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

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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’.