Acetylcholinesterase (AChE) inhibitors are the only drugs that have demonstrated success in slowing shrinkage (atrophy) of the cortex, hippocampus, and basal forebrain, major areas of Alzheimer's disease (AD)-associated brain damage and dementia. The main barrier to taking advantage of this new success in treating, or even preventing, AD is that the old available AChE inhibitors are weak 

reversible

inhibitors that cause intolerable nausea, vomiting, and diarrhea if given in the higher doses needed. A promising new strategy for producing high-level AChE inhibition in the brain as needed for effective treatment of AD is the use of AChE inhibitors that are of a different type, the 

irreversible

inhibitors.