Advertisement
Mayo Clinic Proceedings Home

Physical Activity and Alzheimer Disease: A Protective Association

      Abstract

      Objective

      To explore whether being physically active can decrease Alzheimer disease (AD) risk.

      Participants and Methods

      We conducted a meta-analysis of prospective observational cohort studies reporting the association between physical activity (PA) and incident AD. Relevant articles were identified by title and abstract in the electronic databases PubMed, ScienceDirect, and Scopus using the keywords Alzheimer, Alzheimer disease, Alzheimer’s, Alzheimer’s disease, physical activity, sport, exercise, sedentary, fitness, and combinations thereof for articles published in any language up to February 15, 2016. Criteria for consideration included division of the study cohort by PA levels and sample size specification for each PA level group, quantification (number) of persons who had development of AD, and PA assessment during time off work (not just work time). We followed the MOOSE (Meta-analyses of Observational Studies in Epidemiology) recommendations and used the Newcastle-Ottawa scale for study quality assessment.

      Results

      Ten high-quality studies were included in meta-analysis I (23,345 participants). Follow-up ranged from 3.9 to 31 years, and the participants’ age ranged from 70 to 80 years. The pooled odds ratio for development of AD in participants who were more vs less physically active was 0.65 (95% CI, 0.56-0.74; P<.001; no publication bias [P=.24] but with heterogeneity among studies [I2=31.32%]). We could identify participants’ adherence to international PA recommendations in 5 studies, which constituted meta-analysis II (10,615 participants). The pooled odds ratio for development of AD in participants who were active vs those who were inactive was 0.60 (95% CI, 0.51-0.71; P<.001; no publication bias [P=.34] and no heterogeneity [I2=5.63%]).

      Conclusion

      Although the limitations of self-reported PA data must be considered, regular PA performed by elderly people might play a certain protective role against AD.

      Abbreviations and Acronyms:

      AD (Alzheimer disease), APOE (apolipoprotein E gene), MET (metabolic equivalent), MVPA (moderate to vigorous physical activity), OR (odds ratio), PA (physical activity)
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Mayo Clinic Proceedings
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Liu R.
        • Sui X.
        • Laditka J.N.
        • et al.
        Cardiorespiratory fitness as a predictor of dementia mortality in men and women.
        Med Sci Sports Exerc. 2012; 44: 253-259
        • Ahlskog J.E.
        • Geda Y.E.
        • Graff-Radford N.R.
        • Petersen R.C.
        Physical exercise as a preventive or disease-modifying treatment of dementia and brain aging.
        Mayo Clin Proc. 2011; 86: 876-884
        • Braskie M.N.
        • Boyle C.P.
        • Rajagopalan P.
        • et al.
        Physical activity, inflammation, and volume of the aging brain.
        Neuroscience. 2014; 273: 199-209
        • Yang S.Y.
        • Weng P.H.
        • Chen J.H.
        • et al.
        Leisure activities, apolipoprotein E e4 status, and the risk of dementia.
        J Formos Med Assoc. 2015; 114: 1216-1224
        • Erickson K.I.
        • Weinstein A.M.
        • Lopez O.L.
        Physical activity, brain plasticity, and Alzheimer's disease.
        Arch Med Res. 2012; 43: 615-621
        • Verdelho A.
        • Madureira S.
        • Ferro J.M.
        • et al.
        Physical activity prevents progression for cognitive impairment and vascular dementia: results from the LADIS (Leukoaraiosis and Disability) study.
        Stroke. 2012; 43: 3331-3335
        • Garatachea N.
        • Pareja-Galeano H.
        • Sanchis-Gomar F.
        • et al.
        Exercise attenuates the major hallmarks of aging.
        Rejuvenation Res. 2015; 18: 57-89
        • Lucia A.
        • Ruiz J.R.
        Exercise is beneficial for patients with Alzheimer's disease: a call for action.
        Br J Sports Med. 2011; 45 ([editorial]): 468-469
        • Geda Y.E.
        • Silber T.C.
        • Roberts R.O.
        • et al.
        Computer activities, physical exercise, aging, and mild cognitive impairment: a population-based study.
        Mayo Clin Proc. 2012; 87: 437-442
        • Hamer M.
        • Chida Y.
        Physical activity and risk of neurodegenerative disease: a systematic review of prospective evidence.
        Psychol Med. 2009; 39: 3-11
        • Gelber R.P.
        • Petrovitch H.
        • Masaki K.H.
        • et al.
        Lifestyle and the risk of dementia in Japanese-American men.
        J Am Geriatr Soc. 2012; 60: 118-123
        • Daviglus M.L.
        • Plassman B.L.
        • Pirzada A.
        • et al.
        Risk factors and preventive interventions for Alzheimer disease: state of the science.
        Arch Neurol. 2011; 68: 1185-1190
      1. US Department of Health and Human Services, Office of Disease Prevention and Health Promotion. 2008 Physical activity guidelines for Americans. Office of Disease Prevention and Health Promotion website. http://www.health.gov/paguidelines/guidelines. Updated April 27, 2016. Accessed December 6, 2015.

