Exploring the layers of fatigue in Parkinson's Disease: A comprehensive analysis of its prevalence and contributing factors.

Background: Fatigue is a prevalent yet under-recognized non-motor symptom (NMS) of Parkinson's disease (PD), significantly impacting patients' quality of life. Despite its clinical importance, the relationship between fatigue and other motor and non-motor symptoms remains poorly understood. Its frequent co-occurrence with other NMS further complicates both diagnosis and management, often leading to underdiagnosis and suboptimal treatment. This gap in understanding is largely due to the limited exploration of fatigue in PD. Objective: This study aimed to evaluate the prevalence of fatigue at baseline and up to 10 years after symptom onset in a large, well-characterized PD cohort (PPMI) and to explore its associations with other non-motor symptoms (NMS). By providing insights into the prevalence and correlations of fatigue, our goal is to highlight the need for early identification and management, guiding future research efforts. Methods: We conducted a retrospective study using the PPMI database. Fatigue was assessed using item 1.13 of the Movement Disorders Society Unified Parkinson's Disease Rating Scale. Logistic regression was used to analyze the impact of different variables on fatigue, while point-biserial correlation analysis gauged the relationship between continuous variables and fatigue. Results: At baseline study visit, 52% (575) of patients reported experiencing fatigue, with 9% reporting moderate to severe fatigue early in the disease course. Higher scores on several scales were significantly associated with an increased risk of fatigue, though most associations were weak. Significant associations included the REM Sleep Behavioral Disorder Questionnaire (OR: 1.09, 95% CI: 1.06-1.11), Geriatric Depression Scale (OR: 1.07, 95% CI: 1.03-1.11), State-Trait Anxiety Inventory (OR: 1.01, 95% CI: 1.00-1.02), SCOPA-Autonomic Dysfunction (OR: 1.05, 95% CI: 1.03-1.06), Epworth Sleepiness Scale (OR: 1.06, 95% CI: 1.04-1.08), and Apathy (OR: 2.90, 95% CI: 2.4-3.5). Conclusion: Over half of patients reported fatigue at baseline, underscoring its significant prevalence early in PD. The predominantly weak associations with other NMS highlight the necessity for comprehensive patient screening and targeted interventions, as addressing one NMS may not effectively alleviate others.