An Examination of Cognitive Heterogeneity in Parkinson Disease: The Dual-Syndrome Hypothesis

Purpose: Cognitive impairment is one of the most debilitating nonmotor symp-toms in Parkinson disease (PD), and its presentation is heterogeneous. One pro-posed model to explain cognitive variability in PD is the dual-syndrome hypothesis. This hypothesis delineates two cognitive profiles, a “fronto-striatal” profile and a “posterior cortical” profile according to symptom presentation, associated motor phenotype, and risk for dementia. The current study examined the dual-syndrome hypothesis in individuals with idiopathicPDtoevaluatethe existenceofthese pro-files, determine the association with the motor phenotype (tremor dominant vs. postural instability/gait disorder), and assess the relative risk for dementia. Method: A retrospective examination was conducted using data from the Par-kinson’s Progression Markers Initiative database at baseline (within 2 years of diagnosis) and 5 years after baseline. Descriptive categorizations, cluster analy-ses, generalized linear mixed models, and logistic regressions were used to address the research questions. Results: There was emerging evidence of cognitive profiles; however, these were not fully supported by cluster analyses. Baseline cognitive profile was associated with later motor phenotype, and as predicted, dementia risk was greatest in persons with baseline posterior cortical impairments. Conclusion: The current results provide mixed support for the dual-syndrome hypothesis, with some evidence that the posterior cortical cognitive profile is asso-ciated with postural instability and gait disorder as well as greater dementia risk.