Predicting Cognition and Affective Changes in Newly Diagnosed Parkinson’s Disease Through Longitudinal Data-Driven Clustering

<b>Background:</b> Although primarily characterised as a motor disorder, Parkinson's Disease (PD) also presents with non-motor symptoms, including cognitive decline and affective dysfunction, which are major predictors of quality of life and mortality for individuals. However, factors associated with these non-motor symptom trajectories remain under-characterised. <b>Purpose:</b> This study aimed to investigate predictors of cognitive and affective function over a 5-year follow-up period using data from the Progressive Parkinson's Marker Initiative. <b>Results:</b> Fuzzy C-means clustering analysis of year-5 cognitive and affective function scores showed two clusters. The second group (n = 96) were older and had worse cognition, affective, and motor functioning at year-5 follow-up compared to the first (n = 213). Predictors of cluster membership was assessed in n = 113 individuals for whom data on all variables of interest were available (cluster 1/2 = 79/34). Cluster membership at 5-year follow-up was significantly predicted by baseline cognitive and affective function, as well as decreased levels of CSF amyloid-beta and increased CSF concentrations of phosphorylated-tau at baseline. Alternative non-linear supervised machine learning model (support vector regressor) using the same predictors improved classification accuracy by 5%. <b>Conclusion:</b> Our analysis highlights that including established biomarkers of other neurocognitive disorders (namely, amyloid-beta and phosphorylated-tau) also has utility for predicting cognitive and affective trajectory in PD. This suggests that assessing a multi-modal panel of prognostic markers, beyond clinical symptom presentation alone, may have utility for informing prognosis of cognitive and affective outcomes in PD. This is significant, potentially allowing for the earlier development of personalised therapeutic interventions for those at highest risk of impairment within these non-motor domains.