Predictive value of Galectin-3 in cognitive impairment: a systematic review and meta-analysis

Cognitive Impairment (CI) is an increasingly serious public health problem in an aging society. Its rising incidence rate is closely linked to functional decline and increased mortality risk. Because of its insidious onset and irreversible progression, early identification is particularly crucial. Neuroinflammation and vascular injury play important roles in the occurrence and development of CI. Galectin-3 (Gal-3), as a biomarker involved in the inflammatory response and vascular lesion process, may have potential value in the early prediction and risk assessment of CI.

This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline. Seven databases were systematically retrieved from their establishment until March 8, 2026. Two independent researchers conducted literature screening, data extraction, and quality evaluation using the Newcastle-Ottawa Scale. The combined effect size was calculated using the weighted mean difference (WMD) or standardized mean difference (SMD), with a 95% confidence intervals (CIs). Heterogeneity was evaluated using the chi-square (χ ²) test (Cochran's Q) and the inconsistencies index test (I ²), and publication bias was assessed using funnel plots and Egger's regression tests.

This systematic review included nine studies comprising 877 patients with cognitive impairment (CI) and 715 healthy controls. The meta-analysis demonstrated that peripheral Gal-3 levels were significantly higher in the CI group compared with controls (WMD: 0.85; 95%CI: 0.42-1.28; p < 0.0001), despite substantial heterogeneity across studies (I ² = 98%). Subgroup analyses further revealed that Gal-3 levels were significantly elevated in CI with vascular risk factors (WMD: 1.76; 95%CI: 0.10-3.43; p = 0.04), whereas no statistically significant difference was observed in CI without vascular risk factors (p = 0.06). Regarding specific disease types, Gal-3 levels were significantly higher in patients with mild cognitive impairment (MCI) (WMD: 0.72; 95%CI: 0.04-1.40; p = 0.04), but not in those with Alzheimer's disease (AD) (p = 0.11).

Elevated Gal-3 levels are significantly associated with cognitive impairment and may serve as a convenient and effective biomarker for its early detection, particularly in CI with vascular risk factors and MCI. However, the evidence remains insufficient for AD, warranting further large-scale studies.

https://www.crd.york.ac.uk/PROSPERO/view/CRD420261293666, identifier CRD420261293666.