REVIEW – December 2004

Treatment of Alzheimer’s disease with cholinesterase inhibitors


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Among the multiple neurotransmitter deficits, which have been described in Alzheimer’s disease (AD), reduction in cortical and hippocampal choline acetyltransferase activity explains best the progressive deterioration of memory and other cognitive functions. It is assumed to be related mainly to the degeneration of cerebral presynaptic cholinergic neurons. When the number of neurons producing acetyl-choline (ACh) decreases, the amount of ACh produced by these neurons decreases proportionally and quantitative changes in this cholinergic system correlate with severity of the dementia. According to the cholinergic hypothesis, many of the cognitive functional and behavioral symptoms associated with AD are caused by loss of cholinergic neurons in the Nucleus Basalis of Meynert. Other dementias, such as Lewy Body dementia, Mixed AD-vascular dementia involve cholinergic deficits similar to AD, but not Pick disease.

Cholinergic therapy with cholinesterase inhibitors (CI) is now a component of the global management of AD. The paper analyses different aspects of the action of chronic CI-s available in Estonia. The value of CIs in the symptomatic therapy of AD has been established by randomized clinical trials and clinical experience for periods of six to twelve months. Beyond that period of time, a slowing of decline is a more realistic goal, until safe and effective pharmacological combination therapies become available.