Early detection of type 2 diabetes mellitus‐associated cognitive dysfunction: The potential of amide proton transfer‐weighted imaging

Aims Type 2 diabetes mellitus (T2DM) may lead to diabetes‐associated cognitive dysfunction (DACD). We aimed to develop an amide proton transfer‐weighted (APTw) magnetic resonance imaging (MRI) biomarker to assist early identification of T2DM with DACD. Materials and Methods The study included 27 T2DM patients, comprising 19 with mild cognitive impairment (T2DM‐MCI) and 8 without (T2DM‐nMCI), along with 11 community‐based controls without MCI (CG‐nMCI). All participants completed neuropsychological tests and APTw‐MRI. We measured hippocampal APTw signal intensity (SI) in both groups, analysed its correlation with cognitive scores and assessed diagnostic performance using area under the curve (AUC). Results In T2DM‐nMCI patients, left hippocampal head APTw SI showed a positive correlation with semantic verbal fluency (SVF; r = 0.770, R 2 = 0.593, p = 0.025) but a negative correlation with Wechsler Memory Scale‐Digit Span Test‐Backward ( r = −0.802, R 2 = 0.643, p = 0.017). In T2DM‐MCI patients, left hippocampal head APTw SI positively correlated with SVF scores ( r = 0.414, R 2 = 0.172, p = 0.044), while left tail values showed negative associations with Trail‐Making Test‐A ( r = −0.333, R 2 = 0.111) and Auditory Verbal Learning Test‐Huashan version‐delayed recall ( r = −0.376, R 2 = 0.141, both p ≤ 0.021). The left hippocampal body demonstrated diagnostic potential for T2DM‐nMCI (AUC = 0.793, p = 0.045), while the left hippocampal head showed higher discriminative power for T2DM‐MCI (AUC = 0.732, p = 0.034). Conclusions APTw imaging suggested a spatially evolving pattern of hippocampal damage in T2DM, where the left body may show early alterations, with the left head potentially becoming more implicated upon MCI onset. These findings provide preliminary evidence supporting the potential of APTw as an early, non‐invasive biomarker for tracking neuropathological progression in DACD.