Association of homocysteine with hippocampal volume independent of cerebral amyloid and vascular burden.

This study aimed to clarify whether homocysteine has independent association, not mediated by cerebral beta amyloid protein deposition and vascular burden, with whole brain or hippocampal volume in elderly individuals with normal cognition, mild cognitive impairment, and Alzheimer's disease. Nineteen mild cognitive impairment and 24 Alzheimer's disease patients were recruited from the Dementia Clinic of the Seoul National University Hospital. Fourteen cognitively normal elderly subjects were also selected from a pool of elderly volunteers. Multiple linear regression analyses showed that plasma total homocysteine level was significantly associated with hippocampal volume even after controlling the degree of global cerebral beta amyloid deposition and vascular burden as well as other potential confounders including age, gender, education, and apolipoprotein E ε4 genotype. On the contrary, plasma total homocysteine level did not show any significant association with whole brain volume. Our finding of the independent negative association between homocysteine and hippocampal volume suggests that homocysteine has a direct adverse effect, not mediated by cerebral beta amyloid deposition and vascular burden, on the hippocampus.