High Estrogen, Diabetes Linked to Dementia in Women Pauline Anderson January 29, 2014 Postmenopausal women with elevated estrogen levels are at increased risk of developing dementia, and those who also have diabetes may face an even greater threat of cognitive decline, a new study suggests. The study results are surprising, given that the prevailing belief is that estrogen protects a womans brain as well as her heart, said lead author Pierre-Yves Scarabin, MD, director of research, National Institute of Health and Medical Research (INSERM), and hormones and cardiovascular disease team leader, Center for Research in Epidemiology and Population Health, Villejuif, France. Results of this new study, together with other recent research, challenge this dogma, and show that findings from animal models dont necessarily apply to women, Dr. Scarabin told Medscape Medical News. At the other end of the spectrum, the study found that low levels of estrogen may also confer a higher risk for dementia, but reverse causation is probably driving this finding, said Dr. Scarabin. Their results are published online January 29 in Neurology. Determining Dementia From participants in the ongoing Three-City Study of vascular risk factors for dementia in French persons aged 65 and older, the analysis included 132 women with incident dementia and 543 without, none of whom were taking hormonal treatment. Dementia was determined through a process that started with a neuropsychological examination. Participants suspected of having dementia then underwent further examination by a neurologist, with potential cases being reviewed by an independent committee of neurologists and determined using Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Revised, criteria. The study showed a J-shaped relationship between total levels of estradiol (E2) or bioavailable E2 levels and 4-year all-cause dementia. The hazard ratio (HR) for total E2 in quartile 1 (E2 ≤ 3.49 pg/mL) was 2.20 (95% confidence interval [CI], 1.07 - 4.52; P = .03), while the HR in quartile 4 (E2 > 8.00 pg/mL) was 2.43 (95% CI, 1.15 - 5.20; P = .02) in a model that adjusted for age, center, education, apolipoprotein E4 status, depressive symptoms, waist-to-hip ratio, Mini-Mental State Examination score at baseline, hypercholesterolemia, and history of myocardial infarction and stroke. Adjustment for triglycerides or high-density lipoprotein cholesterol did not modify the results. The association with lower E2 levels is probably due to reverse causality, said Dr. Scarabin. When women with cognitive impairment at baseline and those who developed dementia within 2 years of follow-up were excluded, the association between low E2 and dementia was no longer increased, while the risk for dementia remained significantly higher among women having a high total E2 value. The new results are in line with other emerging research, noted Dr. Scarabin. Several lines of evidence now suggest that postmenopausal hormone therapy and high levels of endogenous estradiol in postmenopausal women not using therapy have deleterious effects on health. The new study showed that the risk for dementia is even more apparent in patients with both high estrogen and diabetes. In diabetic patients with a total E2 value in the highest quartile, the adjusted HR for dementia was 14.2 ( P = .02) compared with 1.9 ( P = .04) for women without diabetes in the same quartile. Importantly, our study reported, for the first time, a dramatic rise in future dementia risk in women with both diabetes, which is a well-known risk factor for dementia, and high estradiol levels, commented Dr. Scarabin. Although the mechanisms by which elevated estrogen might boost dementia risk still need to be clarified, it could be that, like diabetes, high levels have detrimental effects on vessels, said Dr. Scarabin. Its possible, he said, that diabetes and elevated estrogen act synergistically. He suggested that women with both diabetes and hyperestrogenicity could be a target for future prevention studies. As indicated by the authors, in addition to microvascular abnormalities, the mechanistic route from diabetes to dementia could also involve brain infarcts; inflammation; and alteration of glucose, insulin, and amyloid metabolism. There might be a sort of ideal estrogen level above which the effect on cognition begins to be apparent, but Dr. Scarabin pointed out that the estradiol effects also depend on factors such as age and history of vascular disease. However, he added, perhaps there are protective effects among young postmenopausal women and harms in older women with damaged vessels. Intriguing Clue Reached for a comment, Glen R. Finney, MD, assistant professor, neurology, and co-director, Memory and Cognitive Disorders Program, University of Florida, Gainesville, and a spokesperson for the American Academy of Neurology, said the study is yet another intriguing clue in the story of dementia. One of the strengths of the study was its prospective surveillance, which is more reliable than retrospective data, Dr. Finney told Medscape Medical News. Although he felt that the testing for dementia could have been more robust, he acknowledged that this might have been difficult given the numbers. He expressed concern that with the number of factors analyzed, the level of significance for the estradiol results may be low. Dr. Finney found the combination of high estradiol and diabetes striking as a risk factor. It again stresses the importance of preventing diabetes, he said. It also suggests that a clinical study using an intervention to lower estradiol levels in diabetics to forestall dementia may be interesting, although more work needs to be done to prove causality. Dr. Finney said he will continue to advise patients that estrogen replacement therapy should not be pursued for cognitive benefit but rather for medical need, such as easing osteoporosis. I may give an additional caution to diabetics that there may be a relationship between high estrogen levels and dementia in diabetes, and thus some further theoretical risk in people with diabetes, he added. Dr. Scarabin received a grant from the National Research Agency for the work under consideration and a grant from the National Health Ministry for research outside the submitted work. Dr Finney has disclosed no relevant financial relationships. Neurology. 2014;82:504-511. Published online January 29, 2014. Abstract Medscape Medical News © 2014 WebMD, LLC
Posted on: Thu, 30 Jan 2014 17:53:17 +0000
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