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(ADRD)，是一种公共健康 影响生活质量和残疾的当务之急。急性外科或内科疾病的幸存者贡献 极大地加剧了认知衰退的危机。住院使新发病的几率增加1.5-2倍 痴呆症。此外，超过三分之一的危重患者在1年后出现新的ADRD。的主要风险因素 急性疾病后的ADRD包括病前虚弱、认知障碍和在医院出现的精神错乱。内皮细胞 血脑屏障(BBB)功能障碍、脑萎缩和脑白质连接性改变 与精神错乱和ADRD有关。手术在老年人中很常见，但它(以及由此导致的住院治疗) 与显著的认知功能减退有关。为减少这一下降而进行的个别干预已显示出 有限的成功。康复训练是在急性应激源到来之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理想的人群 康复训练。这些患者在手术前有准备时间，通常身体虚弱，手术后时间较长。 ICU和医院课程，新的ADRD风险很高。到目前为止，康复研究主要是 注重体育锻炼，以提高身体成绩。基于物理和计算机相结合的认知 培训计划与全球认知功能的显著改善有关， 计算机化的大脑训练练习显示出记忆、处理速度和 一心多用。然而，这种培训还没有在外科或住院患者中进行过检验。我们有 证明认知训练和体能锻炼在大手术前和手术中是可行的。 出院后认知和身体康复相结合的计划可以减少ADRD，以及 计算机化的认知康复计划可以改善ICU幸存者的多个认知领域。 此外，运动可以增强血管内皮细胞和血脑屏障功能，减少脑萎缩，增加功能 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 住院前(康复)、期间和之后(康复)的身体训练计划可能是最多的 在减少ADRD和大手术后的残疾方面有效，但尚未进行评估。主 认知和体育锻炼以改善术后结果的假说(COPE-IOS) 研究表明，整个围手术期的认知和体能训练计划将 改善老年手术患者的长期认知和残疾结果，这些患者有下降的风险。 我们将随机选择250名60岁的≥患者进行非心脏手术。 住院3天，参加全面的培训计划或在手术前、期间进行积极的控制 外科住院，出院后。我们将评估全球认知(目标1)、残疾(目标2)和 基线和出院后最多12个月的血浆生物标志物和神经成像(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.