Objective: To identify PD clinical subtypes based on patterns of motor, cognitive, and psychiatric symptoms; to assess the clinical utility of each subtype in predicting conversion to dementia and mortality.

Background: People with PD have distinct patterns of motor, cognitive, and psychiatric symptoms which may predict prognosis and treatment response. A comprehensive, multi-domain clinical assessment may permit identification of clinically relevant subtypes based on the spectrum of symptoms rather than on a single domain of assessment (i.e., motor deficits only).

Method: Comprehensive clinical evaluations were completed at baseline from a prospective, longitudinal sample of 162 non-demented PD participants who are followed until death. Latent class analysis (LCA) defined subtypes based on score patterns across motor, cognitive, and psychiatric measures. Cox regression models tested PD subtype differences in relative risks (RR) for conversion to dementia and mortality.

Results: LCA identified three distinct clinical subtypes: “motor only” (N=63) characterized by motor deficits but preserved cognitive and psychiatric function; “psychiatric & motor” (N=17) characterized by prominent psychiatric symptoms, moderate motor deficits, but intact cognition; “cognitive & motor” (N=82) characterized by impaired cognition, moderate motor deficits, but preserved psychiatric function. Dementia conversion occurred at a higher rate in the “cognitive & motor” subtype compared to “motor only” and “psychiatric & motor” subtypes (RR=4.45, 3.08), while “psychiatric & motor” and “motor only” did not significantly differ (RR=1.45). Analysis of mortality cases (N=38) revealed higher mortality risk for the “cognitive & motor” and “psychiatric & motor” subtypes compared to the “motor only” subtype (RR=3.85, 4.41), while “cognitive & motor” and “psychiatric & motor” did not significantly differ (RR=0.87).

Conclusion: Psychiatric and cognitive function, rather than motor deficits, drive PD clinical subtypes. Our results stress the importance of multi-domain assessments which include comprehensive cognitive and psychiatric measures to better characterize clinical variability in PD. Further, the PD clinical subtypes differ in relative risks for conversion to dementia and mortality demonstrating significant prognostic value for these subtypes.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/parkinson-disease-clinical-subtypes-predict-dementia-and-mortality-risk/