Cerebellar Glutamate Chemical Exchange Saturation Transfer Alterations Correlated With Cognitive Impairment in Parkinson's Disease

ABSTRACT The role of cerebellar glutamatergic dysfunction in cognitive impairment of Parkinson's disease (PD) remains poorly understood. Glutamate chemical exchange saturation transfer (GluCEST) imaging enables noninvasive assessment of regional glutamate levels. To investigate the associations between cerebellar GluCEST–derived alterations and cognitive impairment as well as other clinical characteristics in patients with PD, 64 PD patients underwent 3 T MRI including GluCEST sequence and clinical assessments. Patients were divided into PD with preserved cognition (PD‐CN, MoCA > 22, n = 23) and PD with impaired cognition (PD‐CI, MoCA ≤ 22, n = 41) subgroups. GluCEST‐derived parameters including MTR asym , CESTR nr , and MTR Rex were obtained from the bilateral cerebellar cortex and white matter. Between‐group differences in the GluCEST‐derived parameters were assessed using ANOVA, adjusting for age and sex. Pearson or Spearman correlation analyses were used to examine associations between GluCEST‐derived parameters and cognitive performance. Benjamini–Hochberg false discovery rate (FDR) correction was applied for multiple comparisons. Compared with the PD‐CN group, the PD‐CI group showed lower MTR asym values in the bilateral cerebellar cortex (CC) and the right cerebellar white matter (CWM) ( p < 0.05) and a lower CESTR nr value in the right CWM ( p = 0.016). Within the PD‐CI group, MoCA total score was negatively correlated with MTR Rex in the left CC ( p = 0.013). Attention/working memory was negatively correlated with CESTR nr ( p = 0.021) and MTR Rex ( p = 0.007) in the left CC. Orientation was negatively correlated with MTR Rex in the left CWM, right CC, and right CWM ( p < 0.05). In addition, negative correlation between disease duration and MTR Rex in the right CWM remained significant after FDR correction ( p = 0.020). Cerebellar GluCEST alterations are associated with cognitive impairment in PD. GluCEST may serve as a possible neuroimaging marker in PD.