Clinical and Cognitive Profiles of Individuals with Alzheimer's Disease and Comorbid Seizures

Seizures are a highly prevalent comorbidity in Alzheimer's disease (AD), with a 2- to 6-fold increased risk, and are associated with accelerated cognitive decline. Despite growing research on seizure detection and treatment in AD, the cognitive profiles of individuals with both AD and seizures remain poorly characterized using comprehensive neuropsychological methods.

Clinical and cognitive data from individuals age 65+ with AD were analyzed from the National Alzheimer's Coordinating Center (NACC) dataset. Cognitive domains assessed included memory, language, attention, processing speed, and executive function. Raw scores were converted into z-scores using a control sample (n = 14,665). Group comparisons were conducted using independent t tests, χ² tests, and Kruskal-Wallis tests, and logistic regression was used to examine factors associated with seizures.

Among 9,662 individuals with AD, 1.2% (n = 117) had active seizures (AD-S). The AD-S group was younger, had higher stroke and transient ischemic attack rates, earlier cognitive decline, longer symptom duration, cognitive fluctuations, abrupt cognitive changes, and worse cognitive and functional outcomes. Cognitive deficits in AD-S, particularly in executive function and processing speed, persisted after adjusting for dementia severity. Compared to vascular dementia, AD-S individuals exhibited greater impairments in fluency, naming, and processing speed.

Comorbid AD and seizures are associated with distinct cognitive and clinical profiles, greater vascular disease burden, and more severe dementia. Findings emphasize the need for early seizure detection, comprehensive cognitive evaluations, and research on cerebrovascular contributions to inform targeted interventions. ANN NEUROL 2025;98:533-546.