Impacts of Hyper-Homocysteinemia and White Matter Hyper-Intensity in Alzheimers Disease Patients with Normal Creatinine: An MRI-Based Study with Longitudinal Follow-up

Background: White matter hyper-intensities (WMHs) on magnetic resonance imaging (MRI) are commonly found in Alzheimers disease (AD). Cerebro-vascular risk factors including plasma total homocysteine (tHcy) may result in WMHs. This study examined the association between tHcy and WMHs, and their effects on cognitive functions in AD patients over a two-year follow-up period. Methods: One hundred and fifty-seven AD patients with a clinical dementia rating of 1 or 2 were enrolled and follow-up for two years. tHcy, biochemistry tests, and mini-mental state examination (MMSE) scores were collected. WMHs were visually rated on brain MRI and classified as deep white matter hyper-intensities (DWMHs) or peri-ventricular white matter hyper-intensities (PWMHs). MMSEs were performed every six months to survey cognitive decline. Results: In the cross sectional study, tHcy was significantly associated with total WMHs especially in DWMHs even after adjusting for age and other cerebrovascular risk factors. Initial MMSE was inversely correlated with WMH severity but not with tHcy level. In the longitudinal analysis, no differences were found either in tHcy or WMHs score in the two AD groups defined by the cognitive decline rate. Conclusions: tHcy is an independent risk factor for developing moderate to severe DWMHs in AD but shows nonsignificant effect on cognitive performance. The close association between high WMH score and poor initial MMSE suggests an additive impact in AD. The long-term effect of elevated tHcy on cognitive decline was not conclusive in the twoyear follow-up period. Keywords: White matter, homocysteine, Alzheimer's disease, cognitive decline, FLAIR