Estrogen plus progestin and the incidence of dementia and mild cognitive impairment in postmenopausal women: the Women's Health Initiative Memory Study: a randomized controlled trial.
TL;DR: Estrogen plus progestin therapy increased the risk for probable dementia in postmenopausal women aged 65 years or older and did not prevent mild cognitive impairment in these women, supporting the conclusion that the risks of estrogen plus progESTin outweigh the benefits.
Abstract: ContextPostmenopausal women have a greater risk than men of developing Alzheimer
disease, but studies of the effects of estrogen therapy on Alzheimer disease
have been inconsistent. On July 8, 2002, the study drugs, estrogen plus progestin,
in the Women's Health Initiative (WHI) trial were discontinued because of
certain increased health risks in women receiving combined hormone therapy.ObjectiveTo evaluate the effect of estrogen plus progestin on the incidence of
dementia and mild cognitive impairment compared with placebo.Design, Setting, and ParticipantsThe Women's Health Initiative Memory Study (WHIMS), a randomized, double-blind,
placebo-controlled clinical trial, began enrolling participants from the Women's
Health Initiative (WHI) estrogen plus progestin trial in May 1996. Of the
4894 eligible participants of the WHI study, 4532 (92.6%) postmenopausal women
free of probable dementia, aged 65 years or older, and recruited from 39 of
40 WHI clinical centers were enrolled in the WHIMS.InterventionParticipants received either 1 daily tablet of 0.625 mg of conjugated
equine estrogen plus 2.5 mg of medroxyprogesterone acetate (n = 2229), or
a matching placebo (n = 2303).Main Outcome MeasuresIncidence of probable dementia (primary outcome) and mild cognitive
impairment (secondary outcome) were identified through a structured clinical
assessment.ResultsThe mean (SD) time between the date of randomization into WHI and the
last Modified Mini-Mental State Examination (3MSE) for all WHIMS participants
was 4.05 (1.19) years. Overall, 61 women were diagnosed with probable dementia,
40 (66%) in the estrogen plus progestin group compared with 21 (34%) in the
placebo group. The hazard ratio (HR) for probable dementia was 2.05 (95% confidence
interval [CI], 1.21-3.48; 45 vs 22 per 10 000 person-years; P = .01). This increased risk would result in an additional 23 cases
of dementia per 10 000 women per year. Alzheimer disease was the most
common classification of dementia in both study groups. Treatment effects
on mild cognitive impairment did not differ between groups (HR, 1.07; 95%
CI, 0.74-1.55; 63 vs 59 cases per 10 000 person-years; P = .72).ConclusionsEstrogen plus progestin therapy increased the risk for probable dementia
in postmenopausal women aged 65 years or older. In addition, estrogen plus
progestin therapy did not prevent mild cognitive impairment in these women.
These findings, coupled with previously reported WHI data, support the conclusion
that the risks of estrogen plus progestin outweigh the benefits.
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01 Feb 2009
TL;DR: This Secret History documentary follows experts as they pick through the evidence and reveal why the plague killed on such a scale, and what might be coming next.
Abstract: Secret History: Return of the Black Death Channel 4, 7-8pm In 1348 the Black Death swept through London, killing people within days of the appearance of their first symptoms. Exactly how many died, and why, has long been a mystery. This Secret History documentary follows experts as they pick through the evidence and reveal why the plague killed on such a scale. And they ask, what might be coming next?
5,234 citations
TL;DR: In this paper, the European Foundation for Osteoporosis and Bone disease (subsequently the International osteopo- rosis Foundation) published guidelines for the diagnosis and management of osteoporrosis in a European setting.
