Alzheimer’s Disease and Cholinesterase Inhibitors

The management of Alzheimer’s disease consists of medication based and non-medication based treatments. Two different classes of pharmaceuticals are approved by the FDA for treating Alzheimer’s disease: cholinesterase inhibitors and partial glutamate antagonists. Neither class of drugs has been proven to slow the rate of progression of Alzheimer’s disease. Nonetheless, many clinical trials suggest that these medications are superior to placebos (sugar pills) in relieving some symptoms.

In patients with Alzheimer’s disease there is a relative lack of a brain chemical neurotransmitter called acetylcholine. (Neurotransmitters are chemical messengers produced by nerves that the nerves use to communicate with each other in order to carry out their functions.) Substantial research has demonstrated that acetylcholine is important in the ability to form new memories. The cholinesterase inhibitors (ChEIs) block the breakdown of acetylcholine. As a result, more acetylcholine is available in the brain, and it may become easier to form new memories.

Four ChEIs have been approved by the FDA, but only donepezil hydrochloride (Aricept), rivastigmine (Exelon), and galantamine (Razadyne – previously called Reminyl) are used by most physicians because the fourth drug, tacrine (Cognex) has more undesirable side effects than the other three. Most experts in Alzheimer’s disease do not believe there is an important difference in the effectiveness of these three drugs. Several studies suggest that the progression of symptoms of patients on these drugs seems to plateau for six to 12 months, but inevitably progression then begins again.

Of the three widely used AchEs, rivastigmine and galantamine are only approved by the FDA for mild to moderate Alzheimer’s disease, whereas donepezil is approved for mild, moderate, and severe Alzheimer’s disease. It is not known whether rivastigmine and galantamine are also effective in severe Alzheimer’s disease, although there does not appear to be any good reason why they shouldn’t.

The principal side effects of ChEIs involve the gastrointestinal system and include nausea, vomiting, cramping, and diarrhea. Usually these side effects can be controlled with change in size or timing of the dose or administering the medications with a small amount of food. Between 75% and 90% of patients will tolerate therapeutic doses of ChEIs.