Early Cognitive Training and Rehabilitation to Prevent Cognitive Decline in Older Hospitalized Adults with Delirium

早期认知训练和康复以防止老年谵妄住院患者认知能力下降

• 批准号: 10355447
• 负责人: Jin Ho Han
• 金额: $ 81.42万
• 依托单位: VANDERBILT UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-03-01 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10355447
• 关键词: Acceleration; Accident and Emergency department; Acute; Acute Brain Injuries; Address; Admission activity; Adult; Affect; Alzheimer' s disease patient; Alzheimer' s disease related dementia; Arousal; Biological Markers; Blood brain barrier dysfunction; Brain; Central Nervous System; Classification; Cognition; Cognitive; Cognitive deficits; Complex; Data; Delirium; Development; Early identification; Effectiveness of Interventions; Enrollment; Etiology; Exercise; Failure; Family; Foundations; Functional Magnetic Resonance Imaging; Functional disorder; Future; Goals; Heterogeneity; Hospitalization; Hospitals; Hour; Impaired cognition; Injury; Intervention; Metabolic; Methods; Modification; Neurons; Outcome; Patients; Phenotype; Pilot Projects; Play; Randomized; Randomized, Controlled Trials; Rehabilitation therapy; Reporting; Risk Factors; Role; Sample Size; Sepsis; Serum; Severities; Stroke; Symptoms; Syndrome; Techniques; Work; acute coronary syndrome; adverse outcome; cognitive control; cognitive rehabilitation; cognitive task; cognitive training; design; efficacious intervention; endothelial dysfunction; high risk; improved; improved outcome; innovation; neuronal survival; novel; novel strategies; older patient; preservation; prevent; skill acquisition; systemic inflammatory response; treatment as usual; trial design

PROJECT SUMMARY Delirium is a form of acute brain failure that occurs in 17% of older emergency department (ED) and 25% of older hospitalized patients. Numerous studies have reported that delirium is significantly associated with accelerated cognitive decline, particularly in patients with Alzheimer’s disease and related dementias (ADRD). Even in cognitively intact older patients, 50% will develop incident ADRD at 6-months after an episode of delirium. While interventions that efficaciously prevent delirium exist, there is no universally accepted intervention for delirium after it has developed. Most studies have demonstrated that they have minimal effect on outcomes including cognition. We posit that the lack of efficacy exists because these interventions modify risk factors for delirium development rather than the adverse outcome itself. Additionally, these interventions are uniformly administered to all delirious patients without taking into account this syndrome’s heterogeneity. Many interventions are also initiated 24 to 48 hours after admission, further limiting their efficacy. To preserve long-term cognition after delirium has developed, we must develop a novel and innovative approach to delirium management that emphasizes early (<24 hours) identification of delirious patients at higher risk for poorer long-term cognition and early modification of risk factors that are associated with accelerated cognitive decline. Unfortunately, the data needed to develop such an approach is lacking. To address this dearth in data, we completed several pilot studies that demonstrated that initiating cognitive training during hospitalization and following up with cognitive rehabilitation for 12 weeks after hospital discharge can be feasibly implemented and may improve cognitive outcomes. We also identified that delirious patients with normal arousal, more severe symptoms, metabolic, infectious, and central nervous system etiologies, and higher serum biomarkers of systemic inflammation, endothelial dysfunction, and blood brain barrier injury were also more likely to have poorer 6-month cognition. It is possible that performing the cognitive intervention in delirious patients at higher risk for poorer cognition may improve its efficacy and efficiency. To build upon our pilot studies, we propose this R01 with the following specific aims: (1) Using a randomized control trial design, determine if early (<24 hours) cognitive training performed twice daily during hospitalization and cognitive rehabilitation performed weekly for 12-weeks post-hospital discharge are associated with improved 6-month global cognition in older delirious patients with and without ADRD. (2) Determine whether the cognitive training / rehabilitation intervention is associated with improved network connectivity in the frontoparietal cortex at 6-months as determined by functional magnetic resonance imaging (fMRI) compared with controls. (3) Perform latent class analysis to identify delirium phenotypes and determine if they modify the relationship between early cognitive training / rehabilitation and 6-month global cognition. To complete these specific aims, this R01 will enroll a total of 336 patients and of these, approximately 235 will have pre-existing ADRD.

项目摘要 谵妄是一种急性脑衰竭，发生在17%的老年急诊科（艾德）和25%的老年人。 老年住院患者。许多研究报告说，谵妄与 加速认知能力下降，特别是阿尔茨海默病和相关痴呆症（ADRD）患者。 即使在认知功能完好的老年患者中，50%的患者在发作后6个月内也会发生ADRD事件。 精神错乱虽然存在有效预防谵妄的干预措施，但没有普遍接受的方法。 精神错乱后的干预。大多数研究表明， 包括认知在内的结果。我们认为，缺乏疗效的存在，因为这些干预措施修改 谵妄发展的危险因素，而不是不良后果本身。此外，这些干预措施 对所有的谵妄患者都是统一的，而没有考虑到这种综合征的异质性。 许多干预措施也是在入院后24至48小时开始的，这进一步限制了它们的功效。保存 谵妄发展后的长期认知，我们必须开发一种新颖的和创新的方法来治疗谵妄 强调早期（<24小时）识别谵妄患者的管理， 长期认知和早期修改与加速认知衰退相关的风险因素。 不幸的是，缺乏制定这种方法所需的数据。为了解决数据不足的问题，我们 完成了几项试点研究，证明在住院期间开始认知训练， 出院后12周的认知康复随访是可行的， 可以改善认知结果。我们还发现，具有正常觉醒的谵妄患者， 症状，代谢，感染和中枢神经系统病因，以及更高的血清生物标志物 全身性炎症、内皮功能障碍和血脑屏障损伤也更有可能导致 6个月认知能力较差。对谵妄患者进行认知干预可能会在更高的 认知能力较差的风险可能会提高其疗效和效率。在试点研究的基础上，我们建议 本R 01的具体目的如下：（1）使用随机对照试验设计，确定早期（<24 小时），在住院期间每天进行两次认知训练，并进行认知康复 出院后每周一次持续12周与老年人6个月整体认知改善相关。 伴有和不伴有ADRD的谵妄患者。(2)确定认知训练/康复是否 干预与6个月时额顶叶皮层的网络连接改善相关， 通过功能性磁共振成像（fMRI）确定与对照组相比。(3)执行潜在类 分析，以确定谵妄表型，并确定它们是否改变了早期认知障碍之间的关系， 训练/康复和6个月的整体认知。为了完成这些具体目标，R 01将招募 共336例患者，其中约235例患者既存ADRD。