Abstract: Summary Guidance is provided in a European setting on the assessment and treatment of postmenopausal women with or at risk from osteoporosis. Introduction The European Foundation for Osteoporosis and Bone disease (subsequently the International Osteopo- rosis Foundation) published guidelines for the diagnosis and management of osteoporosis in 1997. This manuscript updates these in a European setting. Methods The following areas are reviewed: the role of bone mineral density measurement for the diagnosis of osteoporo- sis and assessment of fracture risk; general and pharmaco- logical management of osteoporosis; monitoring of treatment; assessment of fracture risk; case finding strategies; investigation of patients; health economics of treatment. Results and conclusions A platform is provided on which specific guidelines can be developed for national use.
2,292 citations
TL;DR: Investigative and drug development efforts should be diversified to fully address the multifactoriality of Alzheimer's disease.
1,558 citations
TL;DR: These Standards will inform efforts in the field to find prevention Programs and policies that are of proven efficacy, effectiveness, or readiness for adoption and will guide prevention scientists as they seek to discover, research, and bring to the field new prevention programs and policies.
Abstract: Ever increasing demands for accountability, together with the proliferation of lists of evidence-based prevention programs and policies, led the Society for Prevention Research to charge a committee with establishing standards for identifying effective prevention programs and policies. Recognizing that interventions that are effective and ready for dissemination are a subset of effective programs and policies, and that effective programs and policies are a subset of efficacious interventions, SPR’s Standards Committee developed overlapping sets of standards. We designed these Standards to assist practitioners, policy makers, and administrators to determine which interventions are efficacious, which are effective, and which are ready for dissemination. Under these Standards, an efficacious intervention will have been tested in at least two rigorous trials that (1) involved defined samples from defined populations, (2) used psychometrically sound measures and data collection procedures; (3) analyzed their data with rigorous statistical approaches; (4) showed consistent positive effects (without serious iatrogenic effects); and (5) reported at least one significant long-term follow-up. An effective intervention under these Standards will not only meet all standards for efficacious interventions, but also will have (1) manuals, appropriate training, and technical support available to allow third parties to adopt and implement the intervention; (2) been evaluated under real-world conditions in studies that included sound measurement of the level of implementation and engagement of the target audience (in both the intervention and control conditions); (3) indicated the practical importance of intervention outcome effects; and (4) clearly demonstrated to whom intervention findings can be generalized. An intervention recognized as ready for broad dissemination under these Standards will not only meet all standards for efficacious and effective interventions, but will also provide (1) evidence of the ability to “go to scale”; (2) clear cost information; and (3) monitoring and evaluation tools so that adopting agencies can monitor or evaluate how well the intervention works in their settings. Finally, the Standards Committee identified possible standards desirable for current and future areas of prevention science as the field develops. If successful, these Standards will inform efforts in the field to find prevention programs and policies that are of proven efficacy, effectiveness, or readiness for adoption and will guide prevention scientists as they seek to discover, research, and bring to the field new prevention programs and policies.
1,264 citations
Cites background from "Estrogen plus progestin and the inc..."
...A prominent recent example is the research on hormone replacement therapy for women where prior nonrandom trials suggested positive effects but a randomized trial found negative effects (Shumaker et al., 2003)....
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Karolinska University Hospital1, Karolinska Institutet2, Pasteur Institute3, University of Toulouse4, Wolfson Centre for Age-Related Diseases5, University of Cambridge6, University of New South Wales7, Pierre-and-Marie-Curie University8, Umeå University9, La Trobe University10, University of British Columbia11, University of Geneva12, Douglas Mental Health University Institute13, Alzheimer Europe14, University of Cologne15, German Center for Neurodegenerative Diseases16, London School of Economics and Political Science17, Radboud University Nijmegen18, Rockefeller University19, VU University Medical Center20, University of Southern California21, Brigham and Women's Hospital22, University of Copenhagen23, University of Gothenburg24, UCL Institute of Neurology25
TL;DR: This poster aims to demonstrate the efforts towards in-situ applicability of EMMARM, which aims to provide real-time information about the physical and cognitive properties of Alzheimer's disease and other dementias.
