Brain Metabolic and Network Profiles Characterized by Comorbid Depressive Symptoms and Sleep Disturbances in Parkinson’s Disease: An 18F-FDG PET Study

Abstract

Background: Parkinson’s Disease (PD) is a globally increasing neurodegenerative disorder. Its complex, multi-system pathophysiology extends beyond dopaminergic neuron loss, leading to diverse clinical manifestations that present significant challenges for diagnosis and treatment. This study aimed to investigate the distinct brain metabolic characteristics of patients with Parkinson's disease (PD) comorbid with depressive symptoms (PD-Dep) and sleep disturbances (PD-SD), to inform early diagnosis and individualized treatment strategies. Methods: Twenty-eight patients diagnosed with PD at the Affiliated Hospital of Inner Mongolia Medical University between December 2019 and January 2024 were recruited for this study. The patient cohort included 16 individuals with PD-Dep and 21 with PD-SD, indicating potential comorbidity. Seventeen healthy individuals were included as healthy controls (HC). All participants underwent 18F-FDG PET brain metabolic imaging and were evaluated using the Hamilton Depression Rating Scale (HAMD) and the Pittsburgh Sleep Quality Index (PSQI). The distinct cortical metabolic patterns in the PD-SD and PD-Dep groups were analyzed and compared with those of healthy controls. Results: Both PD-Dep and PD-SD patients exhibited widespread frontoparietal hypometabolism compared to HCs. In the PD-Dep group, depressive severity (HAMD) negatively correlated with metabolism in the cortico-striatal-pallidal-thalamic (CSPT) loop (putamen, thalamus, and pallidum) and cortical regions (supramarginal/postcentral gyri), while motor deficits (UPDRS-III) correlated with frontoparietal control network (FPCN) hypometabolism. In the PD-SD group, sleep quality (PSQI) showed a bidirectional correlation pattern (negatively with somatomotor/FPCN regions; positively with temporo-limbic structures). Network mapping revealed that PD-Dep was characterized by default mode network (DMN, 22.2%) impairment and subcortical CSPT involvement. In contrast, the limbic network (34.8%) dominated the metabolic alterations in PD-SD. Conclusion: PD-Dep and PD-SD exhibit notable metabolic and network-level profiles that may align with different neuropathological models. PD-Dep is characterized by bottom-up subcortical-cortical (CSPT) loop dysfunction, potentially supporting the “body-first” PD subtype. Conversely, PD-SD is dominated by top-down limbic network degeneration, which is tentatively consistent with the “brain-first” subtype. Although these proposed associations remain preliminary and hypothesis-generating rather than definitive confirmations of separate pathological subtypes, these findings provide novel neuroimaging evidence for PD subtyping and targeted therapeutic interventions.