The role of Alzheimer's risk factors in cognitive decline after spine surgery

项目总结 我们的长期研究目标是了解术后认知功能障碍的机制。 对老年人的POCD和术后痴呆症进行治疗，以最终预防这一并发症。整体而言 本应用的目的是确定已知的AD危险因素是否代表POCD的危险因素。 这些目标的实现将使研究人员能够朝着开发新的预防或治疗方法迈进 战略，并将允许临床医生提供准确的知情同意，适当的咨询照顾者， 并为老年患者个体量身定做最安全的围手术期护理。 神经认知功能障碍是个人最常见的术后并发症之一。 65岁及以上，而这些老年人占美国外科患者的三分之一以上 每年都有。几十年来，患者和他们的家人都报告了持续的术后认知 改变。然而，并不是每个有手术和麻醉史的人都会发展术后认知能力。 功能障碍(POCD)，表明生物危险因素参与其中。在我们的国家中有很大的差距 关于谁有患POCD的风险的知识。根据我们从一个 对纵向衰老研究的分析，我们的中心假设是生物学性别和存在 特定的基因多态性使老年人在以下情况下面临更高的认知能力减退风险 暴露在手术和麻醉下。虽然回溯性研究在以下方面的细节方面有限 手术和麻醉，以及基于自我报告的暴露，前瞻性研究是必要的 最终评估到目前为止产生的假设，并对其进行适当的注释和调整 围手术期因素。建议研究的前提是，一旦特定的危险因素对术后 认知功能障碍被识别，高危个体可以作为未来临床研究的目标，以降低风险 是POCD的。我们计划通过对至少65名男性和女性进行前瞻性队列研究来检验我们的中心假设 在全身麻醉下接受择期脊柱手术的患者。我们会致力达致以下具体目标： 目的1：确定载脂蛋白E、聚乳酸、PDE4D或COMT基因多态性是否会增加术后风险 老年人认知功能减退 目的2：确定生物性别和基因对术后认知功能下降的交互作用 以及老年人的功能状态。

PROJECT SUMMARY Our long-term research goal is to understand the mechanisms underlying postoperative cognitive dysfunction (POCD) and postoperative dementia in older adults in order to ultimately prevent this complication. The overall objective of this application is to determine whether known AD risk factors represent risk factors for POCD. Realization of these goals will enable researchers to move toward developing novel preventive or therapeutic strategies, and will allow clinicians to provide accurate informed consent, appropriate counseling to caregivers, and deliver the safest perioperative care tailored to the individual geriatric patient. Neurocognitive dysfunction is one of the most common postoperative complications experienced by individuals aged 65 years and older, and these older adults comprise more than 1/3 of the surgical patients in the United States each year. For decades, patients and their families have reported lasting postoperative cognitive changes. However, not everyone with a history of surgery and anesthesia develops postoperative cognitive dysfunction (POCD), suggesting biological risk factors are involved. There are important gaps in our knowledge regarding who is at risk for developing POCD. Based on our preliminary data obtained from an analysis of longitudinal aging studies, our central hypothesis is that both biological sex and presence of specific genetic polymorphisms place older adults at higher risk for accelerated cognitive decline following exposure to surgery and anesthesia. While retrospective studies are limited in terms of details regarding surgery and anesthesia, and are based on self-report of exposures, a prospective study is necessary to more definitively evaluate the hypotheses generated to date with appropriate annotation of and adjustment for perioperative factors. The premise of the proposed research is that once specific risk factors for postoperative cognitive dysfunction are identified, at-risk individuals can be targeted for future clinical studies to reduce risk of POCD. We plan to test our central hypothesis with a prospective cohort study of men and women at least 65 years old who undergo elective spine surgery under general anesthesia. We will pursue these specific aims: Aim 1: Determine whether polymorphisms in APOE, PLA, PDE4D, or COMT increase the risk of postoperative cognitive decline in older adults Aim 2: Determine the interaction between biological sex and genotype on postoperative decline in cognition and functional status in older adults.