PeerJ Reviewer Match - 18F-FDG for Parkinson's with frailty

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18F-FDG PET reveals specific brain metabolic features in Parkinson's disease with frailty

Abstract

Objective: Frailty is significantly more common among individuals with Parkinson’s disease (PD) compared to the general population, yet the underlying neuropathophysiological mechanisms remain poorly understood. This study aimed to characterize the clinical features and cerebral metabolic patterns of frail PD patients using [¹⁸F]-fluorodeoxyglucose positron emission tomography (¹⁸F-FDG PET), and to explore potential pathophysiological mechanisms.
Methods: From June to December 2024, patients with PD treated at Shenzhen People’s Hospital underwent ¹⁸F-FDG PET imaging. Age- and sex-matched healthy controls were also recruited. Frailty was assessed using the Fried criteria, comprising five components: gait speed, grip strength, physical activity, fatigue, and unintentional weight loss. Demographic characteristics, cognitive performance, and clinical variables—including UPDRS-III scores—were compared between frail and non-frail PD patients. Regional brain metabolism was analyzed across predefined regions of interest (ROIs).
Results: A total of 81 participants were enrolled, including 64 PD patients and 17 healthy controls. Among the PD cohort ( 66.86 ± 6.97 years; 30 female), 34 were classified as non-frail (64.29 ± 6.61 years; 16 female) and 30 as frail (69.77 ± 6.17 years; 14 female). Compared to the non-frail group, frail PD patients were significantly older (P = 0.001) and exhibited more severe motor symptoms (UPDRS-III, P < 0.001; modified H&Y, P = 0.028), along with greater cognitive impairment (P < 0.001). Although the daily levodopa equivalent dose did not differ significantly between groups (P = 0.076), a trend toward higher dosage was observed in the frail group. ¹⁸F-FDG PET analysis revealed significantly reduced glucose metabolism in 13 ROIs in frail PD patients compared to non-frail patients. Further analyses linked specific frailty components with hypometabolism in distinct ROIs: weight loss with Frontal_Mid_L, Frontal_Mid_Orb_L, and Temporal_Inf_L; fatigue with Parietal_Inf_R; slower gait speed with Frontal_Inf_Tri_R; and reduced physical activity with Angular_L. No significant association was found between grip strength and any ROI. Correlation analyses revealed distinct region-function associations in the cognitive domains of frail PD patients. Regression analysis indicated that hypometabolism in the Frontal_Mid_Orb_L was significantly associated with UPDRS-III scores in the frail group.
Conclusion: Frailty in PD is associated with advanced age, greater motor severity, and possibly increased medication needs. Frail PD patients exhibit specific patterns of cerebral hypometabolism and more severe cognitive deficits. Distinct brain regions are implicated in different frailty components and cognitive domains. Notably, reduced metabolism in the Frontal_Mid_Orb_L is significantly related to motor symptom severity in frail PD, suggesting a key region in the pathophysiology of frailty in PD.

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