OBJECTIVES: To investigate the timing (mid- vs late life) of physical activity, apolipoprotein (APO)E ε4, and risk of incident mild cognitive impairment (MCI). DESIGN: Prospective cohort study. SETTING: Mayo Clinic Study of Aging (Olmsted County, MN). PARTICIPANTS: Cognitively normal elderly adults (N = 1,830, median age 78, 50.2% female). MEASUREMENTS: Light, moderate, and vigorous physical activities in mid- and late life were assessed using a validated questionnaire. An expert consensus panel measured MCI based on published criteria. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) with age as a time scale after adjusting for sex, education, medical comorbidity, and depression. RESULTS: Light (HR = 0.58, 95% CI = 0.43-0.79) and vigorous (HR = 0.78, 95% CI = 0.63-0.97) physical activity in midlife were associated with lower risk of incident MCI. The association between moderate activity and incident MCI was not significant (HR = 0.85, 95% CI = 0.67-1.09). In late life, light (HR = 0.75, 95% CI = 0.58-0.97) and moderate (HR = 0.81, 95% CI = 0.66-0.99) but not vigorous physical activity were associated with lower risk of incident MCI. A synergistic interaction was also observed between mid- and late-life activity in reducing risk of incident MCI. Furthermore, APOE ε4 carriers who did not exercise had a higher risk of incident MCI than noncarriers who reported physical activity. CONCLUSION: Physical activity reduced the risk of incident MCI. Exercising in mid- and late life had an additive synergistic interaction in reducing the risk of MCI.

Department of Neurology Mayo Clinic Rochester Minnesota

Department of Neurology Mayo Clinic Scottsdale Arizona

Department of Psychiatry and Psychology Mayo Clinic Scottsdale Arizona

Division of Biomedical Statistics and Informatics Department of Health Sciences Research Mayo Clinic Rochester Minnesota

Division of Epidemiology Department of Health Sciences Research Mayo Clinic Rochester Minnesota

International Clinical Research Center Brno Czech Republic

Translational Neuroscience and Aging Program Mayo Clinic Scottsdale Arizona

Zobrazit více v PubMed

Petersen RC, Smith GE, Waring SC, et al. Mild cognitive impairment: Clinical characterization and outcome. Arch Neurol. 1999;56:303–308. PubMed

Petersen RC. Mild cognitive impairment as a diagnostic entity. J Intern Med. 2004;256:183–194. PubMed

Petersen RC, Roberts RO, Knopman DS, et al. Prevalence of mild cognitive impairment is higher in men. The Mayo Clinic Study of Aging. Neurology. 2010;75:889–897. PubMed PMC

Lopez OL, Jagust WJ, DeKosky ST, et al. Prevalence and classification of mild cognitive impairment in the Cardiovascular Health Study Cognition Study: part 1. Arch. Neurol. 2003 Oct;60(10):1385–1389. PubMed

Roberts RO, Geda YE, Knopman DS, et al. The incidence of MCI differs by subtype and is higher in men: The Mayo Clinic Study of Aging. Neurology. 2012;78:342–351. PubMed PMC

Lopez OL, Becker JT, Chang YF, et al. Incidence of mild cognitive impairment in the Pittsburgh Cardiovascular Health Study-Cognition Study. Neurology. 2012;79:1599–1606. PubMed PMC

Lautenschlager NT, Cox K, Cyarto EV. The influence of exercise on brain aging and dementia. Biochim Biophys Acta. 2012;1822:474–481. PubMed

Barnes DE, Whitmer RA, Yaffe K. Physical activity and dementia: The need for prevention trials. Exerc Sport Sci Rev. 2007;35:24–29. PubMed

Churchill JD, Galvez R, Colcombe S, et al. Exercise, experience and the aging brain. Neurobiol Aging. 2002;23:941–955. PubMed

Sofi F, Valecchi D, Bacci D, et al. Physical activity and risk of cognitive decline: A meta-analysis of prospective studies. J Intern Med. 2011;269:107–117. PubMed

Fratiglioni L, Paillard-Borg S, Winblad B. An active and socially integrated lifestyle in late life might protect against dementia. Lancet Neurol. 2004;3:343–353. PubMed

Buchman AS, Boyle PA, Yu L, et al. Total daily physical activity and the risk of AD and cognitive decline in older adults. Neurology. 2012;78:1323–1329. PubMed PMC

Laurin D, Verreault R, Lindsay J, et al. Physical activity and risk of cognitive impairment and dementia in elderly persons. Arch Neurol. 2001;58:498–504. PubMed

