gms | German Medical Science

Background: Antiepileptic drugs (AED) can adversely affect cognition by suppressing neuronal excitability and increasing inhibitory neurotransmission. Several studies report acute cognitive adverse effects (CAE) of AEDs. The association of AED use and dementia risk in older persons, however, has rarely been investigated. Thus, we evaluated the association between AED use and incident dementia in German health insurance and Finnish health care register data.

Materials and methods: We used a case-control study design in both datasets and examined the association between regular and occasional AED prescription and dementia. We further grouped AEDs into those with and without CAE. Patients with Alzheimer’s disease (AD; Finnish data, N=70,718) and dementia of any type (German data, N=20,325) were matched with up to four controls without dementia/ AD. To address potential protopathic bias, we introduced a lag time of 2 years between AED prescription and dementia diagnosis. We calculated odds ratios (ORs) applying conditional logistic regression with adjustment for potential confounding factors such as comorbidities and polypharmacy.

Results: We detected a significantly increased risk of incident dementia with regular use of AEDs (adjusted OR 1.28, 95% confidence interval [CI] 1.14–1.44) and AD (adjusted OR 1.15, 95% CI 1.09–1.22) compared to no AED prescription. There was a slight trend for increased dementia risk with higher exposure. When AEDs with and without known CAE were compared, we detected a significantly increased risk for any dementia and for AD for substances with known CAE (OR: 1.59, 95% CI 1.36–1.86 for any dementia, and OR 1.19, 95% CI 1.11–1.27 for AD), but not for AEDs without known CAE.

Conclusion: Prescription of AEDs, especially those with known CAE, may contribute to incident dementia/AD in older patients.