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. Neurology Parkinson disease (PD) is progressive. Although the dopaminergic nigrostriatal system receives much attention, progression in nondopaminergic circuits eventually becomes the primary substrate for major PD disability. Nursing home placement is typically the consequence of cognitive impairment/dementia or nondopaminergic motor deficits, especially levodopa-refractory balance and gait problems. 1A major focus of PD research has been on "disease-modifying" or "neuroprotective" agents to slow PD progression. No drugs have surfaced, to date, that unequivocally have that property. However, often overlooked in this discussion is the potential benefit of sustained vigorous exercise on PD progression. Exercise is well-known to have general health benefits, including improvement of cardiovascular and cerebrovascular health, reduction of osteoporosis/fracture risk and age-related sarcopenia, improvement of psychological affect, and perhaps even a general anti-inflammatory effect.2 However, accumulating evidence, albeit indirect, suggests that ongoing vigorous exercise may have a neuroprotective effect in PD, beyond th...

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