Late-onset epilepsy and 25-year cognitive change: The Atherosclerosis Risk in Communities (ARIC) study

Objective: To define the association between late-onset epilepsy (LOE) and 25-year change in cognitive performance.

Methods: The Atherosclerosis Risk in Communities (ARIC) study is a multicenter longitudinal cohort study with participants from four U.S. communities. From linked Medicare claims, we identified cases of LOE, defined as ≥2 seizure-related diagnostic codes starting at age ≥67. The ARIC cohort underwent evaluation with in-person visits at intervals of 3-15 years. Cognition was evaluated 4 times over >25 years (including before the onset of seizures) using the Delayed Word Recall Test (DWRT), Digit Symbol Substitution Test (DSST), and Word Fluency Test (WFT); a global z-score was also calculated. We compared the longitudinal cognitive changes of participants with and without LOE, adjusting for demographics and LOE risk factors.

Results: From 8033 ARIC participants with midlife cognitive testing and Medicare claims data available (4523 [56%] female, 1392 [17%] Black), we identified 585 cases of LOE. The rate of cognitive decline was increased on all measures in the participants who developed LOE compared to those without LOE. On the measure of global cognition, participants with LOE declined by -0.43 z-score points more over 25 years than did participants without epilepsy (95% confidence interval [CI] -0.59 to -0.27). Prior to the onset of seizures, cognitive decline was more rapid on the DWRT, DSST, and global z-scores in those who would later develop LOE than it was in non-LOE participants. Results were similar after excluding data from participants with dementia.

Significance: Global cognition, verbal memory, executive function, and word fluency declined faster over time in persons developing LOE than without LOE. Declines in cognition preceding LOE suggest these are linked; it will be important to investigate causes for midlife cognitive declines associated with LOE.

Keywords: cognition; dementia; epilepsy; late-onset; longitudinal.