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September 17, 2025

Cognitive impairment is associated with glymphatic system dysfunction and whole-brain white matter damage in type 2 diabetes mellitus

Key Points

Cognitive impairment is more severe in MCI patients with type 2 diabetes compared to non-MCI individuals.
Impairments in white matter and glymphatic system function correlate significantly with cognitive deficits.
Using DTI and DTI-ALPS, the study assessed structural brain integrity alongside the glymphatic system.
The findings suggest the need to focus on glymphatic and white matter health when treating MCI in T2DM patients.

Abstract

Motivation: Type-2 diabetes mellitus (T2DM) often coexist with cognitive impairment, but the exact mechanism remains unclear. Goal(s): Investigating if white matter (WM) and glymphatic system (GLS) were impaired in T2DM patients and if the damages were associated with cognitive impairment. Approach: 70 T2DM and 35 healthy controls were enrolled. WM integrity and GLS function were assessed using DTI and DTI-ALPS, respectively. Results: The impairments of WM and GLS were more severe in mild cognitive impairment (MCI) than non-MCI T2DM patients. WM and GLS deficient were significantly associated with cognitive impairment. The impact of GLS dysfunction on cognitive impairment was mediated by WM deficient. Impact: For the first time, we showed the potential interplay among brain wide WM damage, GLS dysfunction, and cognitive impairment in T2DM patients. Our study may provide evidence for taking GLS and brain WM into account for MCI T2DM patients treatment.

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