5th European Congress on Menopause

Lorraine Dennerstein, AO, MBBS, PhD, FRANZCP, DPM


July 19, 2000

In This Article

Alzheimer's Disease

Age-associated declines in cognitive abilities are well recognized. Modest decrements initially detectable in middle age are accentuated among the elderly. In general, cognitive tasks that depend on previously learned knowledge are more resistant to decline than tasks involving novel information or the manipulation of information. There is little to suggest that the menopause per se initiates cognitive decline in women, but there is considerable evidence that estrogen measurably influences brain function throughout the lifetime. In a symposium sponsored by Wyeth Ayerst, the role of estrogen in cognition and dementia was reviewed by Victor Henderson, MD, Kenneth and Bette Volk Professor of Neurology, Professor of Gerontology and Psychology, University of Southern California, Los Angeles.

Both types of estrogen receptors (alpha and beta) are found within populations of CNS neurons, where they function as ligand-transcription factors. Estrogen also exerts nongenomic effects on neuronal activity. Estrogen has been shown to be both neurotrophic and neuroprotective. Estrogen affects key neurotransmitter systems (acetylcholine, noradrenaline, serotonin, and dopamine), augments cerebral blood flow, increases glucose uptake into the brain, and protects neurons from oxidative stress and other injuries. In adult oophorectomized animals, estrogen replacement improves learning and memory performance. In younger women, verbal and manual dexterity are modestly enhanced during phases of the menstrual cycle when estrogen levels are greater.

An important concern is whether HRT after the menopause might help maintain cognitive skills. Findings to date do not resolve this issue. Among postmenopausal women, several, but not all, small randomized controlled trials indicate that HRT significantly enhances verbal memory. Cohort studies generally suggest that postmenopausal women who receive estrogens perform better on at least some cognitive tasks. Although mood can affect cognitive performance, and although estrogen appears to affect mood favorably, cognitive effects of estrogen have not been attributable to changes in mood alone.

Estrogen also influences processes associated with Alzheimer's disease, including the production of the beta amyloid protein. There is a strong rationale for the use of estrogen in Alzheimer's disease, including findings from case-control and cohort studies of a reduced risk of approximately one half for postmenopausal estrogen users and a dose-response relationship for length of estrogen exposure evident in most studies. However, the results of recent randomized controlled trials indicate that estrogen begun after the onset of dementia symptoms has little effect on cognition or the short-term disease course.

Clinical implications are that if estrogen has a role for improving cognitive function, it is likely to be for prevention in healthy women without signs of Alzheimer's dementia. There is a possibility that estrogen may enhance benefits of cholinergic therapy in Alzheimer's disease.


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