal of Geriatric Cardiology 16, 143149.Google Scholar
Rovio, S, Kareholt, I, Helkala, EL, Viitanen, M, Winblad, B, Tuomilehto, J, Soininen, H, Nissinen, A, Kivipelto, M (2005). Leisure-time physical activity at midlife and the risk of dementia and Alzheimer's disease. Lancet Neurology 4, 705711.Google Scholar
Schuit, AJ, Feskens, EJ, Launer, LJ, Kromhout, D (2001). Physical activity and cognitive decline, the role of the apolipoprotein e4 allele. Medicine and Science in Sports and Exercise 33, 772777.Google Scholar
Singh-Manoux, A, Hillsdon, M, Brunner, E, Marmot, M (2005). Effects of physical activity on cognitive functioning in middle age: evidence from the Whitehall II prospective cohort study. American Journal of Public Health 95, 22522258.Google Scholar
Small, BJ, Fratiglioni, L, Viitanen, M, Winblad, B, Backman, L (2000). The course of cognitive impairment in preclinical Alzheimer disease: 3- and 6-year follow-up of a population-based sample. Archives of Neurology 57, 839844.Google Scholar
Stroup, DF, Berlin, JA, Morton, SC, Olkin, I, Williamson, GD, Rennie, D, Moher, D, Becker, BJ, Sipe, TA, Thacker, SB (2000). Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. Journal of the American Medical Association 283, 20082012.Google Scholar
Sturman, MT, Morris, MC, Mendes de Leon, CF, Bienias, JL, Wilson, RS, Evans, DA (2005). Physical activity, cognitive activity, and cognitive decline in a biracial community population. Archives of Neurology 62, 17501754.Google Scholar
Sumic, A, Michael, YL, Carlson, NE, Howieson, DB, Kaye, JA (2007). Physical activity and the risk of dementia in oldest old. Journal of Aging and Health 19, 242259.Google Scholar
van Gelder, BM, Tijhuis, MA, Kalmijn, S, Giampaoli, S, Nissinen, A, Kromhout, D (2004). Physical activity in relation to cognitive decline in elderly men: the FINE Study. Neurology 63, 23162321.Google Scholar
Verghese, J, Lipton, RB, Katz, MJ, Hall, CB, Derby, CA, Kuslansky, G, Ambrose, AF, Sliwinski, M, Buschke, H (2003). Leisure activities and the risk of dementia in the elderly. New England Journal of Medicine 348, 25082516.Google Scholar
Wang, JY, Zhou, DH, Li, J, Zhang, M, Deng, J, Tang, M, Gao, C, Li, J, Lian, Y, Chen, M (2006). Leisure activity and risk of cognitive impairment: the Chongqing aging study. Neurology 66, 911913.Google Scholar
Weuve, J, Kang, JH, Manson, JE, Breteler, MM, Ware, JH, Grodstein, F (2004). Physical activity, including walking, and cognitive function in older women. Journal of the American Medical Association 292, 14541461.Google Scholar
Wilson, RS, Bennett, DA, Bienias, JL, Aggarwal, NT, Mendes De Leon, CF, Morris, MC, Schneider, JA, Evans, DA (2002). Cognitive activity and incident AD in a population-based sample of older persons. Neurology 59, 19101914.Google Scholar
Yaffe, K, Barnes, D, Nevitt, M, Lui, LY, Covinsky, K (2001). A prospective study of physical activity and cognitive decline in elderly women: women who walk. Archives of Internal Medicine 161, 17031708.Google Scholar
Yamada, M, Kasagi, F, Sasaki, H, Masunari, N, Mimori, Y, Suzuki, G (2003). Association between dementia and midlife risk factors: the Radiation Effects Research Foundation Adult Health Study. Journal of the American Geriatrics Society 51, 410414.Google Scholar
Yoshitake, T, Kiyohara, Y, Kato, I, Ohmura, T, Iwamoto, H, Nakayama, K, Ohmori, S, Nomiyama, K, Kawano, H, Ueda, K, Sueishi, K, Tsuneyoshi, M, Fujishima, M (1995). Incidence and risk factors of vascular dementia and Alzheimer's disease in a defined elderly Japanese population: the Hisayama Study. Neurology 45, 11611168.Google Scholar