ORLANDO — People with epilepsy are more likely to decline cognitively compared with those without epilepsy, new research suggests.
Results of the large, longitudinal study show that seizures predicted earlier conversion time from normal cognition to mild cognitive impairment (MCI) but were not associated with conversion from MCI to dementia.
"Modifiable cardiovascular risk factors such as hypertension and diabetes need to be treated more aggressively because they can impact cognition, but epilepsy is another risk factor that needs to be treated in a timely fashion because it appears to be also associated with cognitive impairment," said study investigator Ifrah Zawar MD, assistant professor, Department of Neurology, University of Virginia in Charlottesville.
The study (abstract #2.172) was presented on December 2 at the American Epilepsy Society (AES) 2023 Annual Meeting.
An Understudied Issue
Comorbid seizures occur in up to 64% of those with dementia, and patients with dementia and epilepsy have a more aggressive disease course, faster cognitive decline, and more severe neuronal loss, Zawar told Medscape Medical News.
But the impact of seizures on the conversion of cognitively healthy to MCI and from MCI to dementia, after accounting for cardiovascular risk factors, has not been well studied.
Researchers analyzed longitudinal data of 13,726 patients, mean age about 70 years, who were cognitively healthy or had mild cognitive impairment (MCI). Participants were recruited from 39 Alzheimer's Disease (AD) centers in the United States from 2005 to 2021.
Investigators categorized participants into three groups: active (having had seizures in the past year and/or requiring active treatment; N = 118), resolved (not on any treatment for the past year and not having seizures; N = 226), and no seizures (never having had seizures; N = 13,382).
The primary outcome was conversion from cognitively healthy to MCI/dementia and from MCI to dementia in those with and without active epilepsy and resolved epilepsy.
Factors associated with conversion from cognitively healthy to MCI among those with current or active epilepsy included older age (P <.001 for ages 60-80 years and P =.002 for age 80 years or older vs younger than 60 years), male sex (P <.001), lower education (P <.001), hypertension (P <.001), and diabetes (P <.001).
The hazard ratio (HR) for earlier conversion from healthy to worse cognition among those with active epilepsy was 1.76 (95% CI, 1.38-2.24; P <.001), even after accounting for risk factors.
Kaplan-Meier curves showed that the median time to convert from healthy cognition to MCI among people with active epilepsy was about 5 years compared with about 9 years for those with resolved epilepsy and 10.5 years for those without epilepsy.
The story was similar for faster conversion from MCI to dementia. Compared with having no epilepsy, the HR for faster conversion for active epilepsy was 1.44 (95% CI, 1.20-1.73; P <.001).
In addition, the median time to conversion from MCI to dementia was about 3 years for those with active epilepsy compared with about 5 years for those with resolved epilepsy and about 5 years for those without epilepsy.
"It's important for physicians to understand that uncontrolled epilepsy or active epilepsy is going to impact patients' cognition adversely, which in itself is associated with increased comorbidity and mortality," said Zawar.
The mechanism driving the acceleration to worse cognition in people with epilepsy is "complicated and involves a multitude of factors," she said.
The researchers did not specifically investigate how use of antiseizure medications correlated with cognitive outcomes, but Zawar believes that "epilepsy in itself impacts cognition."
The researchers also didn't have EEG data for study participants who were recruited from Alzheimer's disease centers where EEGs aren't routinely carried out, so such data for many patients may not necessarily exist, said Zawar.
Important Research
Commenting for Medscape Medical News, Bruce Hermann, PhD, professor emeritus, Department of Neurology, University of Wisconsin School of Medicine and Public Health, said that the study is important because of the, "tremendous interest and concern about aging with epilepsy."
"We want to know how people with chronic epilepsy age cognitively and what's the cognitive course of those who have late onset epilepsy, particularly those with unknown etiology," he added.
Hermann noted that much of the research in this area has been relatively small and single-center investigations.
"These larger-scale investigations from outside the epilepsy community are so important because they have data on large numbers of subjects, they have cognitive data, and follow-ups over long periods of time, and they're providing some really novel information," Hermann said.
He added that terms used in the dementia world such as MCI and frank dementia are somewhat foreign to epileptologists. In addition, interventions to delay, treat, or prevent cognitive decline such as exercise, diet, social activity, and mental stimulation that are regularly discussed by dementia experts are underrepresented in the epilepsy world.
"The things they talk about in memory clinics in the aging world almost routinely have not penetrated to the epilepsy clinics for aging individuals and for the epilepsy community in general."
The study used the Montreal Cognitive Assessment to identify cognitive decline. "It would be nice to see how these people look with traditional neuropsychological tests," said Hermann.
He added that information on the impact of epilepsy on different MCI phenotypes, for example, pure memory impairment subtype; pure nonmemory subtype; and multiple domain subtype, would also be useful.
The study was supported by the AES and the Alzheimer's Association.
Zawar and Hermann report no relevant disclosures.
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