medwireNews: People with post-traumatic epilepsy (PTE) have a higher risk for dementia than those with head injury or seizure/epilepsy alone, suggest data from the ARIC study.
The prospective community-based cohort study found that participants who developed PTE, classed as a diagnosis of seizure/epilepsy occurring 7 or more days after a head injury, were 4.85 times more likely to develop dementia over a follow-up of 25 years than participants without head injury or seizure/epilepsy, after adjusting for age, sex, race, education, and military service.
This risk was higher than the 1.64- and 2.81-fold increased risk for participants reporting either head injury or seizure/epilepsy alone, respectively.
“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,” write Andrea Schneider (University of Pennsylvania Perelman School of Medicine, Philadelphia, USA) and colleagues in JAMA Neurology.
The team adds that a “growing body of literature suggests that neurodegenerative mechanisms play a role in the pathophysiology of PTE” and that “there is limited understanding of long-term outcomes following a diagnosis of PTE.”
The study involved 12,558 participants with a mean age of 54.3 years, of whom 57.7% were women and the majority (71.8%) identified as White. Based on self-reported data and medical records, 1811 (14.4%) were categorized as having a head injury, 640 (5.1%) as having epilepsy, and 145 (1.2%) as having PTE. The median time between head injury and PTE was 3.1 years.
Over 250,372 person–years of follow-up, there were 2498 incident cases of dementia (19.9% of participants) and the cumulative dementia-free survival was lowest for the individuals with PTE.
The researchers note that the risk for dementia in individuals with PTE was “slightly attenuated” but still significantly increased compared with controls after adjusting for vascular risk factors, such as the presence of diabetes and hypertension, and having the apolipoprotein E Ɛ4 genotype, at hazard ratios (HRs) of 4.78 and 4.56, respectively.
And in models accounting for the competing risks for death and both death and stroke, the risk for dementia among patients with PTE was increased a corresponding 3.04-fold and 3.12-fold.
Schneider and colleagues write that the findings “provide evidence that PTE 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.”
The researchers found that the association between PTE and increased dementia risk was not affected by sex or race and there was no significant difference among participants who developed PTE after a first versus a second head injury, or among those with a mild head injury compared with moderate, severe, or penetrating head injuries.
However, the results showed that the risk for dementia associated with PTE was greater in those younger than 54 years of age at the study baseline (HR=8.53) than in those aged 54 years and older (HR=4.30). One explanation for this might be “related to the higher baseline incidence and prevalence of dementia among older individuals; consequently, PTE may not confer as much extra risk among older individuals as it does among younger individuals,” suggests the team.
The authors note that they were “unable to investigate the potential influence of specific antiseizure medications, changes in antiseizure medication use over time, or measures of epilepsy severity, such as seizure frequency or need for hospitalization on associations of PTE with dementia risk in this study.”
They recommend that these factors “should be a priority for future research as prior studies have suggested that more severe PTE (eg, drug-resistant PTE) is associated with worse short-term outcomes compared with nondrug resistant PTE.”
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