Objective: Identify Parkinson’s disease (PD) clinical subtypes using multi-domain classification; determine subtype symptom progression; assess subtype clinical utility.

Background: People with PD present with combinations of motor, cognitive, and psychiatric symptoms. Using comprehensive, multi-domain assessments to capture the range of PD symptoms may yield subtypes that predict symptom progression and clinical milestones.

Method: A prospective, longitudinal cohort of 162 non-demented people with PD, followed until death, received comprehensive evaluations at baseline and every 1-3 years thereafter. Latent class analysis (LCA) derived subtypes from motor, cognitive, and psychiatric feature patterns. Hierarchical linear modeling (HLM) compared symptom progression between subtypes. Cox regression evaluated subtype differences in relative risks (RR) for DBS surgery, dementia, and mortality.

Results: LCA defined three subtypes: “motor only” (N=63), defined by motor deficits only; “psychiatric & motor” (N=17), defined by motor and psychiatric features; “cognitive & motor” (N=82), defined by motor and cognitive deficits. HLM showed symptom progression consistent with each subtype’s defining characteristics. The “motor only” subtype declined in all motor ratings, as well as executive function and apathy. By contrast, the “cognitive & motor” subtype declined in executive and visuospatial function, as well as postural instability and apathy. The “psychiatric & motor” subtype declined for global psychiatric symptoms, despite also having the greatest rate of improvement in depression. Cox regression showed subtypes did not differ on DBS rates, but the “cognitive & motor” subtype had a higher dementia risk compared to “motor only” and “psychiatric & motor” (RR=4.45, 3.08). Further, the “cognitive & motor” and “psychiatric & motor” subtypes had higher mortality rates than “motor only” (RR=3.85, 4.41).

Conclusion: Psychiatric and cognitive features differentiated PD clinical subtypes. We show the importance of comprehensive assessments for capturing PD symptom variability as well as demonstrate that clinical subtypes predict progression and clinical milestones, illustrating their prognostic utility.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/parkinsons-disease-clinical-subtypes-symptom-progression-dementia-and-mortality/