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

项目总结 精神错乱是一种急性脑衰竭，发生在17%的老年急诊科(ED)和25%的 年龄较大的住院患者。许多研究报告称，精神错乱与 认知功能减退加速，特别是阿尔茨海默病和相关痴呆(ADRD)患者。 即使在认知正常的老年患者中，也有50%会在发病后6个月发生ADRD 精神错乱。虽然存在有效防止精神错乱的干预措施，但还没有被普遍接受的干预措施。 对神志不清发展后的干预。大多数研究表明，它们的影响微乎其微 包括认知在内的结果。我们假设缺乏疗效的存在是因为这些干预措施改变了 精神错乱发展的危险因素，而不是不利后果本身。此外，这些干预措施 统一用于所有神志不清的患者，而不考虑这种综合征的异质性。 许多干预措施也是在入院24至48小时后开始的，进一步限制了其有效性。保存 长期认知在精神错乱发展之后，我们必须发展一种新的和创新的方法来治疗精神错乱。 强调早期(24小时)识别较贫穷风险较高的精神错乱患者的管理 长期认知和对与认知功能减退相关的风险因素的早期修正。 不幸的是，缺乏开发这种方法所需的数据。为了解决数据匮乏的问题，我们 完成了几项试点研究，证明在住院和治疗期间开始认知训练 出院后12周的认知康复随访是可行的， 可能会改善认知结果。我们还发现，神志不清的患者觉醒正常，病情较重 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记物 全身炎症、内皮功能障碍和血脑屏障损伤也更有可能发生 6个月认知能力较差。高海拔地区对精神分裂症患者进行认知干预是可能的 认知能力较差的风险可能会提高其疗效和效率。为了加强我们的试点研究，我们建议 R01的具体目标如下：(1)采用随机对照试验设计，确定早期(&lt；24 小时)住院期间每天进行两次认知训练，并进行认知康复 每周持续12周的出院后与老年人6个月的全球认知改善有关 伴有和不伴有ADRD的神志不清患者。(2)确定是否进行认知训练/康复 干预与6个月时额顶皮质网络连通性的改善有关 通过功能磁共振成像(FMRI)与对照组进行比较。(3)表演潜课 分析以确定精神错乱的表型并确定它们是否改变了早期认知之间的关系 训练/康复和为期6个月的全球认知。为了实现这些具体目标，本次R01将招收一名 总共有336名患者，其中约235人将预先存在ADRD。

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.