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

类风湿关节炎患者全身炎症、心血管风险状况与阿尔茨海默病及相关痴呆症发展之间的时间关联

• 批准号: 10669259
• 负责人: Elena Myasoedova
• 金额: $ 19.01万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2027-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10669259
• 关键词: Acceleration; Accounting; Address; Age; Age-associated memory impairment; Aging; Alleles; Alzheimer disease prevention; Alzheimer' s Disease; Alzheimer' s disease related dementia; Alzheimer' s disease risk; Alzheimer’s disease biomarker; Antirheumatic Agents; Autoimmune; Autoimmunity; Award; Biological Products; Biometry; C-reactive protein; Cardiovascular Diseases; Cardiovascular system; Characteristics; Chronic; Clinic; Collaborations; Data; Dementia; Development; Diabetes Mellitus; Disease; Disease model; Elderly; Ensure; Epidemiology; Erythrocyte Sedimentation Rate; Event; Evolution; Extramural Activities; Female; Fostering; Funding; Future; Goals; Heart Diseases; Hyperlipidemia; Hypertension; Immune system; Impaired cognition; Incidence; Inflammation; Inflammatory; Infrastructure; Intervention; Knowledge; Leadership; Lipids; Longitudinal Studies; Mediating; Mentors; Mentorship; Mid-Career Clinical Scientist Award (K24); Midcareer Investigator Award in Patient-Oriented Research; Mission; Nervous System Trauma; Obesity; Patients; Phenotype; Population Attributable Risks; Prevention; Prevention strategy; Primary Prevention; Process; Public Health; Publications; Publishing; Research; Research Infrastructure; Research Personnel; Research Support; Resources; Rheumatism; Rheumatoid Arthritis; Risk; Risk Factors; Role; Scientist; Time; United States National Institutes of Health; Woman; age related; aging brain; cardiovascular disorder risk; cardiovascular risk factor; career; chronic inflammatory disease; cognitive performance; cohort; comorbidity; dementia risk; experience; follow-up; immunoregulation; improved; indexing; inflammatory marker; innovation; meetings; men; metabolic profile; mid-career faculty; middle age; mild cognitive impairment; neuroimaging marker; next generation; novel; patient oriented; patient oriented research; population based; prevent; programs; prototype; research and development; risk stratification; sex; skills; sociodemographics; systemic inflammatory response; tenure track; therapeutic target; vascular cognitive impairment and dementia

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’.

项目摘要/摘要 该K24应用程序旨在为Elena Myasoedova博士提供受保护的时间，以便患者的心理学生 - 定向研究（POR）旨在定义全身炎症之间的长期临时关系， 关于阿尔茨海默氏病及其他相关风险的心血管危险因素和心血管事件 痴呆症（ADRD），使用类风湿关节炎（RA）作为原型。该奖项将使申请人能够巩固 并在新方向上推进她当前的NIA资助R01研究计划，并扩大她的心理 机会和心理经验。 Myasoedova博士是Mayo诊所的终身助理副教授。 她在直接相关的研究中有很强的高质量POR，出版和心理的记录 提出的研究。申请人在所有职业阶段都表现出重要的心理学员 并将继续从丰富而强大的资源，独特的研究基础设施和大型池中受益 梅奥诊所的患者和导师。在资助期间，申请人的进一步发展将 包括：1）POR中的精神技能提高； 2）增强POR生物统计学知识； 3） 开发衰老和风湿性疾病中的ADRD的合作利基市场； 4）维护 不间断的壁外资金。这些目标将通过结合精神分子，会议， 课程，并与罗切斯特（Kogod）老龄化中心的流行病学系合作，罗切斯特 流行病学项目和梅奥诊所的衰老研究。 Myasoedova博士将进一步整合和进步 这些技能通过当前资助的POR和扩大她的持续心态。 ADRD通过K24机制进行研究。该提案的研究目的包括：1）检查临时性 RA中心血管危险因素，全身注射和ADRD之间的关联； 2）直接评估 慢性炎症对RA中AD​​RD的心血管介导的作用； 3）定义人口 RA的特征归因于事件特征的风险（PAR），对轻度认知障碍和ADRD，总体上以及通过 性别。拟议的研究将在RA总体上的慢性炎症环境中告知ADRD的风险分层 通过性作为推进对ADRD风险的理解并制定预防策略的关键步骤 RA及以后的患者。这些目标与NIA的目标d相符，以提高我们对 衰老的大脑和ADRD，特别定义了炎症过程对发展的影响 AD以及中年肥胖，糖尿病，高血压和心脏病等系统性危险因素是否存在 与加速与年龄相关的认知下降和AD风险增加有关。成功的 该奖项的完成将支持下一代以患者为导向的研究人员的发展 ADRD并将扩大Myasoedova博士的POR计划，以确保继续进行心理机会 未来，符合NIA的使命，即“促进衰老的研究和临床科学家的发展”。