Association of cognitive enhancers and incident seizure risk in dementia: a population-based study

BMC Geriatr. 2022 Jun 3;22(1):480. doi: 10.1186/s12877-022-03120-5.


Background: Although individuals with dementia have a high risk of developing seizures, whether seizures are associated with cholinesterase inhibitors, which are commonly prescribed to treat individuals with dementia, remains unknown. This study investigated the risk of incident seizure following cholinesterase inhibitor use in patients with dementia.

Methods: A nationwide, nested case-control study was conducted using data from the Korean Health Insurance Review and Assessment Service (HIRA) from 2014 through 2018. A total of 13,767 participants aged 65-95 years who experienced incident seizure were propensity score-matched for medical comorbidities and drug exposure at a 1:3 ratio with a control group of 39,084 participants. The study examined the incidence of seizures in patients diagnosed with dementia within one year after receiving cognitive enhancers. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for seizure incidence according to cholinesterase inhibitor use were analyzed using a multivariable conditional logistic regression model.

Results: There was no statistically significant association between duration of cholinesterase inhibitors use and seizure risk. Although there was slight increased seizure risk in patient after receiving donepezil for 1 year compared to memantine, subgroup analyses stratified age and sex did not reveal any significant association between cholinesterase inhibitors use and late-onset seizure.

Conclusions: Our findings suggest no immediate increase in seizure risk is associated with cholinesterase inhibitor use, although the risk of seizure in patients with dementia did increase after one year of continued medication intake. Further study is required to obtain confirmatory results on the seizure-related safety of cognitive enhancers in patients with dementia.

Keywords: Alzheimer's disease; Cholinesterase inhibitors; Dementia; Epilepsy; Seizure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Case-Control Studies
  • Cholinesterase Inhibitors / adverse effects
  • Dementia* / diagnosis
  • Dementia* / drug therapy
  • Dementia* / epidemiology
  • Humans
  • Nootropic Agents* / therapeutic use
  • Seizures / chemically induced
  • Seizures / drug therapy
  • Seizures / epidemiology


  • Cholinesterase Inhibitors
  • Nootropic Agents