Plasma Total Homocysteine Levels are not Associated with Medial Temporal Lobe Atrophy, but with White Matter Changes in Alzheimer's Disease

BACKGROUND AND PURPOSE Elevated plasma total homocysteine (tHcy) levels are reported to be associated with an increased risk of Alzheimer's disease (AD). However, the mechanism by which homocysteine contributes to the pathogenesis of AD is as yet unknown. The aim of this study was to elucidate the relationship between white matter changes (WMC) and medial temporal lobe atrophy (MTA) on brain magnetic resonance imaging (MRI), and plasma levels of tHcy in AD patients. METHODS Seventy-two patients with a clinical diagnosis of probable AD were recruited to the study. Plasma tHcy levels, vascular risk factors, and WMC and MTA on brain MRI were evaluated in all patients. The AD patients were classified into two groups: those with no or minimal WMC (69.2+/-8.8 years, mean+/-SD, n=36) and those with moderate-to-severe WMC (74.6+/-4.6 years, n=36) on brain MRI. RESULTS In a univariate logistic regression analysis, the risk of moderate-to-severe WMC in AD was significantly associated with increasing age, female gender, lower education level, hypertension, high plasma tHcy levels, and lower Mini-Mental State Examination (MMSE) score. Multivariate logistic regression analysis revealed only high plasma tHcy as the independent and significant risk factor for moderate-to-severe WMC [odds ratio (OR; adjusted for age, gender, education level, MMSE score, and hypertension comparing the top tertile - tHcy levels >/=12.9 micromol/L - with the bottom tertile - tHcy levels </=9.4 micromol/L)=7.35; 95% confidence interval, confidence interval=1.36-39.84; p=0.02], and age as a borderline significant risk factor (OR=1.08, 95% CI=0.99-1.19, p=0.09) in AD patients. Plasma tHcy levels were not correlated significantly with either right or left MTA. CONCLUSIONS Our results suggest that the vascular pathway mediates the association between elevated plasma tHcy levels and AD.