Most of the international research that has searched for predictors of cognitive and behavioral complications of the epilepsies has focused on disease-related factors (e.g., duration of disorder, location/laterality of seizure onset) or markers of neurobiological integrity (e.g., quantitative neuroimaging techniques). Now a new study has found that people with pharmacoresistant temporal lobe epilepsy (TLE) appear more likely to have deficits in cognitive function and depressed mood if they live in neighborhoods that are disadvantaged — e.g., having higher poverty levels and fewer educational and job opportunities — than in neighborhoods with fewer disadvantages. The retrospective cross-sectional study was published online in Neurology by researchers from Cleveland Clinic and the University of Wisconsin, Madison.
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“Epilepsy research has largely ignored the influence that the social determinants of health in neighborhoods may have on cognition and mood,” says the study’s lead author, Robyn Busch, PhD, ABPP-CN, a clinical neuropsychologist with Cleveland Clinic’s Epilepsy Center. “Our findings show that these neighborhood social factors are linked to neuropsychological outcomes in people with epilepsy. They call for further research into the mechanisms behind these effects and whether modification of these factors can improve neuropsychological outcomes.”
The researchers reviewed a registry of patients with epilepsy aged 16 or older who were evaluated for epilepsy surgery at Cleveland Clinic between 1986 and 2021. Patients were included if they had pharmacoresistant TLE without prior resective neurosurgery, if they had completed a neuropsychological evaluation and if data were available on their home address around the time of their evaluation.
The researchers focused on TLE because of its association with a high risk for cognitive problems and depressed mood and its status as the most common adult form of epilepsy.
The study drew on the patients’ neuropsychological evaluations to compare their scores on validated measures of intelligence, attention, processing speed, language, executive function, visuospatial skills, verbal/visual memory, depression and anxiety.
The researchers used patients’ home addresses and the Area Deprivation Index (ADI) — an established tool for quantifying neighborhood-level socioeconomic status based on 17 indicators — to assign patients to quintiles of relative neighborhood deprivation, with higher ADI scores indicating greater deprivation. The aim was to examine the relationship between neighborhood deprivation and neuropsychological function in this population of adults with TLE.
A total of 800 patients met all inclusion criteria and were included in the analysis. The cohort had a median age of 38 years and was predominantly female (58%) and non-Hispanic white (90%). Although neuropsychological testing among this group dated back as far as 1990, virtually all patients (98%) completed their testing between 2000 and 2021.
Results showed that increasing ADI quintile (indicating increasing levels of neighborhood deprivation) was associated with significant declines in all neuropsychological measures assessed, with the exception of executive function (where the decline trended toward statistical significance). This effect was seen in measures of both cognition and mood (depression and anxiety).
Additionally, patients in the higher ADI quintiles had significantly higher odds of having a more severe cognitive phenotype across cognitive domains after controlling for age, sex, education, race, duration of epilepsy, number of antiseizure medications and other variables.
Patients who self-identified as Black, Hispanic or other non-white groups were overrepresented in the most disadvantaged neighborhood quintiles and were more likely to have a more severe cognitive phenotype compared with non-Hispanic white patients.
Related neuroimaging research underway
“These results demonstrate a significant correlation between neighborhood deprivation and neuropsychological outcomes in adults with pharmacoresistant TLE,” Dr. Busch observes. “They underscore the importance of considering environmental, social and neighborhood issues in neuropsychological studies of epilepsy.”
The researchers note that the factors behind this effect are likely to be multiple and complex. Previous research suggests that neighborhood deprivation can confer negative effects on cognition and mood via a number of potential mechanisms, including reduced educational opportunities, poor healthcare access, food insecurity or inadequate nutrition, heightened exposure to pollutants, chronic stress, physical inactivity, reduced socialization and increased medical comorbidities.
They also note that recent studies in other patient groups (i.e., without epilepsy) have found strong correlations between neighborhood deprivation and abnormal neuroimaging findings. “We suspect that brain morphology, as evaluated through neuroimaging, may be a mediator of the relationship between neighborhood deprivation and cognition in people with TLE,” says Dr. Busch. “We have research underway to assess this hypothesis.”
The present study is limited by the fact that patients’ ADI assignment was based on assessment at just one point in adulthood, the researchers acknowledge, and that this fails to account for the neighborhood environment during key periods of early development or for changes in neighborhood deprivation over time. Despite this drawback, the findings are broadly consistent with studies of the impact of neighborhood deprivation in other conditions, they note.
“We look forward to confirmation of these findings in larger, more diverse patient groups, which can also help illuminate the complex relationships that may explain these effects,” says senior author Bruce Hermann, PhD, ABPP-CN, a clinical neuropsychologist and professor emeritus at the University of Wisconsin, Madison. “It is time to broaden neuropsychological research in epilepsy. Brains affected by neurological disease have traditionally been viewed as unique windows to advance understanding of problematic cognition and behavior. But these brains reside in unique individuals who live in diverse and sometimes complicated environments, the effects of which are just beginning to be understood. This study is an early step in that direction.”