Is Posttraumatic Epilepsy Associated With Higher Dementia Risk?

Compared with patients without a history of head injury or seizure/epilepsy, patients with posttraumatic epilepsy are at a greater risk of developing dementia, according to study findings published in JAMA Neurology.

Posttraumatic epilepsy, accounting for 5%-20% of acquired epilepsies, has previously been linked to worse short-term outcomes. There is, however, a limited understanding of its long-term consequences. These uncertainties presented the need for additional investigation into the cognitive impacts and dementia susceptibility among individuals with posttraumatic epilepsy in contrast to individuals with either head injury or epilepsy alone.

Using data through December 2019, with a median follow-up of 25.4 years, researchers conducted a prospective cohort study involving 12,558 older adults (mean age, 54.3; women, 57.7%; Black, 28.2%) already enrolled in the Atherosclerosis Risk in Communities (ARIC) study to determine the association between posttraumatic epilepsy and dementia risk.

The primary outcome of interest was dementia, which was defined using cognitive assessments, informant interviews, and International Classification of Diseases (ICD) and death certificate codes. Head injury was defined by self-report and ICD diagnostic codes, seizure/epilepsy was defined using ICD codes, and posttraumatic epilepsy was defined as a diagnosis of seizure/epilepsy occurring more than 7 days after injury. Dementia risk was estimated using adjusted Cox and Fine and Gray proportional hazards models and head injury, seizure/epilepsy, and posttraumatic epilepsy were analyzed as time-varying exposures.

At baseline, patients were grouped into 1 of 4 time-varying exposure categories:

• no head injury and no seizure/epilepsy (n=9962; 79.3%);
• head injury (n=1811; 14.4%);
• seizure/epilepsy (n=640; 5.1%); or
• posttraumatic epilepsy (n=145; 1.2%).

Over a period of 250,372 person-years of follow-up, 2498 cases of dementia were observed. Compared with patients in the no head injury or seizure/epilepsy group, patients with posttraumatic epilepsy demonstrated the lowest cumulative dementia-free survival, which was associated with 4.85 (95% CI, 3.72-6.33) times greater risk for dementia.

Compared with no head injury or seizure/epilepsy, head injury and seizure/epilepsy were associated with 1.64 (95% CI, 1.48-1.82) and 2.81 (95% CI, 2.39-3.31) times the risk for dementia, respectively. This risk for dementia remained significantly higher in patients with posttraumatic epilepsy than that associated with head injury alone or seizure/epilepsy alone, even after adjusting for vascular and genetic risk factors.

Models considering the competing risk for death alone and death and stroke revealed a 3-fold increased risk for dementia with posttraumatic epilepsy. Stronger associations were observed in younger participants, with no evidence for interaction by sex or race.

In secondary analyses, associations were similar for posttraumatic epilepsy occurring post-first (hazard ratio [HR], 4.63; 95% CI, 3.46-6.21) or post-second (HR, 4.24; 95% CI, 2.27-7.92) head injury, and with posttraumatic epilepsy occurring after mild (HR, 5.03; 95% CI, 3.57-7.09) or moderate/severe/penetrating (HR, 3.15; 95% CI, 1.82-5.46) head injuries.

Compared with individuals in the seizure/epilepsy only group, as well as individuals in the head injury only group, individuals with head injuries following seizures/epilepsy were found to have a higher risk for dementia. However, compared with those in the posttraumatic epilepsy group, patients with head injuries following seizures/epilepsy had a lower risk for dementia. 

Compared with later onset (more than 3 years after head injury) posttraumatic epilepsy (HR, 3.06; 95% CI, 2.21-4.08), earlier onset (within 3 years of head injury) posttraumatic epilepsy demonstrated a stronger association with dementia (HR, 7.30; 95% CI, 5.14-10.37). This pattern was maintained even when the timing of posttraumatic epilepsy onset after head injury was stratified by injury severity.

Study limitations included the limited generalizability of results to individuals who sustained a prior head injury at baseline, potentially confounding factors such as frailty, and reliance on self-reported data and ICD codes with inherent sensitivity and specificity limitations.

“These findings provide evidence that PTE [posttraumatic epilepsy] is associated with long-term outcomes and supports both the prevention of head injuries via public health measures and further research into the underlying mechanisms and the risk factors for the development of PTE, so that efforts can also be focused on the prevention of PTE after a head injury,” researchers concluded.

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.