Epilepsy and Neurodegeneration: A Bidirectional Relationship.

Abstract

The Bi-Directional Association Between Epilepsy and Dementia. The Framingham Heart Study Stefanidou M, Beiser AS, Himali JJ, et al. Neurology. 2020. doi:10.1212/WNL.0000000000011077.Objectives:To assess the risk of incident epilepsy among participants with prevalent dementia, and the risk of incident dementia among participants with prevalent epilepsy in the Framingham Heart Study (FHS).Methods:We analyzed prospectively collected data in the Original and Offspring FHS cohorts. To determine the risk of developing epilepsy among participants with dementia and the risk of developing dementia among participants with epilepsy we used separate, nested, case–control designs, and matched each case to 3 age-, sex-, and FHS cohort-matched controls. We used Cox proportional hazards regression analysis, adjusting for sex and age. In secondary analysis, we investigated the role of education level and apolipoprotein ε4 allele status in modifying the association between epilepsy and dementia.Results:A total of 4906 participants had information on epilepsy and dementia and dementia follow-up after age 65. Among 660 participants with dementia and 1980 dementia-free controls there were 58 incident epilepsy cases during follow-up. Analysis comparing epilepsy risk among dementia cases versus controls yielded (hazards ratio [HR] = 1.82 [95% CI:1.05-3.16], P = .034). Among 43 participants with epilepsy and 129 epilepsy-free controls, there were 51 incident dementia cases. Analysis comparing dementia risk among epilepsy cases versus controls yielded (HR = 1.99 [1.11-3.57], P = .021). In this group, among participants with any post-high school education, prevalent epilepsy was associated with a nearly 5-fold risk for developing dementia (HR = 4.67 [1.82-12.01], P = .001) compared to controls of the same educational attainment.Conclusions:There is a bidirectional association between epilepsy and dementia with either condition carrying a nearly 2-fold risk of developing the other when compared with controls. Dementia in Late Onset Epilepsy: The Atherosclerosis Risk in Communities Study Johnson EL, Krauss GL, Kucharska-Newton A, et al. Neurology. 2020.Objective:To determine the risk of dementia after the development of late-onset epilepsy (LOE).Methods:We used data from the Atherosclerosis Risk in Communities (ARIC) cohort study, which started in 1987 to 1989 with 15 792 mostly black and white men and women from 4 US communities. We identified LOE (seizures starting at age 67 or later) from linked Medicare claims data. We used a Cox proportional hazards regression model to evaluate associations between LOE and dementia through 2017 as ascertained from neuropsychological testing, interviews, and hospital discharge surveillance; and we used multinomial logistic regression to assess the risk of dementia and mild cognitive impairment in the subset with full neuropsychological assessments available. We adjusted for demographics, and vascular and Alzheimer disease risk factors.Results:Of 9033 ARIC participants with sufficient Medicare coverage data (4980 [55.1%] female, 1993 [22.1%] black), 671 met the definition of LOE. 279 (41.6%) participants with LOE and 1408 (16.8%) without LOE developed dementia (P < .001). After a diagnosis of LOE, the adjusted hazard ratio for developing subsequent dementia was 3.05 (95% CI: 2.65-3.51). The median time to dementia ascertainment after the onset of LOE was 3.66 years (Q1-Q3 1.28-8.28 years).Interpretation:The risk of incident dementia is substantially elevated in individuals with LOE. Further work is needed to explore causes for the increased risk of dementia in this growing population.