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Updated: Jul 18, 2026
Registered Bioimaging of Nanomaterials for Diagnostic and Therapeutic Monitoring
Published on: December 9, 2010
Macrophage Migration Inhibitory Factor as a Potential Plasma Biomarker of Cognitive Impairment in Cerebral Small
Yachen Shi1,2,3, Jingyu Deng1,2, Haixia Mao4
1Department of Neurology, the Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi 214023, China.
Insights
Plasma macrophage migration inhibitory factor (MIF) shows promise as a biomarker for identifying cerebral small vessel disease with cognitive impairment (CSVD-CI). Elevated MIF levels correlate with cognitive decline and brain changes in CSVD-CI patients.
Area of Science:
- Neurology
- Biomarker Discovery
- Neuroimaging
Background:
- Cerebral small vessel disease with cognitive impairment (CSVD-CI) pathogenesis is not fully understood.
- Effective biomarkers are crucial for managing CSVD-CI.
- Current diagnostic and prognostic tools for CSVD-CI require enhancement.
Purpose of the Study:
- To investigate plasma macrophage migration inhibitory factor (MIF) as a potential biomarker for CSVD-CI.
- To explore the relationship between plasma MIF levels and cognitive function, neuroimaging markers, and blood-brain barrier (BBB) integrity in CSVD-CI.
- To develop and validate a composite biomarker for CSVD-CI detection.
Main Methods:
- Recruitment of healthy controls (HCs), CSVD-CI patients, and cognitively normal CSVD (CSVD-CN) patients.
- Neuropsychological assessments and multimodal magnetic resonance imaging (MRI).
- Plasma MIF level assessment and Least Absolute Shrinkage and Selection Operator (LASSO) model for composite marker development.
Main Results:
- CSVD-CI patients exhibited significantly higher plasma MIF levels compared to HCs and CSVD-CN patients.
- Plasma MIF levels correlated with cognitive scores, BBB indices, white matter hyperintensity (WMH) burden, and brain activity.
- A composite marker including plasma MIF achieved >80% accuracy in distinguishing CSVD-CI patients.
- Meta-analysis confirmed elevated blood MIF in CSVD-CI.
Conclusions:
- Plasma MIF is a potential biomarker for early CSVD-CI identification.
- Plasma MIF may contribute to cognitive decline in CSVD via BBB dysfunction, WMH, and altered brain activity.
- The developed composite marker shows promise for clinical application in CSVD-CI diagnosis.
Abstract:
As the pathogenesis of cerebral small vessel disease with cognitive impairment (CSVD-CI) remains unclear, identifying effective biomarkers can contribute to the clinical management of CSVD-CI. This study recruited 54 healthy controls (HCs), 60 CSVD-CI patients, and 57 CSVD cognitively normal (CSVD-CN) patients. All participants underwent neuropsychological assessments and multimodal magnetic resonance imaging. Macrophage migration inhibitory factors (MIFs) were assessed in plasma. The least absolute shrinkage and selection operator model was used to determine a composite marker. Compared with HCs or CSVD-CN patients, CSVD-CI patients had significantly increased plasma MIF levels. In CSVD-CI patients, plasma MIF levels were significantly correlated with multiple cognitive assessment scores, plasma levels of blood-brain barrier (BBB)-related indices, white matter hyperintensity Fazekas scores, and the mean amplitude of low-frequency fluctuation in the right superior temporal gyrus. Higher plasma MIF levels were significantly associated with worse global cognition and information processing speed in CSVD-CI patients. The composite marker (including plasma MIF) distinguished CSVD-CI patients from CSVD-CN and HCs with >80% accuracy. Meta-analysis indicated that blood MIF levels were significantly increased in CSVD-CI patients. In conclusion, plasma MIF is a potential biomarker for early identification of CSVD-CI. Plasma MIF may play a role in cognitive decline in CSVD through BBB dysfunction and changes in white matter hyperintensity and brain activity.
