The apolipoprotein E ε4 (APOE ε4) genotype and the presence of potentially modifiable risk factors (eg, smoking, hypertension, and diabetes in midlife) are associated with a higher risk for late-onset epilepsy, according to a study published in JAMA Neurology.

Participants from the Atherosclerosis Risk in Communities (ARIC) study with ≥2 years of Medicare fee-for-service coverage were enrolled (n=10,420). At baseline, the investigators collected data on demographics, lifestyle factors, vascular status, and potential epilepsy risk factors. At first study visit, the median participant age was 55 years. The main outcome was the time to late-onset epilepsy development at age ≥60 years. Participants were followed from 1987-1989 through 2013.

During follow-up, a total of 596 patients developed late-onset epilepsy, representing a rate of 3.33 per 1000 person-years. Black patients had a higher incidence rate of late-onset epilepsy compared with white participants (4.71 per 1000 person-years [95% CI, 4.12-5.40] vs 2.88 per 1000 person-years [95% CI, 2.60-3.18], respectively).

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Patients who had hypertension at baseline were more likely to develop late-onset epilepsy during follow-up (hazard ratio [HR] 1.30; 95% CI, 1.09-1.55), according to findings of the multivariable analysis. Additional baseline variables associated with a higher risk of late-onset epilepsy included diabetes (HR 1.45; 95% CI, 1.17-1.80), smoking (HR 1.09; 95% CI, 1.01-1.17), APOE ε4 genotype (1 allele, HR 1.22; 95% CI, 1.02-1.45; 2 alleles, HR 1.95; 95% CI, 1.35-2.81), incident stroke (HR 3.38; 95% CI, 2.78-4.10), and dementia (HR 2.56; 95% CI, 2.11-3.12). The risk for late-onset epilepsy was lower in patients with higher physical activity levels (HR 0.90; 95% CI, 0.83-0.98) and moderate alcohol intake (HR 0.72; 95% CI, 0.57-0.90).

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A limitation of the study included the use of claims codes for identifying epilepsy cases, which may have introduced misclassification of some patients.

Overall, the findings from the study suggest “a possible role of vascular disease and neurodegeneration in the development of late-onset epilepsy.”


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 [published online July 23, 2018]. JAMA Neurol. doi: 10.1001/jamaneurol.2018.1935

This article originally appeared on Neurology Advisor