Neurology
Associations of Interleukin-6 and Interleukin-18 with Incident Epilepsy in Older Adults: Results from the Atherosclerosis Risk in Communities (ARIC) Study Derartu Ahmed* Derartu Ahmed Ahmed Ahmed Ahmed Ahmed Ahmed Ahmed Ahmed Ahmed Department of Biostatistics, Epidemiology and Informatics
Background:
The highest burden of epilepsy occurs among older adults (aged 65+ years) and, notably, a significant proportion of these late-onset epilepsy diagnoses lack an identifiable cause. Recent research suggests a potential link between inflammation and epilepsy. Therefore, we investigated associations of two pro-inflammatory cytokines, interleukin-6 (IL-6) and IL-18, with incident epilepsy.
Methods:
Using data from the Atherosclerosis Risk in Communities (ARIC) Study, we conducted a prospective cohort analysis with follow-up extending from 2011-2013 through 12/31/2022. IL-6 and IL-18 were measured from plasma collected in 2011-2013 using high-sensitivity enzyme-linked immunosorbent assays (categorized into quartiles). Incident epilepsy was defined using International Classification of Diseases, Ninth and Tenth Revision (ICD-9/10) codes. Cause-specific Cox proportional-hazards regression models were used to separately model associations of IL-6 and IL-18 with incident epilepsy with covariate adjustment for age, sex, race/center, education, smoking, alcohol consumption, hypertension, diabetes, cognitive status, stroke, and APOE 4 genotype. Missing covariate data were imputed via multiple imputation using chained equations.
Results:
We included 5,552 participants (mean age 75 years, 56% female, and 21% Black race) with IL-6 and IL-18 data without prevalent epilepsy in the analytic population. Participants were followed for a median of 12 years, over which 4% developed incident epilepsy and 37% died. In adjusted models, IL-6 was not statistically significantly associated with incident epilepsy. In contrast, the upper three higher quartiles of IL-18 were associated with similar increased risk of incident epilepsy (Q2: HR=1.98, 95%CI=1.27-3.07, Q3: HR=2.23, 95%CI=1.45-3.45, and Q4: HR=1.61, 95%CI=1.01-2.55) compared to the lowest quartile (Q1) (Figure).
Conclusions:
Among older adults, higher IL-18, but not IL-6, was associated with risk of incident epilepsy.
