Decline in striatal binding ratio associated with accelerated decline in performance on symbol digit modality but not MoCA in Parkinson's Disease Psychosis.

Abstract

Background: Cognitive deficits and reduced dopamine transporter (DAT) binding ratio have been reported in Parkinson's disease psychosis (PDP). However, it remains unclear whether DAT striatal binding ratio (SBR) may contribute to worsening cognitive performance in PDP.

Objectives: We examined this using data from the Parkinson's Progression Markers Initiative.

Methods: We analysed data from 392 PD patients, from baseline to year 4 follow-up, and classified patients into PD with psychosis (PDP) and without psychosis (PDnP). DAT SBR was available from ¹²³I-FP-CIT-SPECT [(123) I-2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl) nortropane single photon emission computed tomography] imaging. We examined all cognitive measures assessed at each time point; sociodemographic characteristics, neuropsychiatric and PD-specific symptoms were entered as covariates of interest.

Findings: PDP patients had lower DAT SBR compared with PDnP patients (b=-0.092, p=0.035) over all time points, which remained significant after controlling for age, sex and ethnicity. PDP patients also reported worse trajectory of task performance on the Montreal Cognitive Assessment (MoCA) (b=-0.238, p=0.001) and symbol digit modality (b=-0.534, p=0.016) compared with PDnP patients. Declining performance in symbol digit modality (Group×Time×DAT SBR interaction, b=0.683, p=0.028) but not MoCA was differentially associated with the decline in DAT SBR over time. MoCA scores declined more in PDP compared with PDnP patients over all timepoints (Group×Time interaction, b=-0.284, p=0.016).

Conclusions: Decline in striatal presynaptic dopamine function may specifically underlie longitudinal decline in performance in the symbol digit modality task that engages processing speed, associative learning and working memory in PD psychosis. Whether striatal presynaptic dopamine changes explain accelerated longitudinal decline in other cognitive domains in people with PDP remains to be tested.