Comprehensive and stratified meta-analysis of diffusion tensor image analysis along the perivascular space in Alzheimer's disease: Linking glymphatic dysfunction with cognitive decline and amyloid pathology

Background: The glymphatic system clears brain waste, including amyloid-β (Aβ), and it is shown that its dysfunction may contribute to Alzheimer's disease (AD) pathology. This dysfunction can be evaluated using the diffusion tensor image analysis along the perivascular space (DTI-ALPS) index. Objective: This study summarizes the AD literature on the glymphatic system evaluated through neuroimaging methods. Methods: We searched PubMed, Scopus, Embase, and Web of Science databases to find relevant neuroimaging studies. Results: 24 studies were included in this systematic review and meta-analysis. We observed a significant reduction in DTI-ALPS index among patients with AD, compared to healthy controls (standardized mean difference (SMD) of -1.044 (95% CI: -1.304, -0.784) in DTI studies with 1000 s/mm2 b-values and an SMD of -1.063 (95% CI: -1.278, -0.847) in studies with b-value of 2000 s/mm2). Moreover, our study reflected a significant correlation between the DTI-ALPS index and cognitive function assessed by Mini-Mental State Examination (95% CI: 0.37 to 0.51, z-score: 0.44), Montreal Cognitive Assessment (95% CI: 0.45 to 0.61, z-score: 0.54), and Clinical Dementia Rating (95% CI: -0.63 to -0.28, z-score: -0.47). Conclusions: In conclusion, our systematic review and meta-analysis revealed a significant dysfunction of the glymphatic system in patients with AD, compared to healthy participants. These findings suggest the DTI-ALPS index as a linked index to cognitive performance among patients with AD and as a potential parameter in assessing the progression of AD.