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

• 批准号: 8472259
• 负责人: CATHERINE E PRICE
• 金额: $ 51.21万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 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/8472259
• 关键词: Acceleration; Acute; Adult; Age; Alzheimer' 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; time interval; white matter

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. PUBLIC HEALTH RELEVANCE: Older adults are at increased risk for experiencing acute and long-term cognitive after major non-cardiac surgery such as total knee replacement. Other than the effect of age alone, there are no known mechanisms for this risk. This is alarming, for post operative cognitive dysfunction represents a form of un-necessary cognitive decline that may accelerate neurodegenerative processes. Our team will use sophisticated methodological approaches to assess hypotheses regarding the predictive value of presurgery neuroimaging biomarkers on type of post-operative cognitive decline after total knee replacement. Patients (n=160) and non- surgery peers (n=80) will be assessed in a longitudinal study examining neuroimaging predictors of change at three-weeks, three-months, and one-year post surgery/post baseline. The long-term goals of our team are to 1) identify preoperative variables that increase risk for acute and irreversible cognitive decline after surgery and 2) use this information to design peri-operative interventions for patients with specific neuronal risk profile.

描述（由申请人提供）：大型手术后，老年人认知能力下降的风险增加，这对神经退行性加速以及术后和长期护理费用产生影响。全膝关节置换手术等骨科置换手术对老年人的认知能力下降率最高。这是令人震惊的，因为老年人越来越多地寻求关节置换术以减少相关的骨关节炎疼痛并增加活动（即生活质量）。不幸的是，目前还没有针对术后认知功能障碍的具体手术或麻醉机制。然而，我们 NIA 资助的试点培训拨款的结果显示，初步证据表明患者术前大脑完整性是术后结果的重要指标。我们现在寻求使用更大的样本量来获取这些标志物的明确证据，并探索术前神经元完整性和特定围手术期变量（例如麻醉深度、栓子数量）之间的相互作用。目标 1 是检查连接额叶和皮质下结构的白质区域的完整性，并假设深层白质完整性较差的患者容易遭受术后执行能力下降。我们进一步假设这种破坏是由连接背外侧前额叶皮层和尾状核的重要白质回路（subaim 1）的妥协所驱动的。目标 2 是检查内侧颞叶结构的完整性，以支持术前海马-内嗅连接减少的患者容易遭受术后记忆衰退的假设。在目标 3 中，我们探讨了哪些围手术期变量（例如术中栓塞、栓塞性卒中、麻醉持续时间）与基线神经影像学变量产生负相互作用。这些目标将由一个多学科团队来实现，该团队拥有神经心理学、老年病学、痴呆症、术后认知功能障碍、麻醉学和骨科手术方面的专业知识。我们将对两组进行前瞻性纵向研究：接受全膝关节置换术的老年人（年龄 > 60 岁）（n = 80）和非手术年龄和教育程度匹配的骨关节炎同龄人（n = 80）。两组都将使用复杂的扩散和功能测量来获取基线 MRI，以确定感兴趣的特定神经元区域，并在手术前/基线时间点完成认知测试，然后在术后三周、三个月和一年重复测试-手术/基线后。参与者还将在基线扫描 48 小时后重复进行 MRI 扫描，以识别大脑结构的变化（即栓塞性中风）。总体而言，该研究的结果将使我们更深入地了解术后认知功能障碍的神经机制，将有助于为某些老年人进行基本的术前 MRI 筛查，并帮助我们为神经元功能障碍患者制定术中干预措施。漏洞。 公共卫生相关性：老年人在进行全膝关节置换等重大非心脏手术后，出现急性和长期认知障碍的风险增加。除了年龄本身的影响外，这种风险尚无已知的机制。这是令人震惊的，因为术后认知功能障碍代表了一种不必要的认知下降，可能会加速神经退行性过程。我们的团队将使用复杂的方法来评估有关术前神经影像生物标志物对全膝关节置换术后认知能力下降类型的预测价值的假设。将在一项纵向研究中对患者 (n=160) 和非手术同伴 (n=80) 进行评估，检查手术后/基线后三周、三个月和一年的神经影像学预测变化。我们团队的长期目标是 1) 确定术前变量，这些变量会增加术后急性和不可逆认知能力下降的风险，2) 利用这些信息为具有特定神经元风险状况的患者设计围手术期干预措施。