Posttraumatic Epilepsy Tied to Higher Dementia Risk

The risk for long-term dementia is significantly higher among people with posttraumatic epilepsy (PTE) compared with those with no history of either head injury or epilepsy and those with either condition alone, a new study suggested.

After adjusting for confounders, PTE was associated with a > 4.5-fold higher risk of developing dementia during the following 25 years. In contrast, seizure/epilepsy alone was associated with a 2.6-fold higher risk and head injury alone with a 1.6-fold higher risk.

The findings provide evidence that “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,” lead investigator Andrea L.C. Schneider, MD, PhD, of the Department of Neurology, University of Pennsylvania Perelman School of Medicine, Philadelphia, and co authors wrote.

The study was published online on February 26, 2024, in JAMA Neurology.

Examining Risk

PTE includes unprovoked seizures occurring more than 7 days after traumatic brain injury and accounts for 5%-20% of acquired epilepsies. Previous studies have shown that even mild TBI can lead to PTE up to a year after the head injury.

Because head injury and epilepsy are each independently associated with long-term dementia risk, individuals with PTE were thought to have worse cognitive outcomes over time compared to those with TBI or epilepsy alone.

While prior studies have examined functional, psychosocial, and cognitive outcomes within 2 years of PTE, little was known about long-term effects.

Investigators drew on a quarter of a century of data on 12,588 individuals (mean age, 54 years; 58% female; 28% Black) in the ongoing Atherosclerosis Risk in Communities study (ARIC) to determine dementia risk among those with head injury alone, epilepsy alone, or PTE. Participants enrolled in ARIC between 1987 and 1989 and were followed for this study until 2019.

Overall, 14.4% of participants reported having head injury, 5.1% had seizure/epilepsy, and 1.2% had PTE. After a median 25 years of follow-up, 19.9% of the cohort developed dementia.

In their analysis, investigators considered the potential association of PTE with dementia risk by age, sex, race, head injury frequency, and severity subgroups and adjusted for vascular and genetic risk factors.

Overall, dementia risk was more than four times higher in those with PTE (adjusted hazard ratio [aHR], 4.56; 95% CI, 4.49-5.95) than in people with no history of head injury or seizure/epilepsy. Dementia risk with PTE was also higher than the risk associated with seizure/epilepsy alone (aHR, 2.61; 95%, 2.21-3.07) or head injury alone (aHR, 1.63; 95% CI, 1.47-1.80).

Dementia risk was slightly attenuated after adjusting for the competing risks of mortality and stroke but still higher with PTE.

Importance of PTE Prevention

Similar findings were obtained in secondary analyses, which showed increased dementia risk associated with PTE that occurred after the first vs second head injury (in the case of multiple head injuries) and after mild vs moderate/severe injury.

“Results of this study underscore the importance of not only the prevention of head injuries but also of the prevention of PTE after a head injury,” the authors stated.

The ARIC study was conducted in communities in just four states, so the findings may not be generalizable to other regions of the United States or to population subgroups not represented, the authors noted.

Moreover, the results may not be generalizable to those who sustained a head injury earlier in life, and the prospective nature of the study does not rule out the possibility of reverse causation.

The pathophysiological mechanisms underlying the long-term sequelae of head injury and the development of PTE are “complex, but a growing body of literature suggests that neurodegenerative mechanisms may contribute to both, providing biologic plausibility for the observed associations,” investigators added.

The ARIC study was funded by the National Institutes of Health. Schneider was supported by the US Department of Defense. Schneider reported employment (associate editor) with the American Academy of Neurology at Neurology outside the submitted work. The other authors’ disclosures and sources of support are listed on the original paper.

Batya Swift Yasgur MA, LSW, is a freelance writer with a counseling practice in Teaneck, NJ. She is a regular contributor to numerous medical publications, including Medscape and WebMD, and is the author of several consumer-oriented health books as well as Behind the Burqa: Our Lives in Afghanistan and How We Escaped to Freedom.