Objective: To evaluate the validity of motor phenotype classification in response to dopaminergic agents in moderate to advanced Parkinson’s disease (PD) patients enrolled in the BioFIND biomarker study.

Background: PD is a heterogeneous disease. Three motor phenotypes have been empirically described: the postural-instability gait-difficulty (PIGD) group, the tremor-dominant group (TD) and an intermediate phenotype. These motor phenotypes, mostly defined in early PD cases, have been associated with cognitive, motor outcomes, and biomarkers. The stability of the classification based on the MDS-UPDRS scale in the “on” and “off” states in moderate to advanced PD is unknown.

Methods: We analyzed data from 115 PD participants in BioFIND. Inclusion criteria included self-reported motor symptoms for ≥5 years, meeting the UK PD Society Brain Bank criteria, and having bradykinesia, rigidity, and rest tremor. Data consisted of MDS-UPDRS including motor scores both in the “on” state and a practically defined “off” state approximately 2 weeks apart, MoCA, and levodopa equivalent daily dosages (LEDD).

Results: When comparing motor phenotype classification in the “off” and “on” exams, 33 (29%) converted. 13 patients shifted from PIGD to TD or indeterminate group, or from indeterminate to TD group due to increasing ratio of tremor to postural scores, while 20 had the opposite trend. 82 remained stable in their motor subtype classification, including 44 in the TD, 34 in the PIGD, and 4 in the indeterminate group. Between TD and PIGD groups, total MDS-UPDRS and MoCA scores were similar. The PIGD group had a higher average LEDD compared to TD group (PIGD LEDD: 901.3 mg ± 330.3, TD LEDD 598.0 mg ± 316.9, p=0.0001).

Conclusions: Among fluctuators with moderate to advanced PD, traditionally defined motor phenotypes are unstable between “off” to “on” states. Even among those with stable phenotypes, MoCA and MDS-UPDRS scores were not different among them. Motor phenotypes in moderate to advanced PD calculated using MDS-UPDRS may not be the best way to predict progression as the phenotype classification in early PD cases using UPDRS. Shifts in subtype classification can affect previously reported conclusions about differential motor, cognitive, and occupational outcomes within each group.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/motor-phenotype-classification-in-moderate-to-advanced-pd-data-from-the-biofind-study/