Cortical Beta-amyloid Levels and Neurocognitive Performance After Cardiac Surgery

心脏手术后皮质 β-淀粉样蛋白水平和神经认知功能

• 批准号: 8306387
• 负责人: Joseph P Mathew
• 金额: $ 23.55万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-25 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8306387
• 关键词: Affinity; Age; Alzheimer' s Disease; Amyloid; Amyloid Fibrils; Amyloid beta-Protein; Amyloid deposition; Anesthesia procedures; Atherosclerosis; Brain; Cardiac; Cardiac Surgery procedures; Cardiopulmonary Bypass; Cerebral Emboli; Cerebrum; Clinic; Clinical; Cognitive deficits; Complication; Cross-Sectional Studies; Elderly; Event; Family; Functional Imaging; Functional disorder; Genotype; Half-Life; Image; Impaired cognition; Impairment; Incidence; Investigation; Lead; Life; Link; Maps; Memory; Nervous System Trauma; Neurocognitive; Neurologic; Neurological outcome; Neurons; Operative Surgical Procedures; Organ; Outcome; Outcomes Research; Patients; Pattern; Performance; Perioperative; Pharmacology; Phase; Pittsburgh Compound-B; Population; Positron-Emission Tomography; Postoperative Period; Prevention; Process; Quality of life; Relative (related person); Research Proposals; Risk; Role; Senile Plaques; Stroke; System; Technology; Tracer; aged; amyloid pathology; beta amyloid pathology; cardiovascular risk factor; functional loss; gray matter; health care delivery; improved; in vivo; insight; mild neurocognitive impairment; molecular imaging; mortality; multidisciplinary; neocortical; older patient; operation; prevent; uptake

DESCRIPTION (provided by applicant): Cognitive impairment after surgery occurs frequently in the large number of increasingly elderly patients undergoing cardiac surgery every year. Postoperative cognitive deficit (POCD) is present in 36-50% of patients in the early phases after surgery and has been shown to adversely impact quality of life as much as one year after surgery. The objective of our multidisciplinary Neurological Outcome Research Group is to understand the mechanisms underlying neurologic and neurocognitive dysfunction after cardiac surgery and to reduce the incidence of these devastating outcomes. Despite substantial advancement in technology, pharmacology, and perioperative organ protection leading to reductions in mortality associated with cardiac surgery, the incidence of POCD has changed little over the last ten years. While multiple etiologic factors have been proposed for this neurological injury including cerebral embolic processes and hypoperfusion, the role of brain amyloid burden has never been examined. Because cardiac surgery generally takes place in the aged, it is possible that the cognitive dysfunction seen in surgical patients is a form of mild cognitive impairment (MCI), a condition characterized by accumulation of amyloid beta-fibrils. Thus the primary aim of our study is to determine the relationship between b-amyloid deposition and POCD using positron emission tomography (PET) and a newer PET tracer with a high affinity for b-amyloid fibrils. Secondarily, we will assess regional patterns of amyloid deposition in patients with POCD and compare these patterns with a previously imaged group of 40 MCI subjects and 40 elderly controls. Little is more devastating to a patient or the patient's family than to have a successful operation that prolongs life, but is complicated by cognitive impairment resulting in a diminished quality of life and loss of functional independence. The results of our study will be invaluable to the prevention of POCD in that we will define the role of regional amyloid burden in POCD using functional imaging markers that reveal the earliest neuronal changes and thus generate new mechanistic insights.

描述（申请人提供）：手术后的认知障碍经常发生在每年接受心脏手术的日益老年患者中。术后认知缺陷（POCD）在手术后的早期患者中存在于36-50％的患者中，并且已被证明会在手术后一年内对生活质量产生不利影响。我们的多学科神经系统结果研究小组的目的是了解心脏手术后神经系统和神经认知功能障碍的机制，并降低这些破坏性结果的发生率。尽管技术，药理学和围手术器官保护的大幅进步导致与心脏手术相关的死亡率降低，但在过去的十年中，POCD的发生率几乎没有改变。尽管已经提出了有关这种神经系统损伤的多种病因因素，包括脑栓塞过程和灌注不足，但从未研究过脑淀粉样蛋白负担的作用。由于心脏手术通常发生在老年人中，因此在手术患者中看到的认知功能障碍可能是一种轻度认知障碍（MCI），这种疾病以淀粉样β-纤维的积累为特征。因此，我们研究的主要目的是使用正电子发射断层扫描（PET）和更新的宠物示踪剂来确定B淀粉样蛋白沉积与POCD之间的关系，对B-淀粉样纤维纤维具有很高的亲和力。其次，我们将评估POCD患者淀粉样蛋白沉积的区域模式，并将这些模式与先前成像的40名MCI受试者和40个老年对照组进行比较。对患者或患者的家庭来说，几乎没有什么比成功延长寿命的操作更具毁灭性的，但是由于认知障碍而变得复杂，从而导致生活质量下降和功能独立性丧失。我们的研究结果对于预防POCD将是无价的，因为我们将使用功能成像标记物来定义POCD区域淀粉样蛋白负担的作用，该功能成像标记揭示了最早的神经元变化，从而产生了新的机械见解。