Glymphatic Pathway Dysfunction in Mild Cognitive Impairment: A Systematic Review and Meta‐Analysis Using Diffusion Tensor Imaging Along the Perivascular Space
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: = 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.
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Evidence Hub reads this as a systematic review. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid.
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