Glymphatic Pathway Dysfunction in Mild Cognitive Impairment: A Systematic Review and Meta-Analysis Using Diffusion Tensor Imaging Along the Perivascular Space Publisher Pubmed



Ghaderi S ; Mohammadi S ; Jouzdani AF ; Ahmadzadeh AM
Source: CNS Neuroscience and Therapeutics Published:2025

Abstract

Objective: To evaluate glymphatic dysfunction in mild cognitive impairment (MCI) using the diffusion tensor imaging along the perivascular space (DTI-ALPS) index. Methods: Using PRISMA 2020, we searched PubMed, Web of Science, Scopus, and Embase (until May 10, 2025) for studies comparing the ALPS index in MCI patients versus healthy controls. Results: The pooled meta-analysis of 18 studies (1133 MCI patients, mean age 69.3 years; 1275 HCs) revealed a significantly lower ALPS index in MCI patients than in HCs (Cohen's d = −0.70; 95% CI: −1.10, −0.29; p < 0.001), with high heterogeneity (I2 = 95.3%). Sensitivity analyses confirmed the robustness of the effect and a cumulative meta-analysis showed a consistent negative trend from 2021 to 2025. Subgroup analyses showed trends toward larger effect sizes in older patients (> 68 years, d = −0.83) and in studies using ≥ 64 diffusion directions (d = −0.99), although formal tests for subgroup differences were not statistically significant. Small-study effects were found (Egger's p = 0.004; Begg's p = 0.019), but the studies had high methodological quality. Trim-and-fill analysis added six studies, adjusting pooled Cohen's d from −0.70 to −0.98, indicating potential overestimation from publication bias. Conclusions: These findings support the utility of the ALPS index as a noninvasive biomarker for early glymphatic dysfunction in cognitive decline. © 2025 The Author(s). CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.