Movement disorders : official journal of the Movement Disorder Society · 2026
Neuropsychiatric and Cognitive Symptom Evolution over the First Decade of Biomarker-Positive, Sporadic Parkinson's Disease.
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Schoen Izabelle, Wang Jing, Xie Sharon X, Caspell-Garcia Chelsea, Mamikonyan Eugenia, Stark Melanie, Dahodwala Nabila, Siderowf Andrew D, Dobkin Roseanne, York Michele K, Weintraub Daniel
Аннотация
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.
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.