Bi-directional association between epilepsy and dementia: The Framingham Heart Study

Published on Dec 15, 2020in Neurology8.77
· DOI :10.1212/WNL.0000000000011077
Maria Stefanidou12
Estimated H-index: 12
(BU: Boston University),
Alexa Beiser94
Estimated H-index: 94
(BU: Boston University)
+ 4 AuthorsDaniel Friedman36
Estimated H-index: 36
Sources
Abstract
Objective 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 APOE e4 allele status in modifying the association between epilepsy and dementia. Results A total of 4,906 participants had information on epilepsy and dementia and dementia follow-up after age 65. Among 660 participants with dementia and 1,980 dementia-free controls, there were 58 incident epilepsy cases during follow-up. Analysis comparing epilepsy risk among dementia cases vs controls yielded a hazard ratio (HR) of 1.82 (95% confidence interval 1.05–3.16, p = 0.034). Among 43 participants with epilepsy and 129 epilepsy-free controls, there were 51 incident dementia cases. Analysis comparing dementia risk among epilepsy cases vs controls yielded a HR of 1.99 (1.11–3.57, p = 0.021). 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 = 0.001) compared to controls of the same educational attainment. Conclusions There is a bi-directional association between epilepsy and dementia. with either condition carrying a nearly 2-fold risk of developing the other when compared to controls.
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It is not news that people with dementia, including Alzheimer disease (AD), the most frequently identified cause of dementia, are at increased risk to develop epilepsy.1 There has been increased interest in this association because of studies demonstrating accumulation of β -amyloid (Aβ) peptide in animal models of AD leading to recurrent seizure activity.2 These seizures, and in turn the physiologic response to seizures, contribute to hippocampal dysfunction and subsequently to the memory impai...
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