Objective: To determine the longitudinal stability of Parkinson disease (PD) subtype membership.

Background: Previous research demonstrates distinct PD subtypes of “motor only”, “psychiatric & motor”, “cognitive & motor” subgroups based on comprehensive, multi-domain classification [1,2]. However, the longitudinal stability of these subtypes, reflecting either distinct trajectories [3] or disease stages, remains unknown.

Method: 253 PD participants with baseline subtype classification [2] completed longitudinal behavioral evaluations, including motor, cognitive, and psychiatric assessments. Using the longitudinal behavioral evaluations, we conducted latent transition analyses to test the stability of PD subtype membership over time (average follow-up = 3yrs). Importantly, these analyses benefit from our brain autopsy data by excluding participants with non-PD brain autopsy confirmed diagnoses (e.g., MSA, PSP; N =9).

Results: Interestingly, we find the emergence of a new 4^th subtype at the second time point, characterized by more severe motor, cognitive, and psychiatric dysfunction, while still retaining the original 3 subtypes. This new “severe” subtype primarily represents PD participants who developed dementia by the second time point (24/41, 58%). We find that the “motor only” subtype remains very stable (90% membership consistency across time points) and the “cognitive & motor” subtype also remains relatively stable (59% stable; 36% transition to the “severe” subtype), while the “psychiatric & motor” subtype is only moderately stable (55% maintain membership; 31% transition to “cognitive & motor”). The majority of participants (76%) maintain their subtype membership, with some advancing to a more “severe” subtype coincident with dementia onset.

Conclusion: Overall, these results suggest that PD subtypes represent distinct trajectories, with eventual convergence with the development of dementia.

References: 1) Campbell, M.C., Myers, P.S., Weigand, A.J., Foster, E.R., Cairns, N.J., Jackson, J.J., Lessov-Schlaggar, C.N., and Perlmutter, J.S. (2020). Parkinson disease clinical subtypes: Key features and clinical milestones. Annals of Clinical and Translational Neurology. DOI: 10.1002/acn3.51102
2) Cash, T., Lessov-Schlaggar, C.N., Foster, E.R., Myers, P.S., Jackson, J.J., Maiti, B., Kotzbauer, P.T., Perlmutter, J.S., and Campbell, M.C. (2024). Replication and reliability of Parkinson’s disease clinical subtypes. Parkinsonism & Related Disorders. DOI: 10.1016/j.parkreldis.2024.107016
3) Myers, P.S., Jackson, J.J., Clover, A.K., Lessov-Schlaggar, C.N., Foster, E.R., Maiti, B., Perlmutter, J.S., and Campbell, M.C. (2021). Distinct progression patterns across Parkinson disease clinical subtypes. Annals of Clinical and Translational Neurology. DOI: 10.1002/acn3.51436.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/parkinson-disease-subtype-stability-and-eventual-convergence/