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

项目摘要/摘要 此K24应用程序旨在为Elena Myasoedova博士提供受保护的时间来指导受训患者- 定向研究(POR)旨在定义全身性炎症、 心血管危险因素和心血管事件对阿尔茨海默病等相关风险的影响 痴呆(ADRD)，以类风湿性关节炎(RA)为原型。这一奖励将使申请者能够巩固 并以新的方向推进她目前由NIA资助的R01研究计划，并扩大她的指导 机会和指导经验。Myasoedova博士是梅奥诊所的终身教席副教授。 她在与研究直接相关的高质量POR、出版和指导方面拥有强大且持续的记录 对拟议的研究的支持。申请人在职业生涯的各个阶段都表现出了很强的指导能力。 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 梅奥诊所的病人和学员。在资助期内，申请人的进一步发展将 包括：1)改进POR的指导技能；2)加强POR的生物统计学知识；3) 为老龄化中的POR和风湿病中的ADRD开发协作利基；以及4)维护 不间断的校外资金。这些目标将通过研讨会、会议、 课程，以及与罗切斯特科戈德老龄中心流行病学部的合作 流行病学项目和关于老龄化的梅奥诊所研究。Myasoedova博士将进一步整合和推进 通过在当前资助的POR内继续指导学员以及通过扩展HER来实现这些技能 通过K24机制进行ADRD研究。该方案的研究目标包括：1)考察时态 心血管危险因素、全身炎症与类风湿关节炎的相关性2)直接评估 和心血管介导的慢性炎症对RA患者ADRD的影响；以及3)确定人群 RA特征对事件中轻度认知损害和ADRD的归因风险(PAR)，总体和 性。建议的研究将为整个RA慢性炎症环境下ADRD的风险分层提供信息 并将性别作为促进对ADRD风险的了解和制定预防策略的关键一步 类风湿性关节炎及以上的患者。这些目标与NIA的目标D非常一致，以提高我们对 老化的大脑和ADRD，具体定义了炎症过程对发展的影响 AD，以及中年期间是否存在系统性风险因素，如肥胖、糖尿病、高血压和心脏病 与年龄相关的认知衰退加速和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中心的研究人员的发展 并将扩大Myasoedova博士的POR计划，以确保持续的指导机会进入 未来，与NIA的使命相一致，即“促进研究和临床科学家在老龄化中的发展”。

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’.