Abstracts

Late-onset unexplained epilepsy (LOUE) is an increasingly prevalent condition in aging populations. While cognitive changes in this group are increasingly recognized, the impact of neighborhood-level disadvantage remains poorly understood. The Area Deprivation Index (ADI), a validated measure of socioeconomic disadvantage based on residential ZIP code, has been associated with cognitive decline in older adults. Understanding the relationship between ADI, cognitive performance, and structural brain changes in individuals with LOUE may reveal modifiable social risk factors and inform future research and interventions.

We prospectively recruited 85 participants with new-onset unexplained seizures beginning at age 55 or older, within five years of onset, and without cortical lesions on MRI. Cognitive performance was measured using the Preclinical Alzheimer Cognitive Composite (PACC), which includes delayed verbal recall, executive function, and processing speed. ADI-National % scores were derived from ZIP codes. Participants underwent 3T MRI, and T1 MPRAGE sequences were processed using FreeSurfer 5.0. Linear regression assessed associations between ADI and cognition, adjusting for age, sex, and education. Generalized linear models with cluster correction were used to examine ADI and cortical thickness.

This study included 85 participants (49.4% female, 50.6% male; mean age = 71.5 years), with 89.4% residing in Massachusetts. The mean ADI-National % was 18.7 (SD = 12.9), indicating that most participants lived in neighborhoods with low to moderate deprivation. Higher ADI-National % was associated with lower PACC Z-scores (β = -0.027, 95% CI [-0.047 to -0.005], p = 0.016) after adjusting for age, sex, and education. Among the 77 participants with available PACC data, 25% (n = 19) had scores below -1.0, consistent with cognitive impairment. Of these, 63% (n = 12) lived in higher-deprivation areas (in the bottom 50% of distribution), reinforcing the link between neighborhood disadvantage and worse cognitive performance.

Cortical thickness analysis (n = 80) showed significant associations between ADI and reduced thickness in multiple regions. In the left hemisphere, reductions were observed in the superior temporal, supramarginal, fusiform, middle temporal, and superior frontal regions. In the right hemisphere, lower thickness was noted in the superior temporal region and temporal pole (Figure 1).
Figure 1: Cortical thickness maps of the left and right hemispheres illustrating the association between higher Area Deprivation Index (ADI) and reduced cortical thickness.

Neighborhood deprivation was independently associated with lower global cognitive performance and patterns of cortical atrophy in individuals with LOUE.  These findings suggest that social determinants like ADI may help identify individuals at risk of cognitive decline and highlight the value of incorporating environmental context into cognitive screening and care strategies for older adults with epilepsy.