Podewils LJ, Guallar E, Kuller LH, et al. Physical activity, APOE genotype, and dementia risk: Findings from the Cardiovascular Health Cognition Study. Am J Epidemiol. 2005;161:639–651. PubMed

Scarmeas N, Luchsinger JA, Schupf N, et al. Physical activity, diet, and risk of Alzheimer disease. JAMA. 2009;302:627–637. PubMed PMC

Verghese J, Cuiling W, Katz MJ, et al. Leisure activities and risk of vascular cognitive impairment in older adults. J Geriatr Psychiatry Neurol. 2009;22:110–118. PubMed PMC

Larson EB, Wang L, Bowen JD, 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. PubMed

Middleton L, Kirkland S, Rockwood K. Prevention of CIND by physical activity: Different impact on VCI-ND compared with MCI. J Neurol Sci. 2008;269:80–84. PubMed

Roberts RO, Geda YE, Knopman DS, et al. The Mayo Clinic Study of Aging: Design and sampling, participation, baseline measures and sample characteristics. Neuroepidemiology. 2008;30:58–69. PubMed PMC

St Sauver JL, Grossardt BR, Yawn BP, et al. Use of a medical records-linkage system to enumerate a dynamic population over time: The Rochester Epidemiology Project. Am J Epidemiol. 2011;173:1059–1068. PubMed PMC

Geda YE, Roberts RO, Knopman DS, et al. Physical exercise, aging, and mild cognitive impairment: A population-based study. Arch Neurol. 2010;67:80–86. PubMed PMC

Geda YE, Silber TC, Roberts RO, et al. Computer activities, physical exercise, aging, and mild cognitive impairment: A population-based study. Mayo Clin Proc. 2012;87:437–442. PubMed PMC

Moss AJ, Parsons VL. National Center for Health Statistics (U.S.) Vital and Health Statistics, Series 10, No. 160. DHHS Pub. No. (PHS) 86-1588.: Public Health Service. Washington: U.S. Government Printing Office; 1986. Sep, Current estimates from the National Health Interview Survey, United States, 1985. No. 160. DHHS Pub. No. (PHS) 86-1588. PubMed

Folsom AR, Caspersen CJ, Taylor HL, et al. Leisure time physical activity and its relationship to coronary risk factors in a population-based sample. The Minnesota Heart Survey. Am J Epidemiol. 1985;121:570–579. PubMed

Kokmen E, Smith GE, Petersen RC, et al. The Short Test of Mental Status: Correlations With Standardized Psychometric Testing. Arch Neurol. 1991;48:725–728. PubMed

Rey A. L'examen clinique en psychologie. Paris: Presses Universitaires de France; 1964.

Wechsler D. Wechsler Memory Scale-Revised. New York: The Psychological Corporation; 1987.

Kaplan E, Goodglass H, Brand S. Boston Naming Test. Philadelphia: Lea & Febiger; 1983.

Kaplan E, Goodglass H, Weintraub S. Boston Naming Test. 2nd. Philadelphia: Lippincott Williams & Wilkins; 2001.

Lucas JA, Ivnik RJ, Smith GE, et al. Mayo's Older Americans Normative Studies: Category fluency norms. J Clin Exp Neuropsychol. 1998;20:194–200. PubMed

Wechsler D. Wechsler Adult Intelligence Scale-Revised. New York: Psychological Corporation; 1981.

Reitan RM. Validity of the Trail Making Test as an indicator of organic brain damage. Percept Mot Skills. 1958;8:271–276.

Ivnik RJ, Malec JF, Smith GE, et al. Mayo's Older Americans Normative Studies: WAIS-R norms for ages 56 to 97. Clin Neuropsychol. 1992;6(sup001):1–30.

Ivnik RJ, Malec JF, Smith GE, et al. Mayo's Older Americans Normative Studies: WMS-R norms for ages 56 to 94. Clin Neuropsychol. 1992;6(sup001):49–82.

Ivnik RJ, Malec JF, Smith GE, et al. Mayo's Older Americans Normative Studies: Updated AVLT norms for ages 56 to 97. Clin Neuropsychol. 1992;6(sup001):83–104.

Malec JF, Ivnik RJ, Smith GE, et al. Mayo's Older Americans Normative Studies: Utility of corrections for age and education for the WAIS-R. Clin Neuropsychol. 1992;6(sup001):31–47.

