Association of Seizure Control With Cognition in People With Normal Cognition and Mild Cognitive Impairment

Background and Objectives Seizures are common in dementia and associated with accelerated cognitive decline. However, the impact of active vs remote seizures on cognition remains understudied. This study aimed to investigate the impact of active vs remote seizures on cognition in people with normal cognition and mild cognitive impairment (MCI). Methods This longitudinal, multicenter cohort is based on National Alzheimer's Coordinating Center data of participants recruited from 39 Alzheimer's Disease Centers in the United States from September 2005 to December 2021. All participants with normal cognition and MCI and at least 2 visits were included. Primary outcome, that is, cognitive decline, was determined using Clinical Dementia Rating (CDR) from (1) normal-to-impaired (CDR >= 0.5) and (2) MCI-to-dementia (CDR >= 1) groups. The effect of active seizures (over the preceding 12 months), remote seizures (previous seizures but none over the preceding 12 months), and no seizures (controls) on cognition was assessed. Subgroups of chronic seizures at enrollment and new-onset seizures were further analyzed. Cox regression models assessed the risk of all-cause MCI and/or dementia. All models were adjusted for age, sex, education, race, hypertension, and diabetes. Results Of the 13,726 participants with normal cognition at enrollment (9,002 [66%] female; median age 71 years), 118 had active seizures and 226 had remote seizures. Of the 11,372 participants with MCI at enrollment (5,605 [49%] female; median age 73 years), 197 had active seizures and 226 had remote seizures. Active seizures were associated with 2.1 times higher risk of cognitive impairment (adjusted hazard ratio [aHR] 2.13, 95% CI 1.60-2.84, p < 0.001) in cognitively healthy adults (median years to decline: active seizures = similar to 1, remote seizures = similar to 3, no seizures = similar to 3) and 1.6 times higher risk of dementia (aHR 1.58, 95% CI 1.24-2.01, p < 0.001) in those with MCI (median years to decline: active seizures = similar to 1, remote seizures = similar to 2, controls = similar to 2). This risk was not observed with remote seizures. Discussion In this study, active seizures but not remote seizures were associated with earlier cognitive decline in both cognitively normal adults and those with MCI, independent of other dementia risk factors. Therefore, early identification and management of seizures may present a path to mitigation of cognitive decline in the aging epileptic population. A limitation is that causality cannot be confirmed in our observational longitudinal study.