Conjugated equine estrogens and global cognitive function in postmenopausal women: Women's Health Initiative Memory Study

Context  The Women's Health Initiative Memory Study (WHIMS) previously reported that estrogen plus progestin therapy does not protect cognition among women aged 65 years or older. The effect of estrogen-alone therapy, also evaluated in WHIMS, on cognition has not been established for this population. Objectives  To determine whether conjugated equine estrogen (CEE) alters global cognitive function in older women and to compare its effect with CEE plus medroxyprogesterone acetate (CEE plus MPA). Design, Setting, and Participants  A randomized, double-blind, placebo-controlled ancillary study of the Women's Health Initiative (WHI), WHIMS evaluated the effect of CEE on incidence of probable dementia among community-dwelling women aged 65 to 79 years with prior hysterectomy from 39 US academic centers that started in June 1995. Of 3200 eligible women free of probable dementia enrolled in the WHI, 2947 (92.1%) were enrolled in WHIMS. Analyses were conducted on the 2808 women (95.3%) with a baseline and at least 1 follow-up measure of global cognitive function before the trial's termination on February 29, 2004. Interventions  Participants received 1 daily tablet containing either 0.625 mg of CEE (n = 1387) or matching placebo (n = 1421). Main Outcome Measure  Global cognitive function measured annually with the Modified Mini-Mental State Examination (3MSE). Results  During a mean follow-up of 5.4 years, mean (SE) 3MSE scores were 0.26 (0.13) units lower than among women assigned to CEE compared with placebo (P = .04). For pooled hormone therapy (CEE combined with CEE plus MPA), the mean (SE) decrease was 0.21 (0.08; P = .006). Removing women with dementia, mild cognitive impairment, or stroke from the analyses lessened these differences. The adverse effect of hormone therapy was more pronounced among women with lower cognitive function at baseline (all P<.01). For women assigned to CEE compared with placebo, the relative risk of having a 10-unit decrease in 3MSE scores (>2 SDs) was estimated to be 1.47 (95% confidence interval, 1.04-2.07). Conclusion  For women aged 65 years or older, hormone therapy had an adverse effect on cognition, which was greater among women with lower cognitive function at initiation of treatment.      

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

Context  Postmenopausal 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. Objective  To evaluate the effect of estrogen plus progestin on the incidence of dementia and mild cognitive impairment compared with placebo. Design, Setting, and Participants  The 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. Intervention  Participants 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 Measures  Incidence of probable dementia (primary outcome) and mild cognitive impairment (secondary outcome) were identified through a structured clinical assessment. Results  The 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). Conclusions  Estrogen 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.      

Effect of estrogen plus progestin on global cognitive function in postmenopausal women: the Women's Health Initiative Memory Study: a randomized controlled trial

Context  Observational studies have suggested that postmenopausal hormone treatment may improve cognitive function, but data from randomized clinical trials have been sparse and inconclusive. The Women's Health Initiative Memory Study (WHIMS) is an ancillary study of the Women's Health Initiative (WHI) hormone therapy trials. On July 8, 2002, the estrogen plus progestin therapy in the WHI trial was discontinued because of certain increased health risks for women. Objective  To determine whether estrogen plus progestin therapy protects global cognitive function in older postmenopausal women. Design, Setting, and Participants  A randomized, double-blind, placebo-controlled clinical trial, WHIMS is an ancillary study of geographically diverse, community-dwelling women aged 65 years or older from 39 of 40 clinical centers within the WHI estrogen plus progestin trial that started in June 1995. Of 4894 eligible postmenopausal women aged 65 years or older and free of probable dementia at baseline, 4532 (92.6%) were enrolled in the estrogen plus progestin component of WHIMS. A total of 4381 participants (96.7%) provided at least 1 valid cognitive function score between June 1995 and July 8, 2002. Interventions  Participants received either 1 daily tablet containing 0.625 mg of conjugated equine estrogen with 2.5 mg of medroxyprogesterone acetate (n = 2145) or matching placebo (n = 2236). Main Outcome Measure  Global cognitive function measured annually with the Modified Mini-Mental State Examination. Results  The Modified Mini-Mental State Examination mean total scores in both groups increased slightly over time (mean follow-up of 4.2 years). Women in the estrogen plus progestin group had smaller average increases in total scores compared with women receiving placebo (P = .03), but these differences were not clinically important. Removing women by censoring them after adjudicated dementia, mild cognitive impairment, or stroke, and nonadherence to study protocol, did not alter the findings. Prior hormone therapy use and duration of prior use did not affect the interpretation of the results, nor did timing of prior hormone therapy initiation with respect to the final menstrual period. More women in the estrogen plus progestin group had a substantial and clinically important decline (2 SDs) in Modified Mini-Mental State Examination total score (6.7%) compared with the placebo group (4.8%) (P = .008). Conclusions  Among postmenopausal women aged 65 years or older, estrogen plus progestin did not improve cognitive function when compared with placebo. While most women receiving estrogen plus progestin did not experience clinically relevant adverse effects on cognition compared with placebo, a small increased risk of clinically meaningful cognitive decline occurred in the estrogen plus progestin group.      

Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women's Health Initiative randomized controlled trial

Context  Despite decades of use and considerable research, the role of estrogen alone in preventing chronic diseases in postmenopausal women remains uncertain. Objective  To assess the effects on major disease incidence rates of the most commonly used postmenopausal hormone therapy in the United States. Design, Setting, and Participants  A randomized, double-blind, placebo-controlled disease prevention trial (the estrogen-alone component of the Women's Health Initiative [WHI]) conducted in 40 US clinical centers beginning in 1993. Enrolled were 10 739 postmenopausal women, aged 50-79 years, with prior hysterectomy, including 23% of minority race/ethnicity. Intervention  Women were randomly assigned to receive either 0.625 mg/d of conjugated equine estrogen (CEE) or placebo. Main Outcome Measures  The primary outcome was coronary heart disease (CHD) incidence (nonfatal myocardial infarction or CHD death). Invasive breast cancer incidence was the primary safety outcome. A global index of risks and benefits, including these primary outcomes plus stroke, pulmonary embolism (PE), colorectal cancer, hip fracture, and deaths from other causes, was used for summarizing overall effects. Results  In February 2004, after reviewing data through November 30, 2003, the National Institutes of Health (NIH) decided to end the intervention phase of the trial early. Estimated hazard ratios (HRs) (95% confidence intervals [CIs]) for CEE vs placebo for the major clinical outcomes available through February 29, 2004 (average follow-up 6.8 years), were: CHD, 0.91 (0.75-1.12) with 376 cases; breast cancer, 0.77 (0.59-1.01) with 218 cases; stroke, 1.39 (1.10-1.77) with 276 cases; PE, 1.34 (0.87-2.06) with 85 cases; colorectal cancer, 1.08 (0.75-1.55) with 119 cases; and hip fracture, 0.61 (0.41-0.91) with 102 cases. Corresponding results for composite outcomes were: total cardiovascular disease, 1.12 (1.01-1.24); total cancer, 0.93 (0.81-1.07); total fractures, 0.70 (0.63-0.79); total mortality, 1.04 (0.88-1.22), and the global index, 1.01 (0.91-1.12). For the outcomes significantly affected by CEE, there was an absolute excess risk of 12 additional strokes per 10 000 person-years and an absolute risk reduction of 6 fewer hip fractures per 10 000 person-years. The estimated excess risk for all monitored events in the global index was a nonsignificant 2 events per 10 000 person-years. Conclusions  The use of CEE increases the risk of stroke, decreases the risk of hip fracture, and does not affect CHD incidence in postmenopausal women with prior hysterectomy over an average of 6.8 years. A possible reduction in breast cancer risk requires further investigation. The burden of incident disease events was equivalent in the CEE and placebo groups, indicating no overall benefit. Thus, CEE should not be recommended for chronic disease prevention in postmenopausal women.      

Recreational physical activity and the risk of breast cancer in postmenopausal women: the Women's Health Initiative Cohort Study

