Specialized Pro-Resolving Mediators, ADRD Biomarkers, and Sleep: A Multilevel Investigation of Cognitive Health in the Einstein Aging Study - PROJECT SUMMARY/ABSTRACT This K23 proposal aims to establish Dr. Monique S. Balthazar as an independent leader in clinical and translational research focused on sleep and brain health among community-dwelling older adults. Supported by a multidisciplinary team of mentors and guided by the NIA Research Framework and NCATS Translational Science Spectrum, this project addresses a critical gap in understanding how socioenvironmental and biobehavioral factors—specifically neighborhood quality and sleep health—influence cognitive outcomes and Alzheimer’s disease and related dementias (ADRD) risk. Poor sleep, affecting up to 90% of individuals with ADRD, is associated with cognitive decline and pathological markers such as β-amyloid and tau, yet the mechanisms underlying these associations remain elusive. Emerging laboratory evidence implicates lipid metabolism, particularly specialized pro-resolving mediators (SPMs), as playing a key but understudied role in neuroinflammation and ADRD risk. Leveraging longitudinal data and biological samples from the Einstein Aging Study (EAS; P01-AG003949-39), this research will clarify the interplay among sleep health, SPMs, ADRD biomarkers, cognitive function, and neighborhood quality. The specific aims are to: 1) estimate associations among SPMs, cognition, and neighborhood quality; 2) examine associations among SPMs, ADRD biomarkers, and neighborhood quality; and 3) assess associations among SPMs, sleep health, and neighborhood quality. Advanced analytic methods, including multilevel and time-varying effect modeling, will identify critical periods and pathways through which SPMs and sleep health impact ADRD risk, considering neighborhood context as a moderator. Dr. Balthazar will receive comprehensive training in sleep and cognitive assessment, neighborhood quality measurement, biomarker integration, and longitudinal data analysis. Through this work, Dr. Balthazar seeks to generate novel insights into the biological and socioenvironmental mechanisms underlying cognitive decline and inform precision medicine strategies for ADRD prevention, screening, and treatment. Ultimately, the project will bridge laboratory discoveries and community-based research, translating scientific advances into strategies that promote sleep and cognitive health among community-dwelling older adults. Penn State University boasts an intellectually rich research environment whose resources will facilitate the success of the proposed study.
