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Cerebral white matter hyperintensities (WMHs) are central MRI markers of the brain aging process, but the mechanisms for its progression remain unclear. In this study, we aimed to determine whether the baseline serum cystatin C level represented one mechanism underlying WMH progression, and whether it was associated with the long-term progression of cerebral WMH volume in MRI. 166 consecutive individuals who were ≥50 years of age and who underwent initial/follow-up MRI evaluations within an interval of 34–45 months were included. Serum cystatin C level, glomerular-filtration rate (GFR), and other laboratory parameters were measured at their initial evaluation and at the end of follow-up. Cerebrovascular risk factors, medications, and blood-pressure parameters were also reviewed. WMH progression rate was measured by subtracting WMH volume at baseline from that at the follow-up using volumetric analysis, divided by the MRI intervals. At baseline, WMH volume was 9.61±13.17 mL, mean GFR was 77.3±22.8 mL/min, and mean cystatin C level was 0.92±0.52 mg/L. After 37.9±3.4 months, the change in WMH volume was 3.64±6.85 mL, the progression rate of WMH volume was 1.18±2.28 mL/year, the mean ΔGFR was 2.4±7.9 mL/min, and the mean Δcystatin C was 0.03±0.34 mg/L. The progression rate of WMH volume was linearly associated with cystatin C level (B coefficient = 0.856; 95% confidence interval [CI] 0.174−1.538;  P  = 0.014), along with the baseline WMH volume (B = 0.039; 95% CI 0.019−0.059;  P <0.001), after adjusting for the conventional vascular risk factors, laboratory parameters, medication profiles, and GFR. Especially, patients with a baseline level of cystatin C ≥1.00 mg/L exhibited a much higher progression rate of WMH as compared with those with a baseline level of cystatin C <1.00 mg/L (1.60±1.91 mL/year vs. 0.82±1.63 mL/year,  P  = 0.010). We concluded that serum cystatin C level is independently associated with the long-term progression rate of the cerebral WMH volume. Therefore, serum cystatin C level might predict the progression of cerebral WMH.

Cystatin C, a potential marker for cerebral microvascular compliance, is associated with white-matter hyperintensities progression