Effect of Homocysteine on Hippocampal Atrophy Independent of Cerebral Amyloid Deposition and Vascular Burden in normal aging, MCI and AD

Abstract

Objectives: To clarify whether homocysteine has any independent effect, not mediated by cerebral beta amyloid protein (Aβ) deposition and vascular burden, on whole brain or hippocampal atrophy in elderly individuals with normal cognition, mild cognitive impairment (MCI) and Alzheimers disease (AD). Methods: Fourteen cognitively normal, 19 MCI, and 24 AD individuals were included. All subjects received three-dimensional volumetric MRI, Pittsburgh Compound B - positron emission tomography and comprehensive clinical evaluation including vascular burden assessment for diabetes, hypertension, dyslipidemia, coronary artery disease, stroke and transient ischemic attack. Blood homocysteine, vitamin B12, and folate levels were also measured. Results: Multiple linear regression analyses showed that plasma total homocysteine level was significantly associated with hippocampal atrophy even after controlling the degree of global cerebral Aβ deposition and vascular burden as well as other potential confounders including age, gender, education and apolipoprotein E ε4 genotype. In contrast, plasma total homocysteine level did not show any significant association with whole brain volume. Conclusions: Our finding of the independent negative association between plasma homocysteine and hippocampal volume suggests that homocysteine has a direct adverse effect, not mediated by cerebral Aβ deposition and vascular burden, on the hippocampus.