Conference Coverage

Noninvasive testing in midlife flags late-onset epilepsy risk



BOSTON – Noninvasive tests performed in midlife may help identify people who are at risk of late-onset epilepsy, a new study suggests. New data from the Framingham Heart Study show those who scored better on a neurocognitive test that measures executive function were 75% less likely to develop late-onset epilepsy.

An analysis of MRI revealed that those with higher cortical volumes also had a lower risk of epilepsy later in life, while those with higher white matter hyperintensities had an increased risk.

The study could help identify at-risk individuals years before symptoms of epilepsy appear.

“We present possible markers that could potentially identify patients at risk for developing late-onset epilepsy, even in the preclinical phase and before the clinical manifestation of conditions like stroke and dementia that are known now to be linked with the condition,” said lead investigator Maria Stefanidou, MD, assistant professor of neurology at Boston University.

The findings were presented at the 2023 annual meeting of the American Academy of Neurology.

Protection against late-onset epilepsy?

Hypertension and stroke are known risk factors for late-onset epilepsy. Dementia is also a known risk factor. But in about 30% of cases, the cause of epilepsy in older individuals is unknown.

For this study, investigators analyzed data from the offspring cohort of the Framingham Heart Study. Participants were at least 45 years old; underwent neuropsychological evaluation and brain MRI; and had no prior history of stroke, dementia, or epilepsy. Cognitive measures included Visual Reproductions Delayed Recall, Logical Memory Delayed Recall, Similarities, Trail Making B-A (TrB-TrA), and the Hooper Visual Organization Test.

Participants also underwent an MRI to measure total cerebral brain volume, cortical gray matter volume, white matter hyperintensities, and hippocampal volume.

After a mean follow-up of 13.5 years, late-onset epilepsy was diagnosed in 31 of participants who underwent neuropsychological testing (n = 2,349) and in 27 of those who underwent MRI (n = 2,056).

Better performance on the TrB-TrA test (a measure of executive function, processing speed, and occult vascular injury) was associated with a reduced risk of late-onset epilepsy (adjusted hazard ratio, 0.25; P = .011).

The findings held even after adjusting for age, sex, educational level, and known risk factors for late-onset epilepsy, such as hypertension (aHR, 0.30; P = .0401).

Higher white matter hyperintensities, a measure of occult vascular injury, was associated with increased epilepsy risk (aHR, 1.5; P = .042) when adjusted only for age, sex, and education, but was no longer significant after adjusting for hypertension and other risk factors (aHR, 1.47; P = .065).

The analysis also revealed that participants with a higher cortical gray matter volume had a lower risk for late-onset epilepsy (aHR, 0.73; P = .001).

“There is increasing literature supporting that late-onset epilepsy may be secondary to accumulative occult cerebrovascular and neurodegenerative processes that occur during aging,” Dr. Stefanidou said. “Our findings likely reflect that a lesser degree of occult vascular brain injury in midlife may be protective against late-onset epilepsy.”

However, the epidemiological study points to association, not causation, Dr. Stefanidou cautions.

“Further studies will be needed to study our observations in the clinical setting,” she said.

‘Intriguing’ findings

Commenting on the findings, Joseph Sirven, MD, a neurologist at the Mayo Clinic in Jacksonville, Fla., said the findings are “intriguing,” but also raise some questions. “Late-onset epilepsy remains an issue for many and it’s common,” said Dr. Sirven, who has patients with late-onset epilepsy.

Dr. Sirven was particularly interested in the findings on white matter hyperintensities. “Hippocampal volumes have been used but not so much cortical volumes,” he said. “I would like to know more about how white matter changes suggest pathology that would explain epilepsy.”

Study funding was not disclosed. Dr. Stefanidou and Dr. Sirven report no relevant financial relationships.

A version of this article first appeared on

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