| Epilepsy  

Epilepsy and cognitive impairment

Overlapping pathophysiological mechanisms may contribute to some cases of epilepsy and cognitive impairment.

The convergence of epilepsy and dementia is of increasing interest to neuroscientists (Noebels et al., 2011).  In a prospective study, Stefanidou et al., 2020*, demonstrated an augmented risk of epilepsy in dementia patients (Hazard Ratio (HR) 1.82) and a higher risk of dementia in epilepsy patients (HR 1.99).  Among people with epilepsy with a post-high school education, the HR of dementia was 4.67. The results were similar even after the exclusion of patients with incident stroke.  In a related study of the Atherosclerosis Risk in Communities cohort, Johnson et al., 2020**, found that late-onset epilepsy (first seizure at age >67 years) was associated with dementia (HR 3.05). Notably, the mean time to dementia diagnosis following a first seizure was 3.66 years.

Kaestner et al.** conducted a retrospective cross-sectional multicentre cohort study to compare brain atrophy patterns and cognitive profiles between older adults (>55 years old) with TLE and aMCI. Both groups showed bilateral cortical thinning of the medial temporal lobe.  However, the aMCI group also had atrophy in the lateral temporal, left posterior parietal, and frontal regions, whereas the TLE group had atrophy within the precentral gyrus. Cognitively, both groups performed similarly, with the aMCI group performing worse in delayed memory testing. Interestingly, patients with late-onset TLE (first seizure at age >50 years) had an atrophy pattern that was more widespread than patients with early-onset TLE, also involving the prefrontal, lateral temporal, and paracentral regions.

These studies suggest a bidirectional relationship between dementia and epilepsy.  Late-onset TLE may represent a unique epilepsy subtype with some similar pathophysiological features to aMCI.

*Green/level 4 and **Blue/level 5 in theEAN rainbow ranking system of evidence.


Key points:

  • Patients with epilepsy have a higher risk of dementia, and patients with dementia have a higher risk of epilepsy.
  • Patients with temporal lobe epilepsy (TLE) and amnestic mild cognitive impairment (aMCI) have some similar mesiotemporal changes but distinct patterns of atrophy elsewhere in the brain.


Johnson EL, Krauss GL, Kucharska-Newton A, Albert MS, Brandt J, Walker KA, Yasar S, Knopman DS, Vossel KA, Gottesman RF. Dementia in late-onset epilepsy: The Atherosclerosis Risk in Communities study. Neurology. 2020 Dec 15;95(24):e3248-e3256. DOI: 10.1212/WNL.0000000000011080. Epub 2020 Oct 23. PMID: 33097597; PMCID: PMC7836657. https://pubmed.ncbi.nlm.nih.gov/33097597/


Kaestner E, Reyes A, Chen A, Rao J, Macari AC, Choi JY, Qiu D, Hewitt K, Wang ZI, Drane DL, Hermann B, Busch RM, Punia V, McDonald CR; Alzheimer’s Disease Neuroimaging Initiative. Atrophy and cognitive profiles in older adults with temporal lobe epilepsy are similar to mild cognitive impairment. Brain. 2021 Feb 12;144(1):236-250. DOI: 10.1093/brain/awaa397. PMID: 33279986; PMCID: PMC7880670. https://pubmed.ncbi.nlm.nih.gov/33279986/


Noebels J. A perfect storm: Converging paths of epilepsy and Alzheimer’s dementia intersect in the hippocampal formation. Epilepsia 2011; 52 (Suppl. 2): S39 –S46.


Stefanidou M, Beiser AS, Himali JJ, Peng TJ, Devinsky O, Seshadri S, Friedman D. Bi-directional association between epilepsy and dementia: The Framingham Heart Study. Neurology. 2020 Dec 15;95(24):e3241-e3247. DOI: 10.1212/WNL.0000000000011077. Epub 2020 Oct 23. PMID: 33097599; PMCID: PMC7836659. https://pubmed.ncbi.nlm.nih.gov/33097599/