Elevated levels of plasma homocysteine are associated with neurotoxicity

Objective: The aim of the present study is to investigate whether increased plasma homocysteine (tHcy) has an effect on the cerebral metabolic concentrations, reflecting neurotoxicity, measured with Magnetic Resonance Spectroscopy (MRS). Methods: One hundred and thirteen patients had a MRS investigation of the brain and the concentration of N-acetyl-aspartate (NAA), choline and creatine was measured and fasting plasma tHcy was assessed. We used linear regression models to investigate the association between tHcy and cerebral metabolic concentrations. Results: We found that tHcy is associated with cerebral NAA (B=−0.09 mmol/l (95% CI, −0.17 to −0.00)) and with creatine (B=−0.09 mmol/l (95% CI, −0.16 to −0.02)) per 1 μmol/l increase tHcy. Patients with a tHcy ≥14 μmol/l had a lower concentration cerebral of NAA (P<0.05) and creatine (P<0.01) compared with patients with a tHcy<14 μmol/l. No significant association was found for the cerebral choline. Conclusion: Elevated levels of tHcy were associated with low concentrations of cerebral NAA and creatine, independent of renal function or the presence of atherosclerotic disease. These preliminary results suggest that tHcy has a neurotoxic effect in vivo.