Epigenetic and Chronic Drivers of Late-Onset Epilepsy

Late-onset unexplained epilepsy (LOUE) is a chronic condition affecting more than 250,000 older adults in the U.S., and people with LOUE are at high risk of developing dementia within 5 years of epilepsy diagnosis. The current proposal will add DNA methylation and chronic risk factor data to the ongoing multicenter Epilepsy of Late-onset Unknown etiology as a risk factor for Cognitive Impairment and Dementia (ELUCID) study, following 600 adults with LOUE and collecting medical history, MRI, and EEG data as well as longitudinal cognitive testing. The central hypotheses are that lifetime exposures contribute to LOUE and cognitive performance, and that distinct epigenetic markers will be identified associated with LOUE and with cognitive impairment in this group. Three distinct, complementary, independent aims will be pursued: 1) Define the epigenetic markers of LOUE, particularly differentially methylated regions and “epigenetic age,” and compare how epigenetic age is related to “brain age” calculated from MRI and EEG; 2) Define the chronic health drivers associated with LOUE, and how these factors affect the relationship between vascular risk factors and LOUE; and 3) Determine the relationships between epigenetic markers and chronic risk factors in people with LOUE, and how these affect cognition in people with LOUE. This study will establish fundamental knowledge to inform dementia prevention in this high-risk group. Project Number: 1R01NS142275-01A1 | Fiscal Year: 2026 | NIH Institute/Center: National Institute of Neurological Disorders and Stroke (NINDS) | Principal Investigator: Emily Johnson | Institution: JOHNS HOPKINS UNIVERSITY, BALTIMORE, MD | Award Amount: $536,524 | Activity Code: R01 | Study Section: Neurological, Mental and Behavioral Health Study Section[NMBH] View on NIH RePORTER: https://reporter.nih.gov/project-details/11298115