Discrepancy in apathy evaluation between Parkinson’s Disease patients and caregivers: A behavioral and functional magnetic resonance imaging study

Background: Parkinson’s disease is a neurodegenerative disorder characterized by both motor and non-motor symptoms, the latter including mood disorders such as apathy and cognitive decline. Notably, cognitive decline is often associated with anosognosia i.e., the partial or complete lack of awareness of cognitive and behavioral status, which may affect the reliability of patient self-report questionnaires. This study aims to compare apathy evaluation by PD patients classified according to cognitive status (cognitively unimpaired - CU vs cognitively impaired - CI) and by patients’ caregivers. Additionally, the neural correlates of apathy will be investigated using resting-state functional magnetic resonance imaging (rsfMRI). Methods: Twenty-three PD patients participated in this study, which included clinical, behavioral and neuropsychological assessment, as well as rsfMRI. Apathy was evaluated using both the self-report (AES-S) and the informant (AES-I) versions of the Apathy Evaluation Scale (AES). The discrepancy score was calculated as the difference between the AES-I and AES-S scores. This discrepancy score was then compared between PD-CU and PD-CI individuals at behavioral level. Correlation analyses were performed between the discrepancy score and performance on neuropsychological tests. At the neural level, rsfMRI analyses were performed to assess the relationship between apathy scores and brain connectivity, using the bilateral nucleus accumbens as the seed region, following evidence from previous literature. Results: A significant difference in the AES discrepancy score was found between the PD-CI and PD-CU groups (t(20)=2.21, p=0.039). Specifically, PD-CI patients showed a higher discrepancy (mean: 5.44) compared to PD-CU individuals (mean: -2.54), indicating that patients with cognitive decline underestimate their level of apathy if compared to caregivers’ assessments. Notably, the discrepancy score was associated with attentive and visuo-spatial functioning. At the neural level, higher levels of apathy, measured through the AES-I scale, was associated with hyperconnectivity between the right nucleus accumbens and a cluster including the paracingulate cortex and the medial frontal cortex. There was also a significant pattern of hyperconnectivity between the right nucleus accumbens and a posterior cluster located at the occipital level. No significant results were found with the AES-S scale. Discussion: Overall, these results support the use of the AES-I for evaluating apathy in PD patients, particularly in those with mild cognitive impairment who may suffer from anosognosia. Higher levels of apathy are associated with abnormal functional patterns in the areas affected by the neurodegenerative processes of PD.