Modifiable Comorbidities Associated with Cognitive Decline in Parkinson's Disease

Background: Cognitive impairment (CI) is one of the most feared and debilitating complications of PD. No therapy has been shown to slow or prevent CI in PD. Objective: To determine associations between modifiable comorbidities, including cardiovascular disease risk factors, mood disorders, and sleep characteristics, and rate of cognitive decline in Parkinson's disease (PD). Methods: Data from the Parkinson's Progression Markers Initiative (PPMI) cohort was queried for baseline cardiovascular disease risk factors, mood disorders, and sleep characteristics. Linear mixed- effects models (LME) were used to examine the association between baseline factors and change in cognition, evaluated by the Montreal Cognitive Assessment (MoCA) over time. Baseline comorbidities found to affect MoCA decline were assessed for an association with focal cognitive domains using LME. Results: Higher Body Mass Index (BMI) (beta = -0.009, P = 0.039), State Trait Anxiety Inventory (STAI) (beta = -0.005, P < 0.001), Geriatric Depression Scale (GDS) (beta = -0.034, P < 0.001), Epworth Sleepiness Scale (ESS) (beta = -0.017, P = 0.003), and REM Sleep Behavior Disorder Screening Questionnaire (RBDSQ) (beta = -0.037, P < 0.001) were associated with faster rates of MoCA decline. Using established cut-offs for clinically significant symptoms, being overweight, or the presence of depression, excessive day time sleepiness (EDS), and possible REM sleep behavior disorder (pRBD), were all associated with faster rate of cognitive decline. Conclusion: Several modifiable baseline comorbidities are associated with faster rate of CI over time in patients with PD. These associations identify potential opportunities for early intervention that could influence CI in PD.