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Association Between Midlife Risk Factors and Late-Onset Epilepsy: Results From the Atherosclerosis Risk in Communities Study.
JAMA Neurol 2018; 75(11):1375-1382JN

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 15 792 participants followed up since 1987 to 1989 with in-person visits, telephone calls, and surveillance of hospitalizations (10 974 invited without completing enrollment). The ARIC is a multicenter study with participants selected from 4 US communities. This study included 10 420 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 10 420 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.

Authors+Show Affiliations

Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland.Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland.Department of Epidemiology, Johns Hopkins School of Public Health, Baltimore, Maryland.Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland.Department of Neurology, Yale University School of Medicine, New Haven, Connecticut.Department of Epidemiology, University of North Carolina at Chapel Hill.Department of Neurology, University of Mississippi Medical Center, Jackson.Department of Epidemiology, Emory University, Atlanta, Georgia.Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland. Department of Epidemiology, Johns Hopkins School of Public Health, Baltimore, Maryland.

Pub Type(s)

Journal Article
Multicenter Study
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

30039175

Citation

Johnson, Emily L., et al. "Association Between Midlife Risk Factors and Late-Onset Epilepsy: Results From the Atherosclerosis Risk in Communities Study." JAMA Neurology, vol. 75, no. 11, 2018, pp. 1375-1382.
Johnson EL, Krauss GL, Lee AK, et al. Association Between Midlife Risk Factors and Late-Onset Epilepsy: Results From the Atherosclerosis Risk in Communities Study. JAMA Neurol. 2018;75(11):1375-1382.
Johnson, E. L., Krauss, G. L., Lee, A. K., Schneider, A. L. C., Dearborn, J. L., Kucharska-Newton, A. M., ... Gottesman, R. F. (2018). Association Between Midlife Risk Factors and Late-Onset Epilepsy: Results From the Atherosclerosis Risk in Communities Study. JAMA Neurology, 75(11), pp. 1375-1382. doi:10.1001/jamaneurol.2018.1935.
Johnson EL, et al. Association Between Midlife Risk Factors and Late-Onset Epilepsy: Results From the Atherosclerosis Risk in Communities Study. JAMA Neurol. 2018 11 1;75(11):1375-1382. PubMed PMID: 30039175.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Association Between Midlife Risk Factors and Late-Onset Epilepsy: Results From the Atherosclerosis Risk in Communities Study. AU - Johnson,Emily L, AU - Krauss,Gregory L, 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 - 2018/7/25/pubmed PY - 2018/7/25/medline PY - 2018/7/25/entrez SP - 1375 EP - 1382 JF - JAMA neurology JO - JAMA Neurol VL - 75 IS - 11 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 15 792 participants followed up since 1987 to 1989 with in-person visits, telephone calls, and surveillance of hospitalizations (10 974 invited without completing enrollment). The ARIC is a multicenter study with participants selected from 4 US communities. This study included 10 420 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 10 420 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. SN - 2168-6157 UR - https://www.unboundmedicine.com/medline/citation/30039175/Association_Between_Midlife_Risk_Factors_and_Late_Onset_Epilepsy:_Results_From_the_Atherosclerosis_Risk_in_Communities_Study_ L2 - https://jamanetwork.com/journals/jamaneurology/fullarticle/10.1001/jamaneurol.2018.1935 DB - PRIME DP - Unbound Medicine ER -