        • World Health Organization
        Global Recommendations on Physical Activity for Health.
        World Health Organization, Geneva, Switzerland2010 (World Health Organization website) (Accessed December 6, 2015)
        • Sedentary Behaviour Research Network
        Letter to the editor: standardized use of the terms “sedentary” and “sedentary behaviours”.
        Appl Physiol Nutr Metab. 2012; 37: 540-542
        • Garber C.E.
        • Blissmer B.
        • Deschenes M.R.
        • et al.
        • American College of Sports Medicine
        Quantity and quality of exercise for developing and maintaining cardiorespiratory, musculoskeletal, and neuromotor fitness in apparently healthy adults; guidance for prescribing exercise.
        Med Sci Sports Exerc. 2011; 43 ([American College of Sports Medicine Position Stand]): 1334-1359
        • Fletcher G.F.
        • Balady G.
        • Blair S.N.
        • et al.
        Statement on exercise: benefits and recommendations for physical activity programs for all Americans; a statement for health professionals by the Committee on Exercise and Cardiac Rehabilitation of the Council on Clinical Cardiology, American Heart Association.
        Circulation. 1996; 94: 857-862
        • Stroup D.F.
        • Berlin J.A.
        • Morton S.C.
        • et al.
        Meta-analysis of Observational Studies in Epidemiology (MOOSE) Group. Meta-analysis of observational studies in epidemiology: a proposal for reporting.
        JAMA. 2000; 283: 2008-2012
      2. Wells GA, Shea B, O'Connell D, et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Ottawa. Ottawa Hospital Research Institute website. http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp. Accessed February 5, 2016.

