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Nε-(carboxymethyl)-lysine, White Matter, and Cognitive Function in Diabetes Patients

Jian-Hui Zhang1, Hong-Zeng Xu1, Qi-Feng Shen1

  • 11Department of Neurology,Second Hospital,Dalian Medical University,Dalian,China.

The Canadian Journal of Neurological Sciences. Le Journal Canadien Des Sciences Neurologiques
|February 19, 2016
PubMed
Abstract

Insights

Elevated Nε-(carboxymethyl)-lysine (CML) levels in type 2 diabetes mellitus (T2DM) patients correlate with white matter microstructure damage and cognitive decline. This suggests CML may contribute to T2DM-related cognitive impairment.

Area of Science:

  • Neuroscience
  • Endocrinology
  • Biochemistry

Background:

  • Type 2 diabetes mellitus (T2DM) is increasingly linked to cognitive impairment.
  • Advanced glycation end products, such as Nε-(carboxymethyl)-lysine (CML), are implicated in diabetic complications.
  • White matter (WM) integrity is crucial for cognitive function.

Purpose of the Study:

  • To investigate the association between plasma CML levels and WM microstructure changes.
  • To examine the relationship between CML, WM integrity, and cognitive function in T2DM patients.
  • To explore the potential role of CML in T2DM-associated cognitive impairment.

Main Methods:

  • Diffusion tensor imaging (DTI) was used to assess WM microstructure (Fractional Anisotropy - FA) in 22 T2DM patients (age 65-75, disease duration ≥5 years) and 25 healthy controls.
  • Plasma CML levels were quantified using enzyme-linked immunosorbent assay (ELISA).
  • Cognitive function was evaluated using the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA).

Main Results:

  • T2DM patients exhibited significantly lower MMSE and MoCA scores compared to controls.
  • Reduced FA values were observed in multiple WM regions, including the corpus callosum, cingulate fasciculus, and hippocampus, in T2DM patients.
  • Plasma CML levels showed a negative correlation with global brain FA (r=-0.58, p<0.01) and MoCA scores (r=-0.47, p<0.05).

Conclusions:

  • Older T2DM patients demonstrate significant white matter microstructure alterations.
  • Elevated plasma CML levels are associated with reduced white matter integrity and cognitive impairment in T2DM.
  • CML may be a key factor in the pathogenesis of cognitive decline in type 2 diabetes mellitus.
Keywords:
Cognitive impairmentDiffusion tensor imagingHippocampal atrophyMagnetic resonance imagingNε-(Carboxymethyl) lysineType 2 diabetes mellitus

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