Objective: To test whether aerobic walking influences clinical status, biochemical and radiologic markers associated with degenerative parkinsonism unmasked by DRBD.

Background: Failed trials of putative disease-modifying drugs in PD have motivated strategies to allow earlier treatment-optimally in the prodromal phase. We and others have demonstrated that many patients with suspected drug-induced parkinsonism (DIP) caused by DRBD have underlying dopaminergic denervation on DAT-SPECT. This is consistent with unmasking of incipient PD (or related disorder) before motor symptoms would have appeared and could allow early intervention.

Methods: We are conducting a randomized controlled trial of exercise in patients with presumed early/prodromal PD unmasked by DRBD. Screening: DAT-SPECT was performed in subjects with DIP and those with abnormal scans were offered enrollment in the exercise trial. Exercise intervention: Subjects were randomized 1:1 to exercise (30-45 minutes of aerobic walking, 5 days/week) or normal care. The primary outcomes are changes from baseline in motor function (UPDRS-III) at 8 and 52 weeks and semi-quantitative DAT-SPECT at 52 weeks. Other outcomes include a non-motor symptoms survey (NMSQ), cognitive assessment (MoCA) and biochemical markers (urate, ApoA1, BDNF)

Results: Nine of 32 screening DAT-SPECT scans (28%) were abnormal. Subjects with normal and abnormal scans were indistinguishable using basic clinical and demographic characteristics including motor severity (UPDRS-III). However, subjects with abnormal scans had worse olfactory function and reported more non-motor symptoms (prominently gastrointestinal symptoms, including constipation) as would be expected in early or prodromal PD. To date, two exercise subjects and one control have completed the 8 week assessments and 1 exercise subject has completed the 52-week assessment. There was significant improvement in UPDRS-III after 8 weeks in exercise subjects (16.5 ± 2.1 vs 10.1 ± 2.8, p=0.049) but not in the control (15 vs. 23).Plasma BDNF levels increased after 8 weeks in exercise subjects (3126 ± 777 vs. 10216 ± 1037 pg/mL, p=0.016). Regional DAT uptake increased 4.6% to 11% after 52 weeks in the exercise subject compared to annual decreases of 8% to 11% in historical controls from PPMI.

Conclusions: This ongoing trial will inform whether aerobic walking can affect motor and non-motor symptoms in early parkinsonism as well as test a potentially disease-modifying effect of exercise.

« Back to 2018 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/effect-of-exercise-on-neurodegenerative-parkinsonism-unmasked-by-dopamine-blocking-drugs-drbd/