Physical Exercise as a Preventive or Disease-Modifying Treatment of Dementia and Brain Aging

Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA.
Mayo Clinic Proceedings (Impact Factor: 6.26). 09/2011; 86(9):876-84. DOI: 10.4065/mcp.2011.0252
Source: PubMed


A rapidly growing literature strongly suggests that exercise, specifically aerobic exercise, may attenuate cognitive impairment and reduce dementia risk. We used PubMed (keywords exercise and cognition) and manuscript bibliographies to examine the published evidence of a cognitive neuroprotective effect of exercise. Meta-analyses of prospective studies documented a significantly reduced risk of dementia associated with midlife exercise; similarly, midlife exercise significantly reduced later risks of mild cognitive impairment in several studies. Among patients with dementia or mild cognitive impairment, randomized controlled trials (RCTs) documented better cognitive scores after 6 to 12 months of exercise compared with sedentary controls. Meta-analyses of RCTs of aerobic exercise in healthy adults were also associated with significantly improved cognitive scores. One year of aerobic exercise in a large RCT of seniors was associated with significantly larger hippocampal volumes and better spatial memory; other RCTs in seniors documented attenuation of age-related gray matter volume loss with aerobic exercise. Cross-sectional studies similarly reported significantly larger hippocampal or gray matter volumes among physically fit seniors compared with unfit seniors. Brain cognitive networks studied with functional magnetic resonance imaging display improved connectivity after 6 to 12 months of exercise. Animal studies indicate that exercise facilitates neuroplasticity via a variety of biomechanisms, with improved learning outcomes. Induction of brain neurotrophic factors by exercise has been confirmed in multiple animal studies, with indirect evidence for this process in humans. Besides a brain neuroprotective effect, physical exercise may also attenuate cognitive decline via mitigation of cerebrovascular risk, including the contribution of small vessel disease to dementia. Exercise should not be overlooked as an important therapeutic strategy.

