Is it the chicken or the egg: a causality dilemma, which comes first dementia or epilepsy?

Is it the chicken or the egg: a causality dilemma, which comes first dementia or epilepsy?

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Epilepsy with dementia or dementia with epilepsy

Two recent studies have had contradictory results regarding the relationship between dementia and epilepsy.1,2 Johnson et al. 2020 found that 41.6% of participants of the Atherosclerosis Risk in Communities (ARIC) cohort study who had late-onset epilepsy developed dementia compared to only 16.8% of participants who did not have late-onset epilepsy (P<0.001).1 Participants with late-onset epilepsy had triple the risk of developing dementia compared to those without late-onset epilepsy (confidence interval: 2.65–3.51).1 These findings suggest that epilepsy may be a risk factor for dementia.1 However, a cross-sectional study by Lam et al. 2020 found that 53% of participants with Alzheimer’s disease (AD) with late-onset epilepsy and 22% of participants with AD without epilepsy had epileptiform abnormalities on electroencephalogram (EEG).2 In comparison, only 4.7% of the healthy controls had epileptiform abnormalities on EEG.2 Furthermore, both clinical seizures and hyperexcitability were detected in participants with AD.2 These findings suggest that epileptiform abnormalities are common in persons with AD and that some persons with AD may be high risk for seizures.2

 

Epilepsy and dementia — which is the chicken, which is the egg?

The link between dementia and epilepsy appears to be complex. Yet, the question remains is epilepsy a risk factor for dementia or is dementia a risk factor for epilepsy? Stefanidou at al. 2020 explored this question specifically using data from the Original and Offspring Framingham Heart Study cohorts.3 A large, prospective, population-based study with separate, nested, case-control studies with 3:1 matching on age and sex was completed.3

For this study there were 4 906 participants who had information available on both epilepsy and dementia.3 Participants with dementia (n=660) had nearly double the risk of developing epilepsy compared to controls (P=0.034).3 Similarly, participants with epilepsy (n=43) had nearly double the risk of developing dementia compared to controls (P=0.021).3 In a secondary analysis, participants with epilepsy who had any post-high school education had nearly 5 times the risk of developing dementia in comparison to controls (P = 0.001).3 The findings of this study support a bi-directional association between epilepsy and dementia.3

 

What comes next?

Looking to the recent study by Stefanidou et al. 2020 it appears that epilepsy is a risk for dementia but also that dementia is a risk factor for epilepsy.3 Further research is necessary to determine whether the bidirectional association between dementia and epilepsy is causal. This future research could also discover common or shared disease pathways, which could have great implications for novel treatment approaches.

 


References
  1. Johnson EL et al. Neurology. 2020;95(24):e3248-e3256.
  2. Lam AD et al. Neurology. 2020;95(16):e2259-e2270.
  3. Stefanidou M et al. Neurology. 2020;95(24):e3241-e3247.
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