The Role of Iron Homeostasis Imbalance in T2DM‐Associated Cognitive Dysfunction: A Prospective Cohort Study Utilizing Quantitative Susceptibility Mapping

PMCID: PMC12175199

PMID: 40530831

DOI: 10.1002/hbm.70263

Journal: Human brain mapping

Publication Date: 2025-6-18

Authors: Cheng Z, Yang L, Li M, Zhang Q, Li J, et al.

Key Points

• T2DM patients showed significantly higher iron deposition in caudate and putamen nuclei compared to healthy controls
• Higher magnetic susceptibility values in anterior putamen and posterior caudate were associated with a 20-21% reduction in cognitive processing speed
• Elevated HbA1c levels directly correlate with increased brain iron accumulation, suggesting metabolic control could mitigate cognitive decline

Summary

This study investigated brain iron deposition in type 2 diabetes mellitus (T2DM) patients using quantitative susceptibility mapping (QSM), revealing significant associations between iron accumulation in subcortical nuclei and cognitive dysfunction. By examining 224 participants (112 T2DM patients and 112 healthy controls), researchers demonstrated that T2DM patients exhibited pronounced iron deposition in the caudate and putamen regions, which correlated with slower processing speed, reduced memory performance, and impaired executive function.

The research provides critical insights into the neurological mechanisms of T2DM-related cognitive decline, highlighting how metabolic dysregulation contributes to brain iron accumulation. Structural equation modeling revealed that metabolic factors significantly influence subcortical magnetic susceptibility, with HbA1c emerging as a key predictor of iron deposition. These findings suggest that glycemic variability may drive neurological changes through disrupted iron homeostasis and increased oxidative stress, potentially offering new avenues for early cognitive intervention in diabetic patients.