Association Between Deep Gray Matter Iron Deposition Dysregulation and Cognitive Performance in Type 2 Diabetes Mellitus Patients: A Quantitative Susceptibility Mapping Study.

BACKGROUND

Type 2 diabetes (T2DM) heightens cognitive impairment risk, yet the mechanisms remain unclear. Hyperglycemia-induced iron dysregulation in deep gray matter (DGM) nuclei may be a crucial mechanism.

PURPOSE: To investigate DGM iron deposition in T2DM using Quantitative Susceptibility Mapping (QSM) and determine its association with cognitive function.

STUDY TYPE: Prospective.

POPULATION: One hundred and fifteen T2DM patients (59.13% male, 53.04 ± 10.12 years) and 176 healthy controls (29.55% male, 50.18 ± 9.41 years).

FIELD STRENGTH/SEQUENCE: 3 T; 3D T1-weighted and 3D multi-echo gradient-echo sequences.

ASSESSMENT: The magnetic susceptibility of eight bilateral DGM nuclei was quantitatively assessed via QSM. Comprehensive evaluations were conducted for all participants, covering demographic and clinical characteristics, and a battery of multidimensional neuropsychological tests.

STATISTICAL TESTS: Group differences in DGM magnetic susceptibility were assessed using two-sample t-tests. Partial correlation and multiple linear regression analyses were performed to examine associations between regional susceptibility and both cognitive and clinical variables. Mediation and moderation analyses were conducted to examine the relationships between various clinical factors, DGM susceptibility, and cognitive function. A corrected p < 0.05 was considered statistically significant.

RESULTS

T2DM patients showed significantly increased magnetic susceptibility in the thalamus, putamen, substantia nigra, and right red nucleus, while the caudate nucleus showed reduced susceptibility. Iron content in the caudate nucleus positively correlated with MoCA (r = 0.193) and CDT (r = 0.196), whereas putamen iron deposition negatively correlated with AVLT-immediate (r = -0.211) and AVLT-delay (r = -0.187) and positively correlated with GPT-L (r = 0.22). Substantia nigra susceptibility partially mediated the effect of age on MoCA scores (β = -0.008), and diabetes status moderated the age-related rate of iron accumulation in the substantia nigra (interaction coefficient = 0.770). Age, diabetic status, sex, and BMI were significant factors influencing brain iron deposition.

DATA

CONCLUSION

Dysregulated brain iron metabolism in T2DM is associated with cognitive dysfunction. Iron accumulation in the substantia nigra may mediate age-related cognitive decline, and T2DM significantly accelerates this age-dependent iron deposition.

EVIDENCE LEVEL: 2.

TECHNICAL EFFICACY: Stage 2.