Dementia risk prediction in early Parkinson's disease: Validation and genetic integration of the Montreal Parkinson risk of dementia scale (MoPaRDS).

BackgroundPrediction models for dementia in Parkinson disease (PD) are needed to better identify high-risk patients, but existing risk models often lack validation in early-stage PD, when prognosis is most challenging.ObjectiveThis study aims to validate the Montreal Parkinson Risk of Dementia Scale (MoPaRDS) in six population-based cohorts of newly diagnosed PD and to evaluate if incorporating genetic factors (GBA1 and APOE-ε4) enhances its performance.MethodsWe calculated MoPaRDS scores for 1108 newly diagnosed PD patients, and MoPaRDS + GBA1 + APOE for the 941 patients with complete genetic data. We assessed the scores' performance in predicting dementia diagnosed over 10 years using time-dependent receiver operating characteristic (ROC) curves.ResultsOf the 1108 patients (mean age 69.5 ± 10.0 years; 61.0% men), 350 (31.6%) developed dementia. The area under the time-dependent ROC curve (AUC) was 0.79 for MoPaRDS and 0.80 for MoPaRDS + GBA1 + APOE. Subdividing patients based on their MoPaRDS scores revealed annual observed risks of PDD of 39.4% (n = 8; high risk-), 11.4% (n = 176; intermediate risk-), and 5.0% (n = 942; low risk-group). With the suggested cutoff of ≥4, MoPaRDS had a sensitivity of 21.7% and specificity of 94.9%. Including the genetic items improved the sensitivity to 36.4% while maintaining comparable performance for specificity (91.5%).ConclusionsMoPaRDS demonstrates high specificity but limited sensitivity in early PD, highlighting that a one-size-fits-all approach is inadequate for predicting dementia risk in PD across different disease stages. Integrating genetic items increases sensitivity and identifies more newly diagnosed patients at higher risk of dementia, and may be a useful approach to assist dementia risk assessment in early-stage PD.