Young-Onset Dementia and Epilepsy: What’s the Link?

Epilepsy is associated with a significantly higher risk of developing dementia before age 65, although the absolute 10-year risk is small, a study of three nationwide analyses showed.Researchers evaluated data on hundreds of thousands of individuals using two different methods. One technique looked backward, examining whether people with early dementia — also called young-onset dementia (YOD) — had a history of epilepsy or antiseizure medication (ASM) use. In a case-control analysis in France, 12.5% of people with YOD had previously been diagnosed with epilepsy compared with 1.2% of those without dementia. ASM use was reported in 26.5% of the YOD group compared with 10.3% of those without dementia. A replication study using Swedish registry data showed similar results.The other research method followed patients with epilepsy in a French cohort to see if they developed YOD later on. In that analysis, adults with newly diagnosed epilepsy had about six times the risk of developing YOD over 10 years as those without epilepsy, although incidence remained low in this group at just 2.2%. However, among those with four or more comorbidities, incidence reached 9.1%.Epilepsy and dementia have a complex relationship, with prior research suggesting that each condition may increase the risk for the other, particularly in older adults. However, less is known about the relationship between epilepsy and YOD, a gap this study sought to address.“These results support integrating dementia prevention into the care of people with epilepsy,” study investigator Vincent Navarro, MD, PhD, of Sorbonne University in Paris, France, said in a statement. “They may benefit from earlier assessments of their cognitive risks and intensified management of risk factors that can be modified, such as cardiovascular factors like high blood pressure.”The study was published online on October 14 in Neurology.Researchers conducted three nationwide analyses for this study, including case-control analyses from France and Sweden that examined epilepsy diagnoses and ASM use during the 10 years before YOD diagnosis.The French analysis included 11,360 people aged 40-64 years with YOD and 113,600 matched control individuals. The control group was matched by age, sex, and region. The Swedish case-control replication study included 16,433 people with YOD and 164,330 matched control individuals.In France, 12.5% of people with YOD had an epilepsy diagnosis, compared with 1.2% of those without dementia. After adjusting for potential confounders, epilepsy was associated with nearly four times the odds of YOD (adjusted odds ratio [aOR], 3.76). The analyses also accounted for other factors associated with dementia risk, including stroke, mood disorders, and traumatic brain injury.ASM use was also more common among people with YOD than among those without dementia (26.5% vs 10.3%) and was associated with higher odds of YOD after accounting for other factors (aOR, 1.44). However, the association does not establish that the medications themselves increase dementia risk, researchers noted.Analysis of Swedish data revealed similar findings.Tracking Dementia Risk Over TimeThe third nationwide analysis was a French retrospective cohort study that assessed YOD risk among adults with newly diagnosed or previously diagnosed epilepsy and those without epilepsy.The study included 12,901 adults with incident epilepsy, 64,083 with prevalent epilepsy, and 129,010 without epilepsy. Participants were aged 30-55 years at baseline, with a mean age of 44 years, and 55.5% were women. The groups were matched by age, sex, and region, and new YOD diagnoses were tracked over 10 years.The 10-year cumulative incidence of YOD was 2.20% among adults with newly diagnosed epilepsy and 1.74% among those with a prior epilepsy diagnosis, compared with 0.21% among adults without epilepsy.After adjusting for potential confounders, the association between epilepsy and YOD remained significant for both newly (hazard ratio [HR], 6.02) and previously (HR, 5.38) diagnosed epilepsy.Despite these differences, the overall 10-year incidence of early dementia remained low.Among adults with newly diagnosed epilepsy, the 10-year incidence of YOD ranged from 1.40% in those without other conditions to 9.10% in those with four or more comorbidities. Cardiovascular conditions were common comorbidities, affecting 44.4% of those with newly diagnosed epilepsy and dementia compared with 20.6% of those who developed dementia without epilepsy.The association remained even when researchers excluded dementia diagnoses made within the first 5 years of follow-up (HR, 3.87).Implications for Epilepsy CareThe findings suggest that clinicians should consider cognitive health as part of long-term epilepsy care, particularly for patients with additional health conditions.“Integrating dementia prevention into long-term epilepsy follow-up could help identify high-risk patients and guide targeted interventions,” the investigators wrote.Because YOD was more common in people with multiple comorbidities and cardiovascular conditions were frequent among those with both diseases, managing modifiable risk factors is key, they added.Further research is needed to clarify the relationship between epilepsy and YOD, identify which patients are most vulnerable, and determine whether earlier cognitive assessments and targeted interventions can reduce risk.“While causal pathways remain to be clarified, these findings support a prevention-oriented approach in epilepsy care: Patients with epilepsy, particularly those with cardiovascular disease and multimorbidity, may benefit from earlier cognitive risk assessment and intensified management of modifiable risk factors, especially cardiovascular risk,” investigators wrote, adding that it remains uncertain whether epilepsy contributes to dementia or whether both conditions arise from shared underlying factors.The study was limited by a lack of detailed clinical data, the possibility that dementia was more likely to be detected in people with epilepsy, and uncertainty about whether the findings apply beyond France and Sweden.Disclosure information for study authors is available in the original study publication.