Hippocampal subfields atrophy contribute more to cognitive impairment in middle-aged patients with type 2 diabetes rather than microvascular lesions

Aims: Neurodegeneration and microvascular lesions are related to cognitive impairment in type 2 diabetes mellitus (T2DM). We aimed to use the volume of hippocampal subfields and the burden of white matter hyperintensities (WMH) as neurodegeneration and microangiopathy markers, respectively, to investigate their potential associations with cognitive impairment in T2DM patients.

Methods: A total of 76 T2DM patients and 45 neurologically unimpaired normal controls were enrolled between February 2016 to August 2018. All participants underwent structural magnetic resonance imaging (MRI) and Montreal Cognitive Assessment (MoCA). The T2DM patients were divided into the T2DM without mild cognitive impairment (T2noMCI) group (n = 44) and the T2DM with mild cognitive impairment (T2MCI) group (n = 32) according to MoCA scores. We used automatic brain segmentation and quantitative technique to assess the volume of twelve hippocampal subfields and WMH on MRI. We used age, sex, education, and total intracranial volume as our covariates and the Bonferroni method for multiple comparison correction.

Results: Both the T2MCI group and T2noMCI group showed significant hippocampal subfields atrophy compared to the controls, which were mainly in the left hippocampal tail, left CA1, bilateral molecular layer, bilateral dentate gyrus, and bilateral CA4 (all p < 0.0042). No significant differences in the volume of total WMH, deep-WMH, and periventricular-WMH were found among the three groups. The HbA1c levels were significantly negatively correlated with hippocampal atrophy, and the MoCA scores were positively correlated with bilateral hippocampal volume in T2DM patients and all samples. Mediation analyses demonstrated that the association of HbA1c levels with cognitive function was mediated by hippocampal subfields volume.

Conclusion: Widespread hippocampal atrophies across the subfields have been found in middle-aged T2DM patients, which was positively correlated with the MoCA scores and negatively correlated with the HbA1c levels. The association of HbA1c levels with cognitive function was mediated by some crucial hippocampal subfields volume. In middle-aged patients with T2DM, the neurodegeneration is more strongly associated with cognitive impairment than microvascular lesions. Trail Registeration This study was registered on Clinical-Trails.gov (NCT02738671).