Original research: initial development of a pragmatic tool to estimate cognitive decline risk focusing on potentially modifiable factors in Parkinson's disease.

ABSTRACT

Introduction: Cognitive decline is common in Parkinson's disease (PD). Calculating personalized risk of cognitive decline in PD would allow for appropriate counseling, early intervention with available treatments, and inclusion in disease-modifying trials. Methods: Data were from the Parkinson's Progression Markers Initiative de novo cohort. Baseline scores were calculated for Lifestyle for Brain Health (LIBRA) and the Montreal Parkinson Risk of Dementia Scale (MoPaRDS) per prior literature and preliminary Parkinson's disease Risk Estimator for Decline In Cognition Tool (pPREDICT) by attributing a point for fourteen posited risk factors. Baseline and 5-year follow-up composite cognitive scores (CCSs) were calculated from a neuropsychological battery and used to define cognitive decliners (PD-decline) versus maintainers (PD-maintain). Results: The PD-decline group (n = 44) had higher LIBRA (6.76 ± 0.57, p < 0.05), MoPaRDS (2.45 ± 1.41, p < 0.05) and pPREDICT (4.52 ± 1.66, p < 0.05) scores compared to the PD-maintain group (n = 263; LIBRA 4.98 ± 0.20, MoPaRDS 1.68 ± 1.16, pPREDICT 3.38 ± 1.69). Area-under-the-curve (AUC) for LIBRA was 0.64 (95% confidence interval [CI], 0.55-0.73), MoPaRDS was 0.66 (95% CI, 0.58-0.75) and for pPREDICT was 0.68 (95% CI, 0.61-0.76). In linear regression analyses, LIBRA (p < 0.05), MoPaRDS (p < 0.05) and pPREDICT (p < 0.05) predicted change in CCS. Only age stratified by sex (p < 0.05) contributed significantly to the model for LIBRA. Age and presence of hallucinations (p < 0.05) contributed significantly to the model for MoPaRDS. Male sex, older age, excessive daytime sleepiness, and moderate-severe motor symptoms (all p < 0.05) contributed significantly to the model for pPREDICT. Conclusion: Although MoPaRDS is a PD-specific tool for predicting cognitive decline relying on only clinical features, it does not focus on potentially modifiable risk factors. LIBRA does focus on potentially modifiable risk factors and is associated with prediction of all-cause dementia in some populations, but pPREDICT potentially demonstrates improved performance in cognitive decline risk calculation in individuals with PD and may identify actionable risk factors. As pPREDICT incorporates multiple potentially modifiable risk factors that can be obtained easily in the clinical setting, it is a first step in developing an easily assessable tool for a personalized approach to reduce dementia risk in people with PD.