Treadmill exercise elevates striatal dopamine D2 receptor binding potential in patients with early Parkinson's disease.

We have previously demonstrated changes in dopaminergic neurotransmission after intensive exercise in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned mouse model of Parkinson's disease (PD), including an increase in the dopamine D2 receptor (DA-D2R), using noninvasive PET imaging with the radioligand [18F]fallypride. The purpose of this feasibility and translational study was to examine whether intensive exercise leads to similar alterations in DA-D2R expression using PET imaging with [18F]fallypride in individuals with early-stage PD. In this pilot study, four patients with early-stage PD were randomized to receive intensive exercise (treadmill training sessions three times/week for 8 weeks) or no exercise. Two healthy age-matched individuals participated in treadmill training. Alterations in the DA-D2R binding potential (BP) as a marker for receptor expression were determined using PET imaging with [18F]fallypride. Turning performance in the patients with PD as a measure of postural control and the Unified Parkinson's Disease Rating Scale scores pre-exercise and postexercise were determined. Our data showed an exercise-induced increase in [18F]fallypride BP as well as improved postural control in patients with PD who exercised. Changes in DA-D2R BP were not observed in patients with PD who did not exercise. These results suggest that exercise can lead to neuroplasticity in dopaminergic signaling and contribute to improved function that may be task specific (postural control) in early-stage PD.

The effect of exercise training in improving motor performance and corticomotor excitability in people with early Parkinson's disease.

OBJECTIVES: To obtain preliminary data on the effects of high-intensity exercise on functional performance in people with Parkinson's disease (PD) relative to exercise at low and no intensity and to determine whether improved performance is accompanied by alterations in corticomotor excitability as measured through transcranial magnetic stimulation (TMS). DESIGN: Cohort (prospective), randomized controlled trial. SETTING: University-based clinical and research facilities. PARTICIPANTS: Thirty people with PD, within 3 years of diagnosis with Hoehn and Yahr stage 1 or 2. INTERVENTIONS: Subjects were randomized to high-intensity exercise using body weight-supported treadmill training, low-intensity exercise, or a zero-intensity education group. Subjects in the 2 exercise groups completed 24 exercise sessions over 8 weeks. Subjects in the zero-intensity group completed 6 education classes over 8 weeks. MAIN OUTCOME MEASURES: Unified Parkinson's Disease Rating Scales (UPDRS), biomechanic analysis of self-selected and fast walking and sit-to-stand tasks; corticomotor excitability was assessed with cortical silent period (CSP) durations in response to single-pulse TMS. RESULTS: A small improvement in total and motor UPDRS was observed in all groups. High-intensity group subjects showed postexercise increases in gait speed, step and stride length, and hip and ankle joint excursion during self-selected and fast gait and improved weight distribution during sit-to-stand tasks. Improvements in gait and sit-to-stand measures were not consistently observed in low- and zero-intensity groups. The high-intensity group showed lengthening in CSP. CONCLUSIONS: The findings suggest the dose-dependent benefits of exercise and that high-intensity exercise can normalize corticomotor excitability in early PD.