Association Between Epilepsy and Young-Onset Dementia

BACKGROUND AND OBJECTIVES: Epilepsy is linked to late-onset dementia, but evidence for young-onset dementia (YOD; <65 years) is limited. We assessed the epilepsy-YOD association in France and Sweden and YOD risk after midlife epilepsy. METHODS: We conducted 3 nationwide analyses. A French nested case-control analysis included patients with incident YOD aged 40-64 years, diagnosed between January 1, 2016, and December 31, 2018. Index date was the first YOD-related health care event; controls were risk-set matched on age, sex, and region. A Swedish nested case-control replication included patients with YOD diagnosed between January 1, 1987, and December 31, 2016, with matched controls. In both studies, epilepsy-related diagnoses and antiseizure medication (ASM) dispensations were assessed up to 10 years before index date. Odds ratios (ORs) were estimated with conditional logistic regression. A French retrospective cohort included adults aged 30-55 years with incident epilepsy in 2008, matched to individuals with prevalent epilepsy before 2008 or no epilepsy. The cohort index was the first ASM reimbursement in the incident epilepsy group or the matched date for comparators. Follow-up ended at YOD, death, or 10 years. We estimated 10-year cumulative incidence and adjusted (comorbidities, deprivation) hazard ratios (HRs), treating death as a competing event. Sensitivity analyses included lagged entry up to 5 years. RESULTS: Case-control studies included 11,360 cases and 113,600 controls in France and 16,433 cases and 164,330 controls in Sweden. In France, 12.5% of YOD cases vs 1.2% of controls had previous epilepsy-related codes (adjusted OR 3.76, 95% CI 3.42-4.14), and 27.3% vs 10.3% had ASM dispensations (adjusted OR 1.44, 95% CI 1.36-1.52). The French cohort included 12,901 individuals with incident epilepsy, 64,083 with prevalent epilepsy, and 129,010 without epilepsy (mean age 44.0 years; 55.5% female participants). Ten-year cumulative YOD incidence was 2.20% (95% CI 1.94-2.48) with incident epilepsy (adjusted HR compared with individuals without epilepsy 6.02, 95% CI 4.98-7.26), 1.74% (1.64-1.85) with prevalent epilepsy (adjusted HR 5.38, 95% CI 4.64-6.25), and 0.21% (0.19-0.24) without epilepsy. Associations attenuated with longer lags but persisted beyond 5 years. DISCUSSION: Across 2 countries and complementary designs, epilepsy was strongly associated with YOD. Epilepsy conferred higher YOD risk in midlife, especially with multimorbidity, supporting epilepsy inclusion in YOD risk stratification and prevention.