sTREM2 and cerebral blood flow in White Matter Hyperintensity Patients: Associations with Cognitive Impairment

Background: White matter hyperintensities (WMHs) are common neuroimaging markers of cerebral small vessel disease (CSVD) and are strongly associated with cognitive impairment. While cerebral hypoperfusion and neuroinflammation are recognized as major contributors to WMH pathology, the interplay between inflammatory biomarkers and cerebral blood flow (CBF) remains poorly understood. Soluble triggering receptor expressed on myeloid cells 2 (sTREM2), a marker of microglial activation, may play a dual role in neuroinflammation and vascular dysfunction. Methods: A total of 138 participants aged 50–80 years were enrolled, including 75 individuals in WMH group and 63 individuals in healthy control (HC) group. All subjects underwent magnetic resonance imaging (MRI) including arterial spin labeling(ASL) for CBF quantification and neuropsychological assessments. Serum sTREM2 levels were measured. Group comparisons, logistic regression, and partial correlation analyses were performed to explore associations among sTREM2, CBF, and cognitive performance. Results: Compared to HC group, serum sTREM2 levels were significantly elevated in the WMH group (P = 0.036), and gray matter(GM) CBF was significantly lower (P = 0.038). Logistic regression identified sTREM2 (OR = 1.041, P = 0.006) and age (OR = 1.081, P = 0.018) as independent risk factors for WMHs. Partial correlation analyses revealed a positive association between sTREM2 and gray matter CBF in healthy controls, but a negative association in the WMH group. Additionally, GM CBF was positively correlated with global cognitive scores (MMSE, MoCA) and executive function (Stroop Test C) in the WMH group. Conclusion: Our findings suggest that higher serum sTREM2 levels and reduced brain perfusion may be closely linked to the presence and progression of white matter hyperintensities and associated cognitive decline. Notably, the direction of the relationship between sTREM2 and perfusion appears to vary by disease status, indicating a possible shift from compensatory to harmful inflammation. These results highlight the clinical value of combining inflammatory markers and perfusion imaging in identifying individuals at higher risk of small vessel-related cognitive impairment and may provide useful targets for early intervention and monitoring.