CMV and CMV-Immune Responses in Geriatric Conditions Post-Kidney Transplant (CMV-GeriKT)

肾移植后老年病中的 CMV 和 CMV 免疫反应 (CMV-GeriKT)

• 批准号: 10282428
• 负责人: Maheen Zehra Abidi
• 金额: $ 18.88万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-15 至 2026-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10282428
• 关键词: Address; Admission activity; Adult; Aging; Alzheimer' s Disease; Antiviral Agents; Area; Automobile Driving; Cells; Cellular Immunity; Chronic; Cognition; Cognitive; Colorado; Communities; Cytomegalovirus; Cytomegalovirus Infections; Dementia; Development; Development Plans; Diagnosis; Disease; Disease Progression; Elderly; Enrollment; Epidemiology; Funding; Gait speed; Geriatrics; Gerontology; Goals; Health; Health Priorities; Immune; Immune response; Immune system; Immunization; Immunology; Immunosuppression; Impaired cognition; Inflammation; Inflammatory; International; Investigation; Kidney Diseases; Kidney Transplantation; Knowledge; Link; Measures; Mediating; Mentors; Methodology; Mission; Older Population; Outcome; Patients; Phenotype; Physical Function; Physical Performance; Physicians; Physiological; Plasma; Play; Population; Prophylactic treatment; Research; Research Design; Research Personnel; Research Project Grants; Research Training; Risk; Role; Secondary to; Speed; Testing; Time; Trail Making Test; Training; Transplant Recipients; United States National Institutes of Health; Vascular Dementia; Viral; Virus Diseases; Virus Replication; Vulnerable Populations; aged; career; career development; chemokine; chronic infection; clinical decision-making; cognitive function; cognitive reserve; cognitive testing; cohort; cytokine; design; effective therapy; experience; follow-up; frailty; functional decline; high risk; immune reconstitution; improved; inflammatory marker; innovation; novel; post-transplant; reactivation from latency; reconstitution; response; risk prediction; senescence; seropositive; stressor

ABSTRACT Chronic infections like cytomegalovirus (CMV) may contribute to both cognitive and physical function decline in older adults and have been implicated in the development of Alzheimer's Disease (AD), vascular dementia, and frailty. Due to immune senescence and immune suppression, older Kidney Transplant (KT) recipients ≥50 years, are at especially high risk of early and frequent reactivations of latent CMV and may fail to reconstitute CMV-specific cell-mediated immunity (CMV-CMI), leading to high rates of CMV disease. This research will investigate for the first time the role of CMV and CMV-CMI reconstitution in cognitive and physical functional decline in KT recipients. This research is relevant to the NIA mission because it will advance the understanding of the critical mechanisms driving CMV-related aging in older adults by studying the impact of CMV on decline in cognitive and physical function, AD, and frailty. This proposal's central hypothesis is that inflammation secondary to CMV replication may explain the mechanism by which CMV may contribute to cognitive and physical function decline, AD, and progression of frailty. This hypothesis will be tested through the following specific aims: 1) To quantify the association of CMV serostatus with trajectories of cognition and physical function in an existing Functional Assessment of Renal Disease (FAIR) cohort of older KT recipients; 2) To assess the relationship of CMV-CMI reconstitution with trajectories of cognitive and physical function and frailty in a newly established Colorado cohort of CMV+ older KT recipients; 3) To investigate the relationship of inflammatory markers with trajectories of cognition and physical function among CMV+ and CMV- KT recipients at 1-year post-KT in Colorado cohort. This approach is innovative because it: 1) allows the first investigation of the relationship of CMV, with the trajectories of cognitive and physical function among older KT recipients, and 2) may identify the role of CMV-CMI and inflammation driving the relationship of CMV with cognitive and physical function decline. This project is significant because it has the potential to improve health outcomes for older KT recipients. Complimentary to the proposed research plan, a five-year mentored career development training plan has been devised that incorporates research training in geriatrics and viral immunology. The candidate is co- mentored by internationally recognized experts in gerontology, viral immunology, kidney transplantation, and epidemiology. The candidate's long-term career goal is to become an independent investigator studying immune protection in the context of chronic viral infections with geriatric outcomes.

摘要 像巨细胞病毒(CMV)这样的慢性感染可能导致认知和身体功能下降 老年人与阿尔茨海默病(AD)、血管性痴呆、 也很脆弱。由于免疫衰老和免疫抑制，老年肾移植(KT)受者≥50 几年内，潜伏的CMV过早和频繁重新激活的风险特别高，可能无法重建 CMV特异性细胞免疫(CMV-CMI)，导致CMV病发病率高。这项研究将 首次研究CMV和CMV-CMI重建在认知和身体功能中的作用 KT受助者人数下降。这项研究与NIA的任务相关，因为它将促进对 通过研究巨细胞病毒对衰老的影响，研究导致老年人巨细胞病毒相关衰老的关键机制 在认知和身体功能方面，阿尔茨海默病和虚弱。 这一建议的中心假设是继发于CMV复制的炎症可能解释了 巨细胞病毒可能导致认知和身体功能下降、阿尔茨海默病和痴呆进展的机制 脆弱。这一假设将通过以下具体目标进行检验：1)量化巨细胞病毒与 现有肾功能评估中的血清状态与认知和身体功能轨迹的关系 老年KT受者的疾病(一般)队列；2)评估CMV-CMI重建与 科罗拉多州新建立的巨细胞病毒+老年人队列中认知和身体功能与脆弱性的轨迹 3)探讨炎症标志物与认知轨迹和运动轨迹的关系。 科罗拉多州CMV+和CMV-KT受者在接受KT术后1年的身体功能。 这种方法是创新的，因为它：1)允许第一次调查CMV与 老年KT受者的认知和身体功能的轨迹，以及2)可以确定 CMV-CMI和炎症驱动CMV与认知和身体功能下降的关系。这 该项目意义重大，因为它有可能改善老年KT接受者的健康状况。 作为拟议研究计划的补充，一项为期五年的有指导的职业发展培训计划 已设计出结合老年病学和病毒免疫学的研究培训。候选人是联合- 由国际公认的老年学、病毒免疫学、肾移植和 流行病学。候选人的长期职业目标是成为一名独立的调查员，研究 在具有老年后果的慢性病毒感染的背景下的免疫保护。