Long-term Neuropsychiatric Sequelae of SARS-CoV-2 Infection in Late Life

大流行的心理和社会影响是严重的，从长远来看，可能会产生重大的心理影响。也有新的证据表明，新冠肺炎可能对大脑有直接影响，或引发免疫反应，对新冠肺炎患者的大脑功能和心理健康产生额外的不良后果。新冠肺炎对老年人的影响不成比例，65岁及以上的人患严重疾病的风险更高。事实上，大多数患有新冠肺炎的老年人在首次感染后存活下来，并进入临床恢复期数月或更长时间，这通常以持续的症状和不利的健康后果为标志。因此，迫切需要了解新冠肺炎的神经精神后遗症，特别是在老年人中。拟议研究的主要目标是确定新冠肺炎是否与全国65岁及以上患者样本中痴呆症(阿尔茨海默病和相关痴呆症)和新发或再次出现精神障碍的发生率增加有关，并通过退伍军人健康管理局和医疗保险数据完全确定结果。第二个目标是检查与有新冠肺炎病史的老年人中这些神经精神障碍(即阿尔茨海默病和相关痴呆、情绪障碍、焦虑症和精神病)发展相关的风险因素。目前这项提议的目的并不是要确定这些关联的机制，而是要推动该领域的发展，告知当前关于新冠肺炎是晚年神经精神障碍的风险因素的知识空白。目前的提案将利用全面的数据来源和先进的统计方法，在大的地理和种族差异的国家样本中，在小规模研究中证实新冠肺炎对神经精神疾病影响的早期报告，并将提高我们对新冠肺炎是否为AD/ADRD和精神障碍发展的风险因素的理解(目标1)。此外，这项研究将确定新冠肺炎患者中发生AD/ADRD和精神障碍的基线风险因素(目标2)，并确定某些急性和急性后症状是否表明发生AD/ADRD的风险更高(目标3)。鉴于超过7,900万美国人已被诊断出患有新冠肺炎，即使AD/ADRD和精神疾病风险的微小增加也可能对患者、他们的照顾者和美国医疗体系产生重大后果。很可能，拟议的研究将有助于确定可能处于较高风险的个人，并支持参与早期干预战略，以缓解AD和相关疾病以及晚年精神健康障碍。

The psychological and social impact of the pandemic have been severe and likely will have significant mental effects over the long term. There is also emerging evidence that suggests that COVID-19 may have direct effects on the brain or trigger immune responses that have additional adverse consequences on brain function and mental health in patients with COVID-19. COVID-19 has disproportionately impacted older adults, with those 65 years and older at heightened risk of severe illness. In fact, most older adults with COVID-19 survive initial infection and enter a clinical recovery phase for months or longer, which is often marked by persistent symptoms and adverse health outcomes. Thus, there is an urgent need to understand the neuropsychiatric sequelae of COVID-19, especially in older adults. The primary goal of the proposed research is to determine whether COVID-19 is associated with increased incidence of dementia (Alzheimer’s disease and related dementias) and new or reemergence of psychiatric disorders in a national sample of patients 65 years and older, with complete outcome ascertainment from Veterans Health Administration and Medicare data. The secondary aim is to examine risk factors associated with development of these neuropsychiatric disorders (i.e., Alzheimer’s disease and related dementias [AD/ADRD], mood disorders, anxiety disorders, and psychosis) among older adults with history of COVID-19. The intent of the current proposal isn’t to be deterministic about the mechanisms of these associations, but to move the field forward informing current knowledge gaps about COVID-19 as a risk factor for neuropsychiatric disorders in late life. The current proposal will substantiate the early reports of neuropsychiatric effects from COVID-19 in small studies in a large geographically and racially diverse national sample using comprehensive data sources and advanced statistical methods and will improve our understanding of whether COVID-19 is a risk factor for the development of AD/ADRD and psychiatric disorders (Aim 1). Furthermore, this study will identify the baseline risk factors for development of AD/ADRD and psychiatric disorders among individuals with COVID-19 (Aim 2) and determine whether certain acute and post- acute symptoms are indicative of a higher risk for developing AD/ADRD (Aim 3). Given that over 79 million Americans have been diagnosed with COVID-19, even small increases in risk of AD/ADRD and psychiatric disorders may have significant consequences for patients, their caregivers, and the U.S. health care system. It is likely that the proposed research will help to identify individuals that may be at higher risk and support engagement in early intervention strategies that will lead to mitigation of AD and related diseases and late-life mental health disorders.