Parkinson Disease Subtype Stability and Eventual Convergence
Laura M. Rosok, Christina N. Lessov‐Schlaggar, Abdulmunaim M. Eid, Erin R. Foster, Baijayanta Maiti, Hailee Domash, Helen Hwang, Richard J. Perrin, Paul T. Kotzbauer, Joel S. Perlmutter, Meghan C. CampbellABSTRACT
Objective
Previous research identified distinct Parkinson disease (PD) clinical subtypes of “Motor Only,” “Psychiatric & Motor,” and “Cognitive & Motor” based on comprehensive, multidomain classification. Whether these subtypes reflect distinct trajectories or progressive disease stages remains unknown. This study aimed to determine the longitudinal stability of PD subtype membership.
Methods
This study included 250 PD participants with baseline subtype classifications and behavioral evaluations at two timepoints (average interval = 2.51 years), including motor, cognitive, and psychiatric assessments. Latent transition analyses tested the stability of PD subtype membership over time, and logistic regression models examined baseline factors associated with subtype transitions. Available brain autopsy data from 67 participants strengthened analyses by allowing the exclusion of 9 participants with non‐PD neuropathologic diagnoses (e.g., Multiple System Atrophy, Progressive Supranuclear Palsy).
Results
The three baseline subtypes (“Motor Only,” “Psychiatric & Motor,” and “Cognitive & Motor”) persisted at the second timepoint. Individuals in the “Motor Only” subtype at baseline had a high probability of remaining in the same subtype at follow‐up (0.91), demonstrating longitudinal stability. Participants in the “Psychiatric & Motor” and “Cognitive & Motor” subtypes remained in the same subtype with probabilities of 0.55 and 0.59, respectively. A fourth “Severe Multidomain” subtype emerged at follow‐up, characterized by more pronounced motor, cognitive, and psychiatric dysfunction. 64% of the “Severe Multidomain” group had dementia, compared with ≤ 7% in the other three subtypes. Subsequent analyses indicated that higher baseline Clinical Dementia Rating (CDR) sum of boxes was strongly associated with transition to a different subtype.
Interpretation
These findings suggest that PD subtypes reflect relatively stable subgroups that may eventually converge with development of dementia.