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: 6169554
• 负责人: NICOLE SCHUPF
• 金额: $ 53.72万
• 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/6169554
• 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.

有人建议进行一项流行病学研究，以检验这一假设 雌激素的减少与绝经期的开始有关 与唐氏综合征(DS)女性阿尔茨海默病(AD)的发病有关。 我们进一步假设，这种关联在女性中会更强 他们遗传上易患阿尔茨海默病，因为他们携带 载脂蛋白E(ApoE)epsilon 4等位基因。前人的研究概况 人群提示绝经后雌激素水平下降 在阿尔茨海默病的病因中起着重要作用 APOE-epsilon 4等位基因与发病年龄较早和 阿尔茨海默病风险增加。绝经开始时间与载脂蛋白E的关系 和阿尔茨海默病的发病在一般女性中很难研究 人口，因为绝经期和 阿尔茨海默病发作。相比之下，患有DS的女性患AD的风险非常高， 平均发病年龄在50-55岁、10-15岁之间 比普通人群更早。因此，有DS经历的女性 阿尔茨海默病的发病时间比典型的更年期更接近绝经 在普通人群中，提供了一个独特的研究队列 更年期与阿尔茨海默病的关系。我们早些时候假设 绝经年龄与AD发病年龄较早有关。 我们建议对350名女性进行为期5年的痴呆症事件纵向研究。 DS患者，年龄45-52岁，每隔18个月复查一次。我们会 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。我们将对这一措施进行补充 每次评估都要进行生殖激素检测。我们将评估 阿尔茨海默病患者认知和适应能力下降 统一的神经心理测试组合和神经学检查 怀疑受影响的人和未怀疑的人的样本， 确定可能存在的其他身体或精神状况 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。我们将测定DS核型和载脂蛋白E 基因分型。这项研究的结果将提供重要信息 雌激素在阿尔茨海默病发病机制中的作用及优化 激素替代临床试验的发展策略 女性DS患者的治疗。