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: 2899799
• 负责人: NICOLE SCHUPF
• 金额: $ 52.26万
• 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/2899799
• 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来检验这一假设， 绝经期开始时雌激素减少， 与唐氏综合征（DS）女性中阿尔茨海默病（AD）的发病有关。 我们进一步假设这种关联在女性中更强 他们在遗传上易患AD，因为他们携带 载脂蛋白E（apoE）epsilon 4等位基因。以前的研究一般 研究表明绝经后雌激素水平的下降 在AD的病因学中起重要作用， apoE ε 4等位基因与较早的发病年龄相关， AD的风险增加。绝经期发病与载脂蛋白E的关系 和AD的发病是很难研究的妇女在一般情况下， 由于绝经和绝经之间的时间延长， AD的开始。 相比之下，患有DS的女性患AD的风险非常高， AD发病时的平均年龄为50-55岁，10-15岁， 比一般人群早。 因此，有DS经验的女性 AD的发病时间与绝经期的发病时间比典型的更接近 在一般人群中，提供了一个独特的队列研究， 绝经与AD的关系 我们假设早些时候 绝经年龄与AD发病年龄较早相关。 我们建议对350名女性进行为期5年的痴呆事件纵向研究 DS患者，45-52岁，每隔18个月随访一次。 我们将 确定年龄更年期图表审查，因为月经周期是 定期记录在护理记录中。 我们将补充这项措施 在每次评估时进行生殖激素测定。 我们将评估 认知能力和适应能力下降，使用 统一的神经心理学成套测验和神经系统检查 怀疑受影响的人和未被怀疑的人的样本， 确定其他可能 会导致痴呆。 我们将使用痴呆症的标准化标准， 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的信息 关于雌激素在AD病因学中的作用和最佳治疗方法， 发展激素替代临床试验的战略 治疗女性DS。