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

基本信息

  • 批准号:
    8552328
  • 负责人:
  • 金额:
    $ 3.51万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
  • 资助国家:
    美国
  • 起止时间:
  • 项目状态:
    未结题

项目摘要

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. Over the last year, publications have included a number of papers investigating risk factors, especially diabetes, for cognitive decline, brain changes, and dementia. In one study, we examined cognitive function in 179 WHIMS participants with Type 2 diabetes compared to 1984 non-diabetics, followed for an average of 5 years with annual standardized assessments of domain-specific cognitive function. We found that Type 2 diabetes was associated with mean deficits of 0.2-0.4 standard deviations (SD) across follow-up in most cognitive domains. Consistent evidence that rates of decline were accelerated among women with diabetes was evident only for verbal knowledge and verbal memory (p<0.05). Decrements in fine motor speed, but no measure of cognitive function, were greater for women with earlier onset of disease. Through the WHIMS-MRI study, we performed a follow-up study comparing brain and ischemic lesion volume changes in women with and without type 2 diabetes. MRI data were available for 1,366 women, aged 72-89 years, and repeat scans were collected an average of 4.7 years later in 698 women. The 145 women with diabetes (10.6%) at the first MRI had smaller total brain volumes (0.6% less; P = 0.05) and smaller gray matter volumes (1.5% less; P = 0.01), but not white matter volumes, both overall and within major lobes. They also had larger ischemic lesion volumes (21.8% greater; P = 0.02), both overall and in gray matter (27.5% greater; P = 0.06), in white matter (18.8% greater; P = 0.02), and across major lobes. Overall, women with diabetes had slightly (nonsignificant) greater loss of total brain volumes (3.02 cc; P = 0.11) and significant increases in total ischemic lesion volumes (9.7% more; P = 0.05) with time relative to those without diabetes. Diabetes was associated with lower scores in global cognitive function and its subdomains. These relative deficits were only partially accounted for by brain volumes and risk factors for cognitive deficits. In summary, we found that Type 2 diabetes is associated with smaller gray, but not white, matter volumes and that ischemic lesion volumes increased over an approximately 5-year interval. In a third study, we examined cognitive function and brain volumes in WHIMS participants in relation to retinopathy measured in an overlapping sample of 511 women aged 65 and older who had also participated in the Womens Health Initiative Sight Examination Study (WHISE). Retinopathy was assessed using fundus photography (2000-2002) and cognitive performance over time was evaluated using the modified Mini-Mental State Examination (3MSE) (1996-2007). Presence of retinopathy was associated with poorer mental status scores (mean difference = 1.01, SE: 0.43) (p = 0.019) over a 10-year follow-up period and greater ischemic volumes in the total brain (47% larger, p = 0.04) and the parietal lobe (68% larger, p = 0.01). However, retinopathy was not associated with measures of regional brain atrophy. These findings suggest that retinopathy may be a marker of small vessel cerebrovascular disease that may influence cognitive performance and vascular brain changes.
妇女健康倡议 (WHI) 激素疗法 (HT) 的随机、安慰剂对照临床试验旨在检验单独结合马雌激素 (CEE-Alone) 或与醋酸甲羟孕酮 (CEE+MPA) 联合使用可保护绝经后妇女预防心脏病的假设。 WHI 记忆研究 (WHIMS) 是 WHI 试验的一项辅助研究,其中包括平行安慰剂对照随机临床试验,分别在子宫或子宫切除术后的女性中进行 0.625 毫克/天的 CEE 治疗,联合或不联合 2.5 毫克/天的 MPA。 WHIMS 研究了 CEE-Alone 和 CEE+MPA 对 65 岁及以上女性可能患痴呆症和轻度认知障碍的风险的影响,以及这些治疗对整体认知功能的影响。 WHI 认知衰老研究 (WHISCA) 是 WHIMS 的一项辅助研究,旨在研究 HT 对无痴呆女性特定领域认知功能的影响。 WHISCA 在 14 个 WHIMS 站点招募了 2305 名女性,分布在两个平行试验中。 WHISCA 平均在 WHI 随机化后 3 年开始,主要结果是 HT 对认知变化率的影响,并根据随机化后的时间进行调整。由于主要 WHI 试验的风险收益比不利,WHIMS CEE+MPA 试验比计划提前终止(2002 年 7 月)。随后,WHI CEE-Alone 试验也提前终止(2004 年 2 月)。 WHIMS 试验的结果表明,CEE-Alone 或 CEE+MPA 会增加 65 岁或以上女性患痴呆症的风险,并对整体认知产生不利影响。 HT 还被证明会增加 65 岁及以上女性患临床中风的风险。 WHISCA 研究结果的初步报告表明,与安慰剂相比,CEE + MPA 对语言记忆有负面影响 (p < 0.01),并且随着时间的推移,对图形记忆有积极影响 (p = 0.012),而对其他认知领域没有影响。此外,这些效果只有在长期治疗后才会明显。 CEE + MPA 没有显着影响积极情绪、消极情绪或抑郁症状。这些发现表明,HT 可能对不同的认知领域产生不同的影响。对既往接受过子​​宫切除术的女性进行的单独 CEE 试验的结果显示,随着时间的推移,单独使用 CEE 不会影响特定领域的认知功能,这些女性被随机分配到 CEE 或安慰剂组。 WHISCA 和 WHIMS 研究的参与者在经历认知能力下降的风险期时将继续通过电话认知评估进行跟踪。 2011-2015 年期间,NIA 通过研究和开发合同承担了 WHIMS 研究套件的主要资助角色。 该合同还包括对 WHIMS-Younger (WHIMS-Y) 研究中的女性进行持续的认知随访,这些女性在 50-54 岁时通过 WHI 被随机接受激素治疗。 WHIMS-Y 研究将检验以下假设:更年期前后的激素治疗可能有益于以后生活中的认知功能。 WHIMS 研究套件由维克森林大学开展,该大学也是 WHI 东南区域中心的所在地,并领导 WHI 的老龄化、认知和功能状态兴趣小组。 去年,出版物中发表了许多论文,调查了导致认知能力下降、大脑变化和痴呆的危险因素,尤其是糖尿病。 在一项研究中,我们检查了 179 名患有 2 型糖尿病的 WHIMS 参与者与 1984 名非糖尿病参与者的认知功能,并平均随访 5 年,每年对特定领域的认知功能进行标准化评估。我们发现,在大多数认知领域的随访中,2 型糖尿病与 0.2-0.4 个标准差 (SD) 的平均缺陷相关。一致的证据表明,糖尿病女性的下降速度加快,仅在语言知识和语言记忆方面很明显(p<0.05)。对于发病较早的女性来说,精细运动速度的下降更大,但没有认知功能的测量。 通过 WHIMS-MRI 研究,我们进行了一项后续研究,比较了患有和不患有 2 型糖尿病的女性的大脑和缺血性病变体积变化。 MRI 数据适用于 1,366 名年龄在 72-89 岁的女性,平均 4.7 年后收集了 698 名女性的重复扫描数据。 145 名患有糖尿病的女性 (10.6%) 在第一次 MRI 中的总脑体积较小(减少 0.6%;P = 0.05),灰质体积较小(减少 1.5%;P = 0.01),但白质体积较小,无论是整体还是主要脑叶内。他们的缺血性病变体积也更大(增加 21.8%;P = 0.02),无论是整体还是灰质(增加 27.5%;P = 0.06)、白质(增加 18.8%;P = 0.02)以及主要脑叶。总体而言,与非糖尿病女性相比,随着时间的推移,患有糖尿病的女性的总脑容量损失略有(不显着)更大(3.02 cc;P = 0.11),并且总缺血性病变体积显着增加(多出 9.7%;P = 0.05)。糖尿病与整体认知功能及其子领域得分较低有关。这些相对缺陷仅部分由脑容量和认知缺陷的危险因素造成。 总之,我们发现 2 型糖尿病与较小的灰色物质体积有关,但与白色物质体积无关,并且缺血性病变体积在大约 5 年的时间间隔内增加。 在第三项研究中,我们检查了 WHIMS 参与者的认知功能和脑容量与视网膜病变的关系,该样本由 511 名 65 岁及以上的女性组成,这些女性也参加了女性健康倡议视力检查研究 (WHISE)。 使用眼底摄影(2000-2002)评估视网膜病变,并使用改良的简易精神状态检查(3MSE)(1996-2007)评估随时间变化的认知表现。 视网膜病变的存在与 10 年随访期间较差的精神状态评分(平均差 = 1.01,SE:0.43)(p = 0.019)以及全脑(增大 47%,p = 0.04)和顶叶(增大 68%,p = 0.01)的缺血量更大相关。 然而,视网膜病变与区域性脑萎缩的测量结果无关。 这些发现表明,视网膜病变可能是小血管脑血管疾病的标志,可能影响认知能力和血管性大脑变化。

