Neuropsychiatric and Cognitive Symptom Evolution over the First Decade of Biomarker-Positive, Sporadic Parkinson's Disease.

Background

Parkinson's disease (PD) is frequently accompanied by neuropsychiatric symptoms (NPS), including cognitive impairment, which often emerge early and co-occur. Their long-term evolution remains incompletely characterized, particularly in biomarker-positive cohorts.

Objective

The aim was to examine the evolution of NPS in biomarker-positive PD over the first decade following diagnosis.

Methods

Parkinson's Precision Medicine Initiative data were used to evaluate nine NPS in dual biomarker-positive PD (positive cerebrospinal fluid ⍺-synuclein seed amplification assay and abnormal dopamine transporter single-photon emission computed tomography; n = 846) and healthy controls (HCs; n = 282). Analyses included generalized estimating equations (GEEs), principal components analysis (PCA), and cluster analysis.

Results

In PD, absolute prevalence of eight NPS increased over 10 years (6.6%-23.5%), while anxiety declined slightly. Prevalence in HCs remained low and stable. GEE models demonstrated increasing odds of all NPS in PD except anxiety, with notable increases in psychosis (odds ratio [OR], 1.21; 95% confidence interval [CI], 1.17-1.25) and apathy (OR, 1.17; 95% CI, 1.13-1.22). PD participants had higher rates of depression, psychosis, apathy, rapid eye movement sleep behavior disorder, excessive daytime sleepiness, impulse control disorders, and impaired cognition than HCs over time. Mean NPS count increased in PD (1.39 to 2.39), but remained stable in HCs (0.60 to 0.58). PCA identified a stable affective domain, a perceptual domain that included cognitive and sleep symptoms, and a time-varying motivational-behavioral domain. Cluster analysis at diagnosis identified low- and high-burden NPS subgroups that remained applicable at 5- and 10-year timepoints.

Conclusions

NPS increase in prevalence and co-occurrence over 10 years in biomarker-positive, sporadic PD. Time-varying symptom groupings and persistent low- and high-NPS burden phenotypes further highlight the progressive and heterogeneous nature of NPS evolution in PD. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.