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      Physical Activity and Brain Function in Older Adults at Increased Risk for Alzheimer’s Disease

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          Abstract

          Leisure-time physical activity (PA) and exercise training are known to help maintain cognitive function in healthy older adults. However, relatively little is known about the effects of PA on cognitive function or brain function in those at increased risk for Alzheimer’s disease through the presence of the apolipoproteinE epsilon4 (APOE-ε4) allele, diagnosis of mild cognitive impairment (MCI), or the presence of metabolic disease. Here, we examine the question of whether PA and exercise interventions may differentially impact cognitive trajectory, clinical outcomes, and brain structure and function among individuals at the greatest risk for AD. The literature suggests that the protective effects of PA on risk for future dementia appear to be larger in those at increased genetic risk for AD. Exercise training is also effective at helping to promote stable cognitive function in MCI patients, and greater cardiorespiratory fitness is associated with greater brain volume in early-stage AD patients. In APOE-ε4 allele carriers compared to non-carriers, greater levels of PA may be more effective in reducing amyloid burden and are associated with greater activation of semantic memory-related neural circuits. A greater research emphasis should be placed on randomized clinical trials for exercise, with clinical, behavioral, and neuroimaging outcomes in people at increased risk for AD.

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          Most cited references93

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          Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families.

          The apolipoprotein E type 4 allele (APOE-epsilon 4) is genetically associated with the common late onset familial and sporadic forms of Alzheimer's disease (AD). Risk for AD increased from 20% to 90% and mean age at onset decreased from 84 to 68 years with increasing number of APOE-epsilon 4 alleles in 42 families with late onset AD. Thus APOE-epsilon 4 gene dose is a major risk factor for late onset AD and, in these families, homozygosity for APOE-epsilon 4 was virtually sufficient to cause AD by age 80.
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            Physical fitness and all-cause mortality. A prospective study of healthy men and women.

            We studied physical fitness and risk of all-cause and cause-specific mortality in 10,224 men and 3120 women who were given a preventive medical examination. Physical fitness was measured by a maximal treadmill exercise test. Average follow-up was slightly more than 8 years, for a total of 110,482 person-years of observation. There were 240 deaths in men and 43 deaths in women. Age-adjusted all-cause mortality rates declined across physical fitness quintiles from 64.0 per 10,000 person-years in the least-fit men to 18.6 per 10,000 person-years in the most-fit men (slope, -4.5). Corresponding values for women were 39.5 per 10,000 person-years to 8.5 per 10,000 person-years (slope, -5.5). These trends remained after statistical adjustment for age, smoking habit, cholesterol level, systolic blood pressure, fasting blood glucose level, parental history of coronary heart disease, and follow-up interval. Lower mortality rates in higher fitness categories also were seen for cardiovascular disease and cancer of combined sites. Attributable risk estimates for all-cause mortality indicated that low physical fitness was an important risk factor in both men and women. Higher levels of physical fitness appear to delay all-cause mortality primarily due to lowered rates of cardiovascular disease and cancer.
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              Risk factors for Alzheimer's disease: a prospective analysis from the Canadian Study of Health and Aging.

              J. Lindsay (2002)
              A prospective analysis of risk factors for Alzheimer's disease was a major objective of the Canadian Study of Health and Aging, a nationwide, population-based study. Of 6,434 eligible subjects aged 65 years or older in 1991, 4,615 were alive in 1996 and participated in the follow-up study. All participants were cognitively normal in 1991 when they completed a risk factor questionnaire. Their cognitive status was reassessed 5 years later by using a similar two-phase procedure, including a screening interview, followed by a clinical examination when indicated. The analysis included 194 Alzheimer's disease cases and 3,894 cognitively normal controls. Increasing age, fewer years of education, and the apolipoprotein E epsilon4 allele were significantly associated with increased risk of Alzheimer's disease. Use of nonsteroidal anti-inflammatory drugs, wine consumption, coffee consumption, and regular physical activity were associated with a reduced risk of Alzheimer's disease. No statistically significant association was found for family history of dementia, sex, history of depression, estrogen replacement therapy, head trauma, antiperspirant or antacid use, smoking, high blood pressure, heart disease, or stroke. The protective associations warrant further study. In particular, regular physical activity could be an important component of a preventive strategy against Alzheimer's disease and many other conditions.
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                Author and article information

                Journal
                Brain Sci
                Brain Sci
                brainsci
                Brain Sciences
                MDPI
                2076-3425
                14 January 2013
                March 2013
                : 3
                : 1
                : 54-83
                Affiliations
                [1 ] Department of Kinesiology, School of Public Health, University of Maryland, College Park, MD 20742, USA
                [2 ] Department of Psychology, Marquette University, PO Box 1881, Milwaukee, WI 53201, USA; E-Mail: kristy.nielson@ 123456marquette.edu
                [3 ] Department of Neurology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA
                [4 ] Department of Psychology, Wayne State University, 5057 Woodward Ave, Detroit, MI 48202, USA; E-Mail: john.woodard@ 123456wayne.edu
                [5 ] Department of Psychology, Rosalind Franklin University of Medicine and Science, 3333 Green Bay Rd, North Chicago, IL 60064, USA; E-Mail: michael.seidenberg@ 123456rosalindfranklin.edu
                [6 ] Schey Center for Cognitive Neuroimaging, Neurological Institute, Cleveland Clinic, 9500 Euclid Ave/U10, Cleveland, OH 44195, USA; E-Mail: raos2@ 123456ccf.org
                Author notes
                [* ] Author to whom correspondence should be addressed; E-Mail: carson@ 123456umd.edu ; Tel.: +1-301-405-0344; Fax: +1-301-405-5578.
                Article
                brainsci-03-00054
                10.3390/brainsci3010054
                4061823
                24961307
                4444d430-ca38-4e1a-84d6-7394ea754dc1
                © 2013 by the authors; licensee MDPI, Basel, Switzerland.

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/3.0/).

                History
                : 15 September 2012
                : 16 November 2012
                : 20 December 2012
                Categories
                Review

                alzheimer’s disease,cognition,exercise,physical activity,apoe genotype,genetic risk,mild cognitive impairment,memory,mri,neuroimaging

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