Predictors of Cognitive Impairment in Survivors of Critical Illness

描述（由申请人提供）：该指导患者导向研究职业发展奖（K23）将为Timothy D. Girard博士提供机会，发展他在老年重症监护领域的临床研究者的职业生涯，并建立一个独立的衰老研究项目，专注于危重疾病相关认知障碍的临床和分子流行病学。通过老年病学、临床和分子流行病学以及神经心理学的综合教学活动和课程；由当地专家提供密集指导；以及在前瞻性临床研究的设计、实施和分析方面的实践经验，吉拉德博士将利用该奖项成为一名训练有素的老龄化研究研究者。本提案的主要科学目标是识别和研究危重疾病后长期认知障碍（LTCI）的临床和分子预测因素。老年患者占ICU入院人数的大多数，认知障碍是这一弱势群体有意义康复的主要障碍；危重疾病的幸存者有25%-75%的风险发展为LTCI，这是一种与生活质量下降和重大社会成本相关的持续脑功能障碍的表现。利用一项前瞻性队列调查，吉拉德博士将确定重症监护室中LTCI风险最高的患者，并量化重症后重要危险因素对LTCI的影响。具体而言，候选人将确定危重疾病后长期认知障碍发生率和严重程度增加的临床危险因素（目标1）。此外，他将确定炎症和凝血功能障碍是否是危重疾病后LTCI发生率和严重程度增加的危险因素（目的2）。最后，吉拉德博士将确定危重症患者临床危险因素定义的谵妄类别与危重症后LTCI的发生率和严重程度增加有关（目标3）。这项工作将为预防和治疗干预措施的研究铺平道路，确保这些努力将集中在风险最高的患者身上。吉拉德博士的长期研究目标是通过预防和治疗危重疾病相关的认知障碍来改善老年危重患者的预后。

DESCRIPTION (provided by applicant): This Mentored Patient-Oriented Research Career Development Award (K23) will provide Dr. Timothy D. Girard the opportunity to develop his career as a clinical investigator in the field of geriatric critical care and to establish an independent program of aging research focused on the clinical and molecular epidemiology of critical-illness associated cognitive impairment. Through an integrated program of didactic activities and course work in geriatrics, clinical and molecular epidemiology, and neuropsychology; intensive mentorship by local experts; and hands-on experience in the design, implementation, and analysis of a prospective clinical investigation, Dr. Girard will use this award to become a highly trained investigator in aging research. The primary scientific goal of this proposal is to identify and study the clinical and molecular predictors of long-term cognitive impairment (LTCI) after critical illness. Older patients account for the majority of ICU admissions, and cognitive impairment is a major impediment to meaningful recovery in this vulnerable population; survivors of critical illness have a 25%-75% risk of developing LTCI, a manifestation of persistent brain dysfunction associated with reduced quality of life and significant societal costs. Utilizing a prospective cohort investigation, Dr. Girard will identify those ICU patients at highest risk for LTCI and quantify the contribution of important risk factors to LTCI after critical illness. Specifically, the candidate will identify clinical risk factors for an increased incidence and severity of long-term cognitive impairment after critical illness (Aim 1). Furthermore, he will determine whether inflammation and coagulopathy are risk factors for an increased incidence and severity of LTCI after critical illness (Aim 2). Finally, Dr. Girard will determine which categories of delirium defined by clinical risk factors in critically ill patients are associated with an increased incidence and severity of LTCI after critical illness (Aim 3). This work will pave the way for the study of preventive and therapeutic interventions by ensuring that such efforts will be focused on patients at highest risk. Dr. Girard's long-term research goal is to improve the outcomes of older critically ill patients through the prevention and treatment of critical illness-associated cognitive impairment. RELEVANCE: Advances in intensive care medicine have improved the likelihood of survival for patients with critical illness, but studies have shown that many survivors develop persistent cognitive impairment, which reduces quality of life. This study seeks to identify risk factors for cognitive impairment after critical illness in order to guide the development of strategies to prevent and treat this potentially devastating complication of critical illness.