Interactions of SARS-CoV-2 infection and genetic variation on the risk of cognitive decline and Alzheimer’s disease in Ancestral and Admixed Populations

SARS-CoV-2 感染和遗传变异的相互作用对祖先和混血人群认知能力下降和阿尔茨海默病风险的影响

• 批准号: 10628505
• 负责人: GABRIEL Alejandro DE ERAUSQUIN
• 金额: $ 872.52万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-15 至 2028-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10628505
• 关键词: 2019-nCoV; Acute; Address; Admixture; Adult; Affect; Africa; African; African American; African American population; Age Years; Alzheimer' s Disease; Alzheimer' s disease related dementia; Alzheimer' s disease risk; Amerindian; Anosmia; Argentina; Brain; COVID-19; COVID-19 severity; COVID-19 susceptibility; Central Nervous System; Cessation of life; Chronic; Clinical; Cognitive; Complex; DNA; Data; Data Analyses; Data Collection; Dementia; Diet; Disease; Elderly; Emotional; Ensure; Epidemiology; Event; Exposure to; Foundations; Genetic; Genetic Variation; Genome; Genotype; Guidelines; Health; Hispanic; Hispanic Americans; Human; Image; Impaired cognition; In Vitro; Individual; Induced pluripotent stem cell derived neurons; Infection; Inflammation; Institution; International; Knowledge; Latino Population; Long COVID; Longitudinal cohort; Lung; Mediating; Medicine; Mexican Americans; Moods; National Institute on Aging; Native Americans; Nature; Nerve Degeneration; Neurocognitive; Neurologic; Neurologic Symptoms; New York; Nigeria; Obesity; Olfactory Cortex; Participant; Performance; Persons; Phase; Population; Prevention strategy; Protocols documentation; Province; Recovery; Research; Research Personnel; Resources; Risk; Risk Factors; Risk Marker; Rural; SARS-CoV-2 exposure; SARS-CoV-2 infection; Sampling; Science; Secondary Prevention; Severities; Site; Smoking; South America; Symptoms; Testing; Texas; Time; Traditional Medicine; Underrepresented Minority; Universities; Variant; Viral; Virus; Washington; age group; amnestic mild cognitive impairment; apolipoprotein E-4; biomarker evaluation; blood-based biomarker; cerebrovascular; cohort; college; coronavirus pandemic; data management; data quality; data sharing; design; early onset; experience; experimental study; follow-up; gene environment interaction; genetic predictors; genome sequencing; genomic variation; human old age (65+); longitudinal course; medical schools; multidisciplinary; neural; neuroimaging; neuropsychiatric sequelae of COVID-19; neuropsychiatry; neurotoxicity; post SARS-CoV-2 infection; programs; recruit; resilience; resilience factor; respiratory; risk prediction; statistics; treatment strategy; variant of interest; whole genome

The science proposed in this program takes advantage of the unique scientific opportunity created by the ongoing coronavirus pandemic, to study the interaction between a definable and time-limited risk-inducing environmental event (exposure to the virus) and genomic variation on the occurrence of cognitive decline and Alzheimer’s disease and related dementias (ADRD) in large cohorts of older adults from underrepresented minorities in the USA and ancestral groups in Africa and South America. The investigators leading the program have extensive experience in directing international consortia and longitudinal cohorts, including the creation and follow up of an Amerindian cohort in the Andes region for longer than a decade. We have pilot ascertainment of cognitive impairment end-points in newly recruited older adults of Amerindian ancestry. This U19 will investigate the interactions between whole genome sequence genetic variations and COVID-19 infection and disease on the risk of cognitive decline and risk of ADRD in 4,300 individuals as part of newly recruited cohorts in Texas, New York, Washington State, Ibadan (Nigeria), and Jujuy (Argentina). Participant assessments will include neurological, cognitive, imaging and blood-based biomarker evaluations using harmonized protocols and at 3 time points: within a few months of infection and 18 and 36 months afterwards. We propose to answer this complex research question with 3 highly integrated Projects supported by equally integrated Administrative, Clinical, Neuroimaging and Data Management/Statistics Cores. All projects involve integrated multidisciplinary teams of investigators within a consortium of institutions including University of Texas Health San Antonio, University of Texas Rio Grande Valley, Washington University School of Medicine, Albert Einstein College of Medicine, University of Washington, University of Ibadan, the Ministry of Health of the Province of Jujuy (Argentina) and the FULTRA Foundation (Argentina). Resources and study expertise will be tightly coordinated across multiple sites and Cores, and integrated to the National Institute of Aging Alzheimer’s Disease Sequencing Project and National Alzheimer’s Coordinating Center which will help ensure optimal sharing of the acquire data and knowledge.

在这个计划中提出的科学利用了独特的科学机会， 持续的冠状病毒大流行，研究可定义和有时间限制的风险诱发之间的相互作用 环境事件（暴露于病毒）和基因组变异对认知能力下降的影响， 阿尔茨海默病和相关痴呆（ADRD）在来自代表性不足的老年人的大型队列中 美国的少数民族以及非洲和南美洲的祖先群体。领导这个项目的调查人员 在指导国际财团和纵向队列方面有丰富的经验，包括创建 并对安第斯山脉地区的一个美洲印第安人队列进行了长达十多年的随访。我们有飞行员 在新招募的美洲印第安血统的老年人中确定认知障碍终点。这 U19将研究全基因组序列遗传变异与COVID-19之间的相互作用 感染和疾病对4,300名个体认知能力下降和ADRD风险的影响， 在得克萨斯州、纽约、华盛顿州、伊巴丹（尼日利亚）和胡胡伊（阿根廷）招募了同伙。参与者 评估将包括神经、认知、成像和基于血液的生物标志物评估， 协调方案和3个时间点：感染后几个月内以及感染后18个月和36个月。 我们建议通过3个高度集成的项目来回答这个复杂的研究问题， 集成的管理、临床、神经成像和数据管理/统计核心。所有项目涉及 在一个由包括哥伦比亚大学在内的机构组成的联合会内， 德克萨斯健康圣安东尼奥，德克萨斯大学格兰德河谷，华盛顿大学医学院， 阿尔伯特·爱因斯坦医学院、华盛顿大学、伊巴丹大学、 阿根廷胡胡伊省和FULTRA基金会。资源和研究专业知识将 在多个站点和核心之间进行紧密协调，并集成到国家老龄化研究所 阿尔茨海默病测序项目和国家阿尔茨海默病协调中心，这将有助于确保 最佳共享所获得的数据和知识。