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Getting the Brain Into Shape: Exercise in Neurological Disorders

      We all know exercise is good for us. Currently, the recommendations from the US Department of Health and Human Services Physical Activity Guidelines Advisory Committee are at least 30 minutes of moderate-intensity aerobic exercise 5 days per week (total of 150 minutes per week) or at least 75 minutes per week of vigorous aerobic exercise plus moderate- to high-intensity muscle strengthening exercise 2 days per week.

      2008 Physical Activity Guidelines for Americans Summary. 2008. https://health.gov/paguidelines/guidelines/summary.aspx.

      In addition to its powerful benefits on cardiovascular health, exercise is a pluripotent stimulus that influences virtually all cells and organ systems, ultimately reducing all-cause death. There are myriad benefits of physical activity and exercise, for example, improvements in physical functioning, balance (ie, reduction in falls), insulin resistance, inflammation, blood pressure, quality of sleep, mood symptoms, cognitive functioning, and overall quality of life to name a few.
      • Agarwal S.K.
      Cardiovascular benefits of exercise.
      Exercise-related benefits occur throughout one’s life span.
      • Voss M.W.
      • Vivar C.
      • Kramer A.F.
      • van Praag H.
      Bridging animal and human models of exercise-induced brain plasticity.
      These benefits of exercise also extend to neurologic populations, in whom exercise training is making a move from secondary/adjunctive therapy to frontline treatment. Exercise interventions are being applied to neurologic diseases that are difficult to resolve with the available therapies or to bolster the effects of existing therapies. The thought is that when we exercise, our brains are also getting a workout, but we are only beginning to understand the mechanisms by which exercise training exerts its effects at the molecular and cellular levels. In fact, understanding the molecular mechanisms that drive exercise-induced health benefits is a priority for all organ systems, which is the impetus behind the new $170 million National Institutes of Health Common Fund initiative—Molecular Transducers of Physical Activity Consortium.
      • Neufer P.D.
      • Bamman M.M.
      • Muoio D.M.
      • et al.
      Understanding the cellular and molecular mechanisms of physical activity-induced health benefits.
      Many questions remain as to the extent of disease-specific benefits of exercise and ways to maximize and maintain such benefits. Rigorous randomized controlled trials are necessary to properly assess the efficacy of exercise interventions. However, there are a number of considerations when designing exercise intervention trials. As with any other form of medicine, exercise prescriptions are structured, and their impact on symptoms and any disease-modifying benefits depend on a number of dosing variables (ie, mode, intensity, frequency, duration). There is much work to be accomplished to truly optimize the exercise dose for specific conditions, which demands randomized controlled trials to identify the most effective doses of endurance (aerobic) and/or strength training. The field is still in its infancy, and, although we can reference the more prevalent exercise intervention studies in healthy and aging populations, there are issues specific to neurologic disease that will take time to work through, which makes this an exciting time for the field of cutting edge exercise medicine research.
      This issue of Clinical Therapeutics provides state-of-the-field updates and discusses novel research directions for exercise in key neurologic diseases in which exercise training has shown great promise. These neurologic diseases currently have no cure, and exercise may have a significant and direct impact on not only their symptoms but also potentially to change the course of disease progression. Drs. Motl and Sandroff
      • Motl R.
      • Sandroff B.
      Exercise as a countermeasure to declining central nervous system function in multiple sclerosis.
      pull from the rapidly growing literature to report about multimorbidity benefits of exercise in multiple sclerosis (MS) and to propose a model of how to examine whether exercise can combat the central nervous system decline in MS. Although there is also steady accumulation of research on the effects of physical exercise related to motor symptoms of Parkinson disease, Drs. Amara and Memon
      • Amara A.W.
      • Memon A.A.
      Effects of exercise on non-motor symptoms in Parkinson's disease.
      focus on the equally important effects of exercise on nonmotor symptoms. In contrast, studies that investigate exercise in people with epilepsy are scarce, particularly when pertaining to effects on cognitive function, as described by Drs. Allendorfer and Arida.
      • Allendorfer J.B.
      • Arida R.M.
      Role of physical activity and exercise in alleviating cognitive impairment in people with epilepsy.
      Finally, in the first of its kind, Dr. Harnish and colleagues
      • Harnish S.
      • Rodriguez A.D.
      • Blackett D.S.
      • et al.
      Aerobic exercise as an adjuvant to aphasia therapy: theory, preliminary findings, and future directions.
      present pilot study data on exercise as adjunct therapy in persons who experienced a language-debilitating stroke. Overall, exercise research in neurologic disorders is showing great promise, with a number of exciting future directions aimed at both leveraging and understanding the impact of a good workout on the brain.

      References

      1. 2008 Physical Activity Guidelines for Americans Summary. 2008. https://health.gov/paguidelines/guidelines/summary.aspx.

        • Agarwal S.K.
        Cardiovascular benefits of exercise.
        Int J Gen Med. 2012; 5: 541-545
        • Voss M.W.
        • Vivar C.
        • Kramer A.F.
        • van Praag H.
        Bridging animal and human models of exercise-induced brain plasticity.
        Trends Cogn Sci. 2013; 17: 525-544
        • Neufer P.D.
        • Bamman M.M.
        • Muoio D.M.
        • et al.
        Understanding the cellular and molecular mechanisms of physical activity-induced health benefits.
        Cell Metab. 2015; 22: 4-11
        • Motl R.
        • Sandroff B.
        Exercise as a countermeasure to declining central nervous system function in multiple sclerosis.
        Clin Ther. 2018; 40: 16-25
        • Amara A.W.
        • Memon A.A.
        Effects of exercise on non-motor symptoms in Parkinson's disease.
        Clin Ther. 2018; 40: 8-15
        • Allendorfer J.B.
        • Arida R.M.
        Role of physical activity and exercise in alleviating cognitive impairment in people with epilepsy.
        Clin Ther. 2018; 40: 26-34
        • Harnish S.
        • Rodriguez A.D.
        • Blackett D.S.
        • et al.
        Aerobic exercise as an adjuvant to aphasia therapy: theory, preliminary findings, and future directions.
        Clin Ther. 2018; 40: 35-48