Temporal Dynamic of Cognitive Decline in Type 2 Diabetes Mellitus Patients: A Multimodal Biomarker Analysis using Event-Based Modal and Principal Component Analysis

Background Type 2 diabetes mellitus (T2DM) is associated with cognitive impairment, affecting life quality. The progression of cognitive decline and its neural basis in T2DM are unclear due to limitations in previous studies. This study integrates Event-Based Model (EBM) and Principal Component Analysis (PCA) to explore these aspects in T2DM patients. Methods This study assessed 119 T2DM patients and 87 healthy controls with neuropsychological tests (CVLT, Stroop, WCST) and MRI for gray matter volume (GMV). PCA simplified cognitive scores into composites for memory and executive function. EBM estimated the sequence of cognitive and neurostructural changes. Partial correlation analyses were used to examine associations with clinical factors with controlling covariance. Results Cognitive decline in T2DM began with attention and working memory, followed by executive function and episodic memory. GMV loss started in the insular gyrus, spreading to other regions. T2DM showed advanced disease progression (0.54 (0.12) vs. 0.49 (0.10), P = 0.001). A negative correlation linked long-delay memory (CVLT-PC4) to random blood glucose ( r = -0.581, P _FDR = 0.025). Conclusion This study reveals the sequence of cognitive and neuroanatomical changes in T2DM. Memory decline and insular gyrus atrophy may serve as early biomarkers for T2DM-related cognitive impairment, which may be helpful in the development of personalized interventions to improve life quality.