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1st appeared
18 October
1999 Link Between Osteoporosis and Cognitive Decline May Implicate Low Estrogen Levels Women with osteoporosis have worse cognitive function and are at greater risk for losing mental agility than women without this bone-thinning disease, according to a new study by UCSF/SF VA Medical Center epidemiologists and colleagues at the National Institute of Aging and the University of Pittsburgh. The connection between bone loss and cognitive decline was identified in a group of 8,373 women without dementia, 65 years and older, as part of the multi-center Study of Osteoporotic Fractures. The study, begun in 1986, may implicate low levels of estrogen as a common culprit. "Ours is the first study to report an association between bone mineral density and cognitive decline in community-dwelling, non-demented women," says Kristine Yaffe, an assistant professor of psychiatry and neurology at UCSF and chief of geriatric psychiatry at the SF VA Medical Center. "The observation that osteoporosis is associated with poor cognitive function suggests a link between two of the most common diseases affecting aging women." For a decade, researchers have suggested that estrogen may ward off dementia, and there are several reasonable biological explanations for how estrogen might do this, notes Yaffe, primary author of a report published in the October issue of the Journal of the American Geriatric Society. There are estrogen receptors in the brains of both women and men. Studies of rats have shown that estrogen affects some of the brain’s neurotransmitters and their receptors, which are responsible for carrying signals between nerve cells. Other researchers have suggested that estrogen may help keep oxygen flowing to the brain through a role in maintaining the suppleness of arteries. Estrogen may also affect production of a lipid-carrying protein called Apolipoprotein E, and one of the inheritable variants of this molecule, the E4 allele, appears to put women at a higher risk for Alzheimer’s disease. Yet as Yaffe and UCSF colleagues earlier determined in a meta-analysis of several studies, published earlier in the Journal of the American Medical Association, the evidence for a connection between estrogen and cognitive decline is conflicting. Yaffe and her co-authors on the current study set out to approach the question by using bone-density as a proxy for lifetime estrogen exposure. Taking estrogen to ward off osteoporosis and peri- and post-menopausal symptoms is old hat by now, and other associations between estrogen levels and health risks -- a lower incidence of heart disease and an increased incidence of breast cancer being the main examples -- are widely accepted. Yet researchers are far from fully understanding all of estrogen’s physiologic roles. Women differ in the amount of estrogen they make in the course of a lifetime, depending on genetic factors, when they attain puberty, whether or not and when they bear children, and on age of menopause, when estrogen production declines dramatically. One possible contributor to the inconsistent results obtained in earlier studies designed to look for a connection between estrogen loss and cognitive decline, according to Yaffe, is that measuring estrogen itself is problematic. Blood levels of total estrogen vary over time, and as a practical matter in a scientific study, they can only be gauged periodically. Yaffe says that as a follow-up to the newly published results linking bone and cognitive loss, the research team now is measuring only the free-floating fraction of estrogen circulating in the blood, and they are excluding the potentially inactive hormone tied up by circulating proteins. Yaffe and co-authors evaluated other variables that might have confounded their findings, and concluded that differences in weight, health status, physical disability, age, education, alcohol use and levels of emotional depression did not account for the connection identified between bone loss and cognitive performance. The research team gathered data from three different standard tests of cognitive function -- Trails B, Digit Symbol, and a modified version of the Mini-Mental State Examination, at the beginning of the study and again four to six years later. For the measurements taken at the beginning of the study, higher test scores were associated with greater bone density. The researchers did not clinically evaluate cognitive decline. Instead they grouped together women whose scores declined most precipitously over the course of the study on each of the tests, and they regarded these women as having experienced cognitive deterioration. This group, on average, was older, less educated and more physically impaired. After adjusting for age, the researchers found that decreasing bone density was associated with cognitive deterioration over the course of the study. "While estrogen deficiency is a likely explanation for this association, it is possible that other underlying mechanisms could be identified," Yaffe says. It is possible that the bone and cognitive loss measured may reflect a more overarching aging process affected by a genetic predisposition, she adds. Links: Related stories: Efficacy of Estrogen Therapy for Preventing Dementia Suggested but Unclear Genetically Engineered Mice Could Be Ideal Tool for Testing Alzheimer's Therapies Source: Jeffrey Norris |
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