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February 26, 2019; 92 (9) Article

Association between white matter hyperintensities, cortical volumes, and late-onset epilepsy

View ORCID ProfileEmily L. Johnson, Gregory L. Krauss, Alexandra K. Lee, Andrea L.C. Schneider, Anna M. Kucharska-Newton, Juebin Huang, Clifford R. Jack, Rebecca F. Gottesman
First published January 25, 2019, DOI: https://doi.org/10.1212/WNL.0000000000007010
Emily L. Johnson
From 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.
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Gregory L. Krauss
From 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.
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Alexandra K. Lee
From 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.
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Andrea L.C. Schneider
From 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.
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Anna M. Kucharska-Newton
From 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.
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Juebin Huang
From 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.
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Clifford R. Jack Jr
From 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.
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Rebecca F. Gottesman
From 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.
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Association between white matter hyperintensities, cortical volumes, and late-onset epilepsy
Emily L. Johnson, Gregory L. Krauss, Alexandra K. Lee, Andrea L.C. Schneider, Anna M. Kucharska-Newton, Juebin Huang, Clifford R. Jack, Rebecca F. Gottesman
Neurology Feb 2019, 92 (9) e988-e995; DOI: 10.1212/WNL.0000000000007010

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Abstract

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.

Glossary

ARIC=
Atherosclerosis Risk in Communities;
ARIC-NCS=
Atherosclerosis Risk in Communities Neurocognitive Study;
CHS=
Cardiovascular Health Study;
CI=
confidence interval;
CMS=
Centers for Medicare & Medicaid Services;
FFS=
fee-for-service;
HR=
hazard ratio;
ICD-9=
International Classification of Diseases–9;
LOE=
late-onset epilepsy;
OR=
odds ratio;
WMH=
white matter hyperintensity

Footnotes

  • Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Received July 31, 2018.
  • Accepted in final form October 25, 2018.
  • © 2019 American Academy of Neurology
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