Abstract
BACKGROUND: Parkinson’s Disease (PD)-associated subjective cognitive decline (PDSCD) is defined as cognitive complaints without objective cognitive impairment. Based on most studies, it is associated with a greater risk of cognitive decline and may represent a prodromal stage of cognitive impairment. METHODS: The main objectives are to identify cognitive progression patterns and clinical predictors of worse cognitive decline within a large PD-SCD cohort with a 4-year followup. All patients belong to the prospective observational multicenter study COPPADIS. RESULTS: A total of 198 PD-SCD subjects were analyzed. Mean age was 60.9, mean disease duration 5.2, and mean PD-Cognitive Rating Scale (PD-CRS) 97.6. Subjects were classified as Progressors if their Reliable Change Index was ≤ − 1.64 at year 4, and as non-Progressors if it was > − 1.64 (− 1.64 corresponded to − 16 on the PD-CRS). Progressors had significantly higher age, Movement Disorders Society-Unified PD Rating Scale (MDS-UPDRS) III, levodopa equivalent daily-dose, Non-Motor Symptom Scale total score, memory-related cognitive complaints, and prevalence of REM-sleep behavior disorder (RBD) at baseline. A linear mixed-effects model showed divergent cognitive trajectories between Progressors and non-Progressors (estimate = − 26.8; p < 0.001), with no differences in motor trajectories. In the binary regression model, age (OR = 1.09; p = 0.001), MDS-UPDRS III (OR = 1.05, p = 0.008), and RBD (OR = 2.55, p = 0.010) at baseline were independent predictors of cognitive progression. CONCLUSIONS: Subjects with PD-SCD do not consistently show cognitive decline, but rather exhibit a heterogeneous progression. Age, MDS-UPDRS III and RBD significantly increase the risk of a more aggressive cognitive phenotype. Future research on biomarkers will help explore additional cognitive predictors in PD-SCD.