Depressive symptoms interact with CSF levels of p-tau in predicting cognitive performance in the early stages of Parkinson's disease

Amyloid-β deposition and tau pathology are suggested to play a role in the emergence of depressive symptoms and cognitive decline in Parkinson's disease (PD). Additionally, studies have reported an association between presence of the APOE4 allele and poorer cognition in PD. The present study aims to investigate whether amyloid-β, tau pathology and APOE4 carrier status interact with depressive symptoms in predicting global cognition in PD. We analysed data from 348 persons with PD (PwPD) and 160 healthy controls (HCs). Linear mixed effects regression analyses were conducted to examine if CSF levels of Aβ42 and p-tau, and APOE4 carrier status did interact with depressive symptoms, as assessed by the Geriatric Depression Scale (GDS), in predicting cognition performance, as measured by Montreal Cognitive Assessment Test (MoCA) scores, over three years. Results of a first linear regression model conducted considering both PwPD and HC indicated that MoCA scores were significantly predicted by GDS, as well as by the interaction between GDS and p-tau, Group and p-tau, and between Group, p-tau and GDS. Results of the models conducted in the two groups separately indicated that, while in HC MoCA scores were predicted by age and time only, a significant interaction between GDS and CSF levels of p-tau emerged as a predictor of MoCA scores in PwPD. Specifically, post hoc analysis revealed a negative association between CSF levels of p-tau and cognitive performance that was significant only in PwPD with the highest GDS scores. Taken together, results of this study confirm that, in early stages of PD, depressive symptoms interact with CSF levels of p-tau in predicting cognitive performance. Findings highlight the importance of assessing and treating depression in PwPD as early as possible, as it might reduce the likelihood of future cognitive decline.