To investigate whether elevated homocysteine level is associated with damage of white matter microstructural integrity in a community-dwelling population.

Elevated serum homocysteine levels have been associated with increased risk of numerous physical and mental health problems, such as stroke, dementia, and cognitive decline, which indicates underlying neurobiological changes, but their correlation with white matter microstructural integrity is not known.

This study included 1095 participants (mean age: 55.85 ± 9.41 years, 36.9% male) from the community-based Shunyi cohort study. Serum homocysteine levels were measured by latex-enhanced immunoturbidimetry. Four diffusion tensor neuroimaging parameters (ie. fractional anisotropy (FA), mean diffusion (MD), axial diffusivity (AD) and radial diffusivity (RD) were used to represent white matter integrity.

Mean homocysteine level was 18.00 μmol/L (interquartile ranges:12.30 μmol/L-18.90 μmol/L). Increased homocysteine level was associated with decreased mean FA values (β=-0.068, p=0.009), increased mean MD values (β= 0.066, p=0.006), increased mean AD values (β= 0.061, p=0.014), increased mean RD values (β= 0.066, p=0.006), even after additional adjusting for white matter hyperintensities and lacunes. Diffusion tensor imaging abnormalities occurred in widespread region of white matter, predominantly in corpus callosum, bilateral corticospinal tract, and bilateral cerebral peduncle.

Our data showed a significant association between serum homocysteine level and white matter integrity independent of traditional small vessel disease markers, implying the potential impact of homocysteine to brain nerve tract.