Glymphatic system dysfunction and cognitive impairment in post-chemotherapy AML: A novel DTI-ALPS index study

This study aimed to evaluate glymphatic function using the diffusion tensor imaging along the perivascular spaces (DTI-ALPS) index in patients with acute myeloid leukemia (AML) following chemotherapy and to explore its association with cognitive performance. Twenty-one AML patients were assessed 4–8 weeks after their final chemotherapy cycle (PC-AML), along with 20 age- and sex-matched healthy controls (HCs). All participants underwent brain MRI and cognitive assessment. Imaging metrics included cerebrospinal fluid (CSF) volume, basal ganglia perivascular space (BG-PVS) volume fraction, DTI-ALPS index, and blood oxygen level-dependent–CSF coupling. Group comparisons and correlations between glymphatic markers and cognitive scores were analyzed. Post-chemotherapy AML patients exhibited significantly increased CSF volume (P FDR = 0.046) and BG-PVS volume(P FDR = 0.040), alongside a reduced DTI-ALPS index(P FDR = 0.046). Cognitive performance was significantly impaired, with lower Mini-Mental State Examination (MMSE; P < 0.01) and Montreal Cognitive Assessment (MoCA; P < 0.01) scores, and higher Activities of Daily Living (ADL) scores (P < 0.01). BG-PVS volume correlated inversely with MMSE (r = –0.467, P = 0.002) and MoCA (r = –0.396, P = 0.010), while the DTI-ALPS index positively correlated with MoCA (r = 0.417, P = 0.006). Post-chemotherapy AML patients exhibit glymphatic system dysfunction and cognitive decline, with a significant association between these alterations. Impairment in glymphatic function, as suggested by these biomarkers, may contribute to cognitive deficits in this context. The DTI-ALPS index and BG-PVS volume represent potential neuroimaging biomarkers, providing new insights into chemotherapy-related cognitive impairment in AML. • A novel DTI-ALPS index assessed glymphatic function in post-chemotherapy AML. • PC-AML patients showed impaired glymphatic clearance and cognitive performance. • Glymphatic metrics were significantly associated with cognitive function. • The underlying mechanism of chemotherapy-related cognitive impairment is associated with the glymphatic system.