The MIND ICU Study

描述(由申请人提供)：在重症监护病房(ICU)幸存者中，随后的认知和功能衰退是对有意义的康复的最大威胁。六个小队列表明，在越来越年长的数百万ICU幸存者中，有30%到80%的人患上了获得性长期认知障碍(LTCI)，其功能相当于可能持续数年的轻度/中度痴呆症。此外，与健康相关的生活质量(HRQL)、功能状态和“ICU加速”虚弱方面的重大缺陷很常见，尤其是在老年人中。导致这些破坏性后果的一个主要的和潜在的可改变的危险因素可能是ICU精神错乱，它是出院时更高的死亡率、更高的费用和认知功能低下的预测因素。此外，长期大量接触强效精神活性药物，对呼吸机患者常规大剂量使用可能会产生持久但可预防的认知和功能影响。在这项提案中，AIMS 1和AIMS 3将确定精神错乱是否是ICU幸存者LTCI(AIM 1)和HRQL受损(AIM 3)的发生率、严重程度和/或持续时间的独立危险因素。同样，AIMS 2和AIMS 4将确定ICU患者接触镇静和止痛药的程度是否是LTCI(AIM 2)和HRQL受损(AIM 4)的发生率、严重性和/或持续时间的独立危险因素。Mind-ICU研究将是一项前瞻性队列研究，从3个不同的医疗中心招募800名机械通气的内科和外科患者，为期39个月，在出院后3个月和12个月进行全面的随访测试。这项研究将量化精神错乱和镇静/止痛剂暴露是否确实是LTCI和HRQL的危险因素，并控制其他协变量，如年龄、内科和外科ICU入院情况、既往存在的认知障碍、败血症和载脂蛋白E基因。这将为制定预防和/或治疗策略铺平道路，以减少长期的认知损害，并在未来几十年改善老年和年轻ICU患者的功能恢复。总结：ICU幸存者的主要康复威胁是获得性认知和功能下降，这种下降可能会持续数年，特别是在老年患者。为了为未来的预防和干预策略铺平道路，精神ICU队列将确定精神错乱和有效的镇静剂和止痛剂在多大程度上是危重疾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.