Decline in striatal binding ratio associated with accelerated decline in performance on Symbol Digit Modality but not MoCA in Parkinson's disease psychosis

Background: Cognitive deficits have been reported in Parkinson's Disease psychosis (PDP). Reduced dopamine transporter (DAT) binding ratio has also been associated with PDP. However, it remains unclear whether DAT striatal binding ratio (SBR) may contribute to worsening cognitive performance in PDP. Here, we examined this using data from the Parkinson's Progression Markers Initiative study. Methods: We analysed data from 408 PD patients, from baseline to year 4 follow up, and classified patients into PD with (PDP) and without psychosis (PDnP). DAT SBR was available from DaTSCAN imaging with ¹²³ I-FP-CIT-SPECT. We examined all cognitive measures assessed at each time point, socio-demographics, neuropsychiatric and PD-specific symptoms were entered as covariates of interest. Results: PDP patients had lower DAT SBR compared to PDnP patients (b=-0.092, p=0.035) which remained significant after controlling for age, sex, and ethnicity. PDP patients also reported worse trajectory of task performance on MoCA (b=-0.238, p=0.001) and Symbol Digit Modality (b=-0.534, p=0.016) across four years compared to PDnP patients. Worsening of MoCA scores in PDP was independent of DAT SBR decline (interaction group * study years, b=-0.284, p=0.016; three-way interaction group*study years*DAT SBR, b=0.127, p=0.225). However, declining performance in Symbol Digit Modality was significantly associated with the decline in DAT SBR (three-way interaction group*study years*DAT SBR, b=0.683, p=0.028). Conclusion: Overall, longitudinal decline in striatal presynaptic dopamine function may underlie the greater longitudinal decline in performance in the symbol digit modality task that engages processing speed, associative learning and working memory in PD psychosis, whilst declining performance on MoCA seems unrelated to it. Whether striatal presynaptic dopamine changes explain accelerated longitudinal decline in other cognitive domains in people with PDP remains to be tested.