- Design
- Individual participant data meta-analysis of 6 prospective cohorts
- Population
- 42,257 US adults, mean age 71, followed about 9 years
- Primary outcome
- Incident epilepsy with onset at 65 or older
- Effect
- Stroke HR 1.99 (1.63–2.43); diabetes 1.42; smoking 1.39; CKD 1.29; hypertension 1.17
A JAMA Neurology individual participant data meta-analysis pooled six US population cohorts, including ARIC, CHS, MESA and REGARDS, following 42,257 adults (mean age 71) for about nine years. 1,500 (3.5%) developed epilepsy starting at 65 or older.
In adjusted models, risk was higher with prior stroke (HR 1.99), diabetes (1.42), current smoking (1.39), chronic kidney disease (1.29) and hypertension (1.17), and with APOE ε4 (1.22 for one copy, 1.84 for two). The associations were similar across age, sex and ethnic groups.
A new seizure in an older adult without an obvious cause is often labelled cryptogenic. These data suggest many of those cases reflect accumulated small-vessel and cerebrovascular damage, the same burden that drives stroke and vascular cognitive impairment.
Two practical consequences follow. A first seizure after 65 is a reason to review vascular risk factors as carefully as after a transient ischaemic attack. And the APOE ε4 link supports watching cognition in these patients over time.
- Review blood pressure, glucose, kidney function and smoking in every older adult with new-onset seizures
- Look for small-vessel disease and silent infarcts on MRI in late-onset epilepsy
- Treat vascular risk factors in these patients as you would after a transient ischaemic attack
- Screen cognition at baseline and follow it, given the overlap with dementia risk
Why it matters
"Cryptogenic" late-onset epilepsy may often have a vascular explanation that can be treated.
Don't overread it
These are associations; the study cannot show that treating vascular risk prevents seizures.
The statistics, in plain English
A hazard ratio of 1.99 for prior stroke means about twice the rate of new epilepsy. Smaller ratios, such as 1.17 for hypertension, matter because hypertension is so common.
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