Objective:

To relate imaging and cognitive correlates of subclinical brain injury to incident epilepsy in the Framingham Heart Study (FHS), a community-based cohort.

Background:

Late life epilepsy is often due to acquired insults such as strokes and clinical dementia, but its cause remains unknown in up to 30% of cases. There is growing evidence that occult cerebrovascular disease contributes to higher incidence of epilepsy with increasing age.

Design/Methods:

Participants of the Offspring Cohort who attended FHS exam 7(1998-2001), were at least 45 years old at that time, had neuropsychological evaluation (NP), brain MRI, and no prior history of stroke, dementia or epilepsy were included in the study. Cognitive measures included Visual Reproductions Delayed Recall, Logical Memory Delayed Recall, Similarities, Trail Making B-A(TrB-TrA) and the Hooper Visual Organization Test. MRI measures included total cerebral brain volume, cortical grey matter volume (CGMV), white matter hyperintensities (WMHV) and hippocampal volume. Adjudication of epilepsy cases included medical chart review to exclude seizure mimics. Cox proportional hazards regression models were used for the analyses. 

Results:

Among participants who underwent NP testing (n=2353,45.81% male) 30 incident epilepsy cases were identified during follow-up. Better performance in TrB-TrA was associated with lower risk of developing epilepsy (HR 0.25,95%CI[0.08,0.73],p= 0.011). In the subgroup of participants with available MRI (n=2056,46% male), 27 developed epilepsy. Higher WMHV was associated with increased epilepsy risk (HR 1.5,95%CI[1.01,2.20],p= 0.042), but higher CGMV (HR 0.73,95%CI[0.57,0.93],p= 0.001) was protective against epilepsy. All analyses were adjusted for age, sex and educational level.

Conclusions:

Better performance in TrB-TrA, a measure of executive function and processing speed, and higher cortical volumes are protective against epilepsy. Conversely, higher WMHV, a measure of occult vascular injury, increases the risk. Our study shows that non-invasive tests performed in mid-life may help identify people at risk for developing epilepsy later in life.