Abstract
This article highlights the latest findings regarding estrogen replacement therapy in the treatment and prevention of Alzheimer's disease (AD) and mild cognitive impairment in women. Despite considerable evidence from observational studies, recent randomized clinical trials of conjugated equine estrogens, alone and in combination with progestin, have shown no benefit for either the treatment of established AD or for the short-term prevention of AD, mild cognitive impairment, or cognitive decline. Based on the evidence, there is no role at present for estrogen replacement therapy in the treatment or prevention of AD or cognitive decline, despite intriguing results from the laboratory and from observational studies. However, numerous questions remain about the biologic effects of estrogens on brain structure and function. Additional basic and clinical investigations are necessary to examine different forms and dosages of estrogens, other populations, and the relevance of timing and duration of exposure.
Highlights
Alzheimer's disease (AD) affects more than 4 million Americans in the United States, and the number of people with this disorder is projected to quadruple by the middle of this century [1]
It has been proposed that the menopausal loss of normal estrogen production may be associated with a vulnerability of women to acquire AD, or even perhaps account for a greater incidence of symptoms, which are interpreted as AD [5]
The important question is whether hormone replacement therapy (HRT) can prevent or treat cognitive impairment or dementia
Summary
Alzheimer's disease (AD) affects more than 4 million Americans in the United States, and the number of people with this disorder is projected to quadruple by the middle of this century [1]. Some investigations have suggested that women may have a higher incidence or risk of AD, at older ages. Estrogen has been shown to act as a trophic factor for cholinergic neurons, and it has anti-inflammatory and antioxidant properties It modulates amyloid precursor protein metabolism, affects the vasculature, and inhibits apolipoprotein (apo) E levels in plasma [6]. Given these potential mechanisms, the important question is whether hormone replacement therapy (HRT) can prevent or treat cognitive impairment or dementia. Recent clinical trials have attempted to provide guidance on the usefulness and the risk profile of these compounds The majority of these studies involved CEE with and without progestin. Estrogen Replacement Therapy, Alzheimer’s Disease, and Mild Cognitive Impairment Mulnard et al 369
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