Dysregulation of glucose and lipid metabolism are central features of human aging and play major roles in the highly morbid cardiometabolic conditions prevalent among older adults, including cardiovascular disease, diabetes, and congestive heart failure. Non-esterified, or free, fatty acids (NEFAs) have long been implicated as central actors in impaired metabolism and may underlie many of the adverse effects of metabolic aging, including cognitive decline and frailty. Dr. Kenneth Mukamal, a general internist, has undertaken broad-based epidemiological research with a particular focus on metabolic determinants of cardiovascular and cognitive outcomes among older adults. This research has largely centered on the Cardiovascular Health Study (CHS), an NHLBI- and NIA-funded cohort study of 5,888 adults aged 65 and older from four U.S. communities, and the Ginkgo Evaluation of Memory Study (GEMS), a randomized trial that conducted additional dementia follow-up in a subset of CHS participants. Dr. Mukamal serves as a member of the CHS Steering Committee and chairs its Diabetes Working Group. Dr. Mukamal?s ongoing research support (R01-AG-053325) funds measurement of total, individual and post-glucose-load NEFAs in the unique CHS cohort. His recent work has demonstrated that total NEFAs are associated with cognitive decline and adjudicated dementia in CHS. Supported by two recent supplements ? one to support an underrepresented minority scientist whom Dr. Mukamal mentors and a second to support ADRD research in response to NOT-AG-18-008 ? Dr. Mukamal is now actively investigating the role of individual and post-load NEFAs in dementia and frailty in CHS and elsewhere. Dr. Mukamal has a long, consistent, and distinguished track record of mentoring young scientists, serving in major educational roles across a variety of settings and having received formal recognition for his outstanding research mentorship. A Midcareer Investigator Award in Patient-Oriented Research would enable him to expand and deepen his commitment to mentoring by reducing his administrative responsibilities and providing direct support for focused, intensive mentoring activities that specifically relate to metabolic impairment in aging. In addition, this award would enable Dr. Mukamal to further develop his own career and gain knowledge, familiarity, and expertise in domains crucial to the further extension of his work into dementia, such as advances in cognitive assessment and neuroimaging. In conjunction with the outstanding environments for training and mentoring at Beth Israel Deaconess Medical Center, Harvard Medical School, and the Harvard TH Chan School of Public Health, this award will enable Dr. Mukamal to expand and improve his mentoring experience and, as a result, help to train the next generation of investigators in metabolic aging.
Abnormal metabolism of sugars, fats, and related molecules is a central feature of human aging and plays major roles in age-related conditions like cardiovascular disease, diabetes, and dementia. Dr. Mukamal has undertaken broad-based epidemiological research on metabolic determinants of aging, including recent research to understand the health effects of fatty acids that circulate in the blood and affect organs throughout the body. The goals of this K24 award are to enable Dr. Mukamal to expand his knowledge in the measurement of dementia in large clinical studies of metabolism and to train new clinical investigators in research devoted to metabolic aging.