Temporal associations between systemic inflammation, cardiovascular risk profile and development of Alzheimer’s disease and related dementias in patients with rheumatoid arthritis

项目总结/摘要 此K24应用程序旨在为Elena Myasoedova博士提供受保护的时间，以指导患者中的学员- 定向研究（POR）旨在确定全身性炎症之间的长期时间关系， 心血管危险因素和心血管事件对阿尔茨海默病及其他相关疾病的风险 痴呆症（ADRD），使用类风湿性关节炎（RA）作为原型。该奖项将使申请人能够巩固 并在新的方向上推进她目前由国家情报局资助的R 01研究项目，并扩大她的指导范围 机会和指导经验。Myasoedova博士是马约诊所的终身副教授。 她在高质量的POR、出版物和直接相关研究的指导方面有着良好的记录， 在拟议的研究中。申请人在所有职业阶段都表现出指导学员的显著能力 并将继续受益于丰富而强大的资源，独特的研究基础设施和庞大的人才库 马约诊所的病人和学员。在资助期间，申请人的进一步发展将 包括：1）提高POR的指导技能; 2）提高POR的生物统计学知识; 3） 开发针对衰老中POR和风湿性疾病中ADRD的协作生态位;以及4）维持 不间断的校外资助这些目标将通过研讨会、会议 课程，并与流行病学部，科戈德老龄化中心，罗切斯特 流行病学项目和马约诊所老龄化研究。Myasoedova博士将进一步整合和推进 这些技能，通过继续指导受训人员在目前资助的POR，并通过扩大她的 通过K24机制进行ADRD研究。本研究的主要目的包括：1）考察时间 RA患者心血管危险因素、全身炎症和ADRD之间的相关性; 2）评估直接 以及慢性炎症对RA中ADRD的心血管介导作用;以及3）定义人群 RA特征对偶发轻度认知功能障碍和ADRD的归因风险（PAR），总体和按 性拟议的研究将为RA慢性炎症背景下ADRD的风险分层提供信息 作为提高对ADRD风险的认识和制定预防战略的关键步骤， RA患者及以上。这些目标与NIA的目标D非常一致，以提高我们对 大脑老化和ADRD，特别是定义炎症过程对发展的影响， AD，以及中年期间是否存在肥胖、糖尿病、高血压和心脏病等全身性风险因素 与加速的年龄相关认知能力下降和AD风险增加有关。成功 该奖项的完成将促进下一代以患者为导向的研究人员的发展， ADRD将扩大Myasoedova博士的POR计划，以确保持续的指导机会， 未来，与NIA的使命“促进老龄化研究和临床科学家的发展”保持一致。

PROJECT SUMMARY/ABSTRACT This K24 application seeks to provide protected time for Dr. Elena Myasoedova to mentor trainees in patient- oriented research (POR) aiming at defining the long-term temporal relationship between systemic inflammation, cardiovascular risk factors and cardiovascular events on the risk of Alzheimer’s Disease and other related dementias (ADRD), using rheumatoid arthritis (RA) as a prototype. This award will enable the applicant to solidify and advance her current NIA-funded R01 research program in new directions and to expand her mentoring opportunities and mentoring experience. Dr. Myasoedova is a tenure-track Associate Professor at Mayo Clinic. She has a strong and ongoing record of high-quality POR, publication, and mentoring in research directly related to the proposed studies. The applicant has shown significant abilities in mentoring trainees at all career stages and will continue to benefit from the rich and robust resources, unique research infrastructure and a large pool of patients and mentees at Mayo Clinic. During the funding period, further development of the applicant will include: 1) Improvement in mentorship skills in POR; 2) Enhancement of knowledge in biostatistics for POR; 3) Development of a collaborative niche for POR in aging and ADRD in rheumatic diseases; and 4) Maintaining uninterrupted extramural funding. These goals will be achieved through a combination of seminars, meetings, courses, and collaboration with the Division of Epidemiology, the Kogod Center on Aging, the Rochester Epidemiology Project and the Mayo Clinic Study on Aging. Dr. Myasoedova will further integrate and advance these skills through continued mentorship of trainees within currently funded POR and through expansion of her ADRD research through the K24 mechanism. Research aims of the proposal include: 1) Examining the temporal association between cardiovascular risk factors, systemic inflammation and ADRD in RA; 2) Evaluating direct and cardiovascular-mediated effects of chronic inflammation on ADRD in RA; and 3) Defining the population attributable risk (PAR) of RA characteristics on incident mild cognitive impairment and ADRD, overall and by sex. The proposed studies will inform risk stratification of ADRD in a chronic inflammatory setting of RA overall and by sex as a key step for advancing the understanding of ADRD risk and developing prevention strategies in patients with RA and beyond. These aims are well-aligned with NIA’s Goal D to improve our understanding of the aging brain and ADRD, specifically defining the impact of inflammatory processes on the development of AD, and whether systemic risk factors such as obesity, diabetes, hypertension, and heart disease during midlife are associated with accelerated age-related cognitive decline and with increased risk for AD. Successful completion of this award will facilitate the development of the next generation of patient-oriented researchers in ADRD and will expand Dr. Myasoedova’s POR program to ensure continued mentoring opportunities into the future, aligning with the NIA’s mission to “Foster the development of research and clinician scientists in aging’.