Previous clinical trials testing whether cholinesterase inhibitors can slow the rate of progression from MCI to AD dementia have yielded disappointing results.
Although BuChE-K alone does not seem to play a major role in progression to AD in MCI patients, a synergistic effect with the ApoE ɛ4 allele was found, highlighting the importance of assessing these combined genotypes for evaluating risk progression in MCI patients.
Randomised controlled trials on the two major classes of anti-dementia pharmaceuticals, cholinesterase inhibitors and glutamate receptor antagonists, have produced poor results in MCI cohorts.
We found significant interactions between BChE-K genotype and the duration of donepezil treatment, with increased changes in MMSE and CDR-SB scores compared to the common allele in MCI subjects treated during the 3-year trial.
To determine if decline in odor identification ability with anticholinergic challenge can predict improvement with donepezil, a cholinesterase inhibitor (ChEI), in patients with mild cognitive impairment (MCI).
Conversely, chronic glial overactivation can also drive degenerative processes and in butyrylcholinesterase K-variant negative females generalized glial overactivation may be the main driver from mild cognitive impairment to AD.
Sex and BuChE genotype seem to differentially influence the type of decline in MCI patients, with more rapid progression of cognitive decline in male BuChE-K, and more incident AD and functional decline in female BuChE wt/wt.
Synergistic effect of apolipoprotein E epsilon4 and butyrylcholinesterase K-variant on progression from mild cognitive impairment to Alzheimer's disease.