DTI-ALPS index and cognitive impairment in cerebral small vessel disease: a systematic review and meta-analysis

Abstract

Objective The diffusion tensor image analysis along the perivascular space (DTI-ALPS) index is a non-invasive diffusion tensor imaging-based metric proposed to reflect glymphatic processes. This meta-analysis aimed to evaluate the association of the DTI-ALPS index with cerebral small vessel disease (CSVD) and CSVD-associated cognitive impairment. Methods This meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Eight databases were systematically searched from inception up to February 1, 2026. Study selection and data extraction were performed independently by two reviewers. Study quality was assessed using the Newcastle–Ottawa Scale adapted for cross-sectional studies (NOS-xs). Pooled effect sizes were expressed as weighted mean differences (WMDs) with 95% confidence intervals (CIs). Heterogeneity was evaluated using Cochran’s Q (χ2 test) and the I2 statistic, while publication bias was assessed by funnel plots and Egger’s regression test. Results A total of 14 studies involving 2,149 participants were included. The median NOS-xs score was 8 (range, 6–9). Heterogeneity was observed across comparisons, with I2 values of up to 80%. Publication bias was assessed only for the comparison between CSVD and healthy controls, and no evidence of publication bias was detected (Egger’s test, P = 0.189). The pooled analysis showed that the DTI-ALPS index was significantly lower in patients with CSVD than in healthy controls (WMD = -0.12, 95% CI: -0.15 to -0.10). Furthermore, compared with cognitively normal participants, the DTI-ALPS index was significantly reduced in patients with CSVD-associated cognitive impairment (CSVD-CI), mild cognitive impairment (CSVD-MCI), and vascular dementia (CSVD-VaD) (all P < 0.05). However, no significant difference was observed between the CSVD-MCI and CSVD-VaD groups (WMD = -0.03, 95% CI: -0.08 to 0.02; P = 0.19). Conclusion Patients with CSVD exhibit reduced DTI-ALPS indices, which are associated with the presence of cognitive impairment. Reduced DTI-ALPS indices were observed in patients with CSVD-MCI compared with cognitively normal patients with CSVD, indicating that this association is present at the MCI stage. However, because no significant difference was observed between the CSVD-MCI and CSVD-VaD groups, the value of the DTI-ALPS index for disease staging remains uncertain and requires confirmation in future longitudinal studies. Systematic Review Registration https://www.crd.york.ac.uk/prospero/ #recordDetails, identifier [CRD420261322688].