One-year practice effects predict long-term cognitive outcomes in Parkinson's disease

Background: Predicting which individuals with Parkinson's disease (PD) will develop cognitive deficits is challenging, but important towards selecting those individuals at higher risk of progression for personalized early intervention and enriching samples for clinical trials of disease modifying agents. Objective: To examine whether practice effects on cognitive tests across one-year are predictive of eventual cognitive impairment (CI) and dementia (PDD) in individuals with PD. Methods: Individuals with PD (n = 549) from the PPMI database who were cognitively intact at baseline were included for analysis. The Montreal Cognitive Assessment (MoCA) was administered at baseline and during annual follow-up visits over at least five years to determine if participants remained intact (MoCA ≥ 26) or developed CI (MoCA ≤ 25) or dementia (MoCA ≤ 21). Participants also completed a neuropsychological battery at baseline and again after a one-year interval. Practice effects on the cognitive tests across one-year were quantified with standardized regression-based change scores using PPMI data from cognitively intact subjects without PD. Results: Based on MoCA scores, 39% of patients developed CI and 10% developed PDD during the study. Linear regressions revealed smaller practice effects across one year in people with PD than in controls. Within the PD group, Cox regression analyses showed that smaller practice effects on tests of various cognitive domains were associated with an increased risk for CI. For PDD, only practice effects on a measure of processing speed significantly predicted cognitive outcomes. Conclusions: These findings demonstrate that practice effects have prognostic value in long-term cognitive outcomes in PD. This has important implications for clinical care and research, as one-year practice effects could help identify individuals at risk for CI and PDD and enrich samples for future clinical trials. Limitations of the present study pertain to the classification of cognitive impairment on the basis of a screening instrument (i.e., the MoCA) without evidence of the absence/presence of functional impairment, and the clinical utility of the one-year interval.