👤 Lars Forsgren

An accurate understanding of prognosis in Parkinson's disease (PD) is important for patient information provision, personalized treatment, and clinical trial design, but most previous research has been biased towards younger, healthier patients. To describe key clinical outcomes longitudinally and identify baseline prognostic factors (predictors) for these outcomes using population-representative PD cohorts. We meta-analyzed individual patient data from six incidence cohorts in Western Europe (Norway, Sweden, and UK). Each cohort aimed to recruit and follow up all newly diagnosed cases in defined population/incidence periods (between 2000 and 2011). We described postural instability (Hoehn & Yahr Stage 3), functional dependency (needing help with daily activities), dementia, and death with up to 12 years' follow-up and investigated clinical and genetic predictors using frailty Cox models. In 883 population-based incident patients, median age at motor symptom onset was 69.2 years. Median time to postural instability and functional dependency was 7.4 years. Dementia affected 49.6% by 10 years and 54.7% had died by 12 years (median survival 9.4 years). Older age, higher Movement Disorder Society-Unified Parkinson's Disease Rating Scale-Part III (MDS-UPDRS-III) score, and lower Mini-Mental State Examination (MMSE) were significantly associated with all outcomes; cognitive symptoms and GBA polymorphisms with each outcome except mortality; and APOE ε4 with increased mortality and dementia. This first individual patient data meta-analysis of population-based incidence cohorts provides robust prognostic data, with fewer selection biases than previous PD studies, for informing people with PD about prognosis. In incidence cohorts, overall PD prognosis is worse than previously suggested, with key outcomes often occurring early. Further work should develop validated prognostic models for objective stratification of prognostic risk and for personalized medicine. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. Show less

Given the clinical heterogeneity of Parkinson's disease (PD), identification of early -stage subgroups with shared non-motor symptom (NMS) profiles may clarify its pathophysiology. This study used latent-profile analyses (LPA) to define subgroups based on sleep disturbances, cognitive performance and neuropsychiatric symptoms, and examined dopaminergic function and brain volume differences between them. We analyzed data from 51 cognitively normal non-PD older adults and 105 early-stage PD participants from the iPARK trial, including 19 who underwent [ LPA identified a two-cluster solution as the best fit. Group 1 ( These findings indicate clinically distinct subgroups in early-stage PD. Greater NMS burden is linked to impaired dopaminergic integrity, suggesting a potential neurobiological signature. Early identification of such subgroups may improve understanding of disease heterogeneity and support personalized management and interventions. https://clinicaltrials.gov/study/NCT03680170?id=NCT03680170&rank=1, identifier (NCT03680170). Show less