Association between Midlife Risk Factors and Late-Onset Epilepsy

Results from the Atherosclerosis Risk in Communities Study

Emily Johnson, Gregory Krauss, Alexandra K. Lee, Andrea L.C. Schneider, Jennifer L. Dearborn, Anna M. Kucharska-Newton, Juebin Huang, Alvaro Alonso, Rebecca F Gottesman

Research output: Contribution to journalArticle

Abstract

Importance: The incidence of epilepsy is higher in older age than at any other period of life. Stroke, dementia, and hypertension are associated with late-onset epilepsy; however, the role of other vascular and lifestyle factors remains unclear. Objective: To identify midlife vascular and lifestyle risk factors for late-onset epilepsy. Design, Setting, and Participants: The Atherosclerosis Risk in Communities (ARIC) study is a prospective cohort study of 15792 participants followed up since 1987 to 1989 with in-person visits, telephone calls, and surveillance of hospitalizations (10974 invited without completing enrollment). The ARIC is a multicenter study with participants selected from 4 US communities. This study included 10420 black or white participants from ARIC with at least 2 years of Medicare fee-for-service coverage and without missing baseline data. Data were analyzed betweeen April 2017 and May 2018. Exposures: Demographic, vascular, lifestyle, and other possible epilepsy risk factors measured at baseline (age 45-64 years) were evaluated in multivariable survival models including demographics, vascular risk factors, and lifestyle risk factors. Main Outcomes and Measures: Time to development of late-onset epilepsy (2 or more International Classification of Diseases, Ninth Revision codes for epilepsy or seizures starting at 60 years or older in any claim [hospitalization or outpatient Medicare through 2013]), with first code for seizures after at least 2 years without code for seizures. Results: Of the 10420 total participants (5878 women [56.4%] and 2794 black participants [26.8%]; median age 55 years at first visit), 596 participants developed late-onset epilepsy (3.33 per 1000 person-years). The incidence was higher in black than in white participants (4.71; 95% CI, 4.12-5.40 vs 2.88; 95% CI, 2.60-3.18 per 1000 person-years). In multivariable analysis, baseline hypertension (hazard ratio [HR], 1.30; 95% CI, 1.09-1.55), diabetes (HR, 1.45; 95% CI, 1.17-1.80), smoking (HR, 1.09; 95% CI, 1.01-1.17), apolipoprotein E ϵ4 genotype (1 allele HR, 1.22; 95% CI, 1.02-1.45; 2 alleles HR, 1.95; 95% CI, 1.35-2.81), and incident stroke (HR, 3.38; 95% CI, 2.78-4.10) and dementia (HR, 2.56; 95% CI, 2.11-3.12) were associated with an increased risk of late-onset epilepsy, while higher levels of physical activity (HR, 0.90; 95% CI, 0.83-0.98) and moderate alcohol intake (HR, 0.72; 95% CI, 0.57-0.90) were associated with a lower risk. Results were similar after censoring individuals with stroke or dementia. Conclusions and Relevance: Potentially modifiable risk factors in midlife and the APOE ϵ4 genotype were positively associated with risk of developing late-onset epilepsy. Although stroke and dementia were both associated with late-onset epilepsy, vascular and lifestyle risk factors were significant even in the absence of stroke or dementia.

Original languageEnglish (US)
Pages (from-to)1375-1382
Number of pages8
JournalJAMA Neurology
Volume75
Issue number11
DOIs
StatePublished - Nov 1 2018

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Epilepsy
Atherosclerosis
Dementia
Life Style
Stroke
Blood Vessels
Seizures
Medicare
Hospitalization
Alleles
Genotype
Demography
Hypertension
Apolipoprotein E4
Fee-for-Service Plans
Incidence
International Classification of Diseases
Telephone
Multicenter Studies
Cohort Studies

ASJC Scopus subject areas

  • Clinical Neurology

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Association between Midlife Risk Factors and Late-Onset Epilepsy : Results from the Atherosclerosis Risk in Communities Study. / Johnson, Emily; Krauss, Gregory; Lee, Alexandra K.; Schneider, Andrea L.C.; Dearborn, Jennifer L.; Kucharska-Newton, Anna M.; Huang, Juebin; Alonso, Alvaro; Gottesman, Rebecca F.

In: JAMA Neurology, Vol. 75, No. 11, 01.11.2018, p. 1375-1382.

