Cognitive and Physical Exercise to Improve Outcomes after Surgery in the Elderly

项目摘要 随着年龄的增长，认知能力下降，包括阿尔茨海默病和相关痴呆症（ADRD），是一种公共卫生问题。 影响生活质量和残疾的当务之急。急性手术或内科疾病的幸存者 认知能力下降的危机。住院治疗使新发的几率增加1.5-2倍 痴呆此外，超过三分之一的重症患者在1年内新发ADRD。的主要危险因素 急性疾病后的ADRD包括病前虚弱和认知缺陷以及住院时的谵妄。内皮 和血脑屏障（BBB）功能障碍、脑萎缩和白色物质连接改变都具有 与精神错乱和ADRD有关手术在老年人中很常见，但它（及其导致的住院治疗） 与严重的认知能力下降有关。为减少这一下降而采取的个别干预措施显示， 有限的成功。应激是在急性应激源前增强能力和储备的过程， 提高对即将到来的侮辱的容忍度。老年大手术患者提供了一个理想的人群， 我很抱歉。这些患者在手术前有准备时间，通常身体虚弱，手术后延长 ICU和医院课程，并处于新发ADRD的高风险中。迄今为止的研究主要是 专注于体能训练，以改善身体状况。结合物理和计算机认知 训练计划与整体认知功能的显著改善有关， 计算机化的大脑训练练习已经证明了记忆力、处理速度和 多任务处理然而，这种训练尚未在手术或住院患者中进行过检查。我们有 证明了认知训练和体育锻炼在大手术前和大手术中是可行的。 出院后的认知和身体康复联合计划可以减少ADRD， 计算机化认知康复计划可以改善ICU幸存者的多个认知领域。 此外，运动增强内皮和血脑屏障功能，减少脑萎缩，并增加功能性 连通性，为这些改进提供了潜在的机制基础。因此，一个全面的头脑和 在住院前、住院期间和住院后的身体训练计划可能是最重要的。 有效减少ADRD和大手术后残疾，但尚未进行评估。主要 COPE-iOS：通过认知和体育锻炼改善术后结局的假设 一项研究表明，在围手术期进行认知和体能训练， 改善老年手术患者的长期认知和残疾结果，具有高风险下降。 我们将随机分配250例≥60岁接受择期重大非心脏手术的患者， 住院>3天，以进行全面的训练计划或手术前进行主动控制， 手术住院和出院后。我们将评估整体认知（目标1），残疾（目标2）， 基线和出院后12个月内的血浆生物标志物和神经影像学（目标3）。

Project Summary Cognitive decline with aging, including Alzheimer's Disease and Related Dementias (ADRD), is a public health imperative that impacts quality of life and disability. Survivors of acute surgical or medical illness contribute greatly to the crisis of cognitive decline. Hospitalization confers a 1.5-2-fold increase in the odds of new onset dementia. Furthermore, over a third of critically ill patients have new ADRD by 1 year. Major risk factors for ADRD after acute illness include pre-illness frailty and cognitive deficits and delirium in the hospital. Endothelial and blood brain barrier (BBB) dysfunction, cerebral atrophy, and white matter connectivity changes have all been linked to delirium and ADRD. Surgery is common in older adults but it (and its resulting hospitalization) is associated with significant cognitive decline. Individual interventions to reduce this decline have exhibited limited success. Prehabilitation is the process of enhancing capacity and reserve before an acute stressor to improve tolerance of the upcoming insult. Older major surgical patients provide an ideal population for prehabilitation. These patients have lead time prior to surgery, are frequently frail, have prolonged post-surgery ICU and hospital courses, and are at high risk for new ADRD. Prehabilitation studies to date have primarily focused on physical training to improve physical outcomes. Combined physical and computer-based cognitive training programs have been associated with significant improvements in global cognitive function, and computerized brain training exercises have demonstrated enhancement in memory, processing speed, and multitasking. This training, however, has not been examined in surgical or hospitalized patients. We have demonstrated that cognitive training and physical exercises are feasible prior to major surgery and in the hospital, that a combined cognitive and physical rehabilitation program after discharge can reduce ADRD, and that a computerized cognitive rehabilitation program can improve multiple cognitive domains in ICU survivors. Further, exercise enhances endothelial and BBB function, reduces cerebral atrophy, and increases functional connectivity, providing potential mechanistic basis for these improvements. Thus, a comprehensive mind and body training program prior to (prehabilitation), during, and after (rehabilitation) hospitalization may be most effective in reducing ADRD and disability after major surgery but has yet to be evaluated. The main hypothesis of the COgnitive and Physical Exercise to improve Outcomes after Surgery (COPE-iOS) study is that a program of cognitive and physical training throughout the perioperative period will improve long-term cognitive and disability outcomes in older surgical patients at high risk for decline. We will randomize 250 patients ≥60 years old undergoing elective major non-cardiac surgery with expected hospitalization >3 days to a comprehensive training program or to active control prior to surgery, during the surgical hospitalization, and after discharge. We will assess global cognition (Aim 1), disability (Aim 2), and plasma biomarkers and neuroimaging (Aim 3) at baseline and up to 12 months after discharge.