Guo Z, Cupples L A, Kurz A, Auerbach S H, Volicer L, Chui H, Green R C, Sadovnick A D, Duara R, DeCarli C, Johnson K, Go R C, Growdon J H, Haines J L, Kukull W A, Farrer L A
Department of Medicine, Boston University School of Medicine, MA 02118, USA.
Neurology. 2000 Mar 28;54(6):1316-23. doi: 10.1212/wnl.54.6.1316.
It has been suggested in some studies that head injury is a risk factor for AD, and that this risk is heightened among carriers of the APOE-epsilon4 allele. We examined the effects of head injury and APOE genotype on AD risk in a large family study.
A total of 2,233 probands who met criteria for probable or definite AD and their 14,668 first-degree family members (4,465 parents, 7,694 siblings, and 2,509 spouses) were ascertained at 13 centers in the United States, Canada, and Germany participating in the MIRAGE (Multi-Institutional Research in Alzheimer Genetic Epidemiology) project. Information on head injury was collected by interview of multiple informants and review of medical records. Nondemented relatives and spouses served as control subjects for this study.
Odds of AD for head trauma with or without loss of consciousness were computed by comparing probands with unaffected spouses using conditional logistic regression analysis. To account for the unique biologic relationship between probands and their parents and siblings, odds of AD were computed using a generalized estimating equation (GEE) Poisson regression approach. GEE logistic regression was used to examine the joint effects of APOE genotype and head injury on the odds of AD in probands and a control group comprised of unaffected siblings and spouses.
Comparison of probands with their unaffected spouses yielded odds ratios for AD of 9.9 (95% CI, 6.5 to 15.1) for head injury with loss of consciousness and 3.1 (2.3 to 4.0) for head injury without loss of consciousness. The corresponding odds derived from the comparison of probands with their parents and sibs were 4.0 (2.9 to 5.5) for head injury with loss of consciousness and 2.0 (1.5 to 2.7) for head injury without loss of consciousness. Head injury without loss of consciousness did not significantly increase the risk of AD in spouses (OR = 1.3; 95% CI, 0.4 to 4.1). The joint effects of head injury and APOE genotype were evaluated in a subsample of 942 probands and 327 controls (spouses and siblings). Head injury increased the odds of AD to a greater extent among those lacking epsilon4 (OR = 3.3) than among epsilon4 heterozygotes (OR = 1.8) or homozygotes (OR = 1.3).
Head injury is a risk factor for AD. The magnitude of the risk is proportional to severity and heightened among first-degree relatives of AD patients. The influence of head injury on the risk of AD appears to be greater among persons lacking APOE-epsilon4 compared with those having one or two epsilon4 alleles, suggesting that these risk factors may have a common biologic underpinning.
一些研究表明，头部损伤是患阿尔茨海默病（AD）的一个风险因素，并且在载脂蛋白E-ε4等位基因携带者中这种风险会增加。我们在一项大型家族研究中考察了头部损伤和APOE基因型对AD风险的影响。
在美国、加拿大和德国的13个中心确定了总共2233名符合可能或确诊AD标准的先证者及其14668名一级家庭成员（4465名父母、7694名兄弟姐妹和2509名配偶），这些中心参与了MIRAGE（阿尔茨海默病遗传流行病学多机构研究）项目。通过对多名 informant 的访谈和病历审查收集头部损伤的信息。未患痴呆的亲属和配偶作为本研究的对照对象。
通过使用条件逻辑回归分析比较先证者与未受影响的配偶，计算有无意识丧失的头部创伤患AD的比值比。为了考虑先证者与其父母和兄弟姐妹之间独特的生物学关系，使用广义估计方程（GEE）泊松回归方法计算患AD的比值比。使用GEE逻辑回归来考察APOE基因型和头部损伤对先证者以及由未受影响的兄弟姐妹和配偶组成的对照组患AD比值的联合影响。
先证者与其未受影响的配偶比较，有意识丧失的头部损伤患AD的比值比为9.9（95%可信区间，6.5至15.1），无意识丧失的头部损伤患AD的比值比为3.1（2.3至4.0）。先证者与其父母和兄弟姐妹比较得出的相应比值比，有意识丧失的头部损伤为4.0（2.9至5.5），无意识丧失的头部损伤为2.0（1.5至2.7）。无意识丧失的头部损伤在配偶中并未显著增加患AD的风险（比值比 = 1.3；95%可信区间，0.4至4.1）。在942名先证者和327名对照（配偶和兄弟姐妹）的子样本中评估了头部损伤和APOE基因型的联合影响。头部损伤在缺乏ε4的人群中比在ε4杂合子（比值比 = 1.8）或纯合子（比值比 = 1.3）中更能增加患AD的几率（比值比 = 3.3）。
头部损伤是患AD的一个风险因素。风险程度与严重程度成正比，且在AD患者的一级亲属中更高。与有一个或两个ε4等位基因的人相比，头部损伤对缺乏APOE-ε4的人患AD风险的影响似乎更大，这表明这些风险因素可能有共同的生物学基础。