项目成果

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会议论文数量(0)
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Susan Resnick其他文献

Susan Resnick的其他文献

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{{ truncateString('Susan Resnick', 18)}}的其他基金

Neuroimaging Predictors Of Cognitive Change And Response To Therapy
认知变化和治疗反应的神经影像预测因子
  • 批准号:
    7963881
  • 财政年份:
  • 资助金额:
    $ 3.51万
  • 项目类别:
Early Markers of Alzheimer Disease
阿尔茨海默病的早期标志
  • 批准号:
    10913014
  • 财政年份:
  • 资助金额:
    $ 3.51万
  • 项目类别:
Basic Research In Personality: Aging
人格基础研究:衰老
  • 批准号:
    8148197
  • 财政年份:
  • 资助金额:
    $ 3.51万
  • 项目类别:
Psychosocial Predictors of Mental and Physical Health: HIV
心理和身体健康的社会心理预测因素:艾滋病毒
  • 批准号:
    8335777
  • 财政年份:
  • 资助金额:
    $ 3.51万
  • 项目类别:
Neuroimaging Predictors of Cognitive Decline, Impairment, and Resilience
认知衰退、损伤和弹性的神经影像学预测因子
  • 批准号:
    8335780
  • 财政年份:
  • 资助金额:
    $ 3.51万
  • 项目类别:
Basic Research in Personality: Molecular Genetics of Personality
人格基础研究:人格的分子遗传学
  • 批准号:
    8335783
  • 财政年份:
  • 资助金额:
    $ 3.51万
  • 项目类别:
Neuroimaging Predictors of Cognitive Decline and Impairment
认知衰退和损伤的神经影像学预测因素
  • 批准号:
    9549250
  • 财政年份:
  • 资助金额:
    $ 3.51万
  • 项目类别:
Basic Research In Personality: Aging
人格基础研究:衰老
  • 批准号:
    8736486
  • 财政年份:
  • 资助金额:
    $ 3.51万
  • 项目类别:
Basic Research In Personality: Cross-Cultural Research
人格基础研究:跨文化研究
  • 批准号:
    8552325
  • 财政年份:
  • 资助金额:
    $ 3.51万
  • 项目类别:
Early Markers of Alzheimer Disease
阿尔茨海默病的早期标志
  • 批准号:
    8931478
  • 财政年份:
  • 资助金额:
    $ 3.51万
  • 项目类别:

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