Research output: Contribution to journalArticle

Johnson, Emily ; Krauss, Gregory ; Lee, Alexandra K. ; Schneider, Andrea L.C. ; Dearborn, Jennifer L. ; Kucharska-Newton, Anna M. ; Huang, Juebin ; Alonso, Alvaro ; Gottesman, Rebecca F. / Association between Midlife Risk Factors and Late-Onset Epilepsy : Results from the Atherosclerosis Risk in Communities Study. In: JAMA Neurology. 2018 ; Vol. 75, No. 11. pp. 1375-1382.
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abstract = "Importance: The incidence of epilepsy is higher in older age than at any other period of life. Stroke, dementia, and hypertension are associated with late-onset epilepsy; however, the role of other vascular and lifestyle factors remains unclear. Objective: To identify midlife vascular and lifestyle risk factors for late-onset epilepsy. Design, Setting, and Participants: The Atherosclerosis Risk in Communities (ARIC) study is a prospective cohort study of 15792 participants followed up since 1987 to 1989 with in-person visits, telephone calls, and surveillance of hospitalizations (10974 invited without completing enrollment). The ARIC is a multicenter study with participants selected from 4 US communities. This study included 10420 black or white participants from ARIC with at least 2 years of Medicare fee-for-service coverage and without missing baseline data. Data were analyzed betweeen April 2017 and May 2018. Exposures: Demographic, vascular, lifestyle, and other possible epilepsy risk factors measured at baseline (age 45-64 years) were evaluated in multivariable survival models including demographics, vascular risk factors, and lifestyle risk factors. Main Outcomes and Measures: Time to development of late-onset epilepsy (2 or more International Classification of Diseases, Ninth Revision codes for epilepsy or seizures starting at 60 years or older in any claim [hospitalization or outpatient Medicare through 2013]), with first code for seizures after at least 2 years without code for seizures. Results: Of the 10420 total participants (5878 women [56.4{\%}] and 2794 black participants [26.8{\%}]; median age 55 years at first visit), 596 participants developed late-onset epilepsy (3.33 per 1000 person-years). The incidence was higher in black than in white participants (4.71; 95{\%} CI, 4.12-5.40 vs 2.88; 95{\%} CI, 2.60-3.18 per 1000 person-years). In multivariable analysis, baseline hypertension (hazard ratio [HR], 1.30; 95{\%} CI, 1.09-1.55), diabetes (HR, 1.45; 95{\%} CI, 1.17-1.80), smoking (HR, 1.09; 95{\%} CI, 1.01-1.17), apolipoprotein E ϵ4 genotype (1 allele HR, 1.22; 95{\%} CI, 1.02-1.45; 2 alleles HR, 1.95; 95{\%} CI, 1.35-2.81), and incident stroke (HR, 3.38; 95{\%} CI, 2.78-4.10) and dementia (HR, 2.56; 95{\%} CI, 2.11-3.12) were associated with an increased risk of late-onset epilepsy, while higher levels of physical activity (HR, 0.90; 95{\%} CI, 0.83-0.98) and moderate alcohol intake (HR, 0.72; 95{\%} CI, 0.57-0.90) were associated with a lower risk. Results were similar after censoring individuals with stroke or dementia. Conclusions and Relevance: Potentially modifiable risk factors in midlife and the APOE ϵ4 genotype were positively associated with risk of developing late-onset epilepsy. Although stroke and dementia were both associated with late-onset epilepsy, vascular and lifestyle risk factors were significant even in the absence of stroke or dementia.",
author = "Emily Johnson and Gregory Krauss and Lee, {Alexandra K.} and Schneider, {Andrea L.C.} and Dearborn, {Jennifer L.} and Kucharska-Newton, {Anna M.} and Juebin Huang and Alvaro Alonso and Gottesman, {Rebecca F}",
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TY - JOUR

T1 - Association between Midlife Risk Factors and Late-Onset Epilepsy

T2 - Results from the Atherosclerosis Risk in Communities Study

AU - Johnson, Emily

AU - Krauss, Gregory

AU - Lee, Alexandra K.

AU - Schneider, Andrea L.C.

AU - Dearborn, Jennifer L.

AU - Kucharska-Newton, Anna M.

