The apolipoprotein E epsilon4 allele and memory performance in HIV-1 seropositive subjects: differences at baseline but not after acute oral lorazepam challenge.
The apolipoprotein E epsilon4 allele and memory performance in HIV-1 seropositive subjects: differences at baseline but not after acute oral lorazepam challenge.
复制标题
HIV-1 血清阳性受试者的载脂蛋白 E epsilon4 等位基因和记忆表现：基线时有差异，但急性口服劳拉西泮激发后没有差异。
DOI：
10.1007/s00213-008-1253-1
复制
发表时间：
2008
影响因子：
3.4
通讯作者：
Sidtis,JohnJ
中科院分区：
文献类型：
--
作者：
Pomara,Nunzio;Belzer,KennethD;Silva,Raul;Cooper,ThomasB;Sidtis,JohnJ
APOE β 4等位基因是晚发性阿尔茨海默病的一个既定遗传风险因素，与痴呆风险增加有关，特别是在感染HIV-1的老年人中。该等位基因也与健康老年人口服劳拉西泮后记忆障碍增加相关。劳拉西泮和其他苯二氮卓类药物被广泛用于HIV-1感染的个体，这些个体的认知障碍风险增加。本研究的目的是检查在这一人群中是否有α 4等位基因影响劳拉西泮诱导的记忆缺陷。（15 - 14例携带者，平均年龄= 43.47 ± 8.25; 26 - 14例非携带者，平均年龄= 46.77 ± 8.56）参与了一项双盲、安慰剂对照的交叉设计，接受单次急性口服剂量的劳拉西泮0.5、1.0 mg或安慰剂，分3次给药，每次间隔1周。标准化的神经心理学评估，包括立即和延迟的口头回忆的措施，在基线和在1，2.5，和5小时后，在每个conditions.ResultsAcute劳拉西泮给药产生剂量和时间依赖性损害的口头回忆的措施。然而，e4等位基因没有调节这些不良反应。还发现APOE-β 4组与时间的相互作用，使得APOE-β 4阳性受试者在基线评估时比阴性受试者具有显著更好的即时和延迟言语回忆，但各组在随后的任何时间点均无显著差异。特别是在感染HIV-1的老年人中，这是一个患痴呆症风险增加的群体。
RationaleThe APOE ɛ4 allele, an established genetic risk factor for late-onset Alzheimer’s disease, has been linked to an increased risk for dementia especially in older individuals with HIV-1 infection. This allele has also been associated with increased memory impairment following oral lorazepam challenge in healthy elderly. Lorazepam and other benzodiazepines are widely prescribed in individuals with HIV-1 infection who are at increased risk for cognitive impairment.ObjectiveThe aim of this study was to examine if the ɛ4 allele influences lorazepam-induced memory deficits in this population.Materials and methodsForty-one non-demented, HIV-1 seropositive adults (15 ɛ4 carriers, mean age = 43.47 ± 8.25; 26 ɛ4 non-carriers, mean age = 46.77 ± 8.56) participated in a double-blind, placebo-controlled crossover design, receiving single acute oral doses of lorazepam 0.5, 1.0 mg, or placebo over three sessions, each 1 week apart. Standardized neuropsychological assessments, including measures of immediate and delayed verbal recall, were conducted at baseline and at 1, 2.5, and 5 h post-drug administration in each condition.ResultsAcute lorazepam administration produced dose- and time-dependent impairments in measures of verbal recall. However, the e4 allele did not modulate these adverse effects. An APOE ɛ4 group by time interaction was also found such that the APOE-ɛ4-positive subjects had significantly better immediate and delayed verbal recall than the negative subjects at baseline assessment, but the groups did not significantly differ at any subsequent time point.ConclusionFuture studies should clarify the role of ɛ4 in the modulation of drug-induced cognitive toxicity and baseline performance and their relationship to progressive decline, especially in older individuals with HIV-1 infection, a group at increased risk for dementia.