More Brain Aging in Older Patients With Childhood Epilepsy

Randy Dotinga

December 13, 2021

While the meaning of the findings aren't entirely clear, new research offers insight into the aging brains of people who developed child-onset epilepsy: A cohort with an average age of 63 appears to be more likely than controls to show signs of brain deterioration, according to a study presented at the annual meeting of the American Epilepsy Society.

"A more abnormal aging course was seen among those with continuing active epilepsy, those with focal epilepsy compared with generalized epilepsies, and those who had the highest lifetime load of specific anti-epilepsy medications," lead author Matti Sillanpää, MD, PhD, a researcher and former child neurologist based at the University of Turko in Finland, said in an interview.

The study began 60 years ago when Finnish researchers started to track 99 subjects who were under 16 and had developed uncomplicated epilepsy. In 2012, 51 participants returned for assessments (9 of the original cohort had died, 2 didn't speak Finnish as a mother tongue, and 15 had left the country or couldn't be found).

In 2017, 41 participants agreed to take part in follow-up assessments (1 of the 2012 cohort could not be traced, and 9 declined to participate.)

Researchers launched the follow-up assessments to provide more insight into aging and epilepsy, Sillanpää said. "While we are in the early stages of understanding the brain and cognitive aging processes of people with epilepsy, there are enough worrisome signs from neuroimaging and cognitive studies to suggest that much more clinical and research attention is warranted. Especially important are population-based investigations that include persons with both remitted as well as active epilepsy in order to obtain a clearer understanding of the overall aging risks involved."

The average age of the 41 subjects in the second assessment was 63.2 (4.1), and 58% were female. Just over half (52%) had focal epilepsy, and 48% had generalized epilepsy. In 74%, epilepsy had remitted, and it remained active in the rest (26%).

For the study, researchers compared the subjects with a control group of 46 subjects, 50% of whom were female, with an average age of 63.0 (4.13). The original control group had 99 participants, and 52 took part in 2012. Of those, 6 declined to participate in the 2017 assessments.

The researchers report these findings:

  • Patients with active epilepsy were more likely to have neurologic signs than were those with remitted epilepsy (P = .015), especially the most common signs – cerebellar signs (P < .001). There was a trend toward cerebellar atrophy but it wasn't statistically significant (P = .06).

  • Patients with focal epilepsies were more likely to have neurologic signs (P = .008) and, specifically, cerebellar signs (P = .018) than were those with generalized epilepsies.

  • The study authors calculated the lifetime usage of four drugs: carbamazepine, diphenylhydantoin, phenobarbital, and valproate. They found that patients with higher usage had more peripheral neuropathy, especially those with high levels of diphenylhydantoin, and phenobarbital usage.

  • Overall, patients with epilepsy versus controls and those with active epilepsy versus remitting epilepsy were more likely to show adjusted declines in "cognitive trajectories" (both P < .05)

The researchers also estimated beta-amyloid levels via Pittsburgh Compound B positron emission tomography (PIB-PET); some specialists consider PIB-positive levels to be a sign of more beta amyloid.

From 2012 to 2017, the percentage of patients with epilepsy who were PIB positive grew from 22% to 33% (P = .03), while the percentage grew from 7% to 11% in the controls (P = .04). "The presence of amyloid and increasing positivity is cause for concern, and further research into the course of the participants is critical," Sillanpää said.

It's not clear if higher levels of brain aging are affecting the lives of participants, he said. "No one in the cohort has a diagnosed dementia at present, but going forward it will be important to pay close attention to the day-to-day functional status of participants."

The mechanisms that may cause more brain aging in epilepsy aren't known. However, "the CDC has shown through population-based investigations that people with epilepsy as a group may be more socially isolated, more physically inactive, and may harbor other lifestyle issues that we now know to be counterproductive to successful cognitive and brain aging in the general population," Sillanpää said. "These factors need to be examined in depth in aging persons with epilepsy to gain a sound understanding of the risk and resilience factors that are most important so that people with epilepsy can act accordingly."

The researchers also report that in patients with epilepsy, there's evidence of a link between hypertension and hippocampal atrophy. They reported trends toward links between obesity and ischemic disease and between type 2 diabetes and hippocampal atrophy.

Going forward, "the findings may be helpful in the treatment and counseling of patients with epilepsy and especially advocating for those health and lifestyle practices that may be beneficial to long-term courses," Sillanpää said. As for the study cohort, he said, researchers plan to continue monitoring them to track their long-term outcomes and any development of neurological disorders such as Alzheimer's disease.

This work was funded by CURE Epilepsy, the National Governmental Research Grant, and the Pro Humanitate Foundation Grant. The study authors report no disclosures.

This article originally appeared on, part of the Medscape Professional Network.


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