Alterations of peripheral cytokines, BDNF, and surface-based morphometry indices in T2DM patients without cognitive impairment

Abstract

PurposeThis study aimed to investigate potential biological mechanisms underlying cognitive function alterations in Type 2 diabetes mellitus (T2DM) patients by integrating cortical morphology with peripheral cytokine levels and brain-derived neurotrophic factor (BDNF) levels, and to offer potential insights for the early detection of T2DM-related cognitive impairment.MethodsThis study included 16 T2DM patients with a Montreal Cognitive Assessment (MoCA) score of at least 26 points, as well as 16 healthy controls with normal cognitive function. The participants also completed the digit span test and digit symbol substitution test. Participants’ serum levels of Interleukin 4 (IL-4), IL-6, IL-10, tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), and BDNF were also examined. Each subject underwent a high-resolution 3T structural brain MRI scan. Based on the aparc. a2009s atlas, we calculated the cortical thickness, sulcus depth, gyrification index, and fractal dimension for each participant using surface-based morphometry (SBM). Correlation analysis between cognitive measures, serum levels of cytokines and BDNF, and SBM indices were further performed.ResultsThe levels of IL-4 and BDNF showed significant group differences. In the T2DM group, the sulcus depth exhibited a significant decrease in the left transverse frontopolar gyri and sulci, as well as in the right pole-occipital; the fractal dimension showed a significant increase in the right posterior-dorsal part of the cingulate gyrus; and the gyrification index significantly increased in the left inferior part of the precentral sulcus and right triangular part of the inferior frontal gyrus. Correlation analysis revealed a significant positive correlation between IL-10 levels and the sulcus depth of left transverse frontopolar gyri and sulci; a significant positive correlation between the sulcus depth of the right pole-occipital and the digit span test-forward scores, and a significant negative correlation between the gyrification index of the left inferior part of the precentral sulcus and the digit span test-backward scores among T2DM participants.ConclusionT2DM patients without cognitive impairment displayed reductions in IL 4 and BDNF levels, as well as significant alterations in their SBM indices, indicating that prior to the emergence of cognitive impairment, the SBM indices, peripheral cytokines, and BDNF may have altered in T2DM patients. IL-10 may lessen inflammation-related brain edema and preserve sulcus depth in T2DM patients through its anti-inflammatory activity.

Peripheral inflammation and neurocognitive impairment: correlations, underlying mechanisms, and therapeutic implications

“…AD, the most prevalent neurodegenerative disease, has been reported to have enhanced genotypic effects of the proteins SPI1 and CD33 encoding proteins at the AD inflammation-related SNP locus as peripheral blood CRP levels increase, and an increased risk of conversion to AD in people with mild cognitive impairment (MCI) ( Huang J. et al, 2022 ). One study ( Lyu et al, 2023 ) demonstrated that by comparing diabetic (T2DM) patients aged 29–65 years who did not meet the criteria for a clinical diagnosis of cognitive impairment with the normal population (42.125 ± 10.436 years), although the difference did not gain statistical significance, the Montreal cognitive assessment scale (MoCA) scores of the T2DM patients showed a tendency to be lower than that of healthy controls and peripheral blood laboratory results showed significantly lower levels of peripheral blood IL-4 and brain-derived neurotrophic factor (BDNF) in the T2DM population compared to the healthy population. Suggesting that peripheral blood cytokines and BDNF may have been altered in T2DM patients before the onset of cognitive deficits.…”