Abstract
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.
Highlights
To minimize the potential effects on white matter hyperintensities (WMHs) progression, the following exclusion criteria were applied to the 263 initially-included patients: patients had (1) a significant (! 30%) stenosis in the intra/extracranial arteries according to initial magnetic resonance angiogram (MRA) results; (2) an active systemic illness or an inability to carry out daily activities independently; (3) a history of stroke, but not an old (>90 days) lacunar stroke, and/or major head trauma, brain surgery, intracranial radiation therapy, or other evidence of chronic disorders involving the central nervous system (CNS); and (4) an magnetic resonance imaging (MRI) image of poor quality for evaluation
Correlation analyses of the continuous variables revealed that the progression rate of WMH volume was significantly associated with the baseline WMH volume (P
Among the categorical variables including the cerebrovascular risk factors, microalbuminuria, medication profiles, and the indications for the initial MRI evaluations, no statistically significant association was found with WMH progression rate (Table 3)
Summary
Cerebral white matter hyperintensity (WMH) is a central magnetic resonance imaging (MRI) marker of the brain aging process, and are largely associated with certain neurological diseases including dementia and stroke.[1,2,3] Numerous studies have indicated that the progression of WMH is due to the chronic impairment of the soluble metabolite clearance from the brain parenchyma via the glymphatic system in the perivascular spaces of cerebral penetrating arterioles.[4,5,6,7] As the main motive of the solute clearance via the glymphatic system is the pulsation of cerebral penetrating arterioles,[1,5,6] cerebrovascular stiffness was known to be the major mechanism underlying WMH progression. There is evidence that WMH might be attributable to the distinct physiologic properties of the cerebral penetrating arterioles, with a much higher capacity of pulsation than that of the pial vessels, and a gradually reduced pulsation with the increase in age.[4,17] a marker that reflects the integrity of the cerebral penetrating arterioles and its solute clearance function is required in order to appropriately predict or intervene in the progression of WMH
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