The goal of this study was to evaluate the cognitive, neuroanatomical, and clinical correlates of depressive symptoms in older adults with late-onset unexplained epilepsy (LOUE).

Depression is common in people with epilepsy. Older adults with epilepsy are especially vulnerable due to epilepsy-related factors and aging. Depression may exacerbate cognitive and daily functioning impairment in this population. 

We prospectively recruited adults with LOUE, with epilepsy onset after age 55, who subsequently underwent a cognitive battery, magnetic resonance imaging (MRI), and the 30-item Geriatric Depression Scale (GDS-30). We obtained participants’ apolipoprotein (APOE) genotype and plasma phospho-tau-217 (ptau-217) levels. A global cognition score, the Preclinical Alzheimer Cognitive Composite (PACC-5), was generated. Participants also underwent the Clinical Dementia Rating (CDR) scale, an assessment of global functioning. MRIs were evaluated for white matter hyperintensity volumes (WMV), hippocampal volumes (HV), and amygdala volumes (AV).

The cohort (n=69) had a mean age of 70.72±6.59 years, was 52.17% female, and had an average GDS-30 score of 5.59±4.44. Participants’ GDS-30 scores significantly correlated with their PACC-5 z-scores (Spearman’s ρ=-0.289, p=0.019), and number of anti-seizure medications (ASMs) (Spearman’s ρ=+0.245, p=0.042). Participants with a global CDR=0.5 (n=20, μ=7.75) had higher GDS-30 scores than those with CDR=0 (n=47, μ=4.74, t-test p=0.016), as did APOE4 carriers (n=13, μ=7.85) relative to non-carriers (n=30, μ=3.93, t-test p=0.040).  No association was found between GDS-30 scores and WMV, HV, AV, or plasma ptau-217 levels. Findings related to ASMs remained significant after controlling for age, sex, and pharmacoresistance (p=0.047).

In older adults with epilepsy, worse cognitive and global functioning, greater number of ASMs, and APOE4 carrier status correlated with greater depressive symptoms as measured by the GDS-30. This highlights the importance of reassessing polypharmacy in older adults with epilepsy and supports prior evidence linking depression to cognitive and daily functioning impairment in this population.