Abstract
BACKGROUND: Apathy is a common early symptom of Parkinson's disease (PD), often co-occurring with cognitive decline and associated with fronto-striatal and mesocortico-limbic dysfunctions. Discrepancies between self- and caregiver-reported apathy have been preliminarily associated with cognitive impairments affecting patients' awareness and self-report accuracy. OBJECTIVES: This study investigates discrepancies between PD patient- and informant-reported apathy in relation to the cognitive status (unimpaired-CU vs. impaired-CI), and explores neural correlates of apathy using magnetic resonance imaging (MRI). METHODS: Apathy was assessed in 23 PD participants using self-report (AES-S) and informant (AES-I) versions of the Italian Apathy Evaluation Scale. Discrepancy scores (ΔAES) were compared between groups and correlated with cognitive performance. Resting-state fMRI examined associations between AES indices and connectivity from the bilateral nucleus accumbens, while whole-brain structural analyses assessed associations with gray matter (GM) volume. RESULTS: PD-CI participants showed higher ΔAES, underestimating their apathy compared to PD-CU. ΔAES values correlated with attentional and visuospatial functioning. Higher AES-I scores were associated with hyperconnectivity between right nucleus accumbens, paracingulate, and medial frontal cortices. Structural analyses revealed associations between both AES-I and ΔAES values and GM volume in the cingulate gyrus. DISCUSSION: These findings highlight the impact of cognitive dysfunction on apathy evaluation in PD, emphasizing the importance of caregiver perspective. Neuroimaging results further validated caregiver ratings, showing an association between fronto-striatal network changes and apathy. Further research is needed to clarify the role of such discrepancy in apathy assessment in predicting disease progression.