Context  Women who are physically active have a decreased risk for breast cancer, but the types, amounts, and timing of activity needed are unknown. Objective  To prospectively examine the association between current and past recreational physical activity and incidence of breast cancer in postmenopausal women. Design, Setting, and Patients  Prospective cohort study in 74 171 women aged 50 to 79 years who were recruited by 40 US clinical centers from 1993 through 1998. Main Outcome Measure  Incident invasive and in situ breast cancer. Results  We documented 1780 newly diagnosed cases of breast cancer over a mean follow-up of 4.7 years. Compared with less active women, women who engaged in regular strenuous physical activity at age 35 years had a 14% decreased risk of breast cancer (relative risk [RR], 0.86; 95% confidence interval [CI], 0.78-0.95). Similar but attenuated findings were observed for strenuous physical activity at ages 18 years and 50 years. An increasing total current physical activity score was associated with a reduced risk for breast cancer (P = .03 for trend). Women who engaged in the equivalent of 1.25 to 2.5 hours per week of brisk walking had an 18% decreased risk of breast cancer (RR, 0.82; 95% CI, 0.68-0.97) compared with inactive women. Slightly greater reduction in risk was observed for women who engaged in the equivalent of 10 hours or more per week of brisk walking. The effect of exercise was most pronounced in women in the lowest tertile of body mass index (BMI) (<24.1), but also was observed for women in the middle tertile of BMI (24.1-28.4). Conclusions  These data suggest that increased physical activity is associated with reduced risk for breast cancer in postmenopausal women, longer duration provides most benefit, and that such activity need not be strenuous.      

中国痴呆与认知障碍诊治指南:轻度认知障碍的诊断和治疗

近年来,关于轻度认知障碍(mild cognitive impairment,MCI)的概念、标准、诊断和治疗方面相关研究不断进展,为指南制定提供了依据.本指南旨在结合临床实践,对MCI的临床分型、诊断流程、预防和治疗等方面进行推荐.     

Effect of estrogen plus progestin on stroke in postmenopausal women: the Women's Health Initiative: a randomized trial

Context  The Women's Health Initiative (WHI) trial of estrogen plus progestin was stopped early because of adverse effects, including an increased risk of stroke in the estrogen plus progestin group. Objective  To assess the effect of estrogen plus progestin on ischemic and hemorrhagic stroke and in subgroups, and to determine whether the effect of estrogen plus progestin was modified by baseline levels of blood biomarkers. Design  Multicenter double-blind, placebo-controlled, randomized clinical trial involving 16 608 women aged 50 through 79 years with an average follow-up of 5.6 years. Baseline levels of blood-based markers of inflammation, thrombosis, and lipid levels were measured in the first 140 centrally confirmed stroke cases and 513 controls. Interventions  Participants received 0.625 mg/d of conjugated equine estrogen plus 2.5 mg/d of medroxyprogesterone acetate (n = 8506) or placebo (n = 8102). Main Outcome Measures  Overall strokes and stroke subtype and severity were centrally adjudicated by stroke neurologists. Results  One hundred fifty-one patients (1.8%) in the estrogen plus progestin and 107 (1.3%) in the placebo groups had strokes. Overall 79.8% of strokes were ischemic. For combined ischemic and hemorrhagic strokes, the intention-to-treat hazard ratio (HR) for estrogen plus progestin vs placebo was 1.31 (95% confidence interval [CI], 1.02-1.68); with adjustment for adherence, the HR was 1.50 (95% CI, 1.08-2.08). The HR for ischemic stroke was 1.44 (95% CI, 1.09-1.90) and for hemorrhagic stroke, 0.82 (95% CI, 0.43-1.56). Point estimates of the HRs indicate that excess risk of all stroke was apparent in all age groups, in all categories of baseline stroke risk, and in women with and without hypertension, prior history of cardiovascular disease, use of hormones, statins, or aspirin. Other risk factors for stroke, including smoking, blood pressure, diabetes, lower use of vitamin C supplements, blood-based biomarkers of inflammation, higher white blood cell count, and higher hematocrit levels did not modify the effect of estrogen plus progestin on stroke risk. Conclusions  Estrogen plus progestin increases the risk of ischemic stroke in generally healthy postmenopausal women. Excess risk for all strokes attributed to estrogen plus progestin appeared to be present in all subgroups of women examined.      

