Neurochemical correlates of cognitive dysfunction in patients with leukoaraiosis: a proton magnetic resonance spectroscopy study

Objectives: Leukoaraiosis (LA) is a common radiological finding in the elderly and may reflect cerebral small vessel disease (SVD). Although SVD has been identified as a major cause of vascular cognitive impairment or vascular dementia, the mechanisms for this association remain unclear. We therefore aimed to measure brain metabolites in LA using proton magnetic resonance spectroscopy (H-1-MRS) as to determine the relationship between cognitive function and neurochemical white matter profile. Methods: We recruited 23 patients with LA and 23 age-and sex-matched healthy controls consecutively. Multi-voxel H-1-MRS was performed with a volume of interest located in centrum semiovale that contained mainly white matter voxels. Three main ratios of N-acetyl aspartate (NAA)/Cr, choline (Cho)/Cr and NAA/Cho were obtained. Spearman rank correlation coefficients were calculated between the cognitive function and the measured metabolite ratios. Results: We found significantly lower levels of NAA/Cho and NAA/Cr ratios in lesioned white matter in patients with LA than healthy controls (P<0.05). The ratios of NAA/Cho and NAA/Cr in normal appearing white matter (NAWM) were higher than lesioned white matter and lower than controls, but this difference was not significant (P>0.05). There was a positive relationship between Mini-Mental State Examination (MMSE) and NAA/Cho in NAWM (r=0.417, P=0.048), and also a positive relationship between MMSE and NAA/Cr in lesioned white matter (r=0.551, P=0.006) in patients with LA. A positive relationship between the Z scores of the executive function and NAA/Cho in lesioned white matter (r=0.557, P=0.006) was also found. Conclusion: The main finding of this study was a significant reduction in the ratios of NAA/Cr and NAA/Cho in lesioned white matter, which indicates a marker of neuronal loss or dysfunction in patients with LA, which was correlated with cognitive function. This relationship between cognitive function and metabolic changes suggests that H-1-MRS can be explored as a marker for cognitive dysfunction in patients with LA.