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    • "Consequently, preserving the homeostasis of insulin/IGF-1 signaling and/or glucose metabolism may delay the age-related deficits of the brain. In fact, a caloric restriction and physical exercise can promote brain health during aging by enhancing sensitivity to insulin and expression of BDNF (Duan et al. 2001; Komatsu et al. 2008; Ahlskog et al. 2011; Coelho et al. 2013). However, long-term adherence to these lifestyle interventions is difficult for some individuals (Anton et al. 2013). "
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    ABSTRACT: Several studies have indicated that a caloric restriction mimetic or treatment for type 2 diabetes may reverse brain aging. Therefore, we investigated the effect of 1-deoxynojirimycin (DNJ), an alkaloid acting as an inhibitor of α-glucosidase, on age-related behavioral and biochemical changes. SAMP8 mice were randomly assigned to a control group labeled "old" or to the 10- or 20-mg/kg/day DNJ groups. The mice in the DNJ groups were administered DNJ orally from 3 to 9 months of age, and then, a "young" control group was added to analyze the age effect. The old controls exhibited significant declines in sensorimotor ability, open-field anxiety, spatial and nonspatial memory abilities, and age-related biochemical changes, including decreased serum insulin level; increased levels of insulin-like growth factor 1 receptor, presynaptic protein synaptotagmin-1, and astrocyte activation; and decreased levels of insulin receptor, brain-derived neurotrophic factor, presynaptic protein syntaxin-1, and acetylation of histones H4 at lysine 8 in the dorsal hippocampus. Significant correlations exist between the age-related behavioral deficits and the serological and histochemical data. Chronic DNJ treatment alleviated these age-related changes, and the 20-mg/kg/day DNJ group showed more significant improvement. Thus, DNJ may have the potential to maintain successful brain aging.
    Full-text · Article · Sep 2015 · Age
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    • "Physical activity (PA) is another important pillar of healthy aging. Epidemiological evidence suggests PA increases life span and reduces the risk of chronic conditions such as stroke, heart disease, dementia, and type-2 diabetes (Blair and Brodney, 1999; Nelson et al., 2007; Blair, 2009; Chodzko-Zajko et al., 2009; Hamer and Chida, 2009; Ahlskog et al., 2011; Erickson et al., 2012; Swift et al., 2013). Furthermore, PA in the form of exercise has long been thought to play an important role in the quality of sleep. "
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    ABSTRACT: Given the world’s aging population, the staggering economic impact of dementia, the lack of effective treatments, and the fact a cure for dementia is likely many years away – there is an urgent need to develop interventions to prevent or at least delay dementia’s progression. Thus, lifestyle approaches to promote healthy aging are an important line of scientific inquiry. Good sleep quality and physical activity (PA) are pillars of healthy aging, and as such, are an increasing focus for intervention studies aimed at promoting health and cognitive function in older adults. However, PA and sleep quality are difficult constructs to evaluate empirically. Wrist-worn actigraphy (WWA) is currently accepted as a valid objective measure of sleep quality. The MotionWatch 8© (MW8) is the latest WWA, replacing the discontinued Actiwatch 4 and Actiwatch 7. In the current study, concurrent measurement of WWA and indirect calorimetry was performed during 10 different activities of daily living for 23 healthy older adults (aged 57–80 years) to determine cut-points for sedentary and moderate-vigorous PA – using receiver operating characteristic curves – with the cut-point for light activity being the boundaries between sedentary and moderate to vigorous PA. In addition, simultaneous multi-unit reliability was determined for the MW8 using inter-class correlations. The current study is the first to validate MW8 activity count cut-points – for sedentary, light, and moderate to vigorous PA – specifically for use with healthy older adults. These cut-points provide important context for better interpretation of MW8 activity counts, and a greater understanding of what these counts mean in terms of PA. Hence, our results validate another level of analysis for researchers using the MW8 in studies aiming to examine PA and sleep quality concurrently in older adults.
    Full-text · Article · Aug 2015 · Frontiers in Aging Neuroscience
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    • "Indeed, lifestyle factors such as engagement in exercise (Erickson et al., 2011; Kramer and Erickson, 2007), playing a musical instrument (Hanna-Pladdy and MacKay, 2011; Schlaug et al., 1995; Wan and Schlaug, 2010), and speaking a second language (Bialystok et al., 2004, 2006; Salvatierra and Rosselli, 2010) appear to stave off age-related declines in cognitive functions, especially those requiring executive control (e.g., working memory, inhibition, task-switching, etc.). In addition, corresponding increases in brain volume due to engagement in aerobic exercise (Ahlskog et al., 2011; Colcombe et al., 2006; Erickson et al., 2011) and playing a musical instrument (Gaser and Schlaug, 2003; Zatorre et al., 2012) have been reported. There is an emerging literature that has examined structural differences in the brain with respect to learning a second language (e.g., Mårtensson et al., 2012; Mechelli et al., 2004; Schlegel et al., 2012; Stein et al., 2012). "
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    ABSTRACT: Lifelong bilingualism is associated with the delayed diagnosis of dementia, suggesting bilingual experience is relevant to brain health in aging. While the effects of bilingualism on cognitive functions across the lifespan are well documented, less is known about the neural substrates underlying differential behavior. It is clear that bilingualism affects brain regions that mediate language abilities and that these regions are at least partially overlapping with those that exhibit age-related decline. Moreover, the behavioral advantages observed in bilingualism are generally found in executive function performance, suggesting that the frontal lobes may also be sensitive to bilingualism, which exhibit volume reductions with age. The current study investigated structural differences in the brain of lifelong bilingual older adults (n=14, mean age=70.4) compared with older monolinguals (n=14, mean age= 70.6). We employed two analytic approaches: 1) we examined global differences in grey and white matter volumes; and, 2) we examined local differences in volume and cortical thickness of specific regions of interest previously implicated in bilingual/monolingual comparisons (temporal pole) or in aging (entorhinal cortex and hippocampus). We expected bilinguals would exhibit greater volume of the frontal lobe and temporal lobe (grey and white matter), given the importance of these regions in executive and language functions, respectively. We further hypothesized that regions in the medial temporal lobe, which demonstrate early changes in aging and exhibit neural pathology in dementia, would be more preserved in the bilingual group. As predicted, bilinguals exhibit greater frontal lobe white matter compared with monolinguals. Moreover, increasing age was related to decreasing temporal pole cortical thickness in the monolingual group, but no such relationship was observed for bilinguals. Finally, Stroop task performance was positively correlated with frontal lobe white matter, emphasizing the importance of preserved white matter in maintaining executive function in aging. These results underscore previous findings implicating an association between bilingualism and preserved frontal and temporal lobe function in aging. Copyright © 2015. Published by Elsevier B.V.
    Full-text · Article · Feb 2015 · Brain Research
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