Background Type 2 diabetes mellitus (T2DM) and mild cognitive impairment (MCI) are prevalent conditions in the aging population, with growing evidence indicating a synergistic detrimental effect on brain function when comorbid. However, the distinct neurofunctional signatures of comorbid T2DM-MCI remain poorly characterized. Objective This study aimed to investigate the characteristic brain activation patterns and functional network connectivity in elderly patients with comorbid T2DM-MCI, compared to those with T2DM alone or MCI alone. Methods In this cross-sectional study,75 elderly participants (T2DM = 25, MCI = 25, T2DM-MCI = 25) underwent functional near-infrared spectroscopy (fNIRS) during a verbal fluency task, a 2-back task, single walking, and a dual-task (2-back while walking), followed by 8-min resting-state recording. Task-evoked cortical activation and resting-state functional connectivity were analyzed and compared across groups. Results During cognitive tasks, the T2DM-MCI group showed significantly reduced activation in prefrontal and motor cortices compared to single-disease groups. Dual-task performance specifically revealed hypoactivation in ventrolateral prefrontal and occipital regions in T2DM-MCI. Resting-state analysis demonstrated globally diminished functional connectivity in T2DM-MCI, particularly within prefrontal-motor networks and interhemispheric connections, whereas no significant differences were found between T2DM and MCI groups alone. Conclusions Comorbid T2DM-MCI exhibits a unique dual-pathology profile characterized by concurrent reductions in task-evoked activation and resting-state network connectivity, suggesting compromised neural efficiency from synergistic metabolic and neurodegenerative processes. These impairments may serve as sensitive biomarkers for early detection of diabetes-associated cognitive decline. Trial registration: The Chinese Clinical Trial Registry (ChiCTR) registration # ChiCTR2400084469 ( https://www.chictr.org.cn ).
Sun et al. (2026) studied this question.