Association of Baseline Glymphatic‐Related MRI Metrics With Neoadjuvant Chemotherapy‐Related Cognitive Impairment in Patients With Breast Cancer

Background Chemotherapy‐related cognitive impairment (CRCI) is a common complication for cancer survivors. The glymphatic system is increasingly recognized as playing a role in cognitive health. However, whether the glymphatic system is associated with CRCI and its dynamic change during chemotherapy remains unclear. Purpose To investigate longitudinal changes of glymphatic‐related MRI metrics during chemotherapy and their association with CRCI. Study Type Prospective longitudinal. Population Sixty two female patients with breast cancer underwent brain MRI and neuropsychological assessments at baseline and after chemotherapy. Field Strength/Sequence Resting‐state functional MRI, diffusion tensor imaging (DTI), 3D T1‐weighted magnetization‐prepared rapid gradient echo sequence at 3 T. Assessment Patients were divided into cognitive decline ( n = 22) and cognitive remain ( n = 40) groups according to the Montreal Cognitive Assessment (MoCA) and the Functional Assessment of Cancer Therapy‐Cognitive Function (FACT‐Cog) scale. MR metrics, including blood‐oxygen‐level‐dependent cerebrospinal coupling (BOLD‐CSF coupling), DTI along the perivascular space (DTI‐ALPS) index, fraction of perivascular space (PVS/ICV), and choroid plexus volume to intracranial volume (ChP/ICV), were used to reflect glymphatic function. Statistical Tests Linear mixed‐effects models were utilized to assess longitudinal trajectories. Analysis of covariance was used to identify differences in glymphatic‐related MRI metrics between groups. Multivariable linear regression was used to determine the association between post‐chemotherapy cognitive decline and baseline metrics. Significance was defined as p < 0.05 or FDR corrected p < 0.05. Result After chemotherapy, significant cognitive decline, an increase in PVS/ICV, ChP/ICV, and BOLD‐CSF coupling strength were observed. Longitudinal changes in MRI metrics did not differ between the cognitive remain and cognitive decline groups (FDR‐corrected p = 0.234–0.833). The cognitive decline group had significantly weaker baseline BOLD‐CSF coupling strength and larger baseline PVS/ICV compared to the cognitive remain group. Multivariable linear regression revealed that baseline BOLD‐CSF coupling strength and PVS/ICV were independent predictors for post‐chemotherapy MoCA and FACT‐cog scores. Data Conclusion Weaker baseline BOLD‐CSF coupling strength and larger PVS volume fraction are associated with CRCI. Longitudinal changes of glymphatic‐related MRI metrics may not be associated with CRCI. Evidence Level 2. Technical Efficacy Stage 5.