Two Research Awards Advance Blood-Based Epigenetics Studies of Cognitive Aging and Dementia
University of Miami Miller School of Medicine neuropsychologist Deirdre O’Shea, Ph.D., will investigate whether changes in blood DNA methylation can help explain differences in cognitive aging, dementia risk and Lewy body disease.
Key Takeaways
- Two research awards will support studies examining blood DNA methylation in cognitive aging, dementia and Lewy body disease.
- Researchers will investigate whether epigenetic patterns measured in blood are associated with cognitive decline, dementia risk and underlying disease processes.
- The projects are exploratory and do not establish DNA methylation as a diagnostic or predictive test for individual patients.
Why do some people retain their cognitive abilities as they age while others experience decline?
Two new research awards will allow University of Miami Miller School of Medicine scientist Deirdre O’Shea, Ph.D., to examine whether part of the answer may be found in epigenetic changes detectable in blood.
Dr. O’Shea, an assistant professor of clinical neurology at the Miller School and clinical neuropsychologist at the Comprehensive Center for Brain Health, is studying DNA methylation, a process that helps regulate how genes function without changing the underlying DNA sequence. Her research will test whether instability in these molecular patterns can provide insight into cognitive decline, dementia and the biological effects of cardiovascular health on the aging brain.
The work is supported by a five-year K01 Research Career Development Award from the National Institute on Aging and a one-year Angela S. Taylor New Investigator Pilot Study Award from the Lewy Body Dementia Association. Together, the projects will investigate whether epigenetic information in blood can help researchers better understand why cognitive aging varies from person to person.
What Can DNA Methylation Reveal About Cognitive Aging?
DNA methylation involves chemical modifications to DNA that help regulate gene activity. Unlike a person’s fixed genetic sequence, methylation patterns may reflect the combined influence of aging, health and other biological processes.
Dr. O’Shea’s K01 project, “Epigenetic Instability as a Marker of Age-Related Cognitive Decline and Dementia,” will examine whether growing instability in DNA methylation is associated with later cognitive decline and dementia. The study will also explore whether that instability may provide a biological link between cardiovascular health and changes in cognition as people age.
“Much of my work has focused on understanding why some people maintain their cognitive abilities as they age while others experience decline,” Dr. O’Shea said. “The K01 gives me the opportunity to approach that question from a different level of analysis and ask what changes occurring in the epigenome might tell us about that variability.”
Using longitudinal data from large studies of aging, Dr. O’Shea will investigate whether blood DNA methylation instability is associated with subsequent cognitive decline and dementia. The research will assess whether methylation measures provide information beyond established clinical risk factors and explore how clinicians might eventually interpret and use such information.
The project is designed to study associations and potential clinical value. It does not yet establish DNA methylation instability as a diagnostic or predictive test for an individual patient.
How Will the Lewy Body Disease Study Extend the Research?
A second award will apply a related epigenetic approach to Lewy body disease.
Supported by the Angela S. Taylor New Investigator Pilot Study Award from the Lewy Body Dementia Association, the one-year project will examine blood DNA methylation and measures of epigenetic aging in people with clinically defined Lewy body disease. Participants in the study have undergone skin biopsy for phosphorylated alpha-synuclein, a marker of underlying synuclein pathology.
What Is DNA Methylation?
DNA methylation involves chemical modifications to DNA that help regulate gene activity without changing the underlying DNA sequence. Researchers study these patterns because they may reflect the combined effects of aging, health and other biological processes.
The researchers will study whether epigenetic patterns in blood differ according to the presence of alpha-synuclein pathology. They will also explore methylation differences across the genome.
This pilot study is exploratory. Its findings may help researchers identify biological patterns worth testing in larger studies, but additional validation would be needed before any measure could be considered for clinical use.
Why Study Epigenetics Across Different Forms of Dementia?
Although the two projects address distinct research questions, both examine whether epigenetic information measured in blood can provide a clearer view of the biological processes that contribute to cognitive aging and dementia.
“As a clinical neuropsychologist, I see cognition as the outcome of many interacting processes rather than any single pathology,” Dr. O’Shea said. “What interests me about epigenetics is that it may provide another window into those processes, including the influence of vascular and other systemic factors on brain aging.”
Blood-based measures could give researchers a practical way to study those interactions across large groups of people. For now, however, the projects focus on research discovery rather than patient diagnosis or treatment decisions.
Building an Independent Research Program
The National Institute on Aging supports Dr. O’Shea’s K01 award. Her mentoring team includes:
- James Galvin, M.D., M.P.H., professor of neurology at the Miller School, chief of the Division of Cognitive Neurology, founding director of the Comprehensive Center for Brain Health and director of the Lewy Body Dementia Research Center of Excellence
- Lily Wang, Ph.D., professor of public health sciences at the Miller School
- Melissa Armstrong, M.D., M.Sc., from the University of Florida
Their combined mentorship spans cognitive aging and dementia, epigenetics, biostatistics and clinical research.
The awards will help Dr. O’Shea develop an independent research program integrating clinical neuropsychology, cognitive aging and epigenetics. The program’s broader objective is to improve scientific understanding of the biological differences that may influence cognitive decline and dementia.
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Tags: aging, Alzheimer's disease, brain health, cognitive decline, Comprehensive Center for Brain Health, dementia, Department of Neurology, DNA, Dr. Deidre O'Shea, Dr. James Galvin, epigenetics, Lewy body dementia, memory disorders, neurology