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.