Cholinesterase inhibitors for AD

Cholinesterase inhibitors are a class of medicines that block cholinesterase-an enzyme that breaks down the neurotransmitter acetylcholine. AD is linked with low levels of acetylcholine, hence inhibiting or blocking the breakdown of acetylcholine through cholinesterase inhibitors may help to improve brain function, and possibly slow deterioration of cognitive function.6

§   Treatment effects have been demonstrated with several different cholinesterase inhibitors, indicating that the class of agents is consistently better than placebo. However, the disease eventually continues to progress despite treatment and the average effect is often modest. However, global changes in cognition, behavior and functioning have been detected by both physicians and caregivers, indicating that even small measurable differences may be clinically significant.

§   These drugs are similar yet have distinct pharmacology profiles such as onset of action, side effect profile, potential drug interactions, ease of administration (e.g. twice a day versus three times a day), and route of metabolism. However, the clinically relevance of these differences are unclear and the significance of these differences awaits head-to-head trials.^12,16

§  This class of drugs is indicated for mild to moderate AD. However, no published results are available for severe dementia, though open-label follow up from trials suggests that these drugs continue working as the cholinergic deficit increases.12

§  Benefits reported for these medications tend to occur at higher doses. However, the higher the dose, the more likely the side effects.20

§  Given the increase in AD prevalence, more studies are needed to determine the role of cholinergic medicines in patients with severe AD and to provide comparative data on therapeutic options for this subset of patients.[i]

Cochrane reviews of the cholinesterase inhibitors suggest that treatment effects have been demonstrated with several agents, and that this class is generally more efficacious than placebo.  See also Background Chapter 5. Positive changes in cognition, behavior and function were demonstrated, however, the disease continues to progress and the treatment effect is modest and short lived.

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[i] Bullock R, Hammond G. Realistic Expectations. The Management of Severe Alzheimer’s Disease. Alzheimer Dis Assoc Discord. 2003; 17: Supplement 3: s80-s85.