EPIDEMIOLOGY OF ALZHEIMERS DEMENTIA IN CACHE COUNTY UT

我们提出了一项研究的发生阿尔茨海默氏病（AD）， 其他痴呆与基因型、年龄和其他因素有关。 绘图 在科学和技术的进步，研究寻求重要的新的 了解AD的原因和可能的预防措施。 最近的数据 显示AD和等位基因ε 4之间的关联， 载脂蛋白E（ApoE），一种多态性脂质转运蛋白。 等位基因 AD病例中ε 4的频率为0.40 - 0.50（参见大多数为0.014 人口）。 在平衡状态下，70%的AD流行病例将 至少一个ε 4等位基因（cf.占总人口的26%）。 新证据 表明ε 4足以引发AD：在家族性AD中， 家系中所有ε 4纯合子在80岁时发展为AD;杂合子 到90岁时发展为AD，并且他们的疾病表达似乎是最大的 快80岁了 因此，我们提出测试两个假设：H1）ε 4 足以引发AD，不仅在家族性AD谱系中， 在所有携带等位基因的人中 如果ε 4占AD的70% 例，并且在这种情况下疾病表达在接近80岁时最大，则： H2）AD的发病率在85岁以前最高， 然后 为了验证这些假设，我们提出了一个患病率和 在一个非常长寿和合作的人中AD的发病率分析 5650名老年人样本，将进行ApoE等位基因基因分型。 同时，我们将研究影响疾病风险的其他因素。 新的双胞胎对照研究表明，长期接触抗- 炎性药物（AI）与AD（o.r. 0.24，95% C.I. 0.07- 0.74）。 AI可以通过延迟AD的发作来起作用，但是 AD与AI的相关性仅见于特定年龄或性别 组 因此，我们建议测试三个额外的假设：H3） AI与85岁之前AD发病率降低相关;如果 风险降低是因为AI延迟了AD的发作， （令人惊讶的是）在AI暴露的人群中AD的发病率将是 85岁后增加;和H4）AI与AD风险的关系显示 与ApoE基因型以及年龄或性别的相互作用。 最后我们 将研究ApoE基因型、年龄和性别与 其他AD风险因素，如教育、头部损伤和家族史 老年痴呆症 将在第1年和第2年评估ApoE等位基因和风险因素， 确定痴呆症的疑似流行原因。 在第二年， 3一个关键的线人网络将确定痴呆症的事件病例， 将进行类似的评估。 在第4年和第5年，新一轮的筛选 和评估将确定关键未检测到的事件案例 线人然后将计算特定的发生率， 研究的每一个假设都将得到检验。

We propose a study of the occurrence of Alzheimer's disease (AD) and other dementias in relation to genotype, age and other factors. Drawing on advances in both science and technology, the study seeks important new understanding of the causes and possible prevention of AD. Recent data from several groups show association between AD and allele epsilon4 of Apolipoprotein E (ApoE), a polymorphic lipid transporter. The allele frequency for epsilon4 in AD cases is 0.40 - 0.50 (cf. 0.014 in most populations). At equilibrium, 70% of prevalent AD cases would then bear at least one epsilon4 allele (cf. 26% of most populations.) New evidence suggests that epsilon4 is sufficient to provoke AD: in familial AD pedigrees all epsilon4 homozygotes develop AD by age 80; heterozygotes develop AD by age 90, and their disease expression appears to be maximal near age 80. We therefore propose to test two hypotheses: H1) epsilon4 is sufficient to provoke AD, not only within familial AD pedigrees but in all those bearing the allele. If epsilon4 accounts for 70% of AD cases, and disease expression in such cases is maximal near age 80, then: H2) the incidence of AD will be maximal before age 85 and decline thereafter. To test these hypotheses, we propose a prevalence and incidence analysis of AD in a remarkably long-lived and cooperative sample of 5650 elders who will have been genotyped for ApoE alleles. Simultaneously, we shall study other factors that influence disease risk. New co-twin control studies suggest that chronic exposure to anti- inflammatory drugs (AI's) is inversely associated with AD (o.r. 0.24, 95% c.i. 0.07 - 0.74). AI's may act by delaying the onset of AD, but the association of AD with AI's has been seen only in certain age or sex groups. We therefore propose to test three additional hypotheses: H3) AI's are associated with reduced incidence of AD before age 85; if the reduction in risk occurs because AI's delay the onset of AD, then (surprisingly) the incidence of AD among those with AI exposure will be increased after age 85; and H4) the relation of AI's to AD risk shows interaction with ApoE genotype, and with age or gender. Finally, we shall examine similar interactions of ApoE genotype, age and gender with other AD risk factors such as education, head injury, and family history of dementia. ApoE alleles and risk factors will be assessed in Years 1 and 2, as suspected prevalent causes of dementia are identified. In Years 2 and 3 a key informant network will identify incident cases of dementia who will be similarly evaluated. In Years 4 and 5 a new wave of screening and assessment will identify incident cases not detected by the key informants. Age-specific incidence rates will then be calculated, and each of the study's hypotheses will be tested.