Women's Health Initiative Memory Study Suite of Studies - Extension Study

女性健康倡议记忆研究套件 - 扩展研究

• 批准号: 8335779
• 负责人: Susan Resnick
• 金额: $ 11.53万
• 依托单位: NATIONAL INSTITUTE ON AGING
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8335779
• 关键词: Adverse effects; Affect; Age; Aging; Ancillary Study; Body Weight Changes; Body Weight decreased; Brain; Clinical; Cognition; Cognitive; Cognitive aging; Conjugated Equine Estrogens; Contracts; Controlled Clinical Trials; Dementia; Depressed mood; Development; Disease; Elderly; Enrollment; Funding; Heart Diseases; Hippocampus (Brain); Hysterectomy; Impaired cognition; Individual; Interest Group; Investigation; Life; Long-Term Effects; Magnetic Resonance Imaging; Medial; Medroxyprogesterone 17-Acetate; Memory; Menopause; Outcome; Participant; Pharmaceutical Preparations; Placebo Control; Placebos; Postmenopause; Publications; Randomized; Randomized Clinical Trials; Recording of previous events; Relative (related person); Reporting; Research Personnel; Risk; Role; Signal Transduction; Site; Stroke; Structure; Telephone; Temporal Lobe; Testing; Time; Universities; Uterus; Weight; Weight Gain; Woman; Women' s Health; aged; base; brain volume; clinically significant; cognitive change; cognitive function; critical period; depressive symptoms; design; follow-up; forest; frontal lobe; functional status; hormone therapy; human old age (65+); ischemic lesion; mild neurocognitive impairment; primary outcome; research and development; treatment effect; trend; waist circumference

The Womens Health Initiative (WHI) randomized, placebo-controlled clinical trials of hormone therapy (HT) were designed to test the hypothesis that conjugated equine estrogens alone (CEE-Alone) or in combination with medroxyprogesterone acetate (CEE+MPA) protected postmenopausal women against the development of heart disease. The WHI Memory Study (WHIMS) was an ancillary study to the WHI trials, which consisted of parallel placebo-controlled randomized clinical trials of 0.625 mg/day CEE therapy with and without 2.5 mg/day MPA in women with a uterus or post-hysterectomy, respectively. WHIMS investigated the effect of CEE-Alone and CEE+MPA on risk for probable dementia and mild cognitive impairment in women age 65 and older, as well as the effects of these treatments on global cognitive function. The WHI Study of Cognitive Aging (WHISCA), an ancillary study to WHIMS, was developed to investigate the effects of HT on domain-specific cognitive function in women without dementia. WHISCA enrolled 2305 women at 14 of the WHIMS sites, distributed across the two parallel trials. WHISCA was initiated on average 3 years after WHI randomization and the primary outcome was the effect of HT on rates of cognitive change, adjusted for time since randomization. The WHIMS CEE+MPA trial terminated earlier than planned (July, 2002) due to an adverse risk-to-benefit profile in the main WHI trial. Subsequently, the WHI CEE-Alone Trial also was terminated early (February, 2004). Results from the WHIMS trials showed that CEE-Alone or CEE+MPA increase the risk of dementia and have adverse effects on global cognition in women aged 65 years or older. HT also has been shown to increase the risk of clinical stroke in women 65 years and older. The initial report of WHISCA findings showed that CEE + MPA had a negative impact on verbal memory (p < 0.01) and a trend to a positive impact on figural memory (p = 0.012) over time compared with placebo with no effect on other cognitive domains. In addition, these effects were evident only after long-term therapy. CEE + MPA did not significantly influence positive affect, negative affect, or depressive symptoms. These findings suggest that HT may have different effects across different cognitive domains. The findings from the CEE-Alone Trial in women with prior hysterectomy who were randomized to CEE or placebo show that CEE alone did not affect domain-specific cognitive function over time. Participants in the WHISCA and WHIMS studies continue to be followed through telephone cognitive assessments as they pass through the risk period for cognitive decline. Over the 2011-2015 period the NIA is assuming the primary funding role for the WHIMS Suite of Studies through a Research and Development Contract. This contract also includes continued cognitive follow-up of women in the WHIMS-Younger (WHIMS-Y) study, who were randomized to hormone therapy through the WHI when aged 50-54 years. The WHIMS-Y study will test the hypothesis that hormone therapy around the time of the menopause may benefit cognitive function later in life. The WHIMS Suite of Studies is conducted by Wake Forest University, which is also the site for the Southeast Regional Center for WHI and leads the Aging, Cognition and Functional Status interest group for the WHI. Publications over the last year include investigations of long-term effects of assignment to CEE-based therapies on cognitive function, associations between late-life depressive symptoms and regional brain volumes, and associations between weight change and cognitive change. CEE-based hormone therapy was associated with small mean relative decrements in global cognitive function and several domain-specific cognitive functions during the randomized clinical trial, which largely persisted through up to 4 years after the trial. The strongest statistical evidence was for global cognitive function. For domain-specific scores, the mean decrements were slightly smaller and were less significant; these decrements tended to be larger for CEE-alone compared to CEE+MPA. CEE-based therapies, when initiated after the age of 65, produce a small broad-based decrement in cognitive function that persists after their use is stopped, but the differences in cognitive function are small and would not be detectable or have clinical significance for an individual woman. In a second investigation, WHIMS investigators showed that depressed women had lower baseline global cognition and were more likely to have prior hormone therapy history. Moreover, elevated depressive symptoms were associated with smaller volumes in certain frontal lobe subregions but not in the medial temporal lobe structures, suggesting the importance of frontal lobe brain structures in late-life depressive symptoms in women. In a third investigation of 2283 older postmenopausal WHI women, we found a lack of associations between weight and cognition in women who remained stable or gained weight. However, weight loss (p <0.05), most likely signaling incipient disease, was associated with lower cognition. Cognition was not related to changes in waist circumference.

