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: 5.81). 09/2011; 86(9):876-84. DOI: 10.4065/mcp.2011.0252
Source: PubMed

ABSTRACT 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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    • "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.
    Brain Research 02/2015; 1612. DOI:10.1016/j.brainres.2015.02.034 · 2.83 Impact Factor
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    • "Only one small study has examined the effect of aerobic exercise on cognitive function in persons with HF [14]. A much larger literature supporting the use of exercise as an adjunct therapy for improving CI is derived from older adults and animal models [15–21]. Because there is substantial neuronal loss with dementia and no effective restorative therapies, interventions that slow, reverse, or prevent cognitive decline are essential. "
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    ABSTRACT: Persons with heart failure (HF) are typically older and are at a much higher risk for developing cognitive impairment (CI) than persons without HF. Increasingly, CI is recognized as a significant, independent predictor of worse clinical outcomes, more frequent hospital readmissions, and higher mortality rates in persons with HF. CI can have devastating effects on ability to carry out HF effective self-care behaviors. If CI occurs, however, there are currently no evidence based guidelines on how to manage or improve cognitive function in this population. Improvement in cognition has been reported following some therapies in HF and is thought to be the consequence of enhanced cerebral perfusion and oxygenation, suggesting that CI may be amenable to intervention. Because there is substantial neuronal loss with dementia and no effective restorative therapies, interventions that slow, reverse, or prevent cognitive decline are essential. Aerobic exercise is documented to increase cerebral perfusion and oxygenation by promoting neuroplasticity and neurogenesis and, in turn, cognitive functioning. Few studies have examined exercise as a potential adjunct therapy for attenuating or alleviating cognitive decline in HF. In this review, the potential benefit of aerobic exercise on cognitive functioning in HF is presented along with future research directions.
    07/2014; 2014:157508. DOI:10.1155/2014/157508
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    • "Aerobic exercise reduced the risk of cognitive impairment and dementia which can be explained by either a direct neurotrophic effect of exercise or by an improvement in the cerebrovascular and cardiovascular risk profiles. The authors argue that aerobic exercise attenuates progression of neurodegenerative processes and age-related loss of synapses and neuropil via facilitation of neurotrophic factors and neuroplasticity (30). These findings are in line with animal experiments in which aerobic exercise enhances hippocampal dendritic length and dendritic spine complexity (31). "
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    ABSTRACT: Alzheimer's disease (AD) is the leading cause of dementia, and the most prevalent neurodegenerative disease in the elderly. The prevalence of AD is predicted to rise as life expectancy grows across populations. The exact cause of this devastating disease is still unknown; however, it is an aging-related multi-factorial disorder, and growing evidence supports the contribution of modifiable environmental factors to unmodifiable factors such as gene and ageing itself. The recent advancement of methodologies and techniques for early diagnosis of AD facilitates the investigation of strategies to reduce the risk for AD progression in the earliest stages of the disease. Pharmacological attempts at curing, halting or modifying it have, by and large, been unsuccessful, and no breakthrough is seen in the near future. However, a lot of elements that seem to contribute to the disease such as risk factors have been identified, mainly from epidemiological and basic research studies. Many of these are amenable to lifestyle modification. Therefore, prevention in the preclinical stage is likely the most effective way to decrease the incidence of this age-associated dreadful neurodegenerative condition, and its associated burden for individuals and society. We provide an overview of modifiable risk factors for AD along with the supporting evidence.
    Journal of Korean Medical Science 07/2014; 29(7):886-892. DOI:10.3346/jkms.2014.29.7.886 · 1.25 Impact Factor
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