Memory Dysfunction in Type 2 Diabetes Mellitus Correlates with Reduced Hippocampal CA1 and Subiculum Volumes

BACKGROUND: Little attention has been paid to the role of subcortical deep gray matter (SDGM) structures in type 2 diabetes mellitus (T2DM)-induced cognitive impairment, especially hippocampal subfields. Our aims were to assess the in vivo volumes of SDGM structures and hippocampal subfields using magnetic resonance imaging (MRI) and to test their associations with cognitive performance in T2DM. METHODS: A total of 80 T2DM patients and 80 neurologically unimpaired healthy controls matched by age, sex and education level was enrolled in this study. We assessed the volumes of the SDGM structures and seven hippocampal subfields on MRI using a novel technique that enabled automated volumetry. We used Mini-Mental State Examination and Montreal Cognitive Assessment (MoCA) scores as measures of cognitive performance. The association of glycosylated hemoglobin (HbA1c) with SDGM structures and neuropsychological tests and correlations between hippocampal subfields and neuropsychological tests were assessed by partial correlation analysis in T2DM. RESULTS: Bilaterally, the hippocampal volumes were smaller in T2DM patients, mainly in the CA1 and subiculum subfields. Partial correlation analysis showed that the MoCA scores, particularly those regarding delayed memory, were significantly positively correlated with reduced hippocampal CA1 and subiculum volumes in T2DM patients. Additionally, higher HbA1c levels were significantly associated with poor memory performance and hippocampal atrophy among T2DM patients. CONCLUSIONS: These data indicate that the hippocampus might be the main affected region among the SDGM structures in T2DM. These structural changes in the hippocampal CA1 and subiculum areas might be at the core of underlying neurobiological mechanisms of hippocampal dysfunction, suggesting that degeneration in these regions could be responsible for memory impairments in T2DM patients.