        • Bax L.
        • Yu L.M.
        • Ikeda N.
        • Tsuruta H.
        • Moons K.G.
        Development and validation of MIX: comprehensive free software for meta-analysis of causal research data.
        BMC Med Res Methodol. 2006; 6: 50
        • Abbott R.D.
        • White L.R.
        • Ross G.W.
        • Masaki K.H.
        • Curb J.D.
        • Petrovitch H.
        Walking and dementia in physically capable elderly men.
        JAMA. 2004; 292: 1447-1453
        • Buchman A.S.
        • Boyle P.A.
        • Yu L.
        • Shah R.C.
        • Wilson R.S.
        • Bennett D.A.
        Total daily physical activity and the risk of AD and cognitive decline in older adults.
        Neurology. 2012; 78: 1323-1329
        • Luck T.
        • Riedel-Heller S.G.
        • Luppa M.
        • et al.
        Apolipoprotein E epsilon 4 genotype and a physically active lifestyle in late life: analysis of gene-environment interaction for the risk of dementia and Alzheimer's disease dementia.
        Psychol Med. 2014; 44: 1319-1329
        • Scarmeas N.
        • Luchsinger J.A.
        • Brickman A.M.
        • et al.
        Physical activity and Alzheimer disease course.
        Am J Geriatr Psychiatry. 2011; 19: 471-481
        • Wang L.
        • Larson E.B.
        • Bowen J.D.
        • van Belle G.
        Performance-based physical function and future dementia in older people.
        Arch Intern Med. 2006; 166: 1115-1120
        • Larson E.B.
        • Wang L.
        • Bowen J.D.
        • et al.
        Exercise is associated with reduced risk for incident dementia among persons 65 years of age and older.
        Ann Intern Med. 2006; 144: 73-81
        • Laurin D.
        • Verreault R.
        • Lindsay J.
        • MacPherson K.
        • Rockwood K.
        Physical activity and risk of cognitive impairment and dementia in elderly persons.
        Arch Neurol. 2001; 58: 498-504
        • Norton M.C.
        • Dew J.
        • Smith H.
        • et al.
        • Cache County Investigators
        Lifestyle behavior pattern is associated with different levels of risk for incident dementia and Alzheimer's disease: the Cache County study.
        J Am Geriatr Soc. 2012; 60: 405-412
        • de Bruijn R.F.
        • Schrijvers E.M.
        • de Groot K.A.
        • et al.
        The association between physical activity and dementia in an elderly population: the Rotterdam Study.
        Eur J Epidemiol. 2013; 28 ([published correction appears in Eur J Epidemiol. 2013;28(5):447–448]): 277-283
        • Ferrari C.
        • Xu W.L.
        • Wang H.X.
        • et al.
        How can elderly apolipoprotein E ε4 carriers remain free from dementia?.
        Neurobiol Aging. 2013; 34: 13-21
        • Scarmeas N.
        • Luchsinger J.A.
        • Schupf N.
        • et al.
        Physical activity, diet, and risk of Alzheimer disease.
        JAMA. 2009; 302: 627-637
        • Taaffe D.R.
        • Irie F.
        • Masaki K.H.
        • et al.
        Physical activity, physical function, and incident dementia in elderly men: the Honolulu-Asia Aging Study.
        J Gerontol A Biol Sci Med Sci. 2008; 63: 529-535
        • Ravaglia G.
        • Forti P.
        • Lucicesare A.
        • et al.
        Physical activity and dementia risk in the elderly: findings from a prospective Italian study.
        Neurology. 2008; 70: 1786-1794
        • Rovio S.
        • Kåreholt I.
        • Helkala E.L.
        • et al.
        Leisure-time physical activity at midlife and the risk of dementia and Alzheimer's disease.
        Lancet Neurol. 2005; 4: 705-711
        • Rovio S.
        • Kåreholt I.
        • Viitanen M.
        • et al.
        Work-related physical activity and the risk of dementia and Alzheimer's disease.
        Int J Geriatr Psychiatry. 2007; 22: 874-882
        • Andel R.
        • Crowe M.
        • Pedersen N.L.
        • Fratiglioni L.
        • Johansson B.
        • Gatz M.
        Physical exercise at midlife and risk of dementia three decades later: a population-based study of Swedish twins.
        J Gerontol A Biol Sci Med Sci. 2008; 63: 62-66
        • Lindsay J.
        • Laurin D.
        • Verreault R.
        • et al.
        Risk factors for Alzheimer's disease: a prospective analysis from the Canadian Study of Health and Aging.
        Am J Epidemiol. 2002; 156: 445-453
        • Podewils L.J.
        • Guallar E.
        • Kuller L.H.
        • et al.
        Physical activity, APOE genotype, and dementia risk: findings from the Cardiovascular Health Cognition Study.
        Am J Epidemiol. 2005; 161: 639-651
        • Yoshitake T.
        • Kiyohara Y.
        • Kato I.
        • et al.
        Incidence and risk factors of vascular dementia and Alzheimer's disease in a defined elderly Japanese population: the Hisayama Study.
        Neurology. 1995; 45: 1161-1168
        • Kishimoto H.
        • Ohara T.
        • Hata J.
        • et al.
        The long-term association between physical activity and risk of dementia in the community: the Hisayama Study.
        Eur J Epidemiol. 2016; 31: 267-274
        • Wilson R.S.
        • Bennett D.A.
        • Bienias J.L.
        • et al.
