Women's Health Study: Infrastructure support for continued cohort follow-up

摘要 阿尔茨海默病及相关痴呆（AD/RD）是目前广泛存在的使人衰弱的疾病 影响了超过五百万美国人在65岁时，女性患痴呆症的终生风险为21.1%。 而男性为11.6%。虽然年龄是痴呆症最有影响力的危险因素，但寿命越长， 与男性相比，女性的预期并不能完全解释老年痴呆症的患病率较高， 妇女鉴于AD/RD的负担较高，在以下人群中确定AD/RD的风险因素尤为重要： 妇女此外，越来越多的研究强调，需要检查中年风险因素， 痴呆症，特别是因为痴呆症的病理学往往在诊断前几十年就开始了。我们的首要目标是 利用现有妇女健康研究（WHS）的数据，探索一系列风险因素， AD/RD的妇女从中年到老年。该提案的目标是扩大 WHS的基础设施，使我们能够评估AD/RD的队列，最初的设计不是为了评估 这些重要而及时的问题。WHS始于1992年，是一项随机试验，测试阿司匹林，β- 胡萝卜素和维生素E的初级预防癌症和心血管疾病的39,876显然 年龄≥45岁的健康女性。自2004年试验结束以来，一直对这些妇女进行观察。 2004.截至2018年12月底，平均随访时间近24年，发病率随访 仍接近90%，随访死亡率几乎为100%。大量的数据是可用的，几十年来 每年随访一次问卷调查，内容涉及广泛的人口统计学、生活方式和病史变量。以来 参与者的平均年龄目前为77.1岁（范围为67.3至106.3岁）， 几乎所有参与者都可以使用，医疗保险和医疗补助服务中心（CMS）数据 即使参与者不愿意或无法返回研究问卷，我们建议获得， 评估CMS的数据，以确定2011年至2018年WHS参与者中的痴呆症诊断。有 没有其他可行的和具有成本效益的策略来评估痴呆症在地理上多样化的队列的大小， 的WHS。我们还将评估既定的人口统计学、生活方式、病史和 使用先前从WHS问卷和痴呆数据收集的数据进行痴呆的遗传风险因素 从CMS，并比较我们的研究结果，目前的文献。这些目标是可行的， 这份行政补充文件的时限为一年，将为我们提供关于 使用CMS数据获取WHS中AD/RD诊断信息的可行性。今后，我们将 为探索女性痴呆症的新风险因素提供资金，利用WHS广泛的 24年来收集的风险因素数据，妇女的大样本量，以及遗传数据的可用性。 WHS为我们了解癌症和心血管疾病做出了重大贡献， 我们相信WHS可以有效地用于了解女性AD/RD的危险因素。

ABSTRACT Alzheimer's disease and related dementias (AD/RD) are pervasive and debilitating diseases currently affecting over 5 million Americans. At age 65, the lifetime risk of developing dementia is 21.1% among women compared to 11.6% among men. Although age is the most influential risk factor for dementia, the greater life expectancy of women compared to men does not entirely explain the higher prevalence of dementia among women. Given the higher burden of AD/RD, it is particularly important to identify risk factors for AD/RD among women. In addition, a growing body of research underscores the need to examine midlife risk factors for dementia, especially since dementia pathology often begins decades before diagnosis. Our overarching goal is to leverage data from the existing Women's Health Study (WHS) to explore a large range of risk factors for AD/RD among women followed from middle age into old age. The goal of this proposal is to expand the infrastructure of the WHS to allow us to assess AD/RD in a cohort that was not originally designed to evaluate these important and timely questions. The WHS began in 1992 as a randomized trial testing aspirin, beta- carotene, and vitamin E for the primary prevention of cancer and cardiovascular disease in 39,876 apparently healthy women aged ≥45 years. The women have been followed observationally since the end of the trial in 2004. As of the end of December 2018, average mean follow-up was almost 24 years, with morbidity follow-up still close to 90% and mortality follow-up virtually 100%. An extensive body of data is available, with decades of yearly follow-up questionnaires on a wide range of demographic, lifestyle, and medical history variables. Since the mean age of the participants is currently 77.1 years (range 67.3 to 106.3 years), social security numbers are available on virtually all participants, and Centers for Medicare & Medicaid Services (CMS) data are available even for participants unwilling or unable to return study questionnaires, we propose to obtain and assess data from CMS to identify dementia diagnoses among WHS participants from 2011 to 2018. There is no other feasible and cost-effective strategy to assess dementia in a geographically diverse cohort the size of the WHS. We will also assess the association between established demographic, lifestyle, medical history, and genetic risk factors for dementia using previously collected data from WHS questionnaires and dementia data from CMS, and compare our findings to the current literature. These aims are feasible to accomplish within the one-year time frame of this administrative supplement and will provide us with important information on the feasibility of using CMS data to obtain information on AD/RD diagnoses in the WHS. In the future, we will apply for funding to explore novel risk factors for dementia among women, leveraging from the WHS the broad range of risk factor data collected over 24 years, the large sample size of women, and the availability of genetic data. The WHS has made substantial contributions to our understanding of cancer and cardiovascular disease, and we believe that the WHS can be effectively leveraged to understand AD/RD risk factors among women.