Serum homocysteine level is related to cerebral small vessel disease in a healthy population


To evaluate the relationship between serum total homocysteine (tHcy) levels and cerebral small vessel disease (cSVD) in a healthy population.


We included consecutive participants who visited our department for health checkups between 2006 and 2013. We rated white matter hyperintensity volumes using both the Fazekas score and semiautomated quantitative methods. We also evaluated lacunes, cerebral microbleeds, and enlarged perivascular spaces (EPVS), which are involved in cSVD. To assess the dose-dependent relationship between tHcy and cSVD parameters, we scored the burdens of each radiologic marker of cSVD.


A total of 1,578 participants were included (age 55 ± 8 years, male sex 57%). In the multivariable analysis, tHcy remained an independent predictor of the white matter hyperintensity volume (B = 0.209; 95% confidence interval [CI] = 0.033–0.385, p = 0.020), presence of cerebral microbleeds (adjusted odds ratio = 2.800; 95% CI = 1.104–7.105, p = 0.030), and moderate to severe EPVS (adjusted odds ratio = 5.906; 95% CI = 3.523–9.901, p < 0.001) after adjusting for confounders. Furthermore, tHcy had positive associations with periventricular Fazekas score (p = 0.001, p for trend <0.001), subcortical Fazekas score (p = 0.003, p for trend = 0.005), and moderate to severe EPVS lesion burden (p < 0.001, p for trend <0.001) in a dose-dependent manner.


Serum tHcy level is correlated with cSVD development in a dose-dependent manner. These findings provide us with clues for further studies of the pathophysiology of cSVD.

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