Winblad B, Palmer K, Kivipelto M, et al. Mild cognitive impairment--beyond controversies, towards a consensus: Report of the International Working Group on Mild Cognitive Impairment. J Intern Med. 2004;256:240–246. PubMed

Hixson JE, Vernier DT. Restriction isotyping of human apolipoprotein E by gene amplification and cleavage with HhaI. J Lipid Res. 1990;31:545–548. PubMed

Charlson ME, Pompei P, Ales KL, et al. A new method of classifying prognostic comorbidity in longitudinal studies: Development and validation. J. Chronic Dis. 1987;40:373–383. PubMed

Beck AT, Steer RA, Brown GK. BDI-II, Beck Depression Inventory: Manual. 2nd. San Antonio, TX; Boston, MA: Psychological Corp.; Harcourt Brace; 1996.

Blondell SJ, Hammersley-Mather R, Veerman JL. Does physical activity prevent cognitive decline and dementia?: A systematic review and meta-analysis of longitudinal studies. BMC Public Health. 2014;14:510. PubMed PMC

Verghese J, LeValley A, Derby C, et al. Leisure activities and the risk of amnestic mild cognitive impairment in the elderly. Neurology. 2006;66:821–827. PubMed PMC

Middleton LE, Barnes DE, Lui LY, et al. Physical activity over the life course and its association with cognitive performance and impairment in old age. J Am Geriatr Soc. 2010;58:1322–1326. PubMed PMC

Rovio S, Kareholt I, Helkala EL, et al. Leisure-time physical activity at midlife and the risk of dementia and Alzheimer's disease. Lancet Neurol. 2005;4:705–711. PubMed

Tolppanen AM, 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. PubMed

Etnier JL, Caselli RJ, Reiman EM, et al. Cognitive performance in older women relative to ApoE-epsilon4 genotype and aerobic fitness. Med Sci Sports Exerc. 2007;39:199–207. PubMed

Schuit AJ, Feskens EJ, Launer LJ, et al. Physical activity and cognitive decline, the role of the apolipoprotein e4 allele. Med Sci Sports Exerc. 2001;33:772–777. PubMed

Woodard JL, Sugarman MA, Nielson KA, et al. Lifestyle and genetic contributions to cognitive decline and hippocampal structure and function in healthy aging. Curr Alzheimer Res. 2012;9:436–446. PubMed PMC

Head D, Bugg JM, Goate AM, et al. Exercise engagement as a moderator of the effects of APOE genotype on amyloid deposition. Arch Neurol. 2012;69:636–643. PubMed PMC

Smith JC, Nielson KA, Woodard JL, et al. Interactive effects of physical activity and APOE-epsilon4 on BOLD semantic memory activation in healthy elders. Neuroimage. 2011;54:635–644. PubMed PMC

Deeny SP, Poeppel D, Zimmerman JB, et al. Exercise, APOE, and working memory: MEG and behavioral evidence for benefit of exercise in epsilon4 carriers. Biol Psychol. 2008;78:179–187. PubMed PMC

Smith JC, Lancaster MA, Nielson KA, et al. Interactive effects of physical activity and APOE-epsilon4 on white matter tract diffusivity in healthy elders. Neuroimage. 2015 Aug 8; PubMed PMC

Deeny SP, Winchester J, Nichol K, et al. Cardiovascular fitness is associated with altered cortical glucose metabolism during working memory in varepsilon4 carriers. Alzheimers Dement. 2012;8:352–356. PubMed PMC

Lytle ME, Vander Bilt J, Pandav RS, et al. Exercise level and cognitive decline:The MoVIES project. Alzheimer Dis Assoc Disord. 2004;18:57–64. PubMed

Szklo M, Nieto FJ. Epidemiology: Beyond the Basics. Gaithersburg, Md: Aspen; 2000.

St Sauver JL, Grossardt BR, Leibson CL, et al. Generalizability of epidemiological findings and public health decisions: An illustration from the Rochester Epidemiology Project. Mayo Clin Proc. 2012;87:151–160. PubMed PMC

Rogers RL, Meyer JS, Mortel KF. After reaching retirement age physical activity sustains cerebral perfusion and cognition. J Am Geriatr Soc. 1990;38:123–128. PubMed

Huang T, Larsen KT, Ried-Larsen M, et al. 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. PubMed

Colcombe SJ, Erickson KI, Scalf PE, et al. Aerobic exercise training increases brain volume in aging humans. J Gerontol A Biol Sci Med Sci. 2006;61:1166–1170. PubMed

Blumenthal JA, Emery CF, Madden DJ, et al. Effects of exercise training on cardiorespiratory function in men and women older than 60 years of age. Am J Cardiol. 1991;67:633–639. PubMed