Researchers at the newly formed Optimal Aging Institute at NYU Langone Health have been awarded $31 million by the National Institutes of Health (NIH) for a diverse, 10-university cohort to study how vascular risk factors contribute to dementia and other age-related disorders in those over the age of 85, building upon existing research.

This research is increasingly necessary, with the number of adults older than 65 set to exceed the number of children under 18 in the United States by 2034. While aging is often accompanied by multiple chronic diseases, vascular risk factors identified earlier in life can strongly predict more serious risks like dementia and other types of cognitive and physical decline later in life. The new research will increase understanding of these risk factors and enable the development of biomarkers, which are molecules and changes found in bodily fluids or tissues that can be measured and signal an abnormal process or disease, across all stages of life.

This research is at the core of the Optimal Aging Institute’s mission of building a hub that creates and connects world-leading, cross-disciplinary teams of scientists and clinicians to fuel research into improving how people age, identifying and addressing risk factors earlier in life. The goal of the institute, formed in 2023, is to catalyze studies that move from observational epidemiology to biobanking, biomarker discovery, molecular research, and clinical trials that inform risk factor prediction, prevention, intervention, and policy changes.

The National Heart, Lung, and Blood Institute, a division of the NIH, made the award to NYU Langone’s Optimal Aging Institute to continue work on the Atherosclerosis Risk in Communities—Neurocognitive Study (ARIC-NCS), one of the longest-running heart health studies that includes the longest followed group of Black participants for cognition.

Co-led by Josef Coresh, MD, PhD, founding director of the institute, Dr. Thomas Mosley, director of the Memory Impairment and Neurodegenerative Dementia (MIND) Center at the University of Mississippi Medical Center, and Dr. Rebecca Gottesman, chief of the Stroke, Cognition and Neuroepidemiology Section at the National Institute of Neurological Disorders and Stroke (NINDS, part of the NIH), ARIC-NCS has tracked 15,792 enrolled individuals for more than 35 years in four communities in Maryland, North Carolina, Mississippi, and Minnesota. The study has spurred more than 2,700 publications and is connected to over 2 million biobanked specimens.

“As human life expectancy increases, there is an urgent need to better understand risk among people aged 85 or older and discover biomarkers that may explain the changing risk associations at older age for a wide range of diseases,” said Dr. Coresh, who is also a professor in the Departments of Population Health and Medicine at NYU Grossman School of Medicine. “Vascular disease, while preventable, is linked to heart disease, dementia, and kidney disease. We are grateful for the opportunity to continue gathering rigorous evidence regarding modifiable risk factors in midlife and in older age that may improve dementia prevention efforts and health among even the most elderly adults.”

As part of this funding renewal, Dr. Coresh (who has been working with ARIC since 2002) and a team of investigators from 10 universities across the country will follow approximately 4,000 of the original participants who remain active in the study and are in their 80s and 90s—building on almost 40 years’ worth of health-related and biomarker data to be related with cognitive function, physical decline, and age-related disease. The renewal will expand upon the data obtained to include six types of wearable devices to enable monitoring of sleep, physical activity, blood glucose, and the heart.

Over the next five years, the team of investigators will do the following:

• Study blood biomarkers, which include roughly 5,000 proteins and targeted Alzheimer’s disease and Alzheimer’s disease–related dementias (AD/ADRD) markers across four decades. The biomarkers will be studied in relation to dementia, mild cognitive impairment, multimorbidity and frailty, cognitive and physical decline.
• Evaluate the association and interaction of midlife vascular risk factors, multimorbidity (including sleep disturbances), and social determinants of health with blood and brain imaging dementia biomarkers and their progression.
• Contrast associations of vascular risk factors, cognitive and physical function and multimorbidity with dementia, cognitive and physical decline across ages (65 to 84 versus 85 and older), and their modification by health at older age.
• Ensure research considers race- and sex-specific analyses—70 percent of the approximately 4,000 active study participants are female and 25 percent are Black—to better understand how underlying multimorbidity, vascular risk factors, and social determinants of health influence not only biomarker levels but the timing of their alterations and impact on AD/ADRD biomarkers.

Close integration with partners across the NYU Langone system, Dr. Coresh said, enables the institute to implement and test interventions with real-world impacts in real-time, advancing practice-changing research to improve outcomes for all.

Dr. Coresh, an epidemiologist, has published multiple high-impact studies, including biomarker work examining novel proteins in the blood and pathways that can predict and may contribute to cognitive decline, kidney disease, and heart disease 20 years before symptom onset. He co-authored the results of the ACHIEVE clinical trial that provides the most rigorous evidence to date that suggests treating hearing loss slows down loss of thinking and memory abilities within only three years in older adults with hearing impairment at risk of developing dementia.

On April 15, Dr. Coresh will moderate a special symposium, “Controversies in Population Health: Tight blood pressure control—can we prevent dementia among older adults?” to highlight an important topic at the intersection of vascular health and aging. The event, co-sponsored by NYU Langone’s Department of Population Health and the Optimal Aging Institute, will feature six renowned experts in the field and will showcase recent groundbreaking research on how treating hypertension may prevent dementia. The discussion is open to the public; registration is required.

In addition to NYU Grossman School of Medicine, additional collaborating institutions include Baylor College of Medicine, Johns Hopkins University, Mayo Clinic, University of Minnesota, University of Mississippi Medical Center, University of North Caroline at Chapel Hill, University of Texas Health Science Center at Houston, Wake Forest University Health Sciences, and Washington University in St. Louis.

The research is supported by the National Heart, Lung, and Blood Institute, a division of the NIH, grant number U01HL096812.

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