Structural and functional magnetic resonance imaging abnormalities and plasma GLP-1 levels in Parkinson's disease with cognitive impairment

Objective: To investigate alterations in plasma glucagon-like peptide 1 (GLP-1) levels and structural and functional magnetic resonance imaging (MRI) in patients with Parkinson's disease-related cognitive impairment. Methods: A total of 34 PD patients with cognitive impairment and 37 PD patients without cognitive impairment were prospectively recruited at our hospital from September 2022 to July 2024. Data on the cognitive function, demographics and plasma GLP-1 levels of the participants were collected. PD patients underwent 3.0 T MRI, and plasma GLP-1 concentrations were measured using an enzyme-linked immunosorbent assay (ELISA). Voxel-based morphometry (VBM) results were used to examine structural alterations. Resting-state functional MRI results were used to reveal the extent of changes in brain connectivity. Results: Compared with those in healthy individuals, plasma GLP-1 levels were lower in PD patients and were positively correlated with Montreal Cognitive Assessment (MoCA) scores. We observed volume reductions in the superior temporal gyrus, amygdala, and left frontal operculum in patients with Parkinson's disease-related cognitive impairment (PD-CI). Moreover, these changes were significantly positively correlated with MoCA scores and GLP-1 levels. We observed decreased functional activity in the right cuneal cortex, left occipital lobe and lateral occipital cortex in PD-CI patients. Conclusions: Our findings reveal that more severe Parkinson's disease-related cognitive impairment is associated with abnormalities in the superior temporal gyrus, left frontal operculum and the visual network. These structural and functional abnormalities are associated with plasma GLP-1 levels. Our results may help clarify the pathophysiology of cognitive impairment and suggest potential therapeutic targets.