EPIDEMIOLOGY OF MENOPAUSE AND DEMENTIA IN DOWN SYNDROME

唐氏综合症中更年期和痴呆的流行病学

• 批准号: 6372120
• 负责人: NICOLE SCHUPF
• 金额: $ 55.21万
• 依托单位: INSTITUTE FOR BASIC RES IN DEV DISABIL
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-04-01 至 2003-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6372120
• 关键词: Alzheimer's disease; Downs syndrome; age difference; aging; alleles; apolipoprotein E; blood chemistry; clinical research; dementia; disease /disorder onset; disease /disorder proneness /risk; estrogens; female; genetic susceptibility; hormone regulation /control mechanism; human middle age (35-64); human subject; karyotype; longitudinal human study; menopause; menstrual cycle; mental health epidemiology; neurogenetics; neuropsychological tests; questionnaires

An epidemiologic study is proposed to test the hypothesis that reductions in estrogen, indicated by onset of menopause, are associated with onset of Alzheimer's disease (AD) in women with Down syndrome (DS). We further hypothesize that this association will be stronger in women who are genetically susceptible to AD because they carry the apolipoprotein E (apoE) epsilon4 allele. Prior studies in the general population suggest that declines in estrogen levels following menopause play an important role in the etiology AD and that the presence of the apoE epsilon4 allele is associated with earlier age at onset and increased risk of AD. The relationships between onset of menopause, apoE and onset of AD are difficult to study in women in the general population because of the extended time period between menopause and onset of AD. In contrast, women with DS have a very high risk of AD, with an average age at onset of AD between 50-55 years, 10-15 years earlier than in the general population. Thus, women with DS experience onset of AD more closely in time to onset of menopause than is typical in the general population, providing a unique cohort in which to study the relationship between menopause and AD. We hypothesize that earlier age at menopause will be associated with earlier age at onset of AD. We propose a 5-year longitudinal study of incident dementia in 350 women with DS, 45-52 years of age, followed at 18 month intervals. We will ascertain age a menopause by chart review, as menstrual cycles are regularly charted in nursing notes. We will supplement this measure with assays of reproductive hormones at each assessment. We will assess declines in cognitive and adaptive competence indicative of AD using a uniform neuropsychological test battery and neurological examination of those suspected to be affected and a sample of those not suspected, with ascertainment of other medical or psychiatric conditions that might cause dementia. We will use standardized criteria for dementia and the differential diagnosis of AD. We will determine DS karyotypes and apoE genotypes. The results of this study will provide important information about the role of estrogen in the etiology of AD and the optimal strategy for the development of clinical trials of hormone replacement therapy in women with DS.

提出一项流行病学研究来检验以下假设： 更年期开始时雌激素的减少与 患有唐氏综合症 (DS) 的女性会出现阿尔茨海默病 (AD)。 我们进一步假设这种关联在女性中会更强 因携带 AD 基因而易患 AD 的人群 载脂蛋白 E (apoE) epsilon4 等位基因。之前的一般研究 人口表明绝经后雌激素水平下降 在 AD 的病因学中起重要作用，并且 apoE epsilon4 等位基因与发病年龄较早有关 AD 风险增加。更年期开始与apoE之间的关系 一般而言，在女性中研究 AD 的发生和发病是困难的 由于绝经期和绝经期之间的时间间隔较长，人口 AD 的发作。 相比之下，患有 DS 的女性患 AD 的风险非常高， AD平均发病年龄在50-55岁、10-15岁之间 早于一般人群。 因此，有 DS 经历的女性 AD 的发病时间比典型的更年期更接近 在普通人群中，提供了一个独特的学习群体 更年期与 AD 之间的关系。 我们假设早些时候 绝经年龄与 AD 发病年龄较早有关。 我们提议对 350 名女性的痴呆症进行为期 5 年的纵向研究 DS 患者，年龄 45-52 岁，每 18 个月进行一次随访。 我们将 通过查看图表来确定更年期的年龄，因为月经周期是 定期记录在护理笔记中。 我们将补充这一措施 每次评估时均进行生殖激素测定。 我们将评估 认知和适应能力下降表明AD使用 统一的神经心理学测试电池和神经学检查 疑似受影响者和未疑似受影响者的样本， 确定其他可能的医疗或精神状况 导致痴呆症。 我们将使用痴呆症的标准化标准和 AD 的鉴别诊断。 我们将确定 DS 核型和 apoE 基因型。 这项研究的结果将提供重要信息 关于雌激素在 AD 病因学中的作用以及最佳治疗方案 激素替代临床试验的开展策略 患有 DS 的女性的治疗。