Heidi Taipale1,2,3, Willy Gomm4, Karl Broich5, Wolfgang Maier4,6, Anna-Maija Tolppanen1, Antti Tanskanen3,7, Jari Tiihonen3,7, Sirpa Hartikainen1,2,8, Britta Haenisch4. 1. School of Pharmacy, University of Eastern Finland, Kuopio, Finland. 2. Kuopio Research Center for Geriatric Care, School of Pharmacy, University of Eastern Finland, Kuopio, Finland. 3. Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden. 4. German Center for Neurodegenerative Diseases, Bonn, Germany. 5. Federal Institute for Drugs and Medical Devices, Bonn, Germany. 6. Department of Psychiatry, University of Bonn, Bonn, Germany. 7. Department of Forensic Psychiatry, Niuvanniemi Hospital, University of Eastern Finland, Kuopio, Finland. 8. Department of Psychiatry, Kuopio University Hospital, Kuopio, Finland.
Abstract
OBJECTIVES: To evaluate the association between regular antiepileptic drug (AED) use and incident dementia. DESIGN: Case-control analysis. SETTING: Finnish public health register and German health insurance data. PARTICIPANTS: Individuals with dementia of any type (German data, N=20,325) and Alzheimer's disease (AD; Finnish data, N=70,718) were matched with up to four control persons without dementia. MEASUREMENTS: We analyzed the association between regular AED use and dementia. To address potential protopathic bias, a lag time of 2 years between AED use and dementia diagnosis was introduced. Odds ratios (ORs) were calculated by applying conditional logistic regression, adjusted for potential confounding factors such as comorbidities and polypharmacy. RESULTS: Regular AED use was more frequent in individuals with dementia than controls. Regular use of AEDs was associated with a significantly greater risk of incident dementia (adjusted OR=1.28, 95% confidence interval (CI)=1.14-1.44) and AD (adjusted OR=1.15, 95% CI=1.09-1.22) than no AED use. We also detected a trend toward greater risk of dementia with higher exposure. When AEDs with and without known cognitive adverse effects (CAEs) were compared, a significantly greater risk of dementia was observed for substances with known CAEs (dementia: OR=1.59, 95% CI=1.36-1.86; AD: OR=1.19, 95% CI=1.11-1.27). CONCLUSION: AEDs, especially those with known CAEs, may contribute to incident dementia and AD in older persons.
OBJECTIVES: To evaluate the association between regular antiepileptic drug (AED) use and incident dementia. DESIGN: Case-control analysis. SETTING: Finnish public health register and German health insurance data. PARTICIPANTS: Individuals with dementia of any type (German data, N=20,325) and Alzheimer's disease (AD; Finnish data, N=70,718) were matched with up to four control persons without dementia. MEASUREMENTS: We analyzed the association between regular AED use and dementia. To address potential protopathic bias, a lag time of 2 years between AED use and dementia diagnosis was introduced. Odds ratios (ORs) were calculated by applying conditional logistic regression, adjusted for potential confounding factors such as comorbidities and polypharmacy. RESULTS: Regular AED use was more frequent in individuals with dementia than controls. Regular use of AEDs was associated with a significantly greater risk of incident dementia (adjusted OR=1.28, 95% confidence interval (CI)=1.14-1.44) and AD (adjusted OR=1.15, 95% CI=1.09-1.22) than no AED use. We also detected a trend toward greater risk of dementia with higher exposure. When AEDs with and without known cognitive adverse effects (CAEs) were compared, a significantly greater risk of dementia was observed for substances with known CAEs (dementia: OR=1.59, 95% CI=1.36-1.86; AD: OR=1.19, 95% CI=1.11-1.27). CONCLUSION: AEDs, especially those with known CAEs, may contribute to incident dementia and AD in older persons.
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