The MIND ICU Study

描述（由申请人提供）：在重症监护室（ICU）幸存者中，随后的认知和功能下降是对有意义恢复的最大威胁。六个小队列表明，在年龄越来越大的数百万ICU幸存者中，有30%至80%的人患上了获得性长期认知障碍（LTCI），其功能相当于轻度/中度痴呆，可能持续数年。此外，健康相关生活质量（HRQL）、功能状态和“ICU加速”虚弱的主要缺陷也很常见，尤其是在老年人中。ICU谵妄可能是这些破坏性结局的主要和潜在可改变的风险因素，它是出院时死亡率较高、费用较高和认知功能较差的预测因素。此外，机械通气患者长期大量暴露于常规高剂量的强效精神活性药物可能会产生持久但可预防的认知和功能影响。在本提案中，目标1和3将确定谵妄是否是ICU幸存者中LTCI（目标1）和HRQL受损（目标3）的发生率、严重程度和/或持续时间的独立风险因素。同样，目标2和4将确定ICU患者中镇静和镇痛药物的暴露程度是否是LTCI（目标2）和HRQL受损（目标4）的发生率、严重程度和/或持续时间的独立风险因素。MIND-ICU研究是一项前瞻性队列研究，在39个月内从3个不同的医疗中心招募了800例机械通气的内科和外科患者，并在出院后3个月和12个月进行了全面的随访测试。本研究将量化谵妄和镇静剂/镇痛剂暴露是否确实是LTCI和HRQL的风险因素，控制其他协变量，如年龄、内科与外科ICU入院、既存认知障碍、败血症和apoE基因型。这将为制定预防和/或治疗策略铺平道路，以减少长期认知障碍，并在未来几十年内改善老年和年轻ICU患者的功能恢复。总结：ICU幸存者恢复的主要威胁是获得性认知和功能下降，可能持续数年，尤其是老年患者。为了为未来的预防和干预策略铺平道路，MIND-ICU队列将确定谵妄和强效镇静剂和镇痛剂在多大程度上是危重病后长期认知障碍和功能下降的风险因素。

DESCRIPTION (provided by applicant): Among Intensive Care Unit (ICU) survivors, subsequent cognitive and functional decline are the greatest threats to meaningful recovery. Six small cohorts indicate that an alarming 30% to 80% of the increasingly older millions of ICU survivors develop an acquired long-term cognitive impairment (LTCI) functionally equivalent to mild/moderate dementia that may last years. Additionally, major deficits in health-related quality of life (HRQL), functional status, and an "ICU accelerated" frailty are common, especially in the elderly. A leading and potentially modifiable risk factor for these devastating outcomes may be ICU delirium, which is a predictor of higher mortality, higher cost, and poor cognitive function at discharge. Additionally, heavy and prolonged exposure to potent psychoactive medications routinely administered in high doses to ventilated patients may have lasting yet preventable cognitive and functional effects. In this proposal, Aims 1 and 3 will determine whether delirium is an independent risk factor for the incidence, severity, and/or duration of LTCI (Aim 1) and impaired HRQL (Aim 3) in ICU survivors. Likewise, Aims 2 and 4 will determine whether degree of exposure to sedative and analgesic medications in ICU patients is an independent risk factor for the incidence, severity, and/or duration of LTCI (Aim 2) and impaired HRQL (Aim 4). The MIND- ICU study will be a prospective cohort study enrolling 800 mechanically ventilated medical and surgical patients from 3 diverse medical centers over a 39 month period with comprehensive follow-up testing at 3 and 12 months after hospital discharge. This study will quantify whether delirium and sedative/analgesic exposure are indeed risk factors for LTCI and HRQL, controlling for other covariates such as age, medical vs. surgical ICU admission, pre-existing cognitive impairment, sepsis, and apoE genotype. This will pave the way for development of preventive and/or treatment strategies to reduce long-term cognitive impairment and improve the functional recovery of older and younger ICU patients for decades to come. LAY SUMMARY: Major threats to recovery for ICU survivors are acquired cognitive and functional decline that can last years, especially in older pateints. To pave the way for future preventive and interventional strategies, the MIND-ICU cohort will determine to what degree delirium and potent sedatives and analgesics are risk factors for long-term cognitive impairment and functional decline following critical illness.