SYSTEMATIC REVIEW article
Front. Neurosci.
Sec. Neurodegeneration
Association between Blood Neurofilament Light Chain Levels and Vascular Cognitive Impairment: A Systematic Review and Meta-Analysis
Fu-li Qin 1
Xia He 2
Xia-lian Huang 2
Yan-qiu Wang 1
Fengle Mao 2
Ke-fu Ding 3
1. Chengdu University of Traditional Chinese Medicine School of Health Preservation and Rehabilitation, Chengdu, China
2. Sichuan Provincial Bayi Rehabilitation Center, 成都市, China
3. PACIFIC CARE HOME Chengdu, Chengdu, China
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Abstract
Objective: 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. Methods: 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. Results: This systematic review included 13 studies, comprising 3716 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). Conclusion: 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.
Summary
Keywords
blood NfL, Cognitive Function, Meta-analysis, Systematic review, vascular cognitive impairment
Received
02 January 2026
Accepted
28 January 2026
Copyright
© 2026 Qin, He, Huang, Wang, Mao and Ding. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Xia He
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