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

阿尔茨海默病危险因素在脊柱手术后认知能力下降中的作用

基本信息

批准号：
9751142
负责人：
Katie Jo Schenning
金额：
$ 11.55万
依托单位：
OREGON HEALTH & SCIENCE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-08-01 至 2021-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9751142
关键词：
Activities of Daily Living Adult Age Age-Years Aging Alleles Alzheimer&apos s Disease Alzheimer&apos s disease risk Anesthesia procedures Anesthetics Apolipoprotein E Benefits and Risks Biological COMT gene Cardiac Surgery procedures Caregivers Cause of Death Clinic Clinical Clinical Research Clinical Trials Cognition Cognitive Complication Control Groups Counseling Data Dementia Development Diagnosis Discharge Plannings Elderly Enrollment Exposure to Facilities and Administrative Costs Family Family member Functional disorder Future General Anesthesia Genes Genetic Genetic Polymorphism Genotype Goals Impaired cognition Individual Informed Consent Integrin beta3 Knowledge Learning Link Medical Care Costs Natural History Neurocognitive Neurocognitive Deficit Operative Surgical Procedures Outcome Participant Patient Self-Report Patients Perioperative Perioperative Care Phospholipase A2 Play Population Postoperative Complications Postoperative Period Predisposition Prevention Preventive Productivity Prospective Studies Prospective cohort study Public Health Recording of previous events Reporting Research Research Design Research Personnel Retrospective Studies Risk Risk Factors Role Spinal Spinal Diseases Spine surgery Testing Therapeutic United States Vertebral column Woman Work aged aging brain base biological sex cognitive change cost early onset experience functional decline functional status genetic risk factor high risk human old age (65+)individual patient innovation interdisciplinary approach longitudinal analysis men novel post-operative cognitive dysfunction prevent prospective research study secondary outcome sex study population

项目摘要

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.

项目摘要我们的长期研究目标是了解术后认知功能障碍的基础机制（POCD）和术后痴呆在老年人中，以最终防止这种并发症。总体本应用的目的是确定已知的AD风险因素是否代表POCD的危险因素。实现这些目标将使研究人员能够发展新颖的预防或治疗性策略，并将允许临床医生提供准确的知情同意，适当的咨询，以照顾者并提供针对个体老年患者量身定制的最安全的围手术期护理。神经认知功能障碍是个体最常见的术后并发症之一年龄在65岁以上的年龄，这些老年人在联合每年。几十年来，患者及其家人报告了持久的术后认知更改。但是，并非每个患有手术和麻醉史的人都会发展术后认知功能障碍（POCD），提示涉及生物危险因素。我们有重要的空白关于谁有发展POCD风险的知识。根据我们从一个从纵向老化研究的分析，我们的中心假设是生物学和存在特定的遗传多态性使老年人的认知能力下降较高的风险暴露于手术和麻醉。而回顾性研究的详细信息有限手术和麻醉，并基于对暴露的自我报告，前瞻性研究是必要的明确评估迄今为止生成的假设，并通过适当的注释和调整围手术期因子。拟议研究的前提是，术后的特定风险因素曾经确定认知功能障碍，处于危险中的个人可以作为未来的临床研究，以降低风险 POCD。我们计划通过对男女的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选修课手术的年龄。我们将追求这些具体目标：目标1：确定APOE，PLA，PDE4D或COMT中的多态性是否会增加术后的风险老年人的认知能力下降目标2：确定认知术后下降的生物性别与基因型之间的相互作用和老年人的功能状况。