Pauline Anderson

December 09, 2015

PHILADELPHIA — As the population gets older, interest in learning more about the effect of aging on the brain in patients with epilepsy is becoming an important research focus. So far, it looks like patients with epilepsy show some signals of advanced brain aging.

New data suggest that patients with long-term treatment-resistant epilepsy have a brain that appears older on brain imaging than their chronologic age.

Along with his research team, Heath Pardoe, PhD, assistant professor, neurology, New York University Langone Medical Center, looked at two groups of patients with epilepsy: one with recent-onset focal epilepsy and another with long-term intractable focal epilepsy who were being assessed for surgical resection.

All study participants underwent MRI. The researchers used a computer program that estimates a person's age with information from the MRI. They assessed white matter and gray matter segmentation images separately, yielding two age estimates per patient; included were 42 patients with recent onset, 94 patients with long-term epilepsy, and 74 controls.

"In both groups, we used the MRI scan to predict the individual's age and then we looked at the difference between the predicted age from their brain structure and their actual chronological age," said Dr Pardoe.

The results showed that in patients with recent-onset epilepsy, there was only a nonsignificant difference between their predicted brain age and actual age in both white matter and gray matter assessments.

However, those with long-term intractable epilepsy had a significant difference — on average, 5 years — between predicted brain age and chronologic age compared with healthy controls when the white matter segment was used in the predictor model.

The patients' age strongly contributed to the predicted difference, Dr Pardoe noted. The difference was greater in younger patients (20 to 30 years) than older patients (30 to 50 years).

"Any explanation for this would be speculative at this early stage," he said. "It may reflect some characteristic of patients who come to our center, or it may be related to biological differences directly related to aging."

There was no difference in predicted brain age when the gray matter segment was used in these intractable cases.

"This is a very interesting finding," said Dr Pardoe "It highlights the importance of getting seizures under control."

He shared the results at a press conference here at the American Epilepsy Society (AES) 69th Annual Meeting.

50-Year Follow-up

At the same press briefing, Matti Sillanpää, MD, PhD, professor and senior research scientist, University of Turku, Finland, who has followed children with epilepsy for over 50 years, presented data that offer a unique perspective on the effect of aging in this population.

In the early 1960s, Dr Sillanpää started collecting information on 150 children who had new-onset epilepsy (two or more unprovoked seizures). Of these, 100 had uncomplicated epilepsy (and thus no major impairments, such as cerebral palsy or intellectual disability).

He selected a control group of the same number of children, matched for age, sex, and place of residence, who didn't have epilepsy. Over the years, he regularly followed these two groups in almost every aspect of their lives.

In 2007, 90% of the epilepsy group had been without any seizures for the previous 10 years, and about two thirds were not taking antiepileptic drugs. They were normal in almost every respect: For example, they had graduated from school, they had a driver's license, and their socioeconomic status was similar to that of the healthy controls. They did, however, have fewer children.

Their seizure outcome, Dr Sillanpää told a press briefing, was "excellent."

However, the epilepsy group had more amyloid deposits in their brain compared with controls. Imaging studies revealed that 23% of the childhood epilepsy group was amyloid positive compared with 7% of controls.

Dr Sillanpää's research "is unique in many regards," commented Bruce P. Hermann, PhD, professor, neurology, and director, Charles Matthews Neuropsychology Lab, University of Wisconsin School of Medicine and Public Health, Madison, and AES board member, who attended the press briefing. "These children were about 4 years old when they were recruited and now are in their 50s. It's just an unbelievable cohort."

It's unclear at this point, said Dr Hermann, whether this increased amyloid means they will be at higher risk for dementia. "We don't know if it's progressive at all; they just seem to have this protein deposit in their brain —- at an earlier age, at a higher rate than controls."

Perhaps additional imaging at the next follow-up visit will shed more light, he said.

Higher Epilepsy in Older Populations

It's expected that as the population ages, the incidence of late-onset epilepsy will increase. According to Bernd Pohlmann-Eden, MD, PhD, professor, neurology, Dalhousie University, Halifax, Nova Scotia, Canada, the epilepsy prevalence in the general population is about 1% but is two to three times higher in those older than 60 years of age.

Dr Pohlmann-Eden is investigating the brains of patients who have their first seizure in their 60s and beyond. His research is using imaging and other investigative tools to shed new light on why the aging brain seems to be vulnerable to seizures.

"Our understanding of this population is very poor," he said. "One of the main questions is, do we have the right imaging markers to identify those patients at risk for seizures?"

There are four main causes of epilepsy in the elderly, he said: vascular disease, dementia, tumors, and head trauma.

It's possible that modifiable risk factors for dementia, such as diet and exercise, may also help prevent seizures in older people. Research shows that people with epilepsy are relatively inactive and experience more depression than people without epilepsy, said Dr Hermann.

Dr Pardoe's study was supported by the Epilepsy Study Consortium (ESCI), a nonprofit organization dedicated to accelerating the development of new therapies in epilepsy to improve patient care. The funding provided to ESCI comes from industry, philanthropy, and foundations (UCB Pharma, Pfizer, Eisai, Lundbeck, Finding a Cure for Epilepsy and Seizures, The Andrews Foundation, Friends of Faces, and others).

American Epilepsy Society (AES) 69th Annual Meeting. Abstract 1.146.


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