Parkinson's disease (PD) is associated with various nonmotor symptoms including neuropsychiatric and cognitive dysfunction. We examined the relation between apathy, anxiety, side of onset of motor symptoms, and cognition in PD. We hypothesized that PD patients would show different neuropsychiatric and neurocognitive profiles depending on the side of onset. 22 nondemented PD patients (11 right-side onset (RPD) with predominant left-hemisphere pathology, and 11 LPD) and 22 matched healthy controls (NC) were administered rating scales assessing apathy and anxiety, and a series of neuropsychological tests. PD patients showed a higher anxiety level than NC. There was a significant association between apathy, anxiety, and disease duration. In LPD, apathy but not anxiety was associated with performance on nonverbally mediated executive function and visuospatial measures, whereas, in RPD, anxiety but not apathy correlated with performance on verbally mediated tasks. Our findings demonstrated a differential association of apathy and anxiety to cognition in PD. 1. Introduction Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by the loss of nigrostriatal and mesocortical dopaminergic projections from the brain stem and limbic cortex to the basal ganglia and neocortex. The basal ganglia and related structures are critical structures in parallel frontal subcortical circuits involved in regulation of cognition, emotions, and behavioral activation [1–3]. While primarily characterized as a movement disorder, PD is associated with various nonmotor symptoms [4–6], including cognitive dysfunction [7–10] and neuropsychiatric symptoms, such as apathy [11–17] and anxiety [18–20]. Recent neuroimaging and neuropsychological findings raise the question of the role of apathy and anxiety in PD-related cognitive dysfunction, as these neuropsychiatric conditions reflect dysfunction in brain areas involved in PD. Typically, early motor signs of PD start on one side of the body, and side of onset remains a significant clinical and neuropathological factor in both clinical management and the study of PD. PD patients with symptoms starting on the right side of the body (RPD) have greater inferred left hemisphere pathology and those with left-side onset (LPD) have greater inferred right hemisphere pathology [21]. The motor symptoms of PD are associated with asymmetrical depletion of dopamine in the substantia nigra of the midbrain across the range of disease severity. These changes in the substantia nigra lead to asymmetrical dysregulation of the
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