Homocysteine is associated with hippocampal and white matter atrophy in older subjects with mild hypertension

Background: Plasma homocysteine has been associated with reduced brain volumes in cross-sectional studies. We aimed to investigate if homocysteine is associated with ongoing atrophy, and if so, if this is localized to gray or white matter. Methods: In a group of 80 hypertensive subjects aged 70-90 years (from the SCOPE study) MRI images were obtained at two time points two years apart. Rates of gray and white matter and hippocampal atrophy were determined by calculating the difference in segmentation probability maps using SPM5. Plasma homocysteine, folate, B12 and creatinine were measured at study end. Results: Homocysteine levels correlated with white matter atrophy rate (p = 0.006) hippocampal baseline volume (p = 0.011) and hippocampal atrophy rate (p = 0.004) but not global gray matter atrophy or baseline gray or white matter volumes. The correlations remained significant (p < 0.05) after controlling for subject age, blood pressure, folate levels and white matter lesion volume. Conclusion: In older hypertensives, plasma homocysteine levels are associated with increased rates of progressive white matter and hippocampal atrophy.