BDNF基因多态性与绝经后妇女认知功能障碍关系的研究

目的 探讨BDNF在绝经后妇女认知功能障碍中的作用.方法 60岁以上绝经妇女中随机抽取136例,简易智能量表(MMSE)检测的认知功能,放射免疫法测血浆雌二醇浓度,采用PCR扩增加限制性内切酶酶切的方法检测BDNF基因多态性.结果 认知功能障碍妇女血浆雌二醇水平低于对照组妇女,差异有统计学意义(P＜0.05).BDNF 196A/G基因型分布在认知功能障碍组与对照组之间差异有统计学意义(χ2=6.01,P=0.012),BDNF 196AG杂合子与认知功能障碍的相对危险度是BDNF 196GG基因型的3.45倍(OR=3.45,95%CI:0.133～0.630,P=0.002),BDNF 196AA纯合子与认知功能障碍的相对危险度是1.43倍(OR=1.43,95%CI:0.304～2.175,P=0.680).结论 BDNF 196A/G基因型与绝经后妇女认知功能障碍有关.BDNF196AG基因型是绝经后妇女认知功能障碍发生的致病基因.     

Influence of estrogen plus progestin on breast cancer and mammography in healthy postmenopausal women: the Women's Health Initiative Randomized Trial

Context  The Women's Health Initiative trial of combined estrogen plus progestin was stopped early when overall health risks, including invasive breast cancer, exceeded benefits. Outstanding issues not previously addressed include characteristics of breast cancers observed among women using hormones and whether diagnosis may be influenced by hormone effects on mammography. Objective  To determine the relationship among estrogen plus progestin use, breast cancer characteristics, and mammography recommendations. Design, Setting, and Participants  Following a comprehensive breast cancer risk assessment, 16 608 postmenopausal women aged 50 to 79 years with an intact uterus were randomly assigned to receive combined conjugated equine estrogens (0.625 mg/d) plus medroxyprogesterone acetate (2.5 mg/d) or placebo from 1993 to 1998 at 40 clinical centers. Screening mammography and clinical breast examinations were performed at baseline and yearly thereafter. Main Outcome Measures  Breast cancer number and characteristics, and frequency of abnormal mammograms by estrogen plus progestin exposure. Results  In intent-to-treat analyses, estrogen plus progestin increased total (245 vs 185 cases; hazard ratio [HR], 1.24; weighted P<.001) and invasive (199 vs 150 cases; HR, 1.24; weighted P = .003) breast cancers compared with placebo. The invasive breast cancers diagnosed in the estrogen plus progestin group were similar in histology and grade but were larger (mean [SD], 1.7 cm [1.1] vs 1.5 cm [0.9], respectively; P = .04) and were at more advanced stage (regional/metastatic 25.4% vs 16.0%, respectively; P = .04) compared with those diagnosed in the placebo group. After 1 year, the percentage of women with abnormal mammograms was substantially greater in the estrogen plus progestin group (716 [9.4%] of 7656) compared with placebo group (398 [5.4%] of 7310; P<.001), a pattern which continued for the study duration. Conclusions  Relatively short-term combined estrogen plus progestin use increases incident breast cancers, which are diagnosed at a more advanced stage compared with placebo use, and also substantially increases the percentage of women with abnormal mammograms. These results suggest estrogen plus progestin may stimulate breast cancer growth and hinder breast cancer diagnosis.      

血清铁死亡标记物与绝经后女性认知障碍的关系

目的 研究血清铁死亡标记物与绝经后女性认知障碍的关系。方法 选取2019年8月至2021年12月就诊的148例女性,其中生育期女性22例,围绝经期女性11例,绝经后女性115例。按照蒙特利尔认知评估量表(Montreal cognitive assessment, MoCA)将绝经后女性分为认知障碍组(n=77)和无认知障碍组(n=38),比较两组血清铁死亡标记物有无差异,应用Logistic进行多因素回归分析绝经后女性认知障碍的相关因素。通过受试者工作特征曲线(Receiver operating characteristic curve, ROC)评估相关因素对绝经后女性认知障碍的诊断价值。结果 与生育期和围绝经期女性相比,绝经后女性MoCA评分明显较低,血清ACSL4、System Xc-、GPX4、GSH、ROS、LPO及MDA水平均明显升高(均P<0.05)。与无认知障碍组相比,认知障碍组绝经后女性受教育年限短、患高血压的比例高,且血清ACSL4、System Xc_-^{、GPX4、GSH、ROS、LPO及MDA水平明显}升高 (均P<0.05)。多因素Logistic回归分析显示教育年限和血清谷胱甘肽(glutathione, GSH)与认知障碍独立相关(P<0.05),ROC曲线分析显示两者联合对预测女性是否患认知障碍具有中度诊断价值(AUC: 0.764, P<0.05)。结论 绝经后女性血清铁死亡标志物ACSL4、System Xc_-^{、GPX4、GSH、ROS、LPO及MDA水平}明显升高,其中GSH与女性认知障碍发生独立相关,与受教育年限联合有望成为绝经后女性认知障碍早期诊断的潜在标志物。     

Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial

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, 8.5 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, 0.625 mg/d, plus medroxyprogesterone acetate, 2.5 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 5.2 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, 1.29 (1.02-1.63) with 286 cases; breast cancer, 1.26 (1.00-1.59) with 290 cases; stroke, 1.41 (1.07-1.85) with 212 cases; PE, 2.13 (1.39-3.25) with 101 cases; colorectal cancer, 0.63 (0.43-0.92) with 112 cases; endometrial cancer, 0.83 (0.47-1.47) with 47 cases; hip fracture, 0.66 (0.45-0.98) with 106 cases; and death due to other causes, 0.92 (0.74-1.14) with 331 cases. Corresponding HRs (nominal 95% CIs) for composite outcomes were 1.22 (1.09-1.36) for total cardiovascular disease (arterial and venous disease), 1.03 (0.90-1.17) for total cancer, 0.76 (0.69-0.85) for combined fractures, 0.98 (0.82-1.18) for total mortality, and 1.15 (1.03-1.28) 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 5.2-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.      

中国女性轻度认知障碍的影响因素及其与绝经症状的关系

目的 调查中国女性轻度认知障碍(mild cognitive impairment, MCI)的影响因素及其与各种典型绝经症状之间的关系。方法 采用蒙特利尔认知评估量表(Montreal Cognitive Assessment , MoCA)评估150名志愿者的认知功能,将其中患有轻度认知障碍的61例患者作为病例组(MCI组),认知功能正常的89例患者作为对照组(Non-MCI组)。收集临床、社会人口学和人体测量学数据,用改良Kupperman评分表(Modified Kupperman Index, KMI)评估绝经症状。两组间比较应用t检验和χ²检验。采用二元Logistic回归模型筛选轻度认知功能障碍的危险因素。结果 单因素分析显示,两组患者间年龄(P=0.001)、教育水平(P=0.001)、KMI评分(P <0.001)、失眠(P=0.033)与轻度认知功能障碍有关。多因素分析显示,对于年龄不超过55岁的患者,失眠(P=0.032)、头痛(P=0.021)是MCI的独立危险因素,高教育水平(P=0.004)是MCI的独立保护性因素。结论 各种更年期症状与MCI之间明确关联,这可能为预防痴呆症提供了新的方向。     

Amyloid and tau positive mild cognitive impairment: clinical and biomarker characteristics of dementia progression

Background:According to the amyloid, tau, neurodegeneration research framework classification, amyloid and tau positive (A+T+) mild cognitive impairment (MCI) individuals are defined as prodromal Alzheimer disease. This study was designed to compare the clinical and biomarker features between A+T+MCI individuals who progressed to progressive MCI (pMCI) and those who remained stable MCI (sMCI), and to identify relevant baseline clinical biomarker and features that could be used to predict progression to dementia within 2 years.Methods:We stratified 197 A+T+MCI individuals into pMCI (n = 64) and sMCI (n = 133) over 2 years. Demographics and cognitive assessment scores, cerebrospinal fluid (CSF), and neuroimaging biomarkers (¹⁸F-florbetapir positron emission tomography mean standardized uptake value ratios [SUVR] and structural magnetic resonance imaging [MRI]) were compared between pMCI and sMCI at baseline, 12- and 24-month follow-up. Logistic regression models then were used to evaluate clinical baseline and biomarker features that predicted dementia progression in A+T+MCI.Results:pMCI individuals had higher mean ¹⁸F-florbetapir SUVR, CSF total-tau (t-tau), and p-tau_181P than those in sMCI individuals. pMCI individuals performed poorer in cognitive assessments, both global and domain specific (memory, executive, language, attention, and visuospatial skills) than sMCI. At baseline, there were significant differences in regions of interest of structural MRI between the two groups, including bilateral amygdala, hippocampus and entorhinal, bilateral inferior lateral ventricle, left superior and middle temporal, left posterior and caudal anterior cingulate (P < 0.05). Baseline CSF t-tau levels and cognitive scores of Montreal cognitive assessment, functional assessment questionnaire, and everyday cognition by the patient''s study partner language domain could predict progression to dementia in A+T+MCI within 2 years.Conclusions:In future clinical trials, specific CSF and cognitive measures that predict dementia progression in A+T+MCI might be useful risk factors for assessing the risk of dementia progression.     

