Association of Glymphatic Dysfunction with Cognitive Performance in Type 2 Diabetes Mellitus and Prediabetes

Introduction: The glymphatic system (GS) is a brain-wide clearance pathway whose dysfunction has been implicated in cognitive decline. This study was designed to assess GS alterations in prediabetes and type 2 diabetes mellitus (T2DM) using multiple MRI-derived metrics and to examine their associations with cognitive performance.

This cross-sectional study was conducted from October 2023 to June 2024 at Nanfang Hospital, a tertiary care center. A total of 147 participants were recruited, including 52 patients with T2DM, 44 with prediabetes, and 51 healthy controls (HC). All participants underwent brain MRI, laboratory examinations, and cognitive function assessments. GS function was evaluated using MRI-derived metrics, including choroid plexus (CP) volume, perivascular space (PVS) volume, free water (FW) index, and the diffusion tensor imaging analysis along the PVS (DTI-ALPS) index. Group differences were tested with general linear models adjusted for sex, age, and education, and associations with clinical variables were evaluated using partial correlations.

Compared with HC, prediabetes showed increased CP volume and FW index, without significant changes in DTI-ALPS index or PVS volume. T2DM showed reduced DTI-ALPS index, increased CP volume, and higher FW index, with unchanged PVS volume. In both groups, lower DTI-ALPS index and higher CP volume or FW index correlated with poorer cognitive performance.

Prediabetes and T2DM exhibit GS alterations, including reduced DTI-ALPS index and increased CP volume and FW index, which are associated with poorer cognition. GS metrics may serve as potential neuroimaging biomarkers for cognitive impairment in this population.