# Association between blood neurofilament light chain levels and vascular cognitive impairment: a systematic review and meta-analysis

## TL;DR

This study finds that blood levels of a protein called neurofilament light chain are higher in people with vascular cognitive impairment, suggesting it could be a useful biomarker.

## Contribution

The study is the first meta-analysis to systematically evaluate the association between blood NfL levels and vascular cognitive impairment.

## Key findings

- Blood NfL levels in VCI patients were significantly higher than in non-VCI patients.
- The association remained consistent across various subgroups like study design and detection methods.
- The results suggest blood NfL could serve as a discriminative biomarker for VCI.

## Abstract

Vascular cognitive impairment (VCI) is the second leading cause of cognitive impairment after Alzheimer’s disease, primarily associated with vascular risk factors and cerebrovascular disease. Advances in ultra-low concentration single-molecule array (Simoa) technology have enabled the quantitative monitoring of blood neurofilament light chain (NfL) levels. Consequently, we performed a meta-analysis to evaluate the association between blood NfL levels in VCI.

This meta-analysis was conducted in accordance with the PRISMA guidelines. We systematically searched PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), VIP Information (VIP), and Wanfang Data databases, with a search period extending from database inception to December 3, 2025. Two reviewers independently performed the literature selection, data extraction, and assessed the study quality using the Newcastle-Ottawa Scale (NOS). The weighted mean difference (WMD) and its 95% confidence interval (CI) were used to combine effect sizes. Heterogeneity was evaluated utilizing the Chi-square (χ2) test (Cochran’s Q) and the index of inconsistency (I2) statistic. Publication bias was evaluated by funnel plots and Egger’s regression analysis.

This systematic review included 13 studies, comprising 3,716 patients. The meta-analysis results indicated that blood NfL levels in VCI patients were significantly higher than those in the non-VCI group (WMD = 15.06, 95% CI = [11.41, 18.71], p < 0.00001). Subgroup analysis further demonstrated that the elevated trend of NfL levels in VCI patients remained consistent across different study designs, detection methods, VCI Subtypes, countries, control group types, specimen type, and statistical adjustment (p < 0.05).

Our results suggest that blood NfL levels are significantly higher in VCI patients compared to non-VCI patients, indicating a strong association between blood NfL and VCI. This supports its potential as a discriminative biomarker for VCI.

https://www.crd.york.ac.uk/prospero/, identifier CRD420251240858.