In a recent study published in JAMA Neurology, researchers assessed the associations between post-traumatic epilepsy (PTE) and the risk of dementia.
Study: Posttraumatic Epilepsy and Dementia Risk. Image Credit: Orawan Pattarawimonchai/Shutterstock.com
Background
PTE is the occurrence of unprovoked seizures more than a week after a traumatic brain injury, and it accounts for up to 20% of acquired epilepsies.
Research suggests that PTE is associated with poor short-term psychosocial, cognitive, and functional outcomes; however, less is known about the long-term impact of PTE.
Moreover, epilepsy and traumatic brain injury are independently associated with the risk of dementia. Growing evidence implicates neurodegenerative mechanisms in PTE pathophysiology.
As such, individuals with PTE may likely have adverse cognitive outcomes compared to those with epilepsy or brain injury alone.
About the study
In the present study, researchers examined the associations between PTE and dementia risk using data from the atherosclerosis risk in communities (ARIC) study.
The ARIC study enrolled people aged 45–64 during 1987-89. Participants completed subsequent in-person visits and follow-up telephone calls. Subjects were asked about hospitalizations during telephone calls; reported hospitalization records were obtained.
ARIC study data were linked to the United States (US) Centers for Medicare and Medicaid Services (CMS). Follow-up for the present analysis continued until the diagnosis of dementia, death, discontinuation, or administrative censoring.
Head injury was defined using data from questionnaires, International Classification of Diseases, ninth and tenth revisions (ICD-9/10) codes from ARIC study hospitalization records, and ICD-9/10 codes from linked CMS records.
Epilepsy/seizure was defined using seizure- or epilepsy related ICD-9/10 codes from ARIC and CMS records. PTE was defined as epilepsy/seizure occurring ≥ seven days after (diagnosis of) head injury.
The researchers stratified participants into exposure groups – 1) reference (no epilepsy/seizure and no head injury), 2) head injury, 3) epilepsy/seizure, and 4) PTE. The associations between exposure variables and dementia risk were examined using Cox proportional hazard models.
Model 1 was adjusted for sex, age, education, race, military veteran status, and center. Model 2 was additionally adjusted for smoking/alcohol status, hypertension, and diabetes.
Model 3 was further adjusted for the apolipoprotein E ε4 genotype. Besides, Fine and Gray proportional hazard models accounted for the competing mortality risks individually and with stroke.
Findings
The team included 12,558 participants from the ARIC study for analysis. They were aged 54.3, on average, at baseline. Most participants (57.7%) were female, and 28.2% were Black.
The team categorized 1,811, 640, and 145 participants as having a head injury, epilepsy/seizure, and PTE, respectively, over a median follow-up of 25.4 years.
The median time from baseline to first head injury, epilepsy/seizure, or PTE was 15.1, 13.8, or 3.1 years, respectively. Overall, 2,498 cases of dementia occurred over a follow-up of 250,372 person-years. Notably, individuals with PTE had the lowest cumulative dementia-free survival.
In the first model, PTE was associated with 4.85 times the risk of dementia compared to the reference group.
In contrast, epilepsy/seizure and head injury were associated with 2.81- and 1.64-fold higher dementia risk, respectively. In models (2 and 3) with additional adjustments (for vascular and genetic risk factors), the elevated dementia risk associated with PTE was marginally attenuated.
Nevertheless, this (PTE-associated) increased dementia risk was still significantly higher than that associated with epilepsy/seizure or head injury alone.
PTE was associated with a three-fold increased risk of dementia in models that accounted for the competing risks of death individually and with stroke.
Further, younger participants consistently showed stronger associations between PTE and dementia risk than older subjects across all models. There was no evidence of multiplicative interaction by race or sex.
Conclusions
In sum, the study demonstrated that subjects with PTE had about a 4.5-fold increased risk of dementia relative to those without epilepsy/seizure and head injury.
After accounting for the competing risks of death and stroke, there was approximately three-fold higher dementia risk associated with PTE.
Moreover, dementia risk was significantly higher with PTE than with epilepsy/seizure or head injury alone. Notably, the study population comprised older adults without prior head injury at baseline; thus, the findings may not be generalized to those who sustain a head injury early in life.
The study could not account for physical functioning and frailty, which might confound the observed associations.
Besides, the researchers did not have access to details of injury mechanisms, acute imaging findings, and clinical characteristics.
Taken together, the findings reveal increased dementia risk among people with PTE that was significantly higher than in individuals with head injury or epilepsy/seizure alone.
These results highlight the significance of prevention of not only head injuries but also PTE following these injuries.
Frontotemporal dementia disrupts empathy for pain, study reveals