The precise physiopathological association between the courses of neurodegeneration and cognitive decline in type 2 diabetes mellitus (T2DM) remains unclear. This study sought to comprehensively investigate the distribution characteristics of gray matter atrophy in middle-aged T2DM patients with newly diagnosed mild cognitive impairment (MCI).
Four groups, including 28 patients with early-onset MCI, 28 patients with T2DM, 28 T2DM patients with early-onset MCI (T2DM-MCI), and 28 age-, sex-, and education-matched healthy controls underwent three-dimensional high-resolution structural magnetic resonance imaging. Cortical and subcortical gray matter volumes were calculated, and a structural covariance method was used to evaluate the morphological relationships within the default mode network (DMN).
Overlapped and unique cortical/subcortical gray matter atrophy was found in patients with MCI, T2DM and T2DM-MCI in our study, and patients with T2DM-MCI showed lower volumes in several areas than patients with MCI or T2DM. Volume loss in subcortical areas (including the thalamus, putamen, and hippocampus), but not in cortical areas, was related to cognitive impairment in patients with MCI and T2DM-MCI. No associations between biochemical measurements and volumetric reductions were found. Furthermore, patients with MCI and those with T2DM-MCI showed disrupted structural connectivity within the DMN.
These findings provide further evidence that T2DM may exacerbate atrophy of specific gray matter regions, which may be primarily associated with MCI. Impairments in gray matter volume related to T2DM or MCI are independent of cardiovascular risk factors, and subcortical atrophy may play a more pivotal role in cognitive impairment than cortical alterations in patients with MCI and T2DM-MCI. The enhanced structural connectivity within the DMN in patients with T2DM-MCI may suggest a compensatory mechanism for the chronic neurodegeneration.