Depression, anxiety and apathy are common mood disturbances in Parkinson's disease (PD) but their pathophysiology is unclear. Advanced neuroimaging has been increasingly used to unravel neural substrates linked to these disturbances. A systematic review is provided of neuroimaging findings in depression, anxiety and apathy in PD. A PubMed, MEDLINE and EMBASE search of peer‐reviewed original research articles on these mood disturbances in PD identified 38 studies on depression, eight on anxiety and 14 on apathy in PD. Most of the imaging studies used either position emission tomography or single‐photon emission computed tomography techniques. These studies generally suggest increased neural activity in the prefrontal regions and decreased functional connectivity between the prefrontal−limbic networks in depressed patients. Functional imaging studies revealed an inverse correlation between dopaminergic density in the caudate and putamen with the severity of anxiety in PD. There was no consistent correlation between dopaminergic density of thalamus and anxiety. Studies demonstrated both positive and inverse correlations between apathy and metabolism or activity in the striatum, amygdalar, prefrontal, temporal and parietal regions. The clinical variability of study subjects and differences in image pre‐processing and analytical strategies may contribute to discrepant findings in these studies. Both nigrostriatal and extra‐nigrostriatal pathways (in particular the frontal region and its connecting areas) are affected in mood disorders in PD. Identifying the relative contributions of these neural pathways in PD patients with overlapping motor and mood symptoms could provide new pathophysiological clues for the development of better therapeutic targets for affected patients.

Parkinson’s disease (PD) is a debilitating neurodegenerative disorder. Findings on specific white matter (WM) alterations in PD have been inconsistent. We hypothesized that WM changes occur in early PD patients and unbiased whole-brain analysis may provide additional evidence of pathological WM changes in PD. In this study, we examined various indexes of WM microstructure in newly diagnosed PD patients at the whole-brain level. 64 PDs with Hoehn & Yahr stage 1 (HY1PDs), 87 PDs with Hoehn & Yahr stage 2 (HYPD2s), and 60 controls (HCs) were recruited. Tract-based spatial statistics (TBSS) and diffusion connectometry were used to identify changes of WM pathways associated with PD. There were no significant differences in axial diffusivity, but HY1PDs exhibited greater fractional anisotropy (FA) and decreased mean and radial diffusivities (MD and RD) in callosal, projection, and association fibres than HCs and HY2PDs. Motor severity was inversely correlated with FA, but positively correlated with MD and RD in PD patients. Connectometry analysis also revealed increased WM density in the aforementioned tracts in PD patients, compared with HCs. Our study reveals WM enhancement, suggesting neural compensations in early PD. Longitudinal follow-up studies are warranted to identify the trajectory of WM changes alongside the progression of PD.

TD patients showed regionally increased FA but decreased diffusivities, implying neural reorganization to compensate PD pathology in early stages. PIGD patients, despite having similar disease stages and duration, exhibited more WM degradation. These results demonstrate differential WM regional features between the 2 subtypes in early PD and support the notion of TD being a benign subtype.

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Subjective cognitive complaints (SCC) and affective symptoms are highly prevalent in Parkinson's Disease (PD). In early PD, SCC prevalence and its affective correlates, using recommended Movement Disorders Society (MDS) Level II Criteria to define the underlying cognitive impairment, has not been previously explored. Methods: We recruited 121 participants with early PD from two tertiary hospitals in Singapore. The presence of SCC was defined using a Non-Motor Symptoms Scale Domain-5 Score ≥1. Comprehensive neuropsychological testing was conducted with Mild Cognitive Impairment (PD-MCI) defined using recommended MDS Level II Criteria. Affective symptoms were assessed using the Hospital Anxiety Depression Scale (HADS), Geriatric Depression Scale (GDS) and Apathy Scale (AS). Analysis using multivariable linear regression model was performed. Results: In our early PD cohort, SCC prevalence independent of underlying cognitive status was 38.8%. Prevalence of SCC in cognitively impaired and cognitively normal participants was 10.7% and 28.1% respectively (р = 0.241). In cognitively normal PD participants, multivariable linear regression analysis revealed that SCC was significantly associated with anxiety (β = 0.28, 95% CI = 0.09-0.79, p = 0.014), depression (β = 0.31, 95% CI = 0.10-0.59, p = 0.006) and apathy (β = 0.32, 95% CI = 1.15-5.98, p = 0.004). Such an association was not found in cognitively impaired PD participants. Conclusion: SCC is highly prevalent even in early PD. Its implications in early PD differ depending on underlying cognitive status. SCC in cognitively impaired participants underestimates the true prevalence of PD-MCI. In contrast, SCC in cognitively normal participants is suggestive of an underlying affective disorder.