妇女健康计划（WHI）旨在测试单独结合马雌激素（CEE-NOLONE）或与乙酸酯（CEE+MPA）受保护的后女性抗病女性的妇女妇女抗病的假说，该假设是旨在测试单独的马雌激素（CEE-NOLONE）的假设的假设。 WHI记忆研究（WHIMS）是对WHI试验的辅助研究，该研究分别由子宫或不含2.5 mg/day MPA的女性分别为子宫或休假后切除术的女性，由平行安慰剂对照的随机临床试验进行0.625 mg/day CEE治疗。 WHIMS调查了CEE-Alone和CEE+MPA对65岁及65岁以上女性可能痴呆和轻度认知障碍的风险的影响，以及这些治疗对全球认知功能的影响。对WHI认知衰老（WHISCA）的WHI研究是一项对异想天开的辅助研究，以研究HT对域特异性认知功能对没有痴呆症的女性的影响。在两项平行试验中分布在14个异想天开的14个遗址中，招募了2305名妇女。 Whisca平均在随机分组后3年开始，主要结果是HT对认知变化率的影响，自随机分组以来，对时间进行了调整。由于主要WHI试验中的风险不良对效果的不利，因此，WHIMS CEE+MPA试验终止于计划（2002年7月）（2002年7月）。随后，whi-Cee-nor审判也被终止（2004年2月）。异想天开的试验的结果表明，在65岁或65岁以上的女性中，CEE-OLONE或CEE+MPA会增加痴呆症的风险，并对全球认知产生不利影响。 HT还被证明会增加65岁以上女性临床中风的风险。 WHISCA调查结果的最初报告表明，与安慰剂相比，ECE + MPA会对言语记忆（P <0.01）产生负面影响（P <0.01），对人物记忆的积极影响（P = 0.012）产生了负面影响，对其他认知领域没有影响。此外，这些作用仅在长期治疗后才明显。 CEE + MPA并未显着影响积极影响，负面影响或抑郁症状。这些发现表明，HT可能在不同的认知领域具有不同的影响。随机分配给CEE或安慰剂的先前子宫切除术的女性中CEE-NONE试验的发现表明，仅CEE不会影响域特异性的认知功能。 Whisca和Whims研究的参与者通过电话认知评估通过了认知能力下降的风险期，继续遵循他们的认知评估。 在2011-2015期间，NIA通过研发合同担任研究和研究套件的主要资金角色。 该合同还包括对Whims-Younger（Whims-Y）研究中女性的持续认知随访，她们在50-54岁时通过WHI随机分配了激素治疗。 异想天开的研究将检验以下假设：更年期时期激素治疗可能会在以后的认知功能中受益。 Wake Forest University进行了想法，该套件是Wake Forest University进行的，该大学也是东南地区WHI区域中心的所在地，并领导了WHI的衰老，认知和功能状况兴趣组。 去年的出版物包括对分配对基于CEE的疗法的长期影响对认知功能的长期影响，晚期抑郁症状和区域脑量之间的关联以及体重变化与认知变化之间的关联。 在随机临床试验中，基于CEE的激素治疗与全球认知功能的平均相对降低和几种域特异性认知功能有关，该试验在试验后长达4年。最有力的统计证据是全球认知功能。 对于域特异性得分，平均降低略小，显着较小。与CEE+MPA相比，对于CEE-hore而言，这些减小往往更大。 基于CEE的疗法在65岁之后开始时，在使用后持续存在的认知功能会产生较小的基于广泛的认知功能，但认知功能的差异很小，无法检测到或对单个女性具有临床意义。 在第二次调查中，异想天开的研究人员表明，抑郁妇女的基线全球认知较低，并且更有可能具有先前的激素治疗史。此外，在某些额叶区域中，较小的抑郁症状与较小的体积有关，而在颞叶内侧叶结构中无关，这表明额叶脑结构在女性后期抑郁症状中的重要性。 在第三次对2283个年龄较大的绝经后妇女的调查中，我们发现在保持体重稳定或体重增加的妇女的体重与认知之间缺乏关联。然而，体重减轻（P <0.05），最有可能的信号性疾病与较低的认知有关。认知与腰围的变化无关。