Alzheimer's Disease,Acetylcholine and Oestrogen

Abstract

Common types of dementia occurring in old age are associated with the loss of cholinergic activity from basal forebrain neurons projecting to the cerebral cortex. In Alzheimer's disease this loss correlates with cognitive decline, and in dementia with Lewy bodies with neuropsychiatric features such a hallucinations. New therapies aimed at restoring the levels of acetylcholine, such as the cholinesterase inhibitors tacrine or donepezil, provide some symptomatic benefit and may also be protective. Similar symptomatic and protective effects of oestrogen may operate through stimulation of the affected cholinergic neurons. These neurons have oestrogen receptors and, in animal models, oestrogen elevates cortical cholinergic activity. Cholinergic control of vasodilation is also affected by oestrogen. Declining oestrogen in postmenopausal women is thus likely to contribute to age-related cognitive decline and increased risk of Alzheimer's via cholinergic mechanisms. In addition to accumulating evidence of the protective effect of oestrogen in Alzheimer's, there is already a report that oestrogen replacement therapy enhances the response of female patients to cholinergic medication (eg, tacrine).