AUTHOR=Li Chang , Zhang Jun , Xue Bo , Xia Yuwei , Shi Feng , Le Xingyan , Feng Junbang , Chen Peng , Li Chuanming TITLE=Automatic diagnosis of type 2 diabetes mellitus with mild cognitive impairment using artificial intelligence based on routine T1-weighted MRI JOURNAL=Frontiers in Neurology VOLUME=Volume 16 - 2025 YEAR=2025 URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2025.1599793 DOI=10.3389/fneur.2025.1599793 ISSN=1664-2295 ABSTRACT=BackgroundPatients with type 2 diabetes mellitus (T2DM) exhibit a heightened susceptibility to developing dementia, especially those who already present with mild cognitive impairment (MCI). Nevertheless, the fundamental etiology remains elusive, underscoring the pressing need for an objective and precise diagnostic approach in clinical settings. This study investigates the utilization of machine learning algorithms in conjunction with high-resolution sagittal T1-weighted structural imaging to facilitate automated diagnosis of T2DM patients with MCI, differentiating them from both T2DM patients without MCI and healthy controls (HCs).MethodsThirty patients with T2DM and MCI, thirty T2DM patients without MCI, and thirty matched healthy controls (HCs) were enrolled to identify independent biomarkers and develop a diagnostic model for early cognitive impairment in T2DM. Whole-brain structural features-including cortical surface area, volume, thickness, curvature index, folding index, Gaussian curvature, mean curvature, thickness standard deviation, nuclear volume, hippocampal volume, and white matter volume-were extracted from the images of brains using automated segmentation methods. The minimum redundancy maximum relevance (MRMR) method was employed to filter out irrelevant and redundant features, reducing the dimensionality of the dataset. Subsequently, the least absolute shrinkage and selection operator (LASSO) algorithm was applied for further feature selection, ensuring the retention of only the most diagnostic features. The Random Forest (RF) classifier, a powerful machine learning model within the realm of artificial intelligence, was meticulously trained utilizing a curated feature set that had undergone rigorous refinement. To ensure the robust diagnostic performance and generalizability of the established random forest model, a 5-fold cross-validation was employed, providing a dependable estimation of the model’s effectiveness.ResultsThe FreeSurfer software automatically segmented the cerebral imaging data into up to 70 regions. For model establishment, a comprehensive set of 705 structural features, a series of neuropsychological tests, and standard laboratory tests were utilized. Ultimately, 8 features were selected through two feature selection strategies aimed at refining the optimal features. These included bilateral brainstem volume, left hippocampus volume, left transverse temporal gyrus volume, bilateral posterior corpus callosum volume, left medial orbitofrontal cortex Gaussian curvature, glycosylated hemoglobin, blood sugar levels, and the Digit Span Test (DST) backward score. The Random Forest (RF) model, based on the combined features, exhibited the excellent performance, with mean AUCs of 0.959 (95% CI, 0.940–0.997, mean specificity = 94.2%, mean sensitivity = 88.3%, mean accuracy = 88.3% and mean precision = 88.3%) for the training dataset and mean AUCs of 0.887 (95% CI, 0.746–0.992, mean specificity = 85.0%, mean sensitivity = 70.0%, mean accuracy = 70.0% and mean precision = 69.6%) for the testing dataset, based on 5-fold cross-validation.ConclusionThe RF model, leveraging a combination of features, demonstrates high accuracy in diagnosing T2DM with MCI. The exclusion of T2DM patients with complications may limit generalizability to the broader T2DM population, potentially inflating performance estimates. Among these features, 8 optimal indicators comprising 5 structural features, 1 neuropsychological test feature, and 2 standard laboratory test features emerge as the potential independent biomarkers for detecting early-stage cognitive impairment in T2DM patients. These features hold significant importance in understanding the pathophysiological mechanisms of T2DM-related cognitive impairment. Our fully automated model is capable of swiftly processing MRI data, enabling precise and objective differentiation of T2DM with MCI. This model significantly enhances diagnostic efficiency and holds considerable value in clinical practice, facilitating early diagnosis of T2DM with MCI.