To determine the incidence of cognitive impairment and dementia in parkinsonism and evaluate the predictive value of clinical features for long-term risk of dementia in a population-based cohort of incident parkinsonism cases.

Cognitive dysfunction is among the most common non-motor symptoms in parkinsonism, ranging from subjective complaints to dementia. Although several predictive factors have been described, their incidence and prognostic relevance in early disease stages are still uncertain.

Patients with parkinsonism onset between 1991 and 2020 were identified using the Rochester Epidemiology Project records-linkage system. Subjects with cognitive dysfunction preceding motor symptoms onset were excluded. Diagnoses were confirmed by a movement disorders specialist, and the cohort was classified as mild cognitive impairment (MCI), dementia, and non-MCI. Associations between clinical features and outcomes were assessed using Cox proportional hazards regression adjusted for age, sex, and parkinsonism subtype, and validated using a LASSO-penalized Cox model.

A total of 1,239 patients were included: 154 (12.4%) developed MCI and 548 (44.2%) developed dementia after a median of 4 years from disease onset. Dementia risk was significantly higher among individuals presenting with impaired postural reflexes (HR=1.31, p=0.004), wide-based gait (HR=1.27, p=0.02), eye movement restrictions (HR=2.07, p<0.001), and smooth pursuit abnormalities (HR=1.44, p=0.006). Non-motor symptoms, including REM-sleep behavior disorder (RBD) (HR=1.42, p=0.002), orthostatic hypotension (HR=1.31, p=0.007), and constipation (HR=1.25, p=0.016), were also significantly associated with dementia.

Over a 5- to 20-year follow-up, 56.7% of patients with parkinsonism developed cognitive dysfunction. Predictors of dementia included eye movement abnormalities and RBD, suggesting a more widespread neurodegenerative process that begins in early disease stages and extends beyond dopaminergic pathways. Postural instability also predicted dementia, consistent with a poorer prognosis in akinetic-rigid-predominant parkinsonism. Further associations were observed between dementia and autonomic symptoms, supporting the hypothesis that early involvement of the central autonomic network and cholinergic pathways contributes to cognitive dysfunction.