Parkinson's disease psychosis associated with accelerated multi-domain cognitive decline

Cognitive deficits are associated with poor quality of life and increased risk of development of dementia in people with Parkinson's Disease (PD) with psychosis. However, the pattern of progression of cognitive decline within PD psychosis remains unclear. Here, we examined this using data from the Parkinson's Progression Markers Initiative study. We obtained data on drug-naïve PD patients (n=676) and healthy controls (HC, n=187) who underwent baseline and follow-up (year 1 to 5) assessments. We classified PD patients into PD without psychosis (PDnP) and PD with psychosis (PDP) using the MDS-UPDRS part I hallucinations/psychosis item. We examined all cognitive measures assessed at each time point. We used linear mixed-effect models with restricted maximum likelihood. We examined the role of age, sex, ethnicity, education, and neuropsychiatric and PD-specific symptoms as covariates of interest. There were no baseline differences on any cognitive measures between PD patient groups. There were differences in cognitive performance between PD and HC across the majority of the assessments. PDP patients showed a more prominent cognitive decline from baseline to year 5 compared with PDnP across most domains even after controlling for socio-demographics, depression, sleepiness, REM behaviour sleep disorder, and motor symptom severity (immediate recall, b=-0.288, P=0.003; delayed recall, b=-0.146, P=0.003; global cognition, MoCA, b=-0.206, P <0.001; visuo-spatial, b=-0.178, P=0.012; semantic fluency, b=-0.704, P=0.002; processing speed, b=-0.337, P=0.029). Over five years, PD psychosis patients showed worsening of performance in semantic aspects of language, processing speed, global cognition, visuo-spatial abilities, and memory sub-components, regardless of socio-demographic characteristics, neuropsychiatric and motor symptoms. Collectively, these cognitive domains, particularly semantic aspects of language may therefore play an important role in PD psychosis and warrant further investigation.