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Updated: Jan 28, 2026

A Versatile Murine Model of Subcortical White Matter Stroke for the Study of Axonal Degeneration and White Matter Neurobiology
Published on: March 17, 2016
Association between white matter hyperintensities, cortical volumes, and late-onset epilepsy
Emily L Johnson1, Gregory L Krauss2, Alexandra K Lee2
1From the Department of Neurology (E.L.J., G.L.K., A.L.C.S., R.F.G.), Johns Hopkins University School of Medicine; Department of Epidemiology (A.K.L., R.F.G.), Johns Hopkins School of Public Health, Baltimore, MD; Department of Epidemiology (A.M.K.-N.), University of North Carolina at Chapel Hill; Department of Neurology (J.H.), University of Mississippi Medical Center, Jackson; and Department of Radiology (C.R.J.), Mayo Clinic, Rochester, MN. ejohns92@jhmi.edu.
Objective:
To identify the association between brain vascular changes and cortical volumes on MRI and late-onset epilepsy.
Methods:
In 1993-1995, 1,920 participants (median age 62.7, 59.9% female) in the community-based Atherosclerosis Risk in Communities (ARIC) Study underwent MRI, and white matter hyperintensities were measured. In addition, in 2011-2013, 1,964 ARIC participants (median age 72.4, 61.1% female) underwent MRI, and cortical volumes and white matter hyperintensities were measured. We identified cases of late-onset epilepsy (starting at age 60 or later) from ARIC hospitalization records and Medicare claims data. Using the 1993-1995 MRI, we evaluated the association between white matter hyperintensities and subsequent epilepsy using survival analysis. We used the 2011-2013 MRI to conduct cross-sectional logistic regression to examine the association of cortical volumes and white matter hyperintensities with late-onset epilepsy. All models were adjusted for demographics, hypertension, diabetes, smoking, and APOE ε4 allele status.
Results:
Ninety-seven ARIC participants developed epilepsy after having an MRI in 1993-1995 (incidence 3.34 per 1,000 person-years). The degree of white matter hyperintensities measured at ages 49-72 years was associated with the risk of late-onset epilepsy (hazard ratio 1.27 per age-adjusted SD, 95% confidence interval [CI] 1.06-1.54). Lower cortical volume scores were associated cross-sectionally with higher odds of late-onset epilepsy (odds ratio 1.87, 95% CI 1.16-3.02) per age-adjusted SD.
Conclusions:
This study demonstrates associations between earlier-life white matter hyperintensities on MRI and later-life incident epilepsy, and between cortical volumes measured later in life and late-onset epilepsy. These findings may help illuminate the causes of late-onset epilepsy.
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