Differential effects of lipid-lowering agents on human cholinesterases

Objectives: Epidemiologic reports indicate that lipid-lowering agents (LLAs) protect against dementia. We hypothesized that LLAs might affect cholinergic systems. The effects of LLAs on the activity of cholinesterases were examined. Design and methods: Odds ratios and relative risks were calculated from clinical studies of LLAs and dementia and compared with their impacts on human cholinesterases. Representative LLAs were examined for their effects on the activity of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) using Ellman's assay. Results: Epidemiological studies, but not clinical trials, showed lower odds of dementia in patients taking "statins". Comparison of LLAs indicated that "statins" most consistently produced apparent protection. Individual "statins" showed differential cholinesterase inhibition. Lovastatin and simvastatin significantly inhibited butyrylcholinesterase, while mevastatin, pravastatin and the "non-statins" did not. None of the LLAs inhibited acetylcholinesterase. Conclusions: Some "statins" inhibit butyrylcholinesterase. This inhibition suggests a possible means whereby "statins" could protect against dementia. (C) 2003 The Canadian Society of Clinical Chemists. All rights reserved.