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Importance: Parkinson disease is a progressive neurologic disorder. Limited evidence suggests endurance exercise modifies disease severity, particularly high-intensity exercise., Objectives: To examine the feasibility and safety of high-intensity treadmill exercise in patients with de novo Parkinson disease who are not taking medication and whether the effect on motor symptoms warrants a phase 3 trial., Design, Setting, and Participants: The Study in Parkinson Disease of Exercise (SPARX) was a phase 2, multicenter randomized clinical trial with 3 groups and masked assessors. Individuals from outpatient and community-based clinics were enrolled from May 1, 2012, through November 30, 2015, with the primary end point at 6 months. Individuals with idiopathic Parkinson disease (Hoehn and Yahr stages 1 or 2) aged 40 to 80 years within 5 years of diagnosis who were not exercising at moderate intensity greater than 3 times per week and not expected to need dopaminergic medication within 6 months participated in this study. A total of 384 volunteers were screened by telephone; 128 were randomly assigned to 1 of 3 groups (high-intensity exercise, moderate-intensity exercise, or control)., Interventions: High-intensity treadmill exercise (4 days per week, 80%-85% maximum heart rate [n = 43]), moderate-intensity treadmill exercise (4 days per week, 60%-65% maximum heart rate [n = 45]), or wait-list control (n = 40) for 6 months., Main Outcomes and Measures: Feasibility measures were adherence to prescribed heart rate and exercise frequency of 3 days per week and safety. The clinical outcome was 6-month change in Unified Parkinson's Disease Rating Scale motor score., Results: A total of 128 patients were included in the study (mean [SD] age, 64 [9] years; age range, 40-80 years; 73 [57.0%] male; and 108 [84.4%] non-Hispanic white). Exercise rates were 2.8 (95% CI, 2.4-3.2) days per week at 80.2% (95% CI, 78.8%-81.7%) maximum heart rate in the high-intensity group and 3.2 (95% CI, 2.8-3.6; P = .13) days per week at 65.9% (95% CI, 64.2%-67.7%) maximum heart rate in the moderate-intensity group (P < .001). The mean change in Unified Parkinson's Disease Rating Scale motor score in the high-intensity group was 0.3 (95% CI, -1.7 to 2.3) compared with 3.2 (95% CI, 1.4 to 5.1) in the usual care group (P = .03). The high-intensity group, but not the moderate-intensity group, reached the predefined nonfutility threshold compared with the control group. Anticipated adverse musculoskeletal events were not severe., Conclusions and Relevance: High-intensity treadmill exercise may be feasible and prescribed safely for patients with Parkinson disease. An efficacy trial is warranted to determine whether high-intensity treadmill exercise produces meaningful clinical benefits in de novo Parkinson disease., Trial Registration: clinicaltrials.gov Identifier: NCT01506479.

Importance: Data on the long-term cognitive outcomes of patients with PARKIN-associated Parkinson disease (PD) are unknown but may be useful when counseling these patients., Objective: Among patients with early-onset PD of long duration, we assessed cognitive and motor performances, comparing homozygotes and compound heterozygotes who carry 2 PARKIN mutations with noncarriers., Design, Setting, and Participants: Cross-sectional study of 44 participants at 17 different movement disorder centers who were in the Consortium on Risk for Early-Onset PD study with a duration of PD greater than the median duration (>14 years): 4 homozygotes and 17 compound heterozygotes (hereafter referred to as carriers) and 23 noncarriers., Main Outcomes and Measures: Unified Parkinson Disease Rating Scale Part III (UPDRS-III) and Clinical Dementia Rating scores and neuropsychological performance. Linear regression models were applied to assess the association between PARKIN mutation status and cognitive domain scores and UPDRS-III scores. Models were adjusted for age, education, disease duration, language, and levodopa equivalent daily dose., Results: Carriers had an earlier age at onset of PD (P < .001) and were younger (P = .004) at time of examination than noncarriers. They performed better than noncarriers on the Mini-Mental State Examination (P = .010) and were more likely to receive lower scores on the Clinical Dementia Rating (P = .003). In multivariate analyses, carriers performed better than noncarriers on the UPDRS-III (P = .02) and on tests of attention (P = .03), memory (P = .03), and visuospatial (P = .02) cognitive domains., Conclusions and Relevance: In cross-sectional analyses, carriers demonstrated better cognitive and motor performance than did noncarriers with long disease duration, suggesting slower disease progression. A longitudinal follow-up study is required to confirm these findings.

OBJECTIVE To compare differences in functional brain activity between tremor- and nontremor-dominant subtypes of Parkinson disease (PD) using functional magnetic resonance imaging. DESIGN In our study, patients with tremor-dominant PD and those with nontremor-dominant PD performed a grip task, and the results obtained were compared using voxelwise analysis. Areas of the brain that were significantly different were then examined using a region-of-interest analysis to compare these patients with healthy controls. Voxel-based morphometry was used to determine macroscopic differences in gray and white matter volume between patient groups. SETTING University-affiliated research institution. PARTICIPANTS A total of 20 drug-naive patients with PD (10 with tremor-dominant PD and 10 with nontremor-dominant PD) and a total of 20 healthy controls. MAIN OUTCOME MEASURES Blood oxygenation level-dependent activation and percent signal change. RESULTS Robust findings across both voxelwise and region-of-interest analyses showed that, compared with patients with tremor-dominant PD, patients with nontremor-dominant PD had reduced activation in the ipsilateral dorsolateral prefrontal cortex, the globus pallidus interna, and the globus pallidus externa. Region-of-interest analyses confirmed that patients with nontremor-dominant PD had reduced activity in the ipsilateral dorsolateral prefrontal cortex, the globus pallidus interna, and the globus pallidus externa compared with patients with tremor-dominant PD and healthy controls. Patients with tremor-dominant PD had increased activity in the contralateral dorsolateral prefrontal cortex compared with patients with nontremor-dominant PD and healthy controls. These results could not be explained by differences in gray or white matter volume. CONCLUSIONS Reduced brain activity occurs in the prefrontal cortex and globus pallidus of patients with nontremor-dominant PD compared with both patients with tremor-dominant PD and healthy controls, which suggests that functional magnetic resonance imaging is a promising technique to understand differences in brain activation between subtypes of PD.