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.

提出了一项流行病学研究，以检验以下假设。 更年期发作指示的雌激素的减少是相关的 唐氏综合症女性（DS）的阿尔茨海默氏病（AD）发作。 我们进一步假设这种关联在女性中会更强 谁在遗传上容易受到广告的影响，因为他们携带 载脂蛋白E（APOE）Epsilon4等位基因。一般研究 人口表明更年期后雌激素水平下降 在病因学广告中起重要作用，并且存在 Apoe epsilon4等位基因在发病时与早年相关 AD的风险增加。更年期发作之间的关系，apoe 在一般女性中，广告的发作很难研究 由于更年期和 广告发作。 相比之下，患有DS的妇女的广告风险很高， AD发病的平均年龄在50-55岁，10-15岁之间 比普通人群早。 因此，具有DS经验的女性 广告的发作在更年期的及时发作比典型的发作更紧密 在一般人群中，提供一个独特的人群来研究 更年期和广告之间的关系。 我们假设了这一点 更年期的年龄将与AD发作时的较早年龄有关。 我们提出了一项为期5年的350名女性痴呆症的纵向研究 DS，45-52岁，随后以18个月的间隔。 我们将 确定年龄逐图评审，因为月经周期是 定期在护理笔记中绘制。 我们将补充这项措施 在每种评估时进行生殖激素的测定。 我们将评估 使用A表示AD的认知和适应能力的下降 统一的神经心理测试电池和神经系统检查 那些怀疑受到影响的人，以及那些没有怀疑的人的样本， 确定其他可能的医学或精神病状况 导致痴呆症。 我们将使用痴呆症的标准标准和 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病因和最佳的病因中的作用 制定激素替代临床试验的策略 DS女性的治疗。