Post-Traumatic Epilepsy and the Risk of Dementia

By Robert McInnis, MD

Assistant Professor of Clinical Neurology, Weill Cornell Medical College

Head injury and epilepsy are significant public health concerns, each associated with substantial long-term disability. A notable complication of head injury is post-traumatic epilepsy (PTE), which can develop after trauma and further exacerbate neurological outcomes. In addition, both head injury and epilepsy have been independently linked to an increased risk of developing dementia. However, it remains unclear whether PTE, the specific form of epilepsy arising from head trauma, confers additional dementia risk beyond that of head injury or epilepsy alone.

Schneider et al addressed this gap in a prospective cohort study using data from the Atherosclerosis Risk in Communities (ARIC) study, a multicenter investigation enrolling participants from 1987 to 1989, with follow-up extending to 2019. Their analysis explored whether PTE presents a higher risk for dementia than either head injury or epilepsy alone.

Study Design and Population

The study cohort included 12,558 participants who were initially between 45 and 64 years of age. Individuals with a history of head injury before the study, preexisting dementia, or missing data on head injury or epilepsy were excluded. Over the course of the study, participants were monitored through seven visits for the development of head injury, epilepsy, or dementia. Data were collected using self-reports, hospitalization records with International Classification of Diseases (ICD) 9/10 codes, and Centers for Medicare and Medicaid Services (CMS) data.

Definitions:

• Head injury: Identified using self-report, ICD codes, or CMS data.

• Epilepsy: Defined using seizure-related ICD codes.

• Post-traumatic epilepsy (PTE): Epilepsy occurring seven or more days after head injury.

• Dementia: Identified using ICD codes or death certificate data.

The cohort was divided into four exposure groups:

1. No head injury or epilepsy (reference group)

1. Head injury alone

1. Epilepsy/seizure alone (without preceding head injury)

1. PTE (head injury followed by epilepsy)

Key Findings

Risk of Dementia in Different Exposure Groups

Over a median follow-up of 25.4 years, there were 2,498 cases of dementia identified across 250,372 person-years. The cumulative dementia-free survival was lowest in the PTE group, indicating that individuals with PTE were more likely to develop dementia compared to other groups.

After adjusting for demographic factors, the study found:

• PTE conferred a 4.85-fold increased risk of dementia compared to the reference group.

• Epilepsy without prior head injury increased the risk by 2.81 times, and head injury alone by 1.64 times.

• The higher risk associated with PTE persisted even after controlling for vascular comorbidities and the apolipoprotein E (APOE e4) genotype, both of which are known dementia risk factors.

Age-Related Findings

Interestingly, younger individuals with PTE were found to be at higher relative risk for dementia than older participants. This may partly reflect the higher baseline prevalence of dementia in older individuals, but it also highlights the potentially more severe long-term cognitive consequences of PTE in younger populations.

Impact of Head Injury Severity and Timing

The study showed that the increased risk of dementia associated with PTE was consistent regardless of whether the head injury was mild, moderate, or severe. Additionally, the time between head injury and the onset of PTE influenced dementia risk:

• Earlier onset of PTE (within three years of head injury) was associated with a greater risk of developing dementia compared to later onset of PTE (after three years).

Commentary

This study provides significant evidence that PTE confers a higher risk of dementia than either head injury or epilepsy alone. These findings are crucial because they emphasize the compounded neurological damage caused by the combination of head trauma and subsequent epilepsy. Several aspects of the study design strengthen its conclusions, including the large sample size, long follow-up period, and the prospective nature of the data collection.

One particularly concerning observation is the higher dementia risk in younger individuals with PTE, which could lead to a devastating impact on quality of life, given their longer life expectancy. The results also suggest that early-onset PTE following head injury is particularly harmful in terms of cognitive outcomes, highlighting the importance of early intervention and long-term monitoring in these patients.

Study Limitations

However, there are several limitations to consider:

• Geographic limitations: The study population was drawn from the Midwest and Southern United States, and the exclusion of certain racial groups due to small sample sizes raises concerns about the generalizability of the findings to other populations.

• ICD codes were used to define head injury, epilepsy, and dementia, which may introduce classification bias. ICD codes, while useful for large epidemiological studies, may not always accurately reflect the true onset or nature of these conditions.

Clinical and Public Health Implications

The findings from this study underscore the need for public health measures aimed at preventing head injury, which could help reduce the incidence of both PTE and dementia. Moreover, for individuals who already develop PTE, these results call for the development of tailored medical and surgical treatments to better manage epilepsy and potentially mitigate the associated risk of cognitive decline.

Future Research Directions

Given the limitations regarding the generalizability of the cohort, further research is necessary to explore the relationship between PTE and dementia in more diverse populations. Additionally, the mechanisms driving the neurodegeneration observed in PTE patients require further investigation to develop more effective therapeutic interventions. The role of early treatment and seizure control in modifying long-term dementia risk in PTE should also be explored in future studies.

Summary

This prospective study establishes that PTE significantly increases the risk of developing dementia, more so than head injury or epilepsy alone. The heightened risk in younger individuals and those with early-onset PTE underscores the severe long-term impact of this condition. These findings highlight the importance of early diagnosis, preventive measures, and appropriate treatment strategies to manage PTE and reduce the burden of dementia.

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