Differential effects of lipid-lowering agents on human cholinesterases.
OBJECTIVE
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.


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.
Darvesh
Sultan
S
Division of Neurology, Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada B3H 2E1. sultan.darvesh@dal.ca
Martin
Earl
E
Walsh
Ryan
R
Rockwood
Kenneth
K
D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D002986:Clinical Trials as Topic; D015331:Cohort Studies; D003704:Dementia / Q000378:metabolism / Q000517:prevention & control*; D006801:Humans; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D008148:Lovastatin / Q000031:analogs & derivatives* / Q000494:pharmacology; D015394:Molecular Structure; D017035:Pravastatin / Q000494:pharmacology; D019821:Simvastatin / Q000494:pharmacology
D002800:Cholinesterase Inhibitors; D000960:Hypolipidemic Agents; C012258:mevastatin; D008148:Lovastatin; D019821:Simvastatin; D017035:Pravastatin