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: 8095975
• 负责人: Joseph P Mathew
• 金额: $ 19.63万
• 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 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8095975
• 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. PUBLIC HEALTH RELEVANCE: Cognitive impairment is a common complication of cardiac surgery. In this research proposal, we plan to determine the relationship between brain amyloid plaque formation and postoperative cognitive dysfunction. Understanding this relationship may generate new treatments to prevent cognitive decline and thus improve quality of life and functional independence for the large number of elderly surgical patients.

描述（申请人提供）：每年大量接受心脏手术的老年患者经常出现术后认知障碍。 36-50% 的患者在术后早期阶段会出现术后认知缺陷 (POCD)，并且已被证明会对术后一年内的生活质量产生不利影响。我们的多学科神经结果研究小组的目标是了解心脏手术后神经系统和神经认知功能障碍的机制，并减少这些破坏性结果的发生率。尽管技术、药理学和围手术期器官保护方面的重大进步导致与心脏手术相关的死亡率降低，但 POCD 的发病率在过去十年中几乎没有变化。虽然已经提出了这种神经损伤的多种病因，包括脑栓塞过程和灌注不足，但大脑淀粉样蛋白负荷的作用从未得到研究。由于心脏手术通常发生在老年人中，因此手术患者出现的认知功能障碍可能是轻度认知障碍 (MCI) 的一种形式，这种疾病的特征是淀粉样蛋白 β-原纤维的积累。因此，我们研究的主要目的是使用正电子发射断层扫描 (PET) 和对 b-淀粉样原纤维具有高亲和力的新型 PET 示踪剂来确定 b-淀粉样蛋白沉积与 POCD 之间的关系。其次，我们将评估 POCD 患者淀粉样蛋白沉积的区域模式，并将这些模式与之前成像的 40 名 MCI 受试者和 40 名老年对照组进行比较。对于患者或患者家属来说，没有什么比成功延长生命的手术更具破坏性的了，但由于认知障碍而变得复杂，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 具有无价的价值，因为我们将使用功能成像标记物来定义 POCD 中区域淀粉样蛋白负荷的作用，这些标记物揭示了最早的神经元变化，从而产生新的机制见解。 公共卫生相关性：认知障碍是心脏手术的常见并发症。在这项研究计划中，我们计划确定大脑淀粉样斑块形成与术后认知功能障碍之间的关系。了解这种关系可能会产生新的治疗方法来预防认知能力下降，从而提高大量老年外科患者的生活质量和功能独立性。