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Does vigorous exercise have a neuroprotective effect in Parkinson disease?

ABSTRACT: Parkinson disease (PD) is progressive, with dementia and medication-refractory motor problems common reasons for late-stage nursing-home placement. Increasing evidence suggests that ongoing vigorous exercise/physical fitness may favorably influence this progression. Parkinsonian animal models reveal exercise-related protection from dopaminergic neurotoxins, apparently mediated by brain neurotrophic factors and neuroplasticity (predicted from in vitro studies). Similarly, exercise consistently improves cognition in animals, also linked to enhanced neuroplasticity and increased neurotrophic factor expression. In these animal models, immobilization has the opposite effect. Brain-derived neurotrophic factor (BDNF) may mediate at least some of this exercise benefit. In humans, exercise increases serum BDNF, and this is known to cross the blood-brain barrier. PD risk in humans is significantly reduced by midlife exercise, documented in large prospective studies. No studies have addressed whether exercise influences dementia risk in PD, but exercised patients with PD improve cognitive scores. Among seniors in general, exercise or physical fitness has not only been associated with better cognitive scores, but midlife exercise significantly reduces the later risk of both dementia and mild cognitive impairment. Finally, numerous studies in seniors with and without dementia have reported increased cerebral gray matter volumes associated with physical fitness or exercise. These findings have several implications for PD clinicians. (1) Ongoing vigorous exercise and physical fitness should be highly encouraged. (2) PD physical therapy programs should include structured, graduated fitness instruction and guidance for deconditioned patients with PD. (3) Levodopa and other forms of dopamine replenishment therapy should be utilized to achieve the maximum capability and motivation for patients to maintain fitness.

SUBMITTER: Ahlskog JE

PROVIDER: S-EPMC3136051 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature

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Does vigorous exercise have a neuroprotective effect in Parkinson disease?

Ahlskog J Eric JE

Neurology 20110701 3

Parkinson disease (PD) is progressive, with dementia and medication-refractory motor problems common reasons for late-stage nursing-home placement. Increasing evidence suggests that ongoing vigorous exercise/physical fitness may favorably influence this progression. Parkinsonian animal models reveal exercise-related protection from dopaminergic neurotoxins, apparently mediated by brain neurotrophic factors and neuroplasticity (predicted from in vitro studies). Similarly, exercise consistently im ...[more]

PMID: 21768599

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Project description:Background and objectivesOwing to the lack of long-term observations or comprehensive adjustment for confounding factors, reliable conclusions regarding long-term effects of exercise and regular physical activity in Parkinson disease (PD) have yet to be drawn. Here, using data from the Parkinson's Progression Markers Initiative study that includes longitudinal and comprehensive evaluations of many clinical parameters, we examined the long-term effects of regular physical activity and exercise habits on the course of PD.MethodsIn this retrospective, observational cohort study, we primarily used the multivariate linear mixed-effects models to analyze the interaction effects of their regular physical activity and moderate to vigorous exercise levels, measured with the Physical Activity Scale for the Elderly questionnaire, on the progression of clinical parameters, after adjusting for age, sex, levodopa equivalent dose, and disease duration. We also calculated bootstrapping 95% confidence intervals (CIs) and conducted sensitivity analyses using the multiple imputation method and subgroup analyses using propensity score matching to match for all baseline background factors.ResultsTwo hundred thirty-seven patients with early PD (median [interquartile range] age, 63.0 [56.0-70.0] years, male 69.2%, follow-up duration 5.0 [4.0-6.0] years) were included. Regular physical activity and moderate to vigorous exercise levels at baseline did not significantly affect the subsequent clinical progression of PD. However, average regular overall physical activity levels over time were significantly associated with slower deterioration of postural and gait stability (standardized fixed-effects coefficients of the interaction term [βinteraction] = -0.10 [95% CI -0.14 to -0.06]), activities of daily living (βinteraction = 0.08 [95% CI 0.04-0.12]), and processing speed (βinteraction = 0.05 [95% CI 0.03-0.08]) in patients with PD. Moderate to vigorous exercise levels were preferentially associated with slower decline of postural and gait stability (βinteraction = -0.09 [95% CI -0.13 to -0.05]), and work-related activity levels were primarily associated with slower deterioration of processing speed (βinteraction = 0.07 [95% CI 0.04-0.09]). Multiple imputation and propensity score matching confirmed the robustness of our results.DiscussionIn the long term, the maintenance of high regular physical activity levels and exercise habits was robustly associated with better clinical course of PD, with each type of physical activity having different effects.Trial registration informationClinicalTrials.gov Identifier: NCT01176565.Classification of evidenceThis study provides Class II evidence that sustained increase in overall regular physical activity levels in patients with early PD was associated with slower decline of several clinical parameters.

Project description:ObjectiveTo determine whether falls can be prevented with minimally supervised exercise targeting potentially remediable fall risk factors, i.e., poor balance, reduced leg muscle strength, and freezing of gait, in people with Parkinson disease.MethodsTwo hundred thirty-one people with Parkinson disease were randomized into exercise or usual-care control groups. Exercises were practiced for 40 to 60 minutes, 3 times weekly for 6 months. Primary outcomes were fall rates and proportion of fallers during the intervention period. Secondary outcomes were physical (balance, mobility, freezing of gait, habitual physical activity), psychological (fear of falling, affect), and quality-of-life measures.ResultsThere was no significant difference between groups in the rate of falls (incidence rate ratio [IRR] = 0.73, 95% confidence interval [CI] 0.45-1.17, p = 0.18) or proportion of fallers (p = 0.45). Preplanned subgroup analysis revealed a significant interaction for disease severity (p < 0.001). In the lower disease severity subgroup, there were fewer falls in the exercise group compared with controls (IRR = 0.31, 95% CI 0.15-0.62, p < 0.001), while in the higher disease severity subgroup, there was a trend toward more falls in the exercise group (IRR = 1.61, 95% CI 0.86-3.03, p = 0.13). Postintervention, the exercise group scored significantly (p < 0.05) better than controls on the Short Physical Performance Battery, sit-to-stand, fear of falling, affect, and quality of life, after adjusting for baseline performance.ConclusionsAn exercise program targeting balance, leg strength, and freezing of gait did not reduce falls but improved physical and psychological health. Falls were reduced in people with milder disease but not in those with more severe Parkinson disease.Classification of evidenceThis study provides Class III evidence that for patients with Parkinson disease, a minimally supervised exercise program does not reduce fall risk. This study lacked the precision to exclude a moderate reduction or modest increase in fall risk from exercise.Trial registrationAustralian New Zealand Clinical Trials Registry (ACTRN12608000303347).

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Does vigorous exercise have a neuroprotective effect in Parkinson disease?

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Does vigorous exercise have a neuroprotective effect in Parkinson disease?

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