How heritable is Alzheimer's disease late in life? Findings from Swedish twins
How heritable is Alzheimer's disease late in life? Findings from Swedish twins
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DOI：
10.1002/ana.10999
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发表时间：
2004-02-01
影响因子：
11.2
通讯作者：
Johansson, B
中科院分区：
文献类型：
--
作者：
Pedersen, NL;Gatz, M;Johansson, B
虽然已知遗传效应对早发性阿尔茨海默病很重要，但关于遗传效应对晚发性疾病的重要性知之甚少。此外，以前的研究是基于流行病例。我们的目的是描述遗传和环境因素对老年痴呆症发病的相对重要性，并测试不同年龄遗传效应的重要性差异。研究人员对662对年龄在52岁至98岁之间的瑞典双胞胎进行了平均5年的随访。通过使用认知测试或电话筛查，随后进行痴呆检查，以2至3年的间隔进行随访，检测出痴呆事件。医生、心理学家和护士给出了一致的诊断。在随访期间，5.8%的样本被诊断患有阿尔茨海默病。平均发病年龄为83.9岁（标准差为6.3）。在26对至少有一个双胞胎患阿尔茨海默病的同卵对中，5对是一致的（先证者一致性，32.2%）。双合子对的一致率为8.7%（44对中的2对）。结构模型拟合表明，48%的阿尔茨海默病易感性的变化可以归因于遗传变异。在基线时，年龄小于80岁的双胞胎和年龄大于80岁的双胞胎之间的估计值没有显著差异。虽然这些对偶发疾病的遗传估计值低于对流行疾病的估计值，但遗传因素对阿尔茨海默病易感性的重要性即使在晚年也是相当大的。
Although genetic effects are known to be important for early onset Alzheimer's disease, little is known about the importance of genetic effects for late-onset disease. Furthermore, previous studies are based on prevalent cases. Our purpose was to characterize the relative importance of genetic and environmental factors for incident Alzheimer's disease late in life, and to test for differences in the importance of genetic effects at different ages. A cohort of 662 pairs of Swedish twins 52 to 98 years of age who were without symptoms of dementia was followed up for an average of 5 years. Incident dementia cases were detected through follow-up at 2 to 3-year intervals using either cognitive testing or telephone screening followed by dementia workups. A physician, psychologist, and nurse gave consensus diagnoses. During the follow-up period, 5.8% of the sample was diagnosed with Alzheimer's disease. Average age of onset was 83.9 years (standard deviation, 6.3). Of the 26 monozygotic pairs in which at least one twin developed Alzheimer's disease, 5 were concordant (probandwise concordance, 32.2%). The concordance rate for dizygotic pairs was 8.7% (2 of 44 pairs). Structural model fitting indicated that 48% of the variation in liability to Alzheimer's disease could be attributed to genetic variation. Estimates did not differ significantly between twins younger than age 80 years and those older than age 80 years at baseline. Although these genetic estimates for incident disease are lower than those for prevalent disease, the importance of genetic factors for liability to Alzheimer's disease is considerable even late in life.