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TOPLINE:

Investigators have identified a range of risk factors that significantly increase the odds of late-onset epilepsy (LOE) in people with cognitive decline (PWCD), including having the apolipoprotein E4 (APOE4) allele, early-onset dementia, severe cognitive decline, the Alzheimer’s disease (AD) dementia subtype, a history of stroke or transient ischemic attack (TIA), and Parkinson’s disease (PD).

METHODOLOGY:

• This longitudinal, multicenter analysis was conducted across 39 AD Research Centers in the United States between 2005 and 2021.
• Researchers included more than 14,600 participants (50% men; mean age, 73.8 years) with no history of epilepsy. All had dementia or mild cognitive impairment, which the investigators collectively called PWCD.
• The primary outcome was the occurrence of incident LOE during follow-up, defined as seizures starting at the age of 60 years or older.
• Individuals who did not develop LOE and were at least 60 years of age at the most recent follow-up were included in the control group.

TAKEAWAY:

• About 1.5% of participants developed LOE during follow-up.
• The risk for LOE was significantly higher in participants with the APOE4 allele (adjusted hazard ratio [aHR], 1.39; P = .03), onset of dementia before age 60 years (aHR, 2.46; P < .001), worse cognition (aHR, 2.35; P < .001), the AD subtype of dementia (aHR, 1.68; P = .01), a history of stroke or TIA (aHR, 2.03; P < .001), or PD (aHR, 2.53; P = .03) than those in the control group.
• Significant associations remained for all these risk factors even when the definition of LOE was changed to occurring after the age of 65 years.

IN PRACTICE:

“PWCD with these risk factors may be considered for routine screening with an electroencephalogram for early identification of LOE,” the investigators wrote.

SOURCE:

This study was led by Ifrah Zawar, MD, University of Virginia, Charlottesville, Virginia. It was published online on April 14 in JAMA Neurology.

LIMITATIONS:

This study’s observational design prevented the establishment of causality. The study also lacked data on seizure details, EEG findings, and key confounders such as family history of epilepsy, intellectual disability, and brain tumors. Income and lifestyle factors were not fully assessed, and most AD diagnoses were clinical rather than confirmed using biomarkers. Additionally, follow-up durations varied, risking misclassification, and the sample was drawn from tertiary centers with predominantly White participants, limiting the generalizability of the findings.

DISCLOSURES:

This study was funded by the National Institute on Aging/National Institutes of Health. Several investigators reported receiving grants from various sources during the study, and one received industry-related payments outside the submitted work. Full details are provided in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.