Late-Onset Epilepsy a Distinct Neurodegenerative Subtype?

Epilepsy is most common in older adults, and late-onset epilepsy (LOE), defined as recurrent seizures beginning after the age of 65, has been typically attributed to an acquired brain insult. However, LOE may represent a distinctive neurodegenerative-linked epilepsy subtype. LOE was the subject of many presentations at the annual American Epilepsy Society Meeting, held December 5-9, 2025, in Atlanta, GA.

Preliminary clinical data suggest that LOE has unique characteristics. Patients are more frequently female, have a heavier comorbidity load but lower disability, and rarely develop drug-resistant epilepsy.

Separate autopsy findings extend the picture, revealing that those who develop seizures later in life harbor more advanced Alzheimer-type and related neurodegenerative pathology, supporting the idea that LOE may arise from different underlying mechanisms.

Researchers involved in the study added that recognizing these distinctions could help refine management and screening strategies and ultimately improve patient outcomes. The researchers also found that although stroke and neurodegenerative disorders like Alzheimer’s disease are two of the most common causes of LOE, tumors and autoimmune disorders may also contribute.

A systematic review of 94 studies conducted by Ifrah Zawar, MD, assistant professor of neurology, UVA Health, and colleagues examining late-onset unexplained epilepsy (LOUE) showed focal seizures were the most common seizure type, and vascular risk factors, particularly hypertension, were a common comorbidity. Participants with LOUE often showed interictal epileptiform discharges on EEG. About 84% of individuals with LOUE achieved seizure freedom at 1-3 years of follow-up. Across studies that reported outcomes, an average of 76% of patients with LOUE were on monotherapy.

“Our systematic review highlights the many gaps that remain in understanding the epidemiology, clinical presentation, EEG, etiology, and treatment options for LOUE,” said Zawar.

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