Association between glymphatic dysfunction and glucose hypometabolism in chronic disorders of consciousness: a multimodal PET/MRI Study

Abstract

The glymphatic system is essential for removing metabolic waste from the brain and facilitating the distribution of nutrients, but its status in patients with chronic disorders of consciousness (DoC) remains poorly understood. This study evaluated glymphatic function in chronic DoC and investigated its association with regional cerebral glucose metabolism. Forty-one patients with chronic DoC and 26 healthy controls (HCs) were retrospectively included. All participants underwent 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/magnetic resonance imaging (PET/MRI). Glymphatic function was quantified using the diffusion tensor image analysis along the perivascular space (DTI-ALPS) index. Standardized uptake value ratios (SUVRs) of key hubs within the “mesocircuit model” were calculated using the cerebellum as reference. The characteristic glucose metabolic pattern (GMP) of chronic DoC was identified, and its expression scores were computed. Associations between the glymphatic function and cerebral glucose metabolism, behavioral score, and serological markers were evaluated. Patients with chronic DoC showed significantly lower DTI-ALPS indices than HCs (p < 0.001). Within the patient group, moderate to strong correlations were observed between the DTI-ALPS index and the SUVRs of mesocircuit-associated regions, including the frontal cortex (r = 0.335, p = 0.002), parietal cortex (r = 0.383, p < 0.001), thalamus (r = 0.528, p < 0.001), brainstem (r = 0.665, p < 0.001), striatum (r = 0.537, p < 0.001), and globus pallidus (r = 0.372, p = 0.001), but not with the GMP score, behavioral score, or serological markers (all p > 0.05). Multivariate analysis further revealed that older age (β = −0.312, p < 0.001) and lower SUVRs in the parietal cortex (β = 0.196, p = 0.030) and brainstem (β = 0.482, p < 0.001) independently predicted reduced DTI-ALPS indices. This study provides in vivo evidence that glymphatic dysfunction is significantly associated with regional cerebral hypometabolism in chronic DoC, particularly in the parietal cortex and brainstem, which may serve as physiological drivers of CSF circulation.