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Cerebral Small Vessel Disease-driven Inflammatory Cytokines, Brain Structural Alterations, and Cognitive Function: A
Meng Xue Wang1, Zan Wang2, Jing Ting Kong1
1Department of Neurology, Zhongda Hospital, School of Medicine, Jiangsu Provincial Key Laboratory of Brain Science and Medicine, Southeast University, Nanjing 210009, Jiangsu, China.
Biomedical and Environmental Sciences : BES
|July 8, 2026
Summary
Cerebral small vessel disease (CSVD) is linked to cognitive impairment (CI) through inflammatory cytokines like stem cell factor (SCF). SCF influences brain structure and cognitive function, offering insights into CI mechanisms.
Area of Science:
- Neuroscience
- Genetics
- Immunology
Background:
- Cerebral small vessel disease (CSVD) is a significant contributor to cognitive impairment (CI).
- The precise mechanisms linking CSVD to CI, particularly the role of inflammatory cytokines, require further elucidation.
- Understanding these pathways is crucial for developing targeted interventions.
Purpose of the Study:
- To investigate the role of circulating inflammatory cytokines in the CSVD-CI pathway.
- To explore the neuroimaging mechanisms through which CSVD-related inflammatory cytokines affect cognitive function.
- To identify specific cytokines mediating the relationship between CSVD and cognitive decline.
Main Methods:
- A two-step, two-sample Mendelian randomization (MR) analysis was employed.
- MR was used to assess causal relationships between CSVD, circulating inflammatory cytokines, and CI risk.
- Further MR analyses explored cytokine effects on brain structural imaging outcomes.
Main Results:
- Genetically predicted CSVD causally influenced levels of 11 circulating inflammatory cytokines.
- Growth-regulated oncogene alpha (GROα), stem cell factor (SCF), and tumor necrosis factor-alpha (TNF-α) showed associations with specific cognitive domains.
- SCF mediated the link between small-vessel ischemic stroke and numeric memory, and correlated with brain volumes and white matter integrity.
Conclusions:
- SCF, GROα, and TNF-α are key mediators in the CSVD-CI pathway.
- Circulating SCF may impact cognitive function by altering brain structure, including default mode network volumes and white matter tracts.
- These findings highlight the potential of targeting inflammatory pathways for managing CSVD-related cognitive impairment.
