Analysis of ALPS‐Index: Difference in Type 2 Diabetes Mellitus With or Without Mild Cognitive Impairment and Its Relationship With Hippocampal Microstructure

TL;DR

This study explores how the glymphatic system and hippocampal microstructure relate to cognitive decline in type 2 diabetes patients.

Contribution

The study introduces the ALPS-index as a potential biomarker for cognitive function in T2DM patients.

Findings

The average ALPS-index showed marginal differences among groups with varying cognitive states in T2DM.

The ALPS-index correlated with hippocampal diffusive indicators like FA, MD, and RD in T2DM patients.

The ALPS-index was linked to auditory verbal learning test scores in the general population.

Abstract

Type 2 diabetes mellitus (T2DM) with cognitive impairment has a high incidence rate globally, and there is a need to investigate the relationship among the glymphatic system, hippocampus microstructure, and cognition in T2DM. The present study aims to delineate changes in the perivascular space index (ALPS‐index) among T2DM patients with different cognitive states and investigate any possible correlation between the ALPS‐index and the diffusive indicators of the bilateral hippocampi in T2DM. In addition, we seek to identify specific cognitive domains with substantial correlation with the ALPS‐index in the general population.

A total of 113 participants were recruited, comprising 37 T2DM patients with normal cognitive function (DMNC), 39 T2DM patients with mild cognitive impairment (DMMCI), and 37 healthy controls (HC). Clinical information, neuropsychological assessments, and experienced multimodal magnetic resonance imaging scans were recorded from all the participants. A noninvasive method was applied to obtain all ALPS‐index measures, such as the left, right, and average ALPS‐index, along with diffusive indicators of the bilateral hippocampi, comprising fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD).

A statistically marginal difference in the average ALPS‐index was noted among HC, DMNC, and DMMCI groups. According to binary logistic regression analysis results, the average ALPS‐index significantly altered the cognitive function in T2DM. Partial correlation analyses revealed a positive association between the average ALPS‐index and FA, as well as a negative association with MD and RD in the bilateral hippocampi of the T2DM groups. In the general population, partial correlation analysis indicated that the average ALPS‐index correlated with the auditory verbal learning test (AVLT) immediate recall scores.

In summary, our findings demonstrated that glymphatic system function in the brain progressively deteriorates with worsening cognitive impairment among T2DM patients. Moreover, T2DM significantly disrupts the relationship patterns between the glymphatic system and bilateral hippocampal microstructure. Thus, the mean ALPS‐index may act as a novel neuroimaging biomarker for assessing cognitive function in T2DM.

This study demonstrated that glymphatic system function in the brain progressively deteriorates with worsening cognitive impairment among T2DM patients. Moreover, T2DM significantly disrupts the relationship patterns between the glymphatic system and bilateral hippocampal microstructure.

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