Objective: The goals of this project were to 1) identify putative Parkinson disease (PD) clinical subtypes and 2) investigate resting-state functional connectivity differences between these PD subtypes.

Background: Variability in the clinical features of Parkinson disease (PD) may represent distinct subtypes with unique patterns of neuropathology. Functional connectivity, as a measure of brain function, may provide insight into the underlying pathological differences between PD subtypes.

Methods: Latent class analyses, controlling for age, sex, and education, identified PD subtypes based on the pattern of motor, cognitive, and psychiatric features from 152 non-demented PD participants. Advanced graph-based object-oriented data analyses compared resting-state functional connectivity data from the entire connectome between 87 PD and 37 age-matched controls as well as across PD subtypes. Post-hoc analyses determined subnetworks with the greatest between-group differences.

Results: The latent class model identified three distinct clinical subtypes: 1) “motor only” – motor deficits with normal cognition and psychiatric function; 2) “motor & psychiatric” – elevated psychiatric symptoms, with moderate motor deficits and normal cognition; 3) “motor & cognition” – moderate motor deficits, impaired cognition, but normal psychiatric function. Functional connectivity significantly differed between the control group and both the “motor only” (p = .02) and “motor & cognition” (p < .001) PD subtypes. Importantly, functional connectivity also significantly differed between the “motor only” and “motor & cognition” PD subtypes (p = .05), with qualitative intranetwork and internetwork connectivity differences involving the sensorimotor, subcortical, and cerebellar subnetworks.

Conclusions: Study results emphasize the importance and contribution of cognitive and psychiatric features to the overall pattern of phenotypic variability in PD and demonstrate functional connectivity differences related to these subtypes. Identification of PD clinical subtypes and associated biological mechanisms could facilitate more personalized medicine approaches by improving patient stratification for triaging into different treatment strategies. 

References: Campbell et al., (2016).  Society for Neuroscience annual meeting.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/functional-connectivity-differences-across-parkinson-disease-subtypes/