Apathy in Parkinson's Disease: Distinguishing Overlapping Symptoms Via Network Analysis

Background: Anxiety, fatigue, and excessive daytime sleepiness (EDS) frequently co-occur in Parkinson's disease (PD) and can influence the clinical determination of apathy. Objective: To distinguish patient-reported apathy from other non-motor symptoms. Methods: Individuals with PD meeting UK Brain Bank criteria underwent paired OFF- and ON- dopaminergic medication assessments, including the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Hamilton Anxiety and Depression Rating Scales (HAM-A, HAM-D), Symbol Digit Modalities Test, Stroop, and Scales for Outcomes in Parkinson's Disease-Autonomic Dysfunction assessment. Medication-related changes in anxiety, depression, and cognition were defined using established minimally clinically important differences. Apathy, fatigue, and sleepiness were determined based on MDS-UPDRS Part I scores ≥1. Associations were examined using chi-squared tests, multivariable ordinal logistic regression, and symptom-network analyses. Results: Among 199 participants (36–85 years, 61% male), 90% (53/59) of those with apathy also reported both fatigue and sleepiness. Exploratory network analysis grouped apathy with anxiety and depression, whereas fatigue clustered with somatic symptoms (eg, pain, constipation) and daytime sleepiness remained peripheral. Apathy was independently associated with medication-related change in anxiety after adjustment for fatigue and sleepiness (P < 0.001), while fatigue was associated with autonomic dysfunction (P < 0.05). Conclusion: Despite overlapping presentation, apathy in PD closely tracks affective change linked to dopaminergic state, whereas fatigue and sleepiness reflect broader somatic burden. These distinctions may support more specific recognition and phenotyping of apathy.