GENETIC BASIS OF COGNITIVE DECLINE AFTER SUGERY

描述：认知功能障碍经常发生在手术后， 每年约有40万患者接受心脏手术。 认知功能障碍在心脏病后的早期阶段最为明显。 手术，但持久性发生在一个重要的百分比的患者。 研究小组的成员发现， 晚发性阿尔茨海默病和载脂蛋白E（APOE e-4）基因。 这一发现引发了许多最近的研究，这些研究表明， 载脂蛋白E在确定急性脑梗死相关神经损伤中的作用 缺血性损伤，包括明显更高的死亡率和减少 脑出血患者的功能恢复， APOE e-4等位基因。 载脂蛋白E似乎编码的蛋白质发挥重要作用， 在确定缺血损伤后细胞恢复或死亡中的作用。 研究人员提出，由这种基因编码的生化产物 无法保护和修复中枢神经系统的神经元 心脏手术期间系统的缺陷导致记忆力，注意力， 和专注 试点数据报告支持的假设 APOE e-4与心脏手术后认知障碍的相关性 研究人员将用一个前瞻性、纵向、 一项评估APOE基因型与术后 认知障碍 患者将接受基线（术前） 神经学和心理测量学测试，旨在评估记忆力和其他 认知功能 神经系统评估将在三到五分钟后重复进行。 术后5天，在6周时重复进行心理测量测试 术后1年。 一组血管成形术患者随后 纵向相同的测试将允许研究者 将手术的影响与认知能力的潜在下降分开， 与e-4等位基因相关。 中心假设将通过以下方式进行检验： 使用心理测试分数的变化作为因变量， 以APOE e-4作为多个模型之一的多重协方差分析模型 协变量 如果发现基因型预测了认知能力的丧失， 将使医生能够识别患者可能有术后 认知缺陷 它是认知功能障碍的统一机制， 也就是说，神经元损伤的发生是因为缺乏正常的 神经元对各种缺血性损伤的维持或修复反应 心肺转流术期间的损伤。 这些新知识将提供 基因或药物治疗的前景，以防止这一非常令人不安的 心脏手术对中枢神经系统的影响 康复期病人

DESCRIPTION: Cognitive impairment occurs frequently after surgery in the approximately 400,000 patients who undergo cardiac operations each year. Cognitive impairment is most notable in the early phases after cardiac surgery, but persistence occurs in an important percentage of patients. Members of the investigators' group have found a genetic association between late-onset Alzheimer's disease and the apolipoprotein E (APOE e-4) gene. This finding triggered many recent studies which have shown an important role of APOE in the determination of neurologic injury associated with acute ischemic insults, including a markedly greater mortality and reduction in functional recovery in intracerebral hemorrhage patients who possess the APOE e-4 allele. APOE appears to code for proteins that play a significant role in determination of cellular recovery or demise after ischemic insults. The investigators propose that the biochemical products coded by this gene are not available to protect and repair the neurons of the central nervous system during cardiac surgery resulting in deficits of memory, attention, and concentration. Pilot data are reported that support the hypothesis associating APOE e-4 with cognitive impairment after cardiac surgery. The investigators will test this hypothesis with a prospective, longitudinal study evaluating the association of APOE genotype and postoperative cognitive impairment. Patients will undergo baseline (preoperative) neurologic and psychometric testing designed to evaluate memory and other cognitive functions. Neurologic evaluation will be repeated at three to five days postoperatively, with psychometric testing repeated at six weeks and one year postoperatively. A group of angioplasty patients followed longitudinally with the same testing will allow the investigators to separate the impact of surgery from potential declines in cognition associated with the e-4 allele. The central hypothesis will be tested by using change in psychometric test scores as a dependent variable in a multiple analysis of covariance model with APOE e-4 as one of several covariates. If it is found that genotype predicts loss of cognition, this will enable physicians to identify patients likely to have postoperative cognitive deficits. It is a unifying mechanism of cognitive dysfunction, that is, that neuronal damage occurs because of the lack of a normal neuronal maintenance or reparative response to the variety of ischemic insults during cardiopulmonary bypass. This new knowledge would provide future promise of gene or drug therapy to prevent this very disturbing central nervous system consequence of cardiac surgery in otherwise healthy convalescent patients.