The Use of Cholinesterase Inhibitors Across All Stages of Alzheimer's Disease.

ABSTRACT

Current pharmacological therapy for Alzheimer's disease (AD) includes the cholinesterase inhibitors (ChEIs) donepezil, rivastigmine, and galantamine and the N-methyl D-aspartate receptor antagonist memantine. Based on the results of randomized controlled trials and several meta-analyses, ChEIs appear to show modest but statistically significant improvements on several measures, including cognition and global functioning. Given their modest effects, there is a lack of consensus among clinicians regarding issues related to initiation, optimal duration, and discontinuation of ChEI therapy across the spectrum of AD. There is evidence from long-term observational controlled studies that early initiation and persistent exposure to AD therapy lead to delays in nursing home admission and significantly slower rates of cognitive and functional impairment. In the moderate to severe stages of AD, therapeutic trials of higher dose ChEIs and the addition of memantine are recommended for patients who are no longer responding to lower doses. While side effects are generally mild and gastrointestinal in nature, these events can lead to significant morbidity in more susceptible patients with advanced disease. Patients should thus be regularly monitored for any potential serious side effects of ChEI therapy, which also may include syncope and bradycardia. At the terminal stages of AD, such as when patients become hospice eligible, attempts to cautiously discontinue all medications not necessary for quality of life, including AD drugs, should be made.