Individual morphological brain networks, systemic inflammation, and neurocognitive alterations in type 2 diabetes

Type 2 diabetes mellitus (T2DM) is closely associated with chronic low-grade inflammation and brain impairment, but how systemic inflammation affects brain morphological networks remains unclear. This study aimed to investigate the topological organization of individual-level morphological similarity networks (MSNs) in T2DM and its relationship with systemic inflammation and neuropsychological manifestations.

This study comprised two distinct cohorts. Cohort 1 included 92 T2DM patients and 63 demographically matched healthy controls (HCs); all underwent MRI and neuropsychological assessments. Individual MSNs were constructed using cortical thickness similarity, and graph-theoretical analysis was applied. Cohort 2 included 40 T2DM and 40 well-matched HCs with plasma inflammatory cytokines measured. An overlapping subset (n = 39) further investigated the relationship between cytokines and topological metrics.

Both groups showed small-world properties in MSNs without global differences. At the nodal level, T2DM patients exhibited decreased degree centrality in the left superior frontal gyrus (SFG) and increased degree centrality/nodal efficiency in the right cingulate gyrus (CG). The ventral attention network (VAN) had higher betweenness centrality, which negatively correlated with anxiety scores. T2DM patients showed elevated pro-inflammatory cytokines (e.g., IL-6, IL-8, TNF-α), and IL-4 levels positively correlated with depression severity.

T2DM is associated with distinct alterations in the topological organization of individual morphological brain networks, where the left SFG may be a vulnerable node linked to disease progression and right CG/VAN changes may reflect compensation. Systemic inflammation, particularly IL-4, may contribute to affective symptoms, providing new network neuroscience insights into T2DM-related brain impairment.