Entorhinal Cortex Atrophy in Early, Drug-naive Parkinson's Disease with Mild Cognitive Impairment

Patients with Parkinson's disease (PD) generally have a higher proportion of suffering from mild cognitive impairment (MCI) than normal aged adults. This study aimed to identify the specific neuroanatomical alterations in early, drug-naive PD with MCI (PD-MCI) by comparing to those PD with normal cognition (PD-NC) and healthy controls (HCs), which could help to elucidate the underlying neuropathology and facilitate the development of early therapeutic strategies for treating this disease. Structural MRI data of 237 early, drug-naive non-demented PD patients (classified as 61 PD-MCI and 176 PD-NC) and 69 HCs were included from Parkinson's Progression Markers Initiative (PPMI) database after data quality control. Within these data, a subset of 61 HCs and a subset of 61 PD-NC who were matched to the 61 PD-MCI group for age, gender, and education-level were selected to further eliminate the sample size effect. The gray matter (GM) volume changes between groups were analyzed using voxel-based morphometry (VBM). Furthermore, correlations between GM volume alterations and neuropsychological performances and non-cognitive assessments (including olfactory performance) were further examined. Compared to HC, patients with PD-NC and PD-MCI commonly exhibited atrophies in the bilateral amygdala (AM) and the left primary motor cortex (M1). Patients with PD-MCI exclusively exhibited atrophy in the right entorhinal cortex (ENT) compared to PD-NC. Significantly negative correlations were found between GM loss in the bilateral AM and olfactory performance in all PD patients, and between ENT loss and memory performance in PD-MCI. The findings suggest that the right ENT atrophy may subserve as a biomarker in early, drug-naive PD-MCI, which shed light on the neural underpinnings of the disease and provide new evidence on differentiating the neuroanatomical states between PD-MCI and PD-NC.