Abstract: Defeating Alzheimer's disease and other dementias : a priority for European science and society
1,215 citations
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TL;DR: The analysis of censored failure times is considered in this paper, where the hazard function is taken to be a function of the explanatory variables and unknown regression coefficients multiplied by an arbitrary and unknown function of time.
Abstract: The analysis of censored failure times is considered. It is assumed that on each individual arc available values of one or more explanatory variables. The hazard function (age-specific failure rate) is taken to be a function of the explanatory variables and unknown regression coefficients multiplied by an arbitrary and unknown function of time. A conditional likelihood is obtained, leading to inferences about the unknown regression coefficients. Some generalizations are outlined.
28,264 citations
TL;DR: Overall health risks exceeded benefits from use of combined estrogen plus progestin for an average 5.2-year follow-up among healthy postmenopausal US women, and the results indicate that this regimen should not be initiated or continued for primary prevention of CHD.
Abstract: Context Despite decades of accumulated observational evidence, the balance of risks and benefits for hormone use in healthy postmenopausal women remains uncertain Objective To assess the major health benefits and risks of the most commonly used combined hormone preparation in the United States Design Estrogen plus progestin component of the Women's Health Initiative, a randomized controlled primary prevention trial (planned duration, 85 years) in which 16608 postmenopausal women aged 50-79 years with an intact uterus at baseline were recruited by 40 US clinical centers in 1993-1998 Interventions Participants received conjugated equine estrogens, 0625 mg/d, plus medroxyprogesterone acetate, 25 mg/d, in 1 tablet (n = 8506) or placebo (n = 8102) Main outcomes measures The primary outcome was coronary heart disease (CHD) (nonfatal myocardial infarction and CHD death), with invasive breast cancer as the primary adverse outcome A global index summarizing the balance of risks and benefits included the 2 primary outcomes plus stroke, pulmonary embolism (PE), endometrial cancer, colorectal cancer, hip fracture, and death due to other causes Results On May 31, 2002, after a mean of 52 years of follow-up, the data and safety monitoring board recommended stopping the trial of estrogen plus progestin vs placebo because the test statistic for invasive breast cancer exceeded the stopping boundary for this adverse effect and the global index statistic supported risks exceeding benefits This report includes data on the major clinical outcomes through April 30, 2002 Estimated hazard ratios (HRs) (nominal 95% confidence intervals [CIs]) were as follows: CHD, 129 (102-163) with 286 cases; breast cancer, 126 (100-159) with 290 cases; stroke, 141 (107-185) with 212 cases; PE, 213 (139-325) with 101 cases; colorectal cancer, 063 (043-092) with 112 cases; endometrial cancer, 083 (047-147) with 47 cases; hip fracture, 066 (045-098) with 106 cases; and death due to other causes, 092 (074-114) with 331 cases Corresponding HRs (nominal 95% CIs) for composite outcomes were 122 (109-136) for total cardiovascular disease (arterial and venous disease), 103 (090-117) for total cancer, 076 (069-085) for combined fractures, 098 (082-118) for total mortality, and 115 (103-128) for the global index Absolute excess risks per 10 000 person-years attributable to estrogen plus progestin were 7 more CHD events, 8 more strokes, 8 more PEs, and 8 more invasive breast cancers, while absolute risk reductions per 10 000 person-years were 6 fewer colorectal cancers and 5 fewer hip fractures The absolute excess risk of events included in the global index was 19 per 10 000 person-years Conclusions Overall health risks exceeded benefits from use of combined estrogen plus progestin for an average 52-year follow-up among healthy postmenopausal US women All-cause mortality was not affected during the trial The risk-benefit profile found in this trial is not consistent with the requirements for a viable intervention for primary prevention of chronic diseases, and the results indicate that this regimen should not be initiated or continued for primary prevention of CHD
14,646 citations
TL;DR: Patients who meet the criteria for MCI can be differentiated from healthy control subjects and those with very mild AD, and appear to constitute a clinical entity that can be characterized for treatment interventions.
