APOE E4 AND LORAZEPAM EFFECTS ON ELDERLY

这将是相当有价值的发展预测 老年人对药物引起的认知毒性的易感性， 中枢作用药物，如苯二氮卓类，继续 在这一人群和老年人中广泛使用 可能对某些不利的中枢效应更敏感。 此外，正常的与年龄相关的认知功能下降可能 强调药物引起的缺陷的重要性。 我们的初步数据来自研究的急性影响， 各种苯二氮卓类药物（地西泮、阿普唑仑和劳拉西泮） 对认知完整的正常志愿者的表现表明， 携带ApoE-oplison 4等位基因可能增加易感性 药物引起的认知毒性 布施克总数和延迟 在携带oplison 4等位基因的受试者中， 没有这个等位基因的人 这种损伤与 而opsilon 4等位基因的存在被发现，尽管 研究中纳入了较年轻的受试者，且仅1例受试者 纯合子的e4等位基因，在一组参与者谁是 不是根据阿尔茨海默病家族史选择的 （AD）。 拟议中的研究将更直接地评估 ε 4等位基因与增加的易感性相关， 认知功能正常老年人药物性认知毒性 人士 我们将研究其中一种 苯并二氮卓类药物在最有可能导致 opsilon 4等位基因对脑功能的影响：老年人， 非痴呆的认知完整的个体， 一级亲属中有记录的AD病史， ε 4等位基因纯合子（ApoE ε 4/ε 4 基因型）。 他们将与一个适当的， 年龄匹配的对照组，无ε 4等位基因。

It would be of considerable value to develop predictoors of susceptibility to drug-induced cognitive toxicity in the elderly, since centrally acting medications, such as the benzodiazepines, continue to be widely prescribed in this population and older individuals may be more sensitive to some of the adverse central effects. Moreover, normal age-related decline in cognitive functions may accentuate the significance of drug-induced deficits. Our preliminary data from studies examining the acute effects of various benzodiazepines (diazepam, alprazolam, and lorazepam) on performance of cognitively intact normal volunteers suggest that possession of the ApoE-oplison4 allele may increase susceptibility to drug-induced cognitive toxicity. Buschke total and delayed recall were imparied in subjects with the oplison4 allele but not in those without this allele. This relationship between impairment and the presence of the opsilon4 allele was found despite the inclusion of younger subjects in the study, and only one subject homozygous for the e4 allele, in a group of participants who were not selected on the basis of family history of Alzheimer's disease (AD). The proposed research will more directly assess whether the epsilon4 allele is associated with increased susceptibility to drug-induced cognitive toxicity in normal cognitively intact older persons. We will study the cognitive effects of one of the benzodiazepines in the population most at risk for the deleterious effects of the opsilon4 allele on brain function: older, non-demented cognitively intact individuals who have a documented history of AD in a first degree relative and are homozygous for the epsilon4 allele (ApoE epsilon4/epsilon4 genotype). They will be compared with an appropriate, age-matched control group without the epsilon4 allele.