        Cognitive activity and incident AD in a population-based sample of older persons.
        Neurology. 2002; 59: 1910-1914
        • Hallal P.C.
        • Andersen L.B.
        • Bull F.C.
        • Guthold R.
        • Haskell W.
        • Ekelund U.
        • Lancet Physical Activity Series Working Group
        Global physical activity levels: surveillance progress, pitfalls, and prospects.
        Lancet. 2012; 380: 247-257
        • Radak Z.
        • Hart N.
        • Sarga L.
        • et al.
        Exercise plays a preventive role against Alzheimer's disease.
        J Alzheimers Dis. 2010; 20: 777-783
        • Huang T.
        • Larsen K.T.
        • Ried-Larsen M.
        • Møller N.C.
        • Andersen L.B.
        The effects of physical activity and exercise on brain-derived neurotrophic factor in healthy humans: a review.
        Scand J Med Sci Sports. 2014; 24: 1-10
        • O'Bryant S.E.
        • Hobson V.L.
        • Hall J.R.
        • et al.
        • Texas Alzheimer's Research Consortium
        Serum brain-derived neurotrophic factor levels are specifically associated with memory performance among Alzheimer's disease cases.
        Dement Geriatr Cogn Disord. 2011; 31: 31-36
        • Erickson K.I.
        • Voss M.W.
        • Prakash R.S.
        • et al.
        Exercise training increases size of hippocampus and improves memory.
        Proc Natl Acad Sci U S A. 2011; 108: 3017-3022
        • Giménez-Llort L.
        • García Y.
        • Buccieri K.
        • et al.
        Gender-specific neuroimmunoendocrine response to treadmill exercise in 3xTg-AD mice.
        Int J Alzheimers Dis. 2010; 2010: 128354
        • García-Mesa Y.
        • Pareja-Galeano H.
        • Bonet-Costa V.
        • et al.
        Physical exercise neuroprotects ovariectomized 3xTg-AD mice through BDNF mechanisms.
        Psychoneuroendocrinology. 2014; 45: 154-166
        • Aisen P.S.
        Serum brain-derived neurotrophic factor and the risk for dementia.
        JAMA. 2014; 311: 1684-1685
        • Adlard P.A.
        • Perreau V.M.
        • Pop V.
        • Cotman C.W.
        Voluntary exercise decreases amyloid load in a transgenic model of Alzheimer's disease.
        J Neurosci. 2005; 25: 4217-4221
        • Lazarov O.
        • Robinson J.
        • Tang Y.P.
        • et al.
        Environmental enrichment reduces Abeta levels and amyloid deposition in transgenic mice.
        Cell. 2005; 120: 701-713
        • Qiu C.
        • Kivipelto M.
        • von Strauss E.
        Epidemiology of Alzheimer's disease: occurrence, determinants, and strategies toward intervention.
        Dialogues Clin Neurosci. 2009; 11: 111-128
        • Tolppanen A.M.
        • Solomon A.
        • Kulmala J.
        • et al.
        Leisure-time physical activity from mid- to late life, body mass index, and risk of dementia.
        Alzheimers Dement. 2015; 11: 434-443.e6
        • Groot C.
        • Hooghiemstra A.M.
        • Raijmakers P.G.
        • et al.
        The effect of physical activity on cognitive function in patients with dementia: a meta-analysis of randomized control trials.
        Ageing Res Rev. 2015; 25: 13-23
        • Ströhle A.
        • Schmidt D.K.
        • Schultz F.
        • et al.
        Drug and exercise treatment of Alzheimer disease and mild cognitive impairment: a systematic review and meta-analysis of effects on cognition in randomized controlled trials.
        Am J Geriatr Psychiatry. 2015; 23: 1234-1249
        • Steene-Johannessen J.
        • Anderssen S.A.
        • van der Ploeg H.P.
        • et al.
        Are self-report measures able to define individuals as physically active or inactive?.
        Med Sci Sports Exerc. 2016; 48: 235-244
        • Washburn R.A.
        • Smith K.W.
        • Jette A.M.
        • Janney C.A.
        The Physical Activity Scale for the Elderly (PASE): development and evaluation.
        J Clin Epidemiol. 1993; 46: 153-162
        • Dipietro L.
        • Caspersen C.J.
        • Ostfeld A.M.
        • Nadel E.R.
        A survey for assessing physical activity among older adults.
        Med Sci Sports Exerc. 1993; 25: 628-642
        • Lee I.-M.
        • Shiroma E.J.
        • Lobelo F.
        • Puska P.
        • Blair S.N.
        • Katzmarzyk P.T.
        • Lancet Physical Activity Series Working Group
        Effect of physical inactivity on major non-communicable diseases worldwide: an analysis of burden of disease and life expectancy.
        Lancet. 2012; 380: 219-229
        • Santana-Sosa E.
        • Barriopedro M.I.
        • López-Mojares L.M.
        • Pérez M.
        • Lucia A.
        Exercise training is beneficial for Alzheimer's patients.
        Int J Sports Med. 2008; 29: 845-850
        • Paillard T.
        • Rolland Y.
        • de Souto Barreto P.
        Protective effects of physical exercise in Alzheimer's disease and Parkinson's disease: a narrative review.
        J Clin Neurol. 2015; 11: 212-219
        • Yu F.
        • Kolanowski A.M.
        • Strumpf N.E.
        • Eslinger P.J.
        Improving cognition and function through exercise intervention in Alzheimer's disease.
        J Nurs Scholarsh. 2006; 38: 358-365