The Bi-Directional Association Between Dementia and Epilepsy

01APAEE0 – Electroencephalogram (EEG) chart of simple partial (focal) epilepsy from an unknow origin in a 20 year old patient. The EEG is printed over a 3D MRI of the brain in frontal view. (c) Sovereign
Dementia and epilepsy have a bi-directional relationship as either condition has approximately a 2-fold probability of developing the other.

Epilepsy and dementia are interlinked as patients with epilepsy have a 2-fold risk of developing dementia and those with dementia are at an increased risk for epilepsy, according to study results published in Neurology.

Recent studies have suggested a bi-directional association between dementia and epilepsy with evidence suggesting a 2- to 10-fold increased risk for seizures among patients with dementia. Another study reported an increased risk for dementia among patients with epilepsy.

The objective of the current study was to use data from the Framingham Heart Study to determine the risk for incident epilepsy in patients with prevalent dementia and the risk for incident dementia in patients with prevalent epilepsy.

Study researchers used a nested case-control design to assess incident epilepsy following dementia diagnosis. Each patient with dementia was matched to 3 controls free of dementia from the Original and the Offspring Framingham Heart Study cohorts. Using a similar process, study researchers assessed incident dementia following a diagnosis of epilepsy. In a secondary analysis, they evaluated the role of education level and apolipoprotein ε4 (APOE4) allele status in modifying the association between epilepsy and dementia.

The study included 4906 patients with available data on epilepsy and dementia and follow-up until at least 65 years. Of these, 888 patients were diagnosed with dementia and 90 were diagnosed with epilepsy.

Matched controls were available for each of 660 patients with dementia. The control group included 1980 participants without dementia. During follow-up there were 58 patients with incident epilepsy, including 19 (2.9%) of those with prevalent dementia and 39 (2.0%) of those who were the dementia-free (hazard ratio [HR], 1.82; 95% CI, 1.05-3.16; P =.034). The results were similar after adjustment for education and APOE4.

Among the 43 patients with epilepsy and 129 epilepsy-free controls, there were 51 patients with incident dementia during follow-up, including 18 patients (41.9%) among those with prevalent epilepsy and 33 patients (25.6%) among the epilepsy-free controls (HR, 1.99; 95% CI, 1.11-3.57; P =.021). The results were similar after adjustment for education and APOE4.

Among participants with any post-high school education, prevalent epilepsy was associated with a nearly 5-fold risk for developing dementia (HR, 4.67; 95% CI, 1.82-12.01; P =.001) compared to patients in the control group with the same education.

The study had several limitations, including the confounding presence of a clinical stroke, inability to account for potential anti-seizure medication effect on the diagnosis of dementia, missing data on seizure frequency, and inclusion of a primarily Caucasian population, limiting the generalizability of results.

“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,” concluded the study researchers.


Stefanidou M, Beiser AS, Himali JJ, et al. The bi-directional association between epilepsy and dementia. The Framingham Heart Study. Neurology. Published online, October 23, 2020. doi:10.1212/WNL.0000000000011077