血管性轻度认知障碍及非痴呆性血管性认知障碍患者局部脑血流量的临床研究

目的 评价血管性轻度认知功能障碍(V-MCI)和非痴呆性血管性认知障碍(VCI-ND)患者局部脑血流量的变化特点.探讨局部脑缺血程度与血管性认知功能障碍严重程度的相关性.方法 对22例V-MCI患者,18例VCI-ND患者及年龄,性别匹配的24例正常老年人应用单光子发射断层扫描(SPECT)对局部脑血流量进行定量分析,并对局部脑血流量与简易智能状态量表(MMSE)评分进行相关分析.结果 SPECT显示:V-MCI组,VCI-ND组与对照组相比均有认知相关部位的血流灌注减低,差异有统计学意义(P<0.05).VCI-ND组与V-MCI组相比额叶、颞叶、基底节和顶叶局部脑血流灌注均减少(P<0.05),并且均以额叶、颞叶血流灌注减少最为显著(P<0.01);VCI-ND组额叶、颞叶血流灌注减低与MMSE评分间存在正相关关系(P额<0.01及P颢<0.05).结论 血管性认知功能障碍(VCI)患者在未达到痴呆之前已有认知相关部位脑血流量的降低,即使对V-MCI组SPECT也同样敏感.SPECT定量分析脑血流量对于VCI的预测、早期诊断及治疗都有重要意义.     

Effects of conjugated equine estrogens on breast cancer and mammography screening in postmenopausal women with hysterectomy

Context  The Women's Health Initiative Estrogen-Aone trial comparing conjugated equine estrogens (CEE) with placebo was stopped early because of an increased stroke incidence and no reduction in risk of coronary heart disease. Preliminary results suggesting possible reduction in breast cancers warranted more detailed analysis. Objective  To determine the effects of CEE on breast cancers and mammographic findings. Design, Setting, and Participants  Following breast cancer risk assessment, 10 739 postmenopausal women aged 50 to 79 years with prior hysterectomy were randomized to CEE or placebo at 40 US clinical centers from 1993 through 1998. Mammography screenings and clinical breast examinations were performed at baseline and annually. All breast cancers diagnosed through February 29, 2004, are included. Intervention  A dose of 0.625 mg/d of CEE or an identical-appearing placebo. Main Outcome Measures  Breast cancer incidence, tumor characteristics, and mammogram findings. Results  After a mean (SD) follow-up of 7.1 (1.6) years, the invasive breast cancer hazard ratio (HR) for women assigned to CEE vs placebo was 0.80 (95% confidence interval [CI], 0.62-1.04; P = .09) with annualized rates of 0.28% (104 cases in the CEE group) and 0.34% (133 cases in the placebo group). In exploratory analyses, ductal carcinomas (HR, 0.71; 95% CI, 0.52-0.99) were reduced in the CEE group vs placebo group; however, the test for interaction by tumor type was not significant (P = .054). At 1 year, 9.2% of women in the CEE group had mammograms with abnormalities requiring follow-up vs 5.5% in the placebo group (P<.001), a pattern that continued through the trial to reach a cumulative percentage of 36.2% vs 28.1%, respectively (P<.001); however, this difference was primarily in assessments requiring short interval follow-up. Conclusions  Treatment with CEE alone for 7.1 years does not increase breast cancer incidence in postmenopausal women with prior hysterectomy. However, treatment with CEE increases the frequency of mammography screening requiring short interval follow-up. Initiation of CEE should be based on consideration of the individual woman's potential risks and benefits. Trial Registration  clinicaltrials.gov Identifier: NCT00000611      

绝经后认知功能障碍与血浆性激素水平的关系

目的:探讨绝经后早期认知功能和血浆雌素水平变化的关系.方法:用1∶1病例配对对所有病例进行一般情况、病史、神经病学、神经影像学及血脂检查,血浆性激素水平测定采用放免法.结果:与对照组比较,认知功能障碍组血浆雌二醇、孕酮水平较低,有显著性差异(P＜0.05).结论:绝经雌激素和孕酮水平降低,可能是绝经早期认知功能障碍的危险因素之一.