INDIVIDUALS with cognitive decline (dementia or mild cognitive impairment) carrying the APOE4 allele, experiencing early-onset dementia, or having Alzheimer’s disease, Parkinson’s disease, stroke, or severe cognitive impairment face a significantly higher risk of developing late-onset epilepsy (LOE), according to a longitudinal study of 14,685 participants across 39 US Alzheimer’s research centres.
Late-onset epilepsy, defined as recurrent seizures starting after age 60, is increasingly recognised as a comorbidity in cognitive decline, exacerbating cognitive deterioration and mortality. Identifying risk factors for LOE is critical for early intervention. This study analysed data from participants aged 60+ with cognitive decline but without epilepsy at baseline, tracking LOE incidence from 2005 to 2021. Multivariable Cox regression assessed associations between demographic, genetic, cardiovascular, and neurological factors and LOE development.
Of 14,685 participants (50% female, mean age 73.8), 1.5% (n=221) developed LOE over follow-up. Key risk factors included APOE4 allele (aHR=1.39, 95% CI 1.04–1.86; p=0.03), dementia onset before age 60 (aHR=2.46, 95% CI 1.53–3.95; p<0.001), Alzheimer’s subtype (aHR=1.68, 95% CI 1.13–2.49; p=0.01), severe cognitive impairment (aHR=2.35, 95% CI 1.97–2.79; p<0.001), stroke/TIA (aHR=2.03, 95% CI 1.37–3.01; p<0.001), and Parkinson’s disease (aHR=2.53, 95% CI 1.08–5.95; p=0.03). Sensitivity analyses using LOE onset after age 65 confirmed these associations.
These findings advocate targeted electroencephalogram (EEG) screening for high-risk groups to enable timely epilepsy management. Clinicians should prioritise monitoring patients with APOE4, early dementia onset, or comorbid stroke/Parkinson’s, while addressing modifiable risks like vascular health. Future research should investigate pathophysiological links between LOE and neurodegeneration and evaluate EEG screening’s impact on outcomes.
Reference
Zawar I et al. Risk factors associated with late-onset epilepsy in dementia and mild cognitive impairment. JAMA Neurol. 2025;DOI:10.1001/jamaneurol.2025.0552.
