Glymphatic dysfunction as an imaging biomarker for cognitive impairment in patients with β-thalassemia major: A...

Cerebral lymphatic abnormalities have been associated with neurodegenerative processes. However, brain glymphatic system and its role in cognitive impairment in β-thalassemia major (β-TM) remain unknown. This study assessed brain glymphatic alterations in β-TM using advanced neuroimaging and their correlation with cognitive deficits.

Thirty-five β-TM patients and forty matched healthy controls (HC) underwent standardized cognitive assessment and diffusion tensor imaging (DTI). Automated segmentation derived glymphatic parameters: Analysis Along the Perivascular Space index (DTI-ALPS index), choroid plexus volume fraction (CPVF), perivascular space volume fraction (PVSVF), and fractional volume of free water in white matter (FW-WM) and were compared between groups. Correlations with cognitive scores were analyzed.

Compared with the HC, β-TM patients showed significantly lower DTI-ALPS index values in the left hemisphere (1.4527vs1.5275,P = 0.003), the right hemisphere (1.3648vs1.4492,P = 0.004) and bilateral hemispheres (1.4087vs1.4884,P = 0.001), alongside higher CPVF values in the left hemisphere (0.5426vs0.4655,P = 0.034), the right hemisphere (0.5296vs0.4439,P = 0.018) and bilateral hemispheres (1.0731vs0.9095,P = 0.01). The patient group also had higher PVSVF values in the white matter (0.2848vs0.2488,P = 0.841), the subcortical regions (0.1718vs0.1470,P = 0.349) and whole brain (0.4566vs0.3958,P = 0.678), and had higher FW-WM value (0.1580vs0.1557,P = 0.384). Lower DTI-ALPS index and higher FW-WM value was associated with poorer cognitive performance in the β-TM patients (P < 0.05).

The DTI-ALPS index is a potential neuroimaging biomarker for glymphatic dysfunction and cognitive impairment in β-TM. Increased CP volume implicated underlying glymphatic alterations, supporting integration of glymphatic MRI metrics into clinical cognitive assessment for this population.