MRI-based analysis of glymphatic system biomarkers in alzheimer’s disease

Details

Supervisors

Macq, Benoît ; Dricot, Laurence

Faculty

Ecole polytechnique de Louvain

Degree label

Master [120] : ingénieur civil biomédical, à finalité spécialisée

Abstract

Alzheimer’s disease (AD) is the leading cause of dementia worldwide, yet the mechanisms driving the accumulation of pathological proteins such as amyloid-β remain only partially understood. In this context, growing interest has focused on the glymphatic system (GS), a perivascular pathway involved in cerebrospinal fluid circulation and brain waste clearance, whose dysfunction may contribute to neurodegeneration. This work investigated four MRI-based biomarkers proposed to reflect GS alterations: choroid plexus (CP) volume, enlarged perivascular spaces (ePVS), the DTI-ALPS index, and NODDI-derived metrics (FISO, FINTRA). The aim is to assess their association with cognitive decline and to determine whether these relationships differed according to amyloid status. Analyses were conducted on an AD cohort of 117 participants (26 cognitively normal, 64 with mild cognitive impairment, and 27 with dementia), stratified by amyloid status. Dedicated processing pipelines were implemented for each biomarker, including a hybrid GMM-based CP segmentation method, a complete DTI-ALPS pipeline, and an automated ePVS quantification approach, together with a validation approach for CP segmentation and ePVS count. Finally, associations with age, cognition, diagnostic group, and amyloid status were assessed using partial correlations and ANCOVA models adjusted for age, sex, and education. Results showed that CP volume increased with disease severity and was associated with poorer cognition independently of age. In contrast, the DTI-ALPS index decreased with age and differed between cognitively normal and impaired subjects, suggesting that it may reflect broad brain changes rather than glymphatic dysfunction alone. EPVS burden showed no significant association with the investigated variables, whereas NODDI metrics suggested that FISO may act as a global marker of extracellular alterations and FINTRA as a more region-specific marker. Together, these findings suggest that MRI-derived glymphatic biomarkers capture partly distinct aspects of AD-related brain alterations, although their indirect and non-specific nature limits their interpretation.