AU - Huang, Juebin

AU - Alonso, Alvaro

AU - Gottesman, Rebecca F

PY - 2018/11/1

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N2 - Importance: The incidence of epilepsy is higher in older age than at any other period of life. Stroke, dementia, and hypertension are associated with late-onset epilepsy; however, the role of other vascular and lifestyle factors remains unclear. Objective: To identify midlife vascular and lifestyle risk factors for late-onset epilepsy. Design, Setting, and Participants: The Atherosclerosis Risk in Communities (ARIC) study is a prospective cohort study of 15792 participants followed up since 1987 to 1989 with in-person visits, telephone calls, and surveillance of hospitalizations (10974 invited without completing enrollment). The ARIC is a multicenter study with participants selected from 4 US communities. This study included 10420 black or white participants from ARIC with at least 2 years of Medicare fee-for-service coverage and without missing baseline data. Data were analyzed betweeen April 2017 and May 2018. Exposures: Demographic, vascular, lifestyle, and other possible epilepsy risk factors measured at baseline (age 45-64 years) were evaluated in multivariable survival models including demographics, vascular risk factors, and lifestyle risk factors. Main Outcomes and Measures: Time to development of late-onset epilepsy (2 or more International Classification of Diseases, Ninth Revision codes for epilepsy or seizures starting at 60 years or older in any claim [hospitalization or outpatient Medicare through 2013]), with first code for seizures after at least 2 years without code for seizures. Results: Of the 10420 total participants (5878 women [56.4%] and 2794 black participants [26.8%]; median age 55 years at first visit), 596 participants developed late-onset epilepsy (3.33 per 1000 person-years). The incidence was higher in black than in white participants (4.71; 95% CI, 4.12-5.40 vs 2.88; 95% CI, 2.60-3.18 per 1000 person-years). In multivariable analysis, baseline hypertension (hazard ratio [HR], 1.30; 95% CI, 1.09-1.55), diabetes (HR, 1.45; 95% CI, 1.17-1.80), smoking (HR, 1.09; 95% CI, 1.01-1.17), apolipoprotein E ϵ4 genotype (1 allele HR, 1.22; 95% CI, 1.02-1.45; 2 alleles HR, 1.95; 95% CI, 1.35-2.81), and incident stroke (HR, 3.38; 95% CI, 2.78-4.10) and dementia (HR, 2.56; 95% CI, 2.11-3.12) were associated with an increased risk of late-onset epilepsy, while higher levels of physical activity (HR, 0.90; 95% CI, 0.83-0.98) and moderate alcohol intake (HR, 0.72; 95% CI, 0.57-0.90) were associated with a lower risk. Results were similar after censoring individuals with stroke or dementia. Conclusions and Relevance: Potentially modifiable risk factors in midlife and the APOE ϵ4 genotype were positively associated with risk of developing late-onset epilepsy. Although stroke and dementia were both associated with late-onset epilepsy, vascular and lifestyle risk factors were significant even in the absence of stroke or dementia.

AB - Importance: The incidence of epilepsy is higher in older age than at any other period of life. Stroke, dementia, and hypertension are associated with late-onset epilepsy; however, the role of other vascular and lifestyle factors remains unclear. Objective: To identify midlife vascular and lifestyle risk factors for late-onset epilepsy. Design, Setting, and Participants: The Atherosclerosis Risk in Communities (ARIC) study is a prospective cohort study of 15792 participants followed up since 1987 to 1989 with in-person visits, telephone calls, and surveillance of hospitalizations (10974 invited without completing enrollment). The ARIC is a multicenter study with participants selected from 4 US communities. This study included 10420 black or white participants from ARIC with at least 2 years of Medicare fee-for-service coverage and without missing baseline data. Data were analyzed betweeen April 2017 and May 2018. Exposures: Demographic, vascular, lifestyle, and other possible epilepsy risk factors measured at baseline (age 45-64 years) were evaluated in multivariable survival models including demographics, vascular risk factors, and lifestyle risk factors. Main Outcomes and Measures: Time to development of late-onset epilepsy (2 or more International Classification of Diseases, Ninth Revision codes for epilepsy or seizures starting at 60 years or older in any claim [hospitalization or outpatient Medicare through 2013]), with first code for seizures after at least 2 years without code for seizures. Results: Of the 10420 total participants (5878 women [56.4%] and 2794 black participants [26.8%]; median age 55 years at first visit), 596 participants developed late-onset epilepsy (3.33 per 1000 person-years). The incidence was higher in black than in white participants (4.71; 95% CI, 4.12-5.40 vs 2.88; 95% CI, 2.60-3.18 per 1000 person-years). In multivariable analysis, baseline hypertension (hazard ratio [HR], 1.30; 95% CI, 1.09-1.55), diabetes (HR, 1.45; 95% CI, 1.17-1.80), smoking (HR, 1.09; 95% CI, 1.01-1.17), apolipoprotein E ϵ4 genotype (1 allele HR, 1.22; 95% CI, 1.02-1.45; 2 alleles HR, 1.95; 95% CI, 1.35-2.81), and incident stroke (HR, 3.38; 95% CI, 2.78-4.10) and dementia (HR, 2.56; 95% CI, 2.11-3.12) were associated with an increased risk of late-onset epilepsy, while higher levels of physical activity (HR, 0.90; 95% CI, 0.83-0.98) and moderate alcohol intake (HR, 0.72; 95% CI, 0.57-0.90) were associated with a lower risk. Results were similar after censoring individuals with stroke or dementia. Conclusions and Relevance: Potentially modifiable risk factors in midlife and the APOE ϵ4 genotype were positively associated with risk of developing late-onset epilepsy. Although stroke and dementia were both associated with late-onset epilepsy, vascular and lifestyle risk factors were significant even in the absence of stroke or dementia.

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