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Peer-reviewedCC BY-NC-ND 4.0Annals of Clinical and Translational Neurology

Parkinson Disease Subtype Stability and Eventual Convergence

  • Laura M. Rosok1
  • Christina N. Lessov‐Schlaggar2
  • Abdulmunaim M. Eid1
  • Erin R. Foster1,2,3
  • Baijayanta Maiti1,4
  • Hailee Domash1
  • Helen Hwang1
  • Richard J. Perrin1,5
  • Paul T. Kotzbauer1
  • Joel S. Perlmutter1,3,4,6,7
  • Meghan C. Campbell1,4
7 affiliations
  1. 1Department of Neurology Washington University in St. Louis St. Louis Missouri USA
  2. 2Department of Psychiatry Washington University in St. Louis St. Louis Missouri USA
  3. 3Program in Occupational Therapy Washington University in St. Louis St. Louis Missouri USA
  4. 4Department of Radiology Washington University in St. Louis St. Louis Missouri USA
  5. 5Department of Pathology & Immunology Washington University in St. Louis St. Louis Missouri USA
  6. 6Department of Neuroscience Washington University in St. Louis St. Louis Missouri USA
  7. 7Program in Physical Therapy Washington University in St. Louis St. Louis Missouri USA
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Abstract

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.

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Cite

BibTeXRIS
BibTeX
@article{rosok2026parkinson,
  title = {{Parkinson Disease Subtype Stability and Eventual Convergence}},
  author = {Laura M. Rosok and Christina N. Lessov‐Schlaggar and Abdulmunaim M. Eid and Erin R. Foster and Baijayanta Maiti and Hailee Domash and Helen Hwang and Richard J. Perrin and Paul T. Kotzbauer and Joel S. Perlmutter and Meghan C. Campbell},
  journal = {Annals of Clinical and Translational Neurology},
  year = {2026},
  month = oct,
  doi = {10.1002/acn3.70567},
  url = {https://doi.org/10.1002/acn3.70567},
  note = {CC BY-NC-ND 4.0},
}
RIS
TY  - JOUR
TI  - Parkinson Disease Subtype Stability and Eventual Convergence
AU  - Laura M. Rosok
AU  - Christina N. Lessov‐Schlaggar
AU  - Abdulmunaim M. Eid
AU  - Erin R. Foster
AU  - Baijayanta Maiti
AU  - Hailee Domash
AU  - Helen Hwang
AU  - Richard J. Perrin
AU  - Paul T. Kotzbauer
AU  - Joel S. Perlmutter
AU  - Meghan C. Campbell
PY  - 2026
DA  - 2026/10/25
JO  - Annals of Clinical and Translational Neurology
DO  - 10.1002/acn3.70567
UR  - https://doi.org/10.1002/acn3.70567
AB  - 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.
SN  - 2328-9503
ER  -