Abstract: Background Subjects with a mild cognitive impairment (MCI) have a memory impairment beyond that expected for age and education yet are not demented. These subjects are becoming the focus of many prediction studies and early intervention trials. Objective To characterize clinically subjects with MCI cross-sectionally and longitudinally. Design A prospective, longitudinal inception cohort. Setting General community clinic. Participants A sample of 76 consecutively evaluated subjects with MCI were compared with 234 healthy control subjects and 106 patients with mild Alzheimer disease (AD), all from a community setting as part of the Mayo Clinic Alzheimer's Disease Center/Alzheimer's Disease Patient Registry, Rochester, Minn. Main Outcome Measures The 3 groups of individuals were compared on demographic factors and measures of cognitive function including the Mini-Mental State Examination, Wechsler Adult Intelligence Scale–Revised, Wechsler Memory Scale–Revised, Dementia Rating Scale, Free and Cued Selective Reminding Test, and Auditory Verbal Learning Test. Clinical classifications of dementia and AD were determined according to the Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition and the National Institute of Neurological and Communicative Disorders and Stroke–Alzheimer's Disease and Related Disorders Association criteria, respectively. Results The primary distinction between control subjects and subjects with MCI was in the area of memory, while other cognitive functions were comparable. However, when the subjects with MCI were compared with the patients with very mild AD, memory performance was similar, but patients with AD were more impaired in other cognitive domains as well. Longitudinal performance demonstrated that the subjects with MCI declined at a rate greater than that of the controls but less rapidly than the patients with mild AD. Conclusions Patients who meet the criteria for MCI can be differentiated from healthy control subjects and those with very mild AD. They appear to constitute a clinical entity that can be characterized for treatment interventions.
8,255 citations
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01 Jan 2001
TL;DR: A process for isolating a thromboplastic material from human placentae by solvent extraction techniques and it is obtained that is useful as a blood coagulant is obtained.
4,586 citations
Mayo Clinic1, Baylor College of Medicine2, Technische Universität München3, Icahn School of Medicine at Mount Sinai4, Washington University in St. Louis5, Johns Hopkins University6, French Institute of Health and Medical Research7, University College London8, University of California, San Diego9, Karolinska Institutet10
TL;DR: A group of experts on aging and MCI from around the world in the fields of neurology, psychiatry, geriatrics, neuropsychology, neuroimaging, neuropathology, clinical trials, and ethics was convened to summarize the current state of the field of MCI.
Abstract: The field of aging and dementia is focusing on the characterization of the earliest stages of cognitive impairment. Recent research has identified a transitional state between the cognitive changes of normal aging and Alzheimer's disease (AD), known as mild cognitive impairment (MCI). Mild cognitive impairment refers to the clinical condition between normal aging and AD in which persons experience memory loss to a greater extent than one would expect for age, yet they do not meet currently accepted criteria for clinically probable AD. When these persons are observed longitudinally, they progress to clinically probable AD at a considerably accelerated rate compared with healthy age-matched individuals. Consequently, this condition has been recognized as suitable for possible therapeutic intervention, and several multicenter international treatment trials are under way. Because this is a topic of intense interest, a group of experts on aging and MCI from around the world in the fields of neurology, psychiatry, geriatrics, neuropsychology, neuroimaging, neuropathology, clinical trials, and ethics was convened to summarize the current state of the field of MCI. Participants reviewed the world scientific literature on aging and MCI and summarized the various topics with respect to available evidence on MCI. Diagnostic criteria and clinical outcomes of these subjects are available in the literature. Mild cognitive impairment is believed to be a high-risk condition for the development of clinically probable AD. Heterogeneity in the use of the term was recognized, and subclassifications were suggested. While no treatments are recommended for MCI currently, clinical trials regarding potential therapies are under way. Recommendations concerning ethical issues in the diagnosis and the management of subjects with MCI were made.
4,424 citations