Abstract
Infectious diseases are known to trigger acute seizures, but their long-term impact on epilepsy, especially in later life, is unclear. We conducted nested case-control studies of newly diagnosed epilepsy after age 50 in the UK Biobank (2,486 cases; 12,430 controls) and Swedish registers (56,266 cases; 281,330 controls), including a sibling comparison. Previous hospital-treated infections were associated with a persistently elevated epilepsy risk (for example, >10 years after infection: odds ratio (OR) 1.68, 95% confidence interval: 1.39-2.04 in UK Biobank; 1.46, 1.41-1.51 in Sweden). Associations were robust in sibling analyses and across infection types and sites. We further found that infections, together with a high cardiovascular genetic risk (OR 2.62, 2.22-3.08), a high cardiovascular risk score (OR 3.14, 2.68-3.68) or cardiovascular disease history (OR 4.77, 4.64-4.91), were associated with the highest epilepsy risk. Hospital-treated infections exert prolonged impact on epilepsy risk in older age, especially when in combination with cardiovascular risk factors.