Neuroimaging Biomarkers for Post-Operative Cognitive Decline in Older Adults

老年人术后认知能力下降的神经影像生物标志物

基本信息

批准号：
8551727
负责人：
CATHERINE E PRICE
金额：
$ 47.3万
依托单位：
UNIVERSITY OF FLORIDA
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-09-27 至 2017-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8551727
关键词：
Acceleration Acute Adult Age Alzheimer&apos s Disease Analgesics Anesthesia procedures Anesthesiology Anesthetics Biological Markers Brain Cardiac Surgery procedures Caring Cerebrovascular Disorders Cerebrum Clinical Cognitive Coupled Degenerative polyarthritis Dementia Development Diffusion Disease Education Elderly Embolism Fatigue Frequencies Functional Imaging Functional disorder Funding Future Geriatrics Goals Grant Hemorrhage Hippocampus (Brain)Hospitals Hour Image Impaired cognition Impairment Intervention Learning Length Leukoaraiosis Long-Term Care Longitudinal Studies Magnetic Resonance Imaging Measurement Measures Medial Memory Methods Monitor Nerve Degeneration Neurodegenerative Disorders Neurons Neuropsychology Operative Surgical Procedures Orthopedic Surgery procedures Orthopedics Outcome Oxygen saturation measurement Pain Participant Pathology Patients Perioperative Pilot Projects Postoperative Period Predictive Value Prefrontal Cortex Price Process Protocols documentation Quality of life Relative (related person)Replacement Arthroplasty Research Resolution Risk Sample Size Scanning Screening procedure Severities Short-Term Memory Stroke Structure Testing Thalamic structure Thick Time Tourniquets Training Work age effect cognitive change cost design digital entorhinal cortex executive function experience gray matter imaging modality improved in vivo innovation insight interest knee replacement arthroplasty multidisciplinary neuroimaging neuromechanism peer prevent prospective public health relevance screening time interval white matter

项目摘要

DESCRIPTION (provided by applicant): Older adults are at increased risk for cognitive decline following major surgeries with this having implications for neurodegenerative acceleration as well as post-operative and long-term care costs. Orthopedic replacement surgeries such as total knee replacement surgery have the highest rates of cognitive decline in older adults. This is alarming, for older adults are increasingly seeking joint replacement to reduce associated osteoarthritis pain and increase activity (i.e., quality of life). Unfortunately at present there ae no specific surgical or anesthetic mechanisms for post-operative cognitive dysfunction. Results from our NIA funded pilot training grant, however, show preliminary evidence demonstrating that patients' pre-surgical brain integrity is an important indicator for post-operative outcome. We now seek to acquire definitive evidence for these markers using a larger sample size and also explore the interaction between pre-operative neuronal integrity and specific perioperative variables (e.g., anesthesia depth, emboli number). Aim 1 is to examine the integrity of the white matter regions connecting the frontal to subcortical structures and the hypothesis that patients with less deep white matter integrity will be vulnerable to post-operative executive decline. We further hypothesize that this disruption is driven by compromise to an important white matter circuit connecting the dorsolateral prefrontal cortex to the caudate (subaim 1). Aim 2 is to examine the integrity of the medial temporal structures to support the hypothesis that patients' with reduced pre-surgical hippocampal-entorhinal connectivity are vulnerable to post-operative memory decline. In Aim 3, we explore which peri-operative variables (e.g., intraoperative emboli, embolic stroke, anesthesia duration) interact negatively with baseline neuroimaging variables. These aims will be carried out by a multidisciplinary team with expertise in neuropsychology, geriatrics, dementia, post-operative cognitive dysfunction, anesthesiology, and orthopedic surgery. We will conduct a prospective longitudinal study with two groups: older adults (age > 60 years) having total knee replacement (n=80) and non-surgery age and education matched peers with osteoarthritis (n=80). Both groups will acquire baseline MRI using sophisticated diffusion and functional measures to define specific neuronal regions of interest, and complete cognitive testing at a pre-surgery/baseline time point followed by repeat testing at three weeks, three-months, and one-year post-operative/post-baseline. Participants will also acquire a repeat MRI 48 hours after their baseline scan to identify changes in brain structure (i.e., embolic stroke). Overall, the study's findings will bring us closer to understanding neural mechanisms for post- operative cognitive dysfunction, will help argue for basic pre-operative MRI screening for certain older adults, and assist us in the development of intra-operative interventions for patients with neuronal vulnerabilities.

描述（由申请人提供）：老年人在进行大量手术后的认知能力下降风险增加，这对神经退行性加速以及术后和长期护理费用具有影响。骨科替代手术（例如全膝关节置换手术）的老年人认知能力下降率最高。这令人震惊，对于老年人来说，越来越多地寻求关节替代品来减轻相关的骨关节炎疼痛并增加活动（即生活质量）。不幸的是，目前尚无针对术后认知功能障碍的特定外科手术或麻醉机制。但是，我们NIA资助的试点培训赠款的结果显示了初步证据，表明患者的手术前大脑完整性是术后结局的重要指标。现在，我们寻求使用较大样本量获得这些标记的确定证据，并探索术前神经元完整性与特定围手术期变量（例如，麻醉深度，栓子数）之间的相互作用。目的1是检查将额叶与皮层结构连接起来的白质区域的完整性，并假设白质完整性较低的患者容易受到术后执行后的下降。我们进一步假设，这种破坏是由将背外侧前额叶皮层与尾状结合的重要白质回路的妥协驱动的（Subaim 1）。目的2是检查内侧时间结构的完整性，以支持以下假设：术前海马 - 内嗅连通性降低的患者容易受到术后记忆下降的影响。在AIM 3中，我们探讨了哪些围手术变量（例如术中栓塞，栓塞式卒中，麻醉持续时间）与基线神经影像变量呈负相互作用。这些目标将由具有神经心理学，老年医学，痴呆症，术后认知功能障碍，麻醉学和骨科手术的多学科团队进行。我们将对两组进行前瞻性纵向研究：老年人（> 60岁）总膝盖置换（n = 80）和非手术年龄和教育与骨关节炎的同伴相匹配（n = 80）。这两组将使用复杂的扩散和功能措施获得基线MRI，以定义特定的神经元区域，并在术前/基线时间点上进行完全认知测试，然后在三个星期，三个月和一年的后重复测试 - 术语/基线后。参与者还将在基线扫描后48小时获得重复的MRI，以识别大脑结构的变化（即栓塞性中风）。总体而言，该研究的发现将使我们更加了解后手术后认知功能障碍的神经机制，将有助于为某些老年人的基本术前MRI筛查，并帮助我们开发针对神经元患者的术中干预措施漏洞。