Alzheimer's disease and late-onset epilepsy of unknown origin: two faces of beta amyloid pathology

Although amyloid pathology plays a role in epilepsy, little is known about the relationship between beta amyloid and progression to Alzheimer's disease (AD) among patients with late-onset epilepsy of unknown origin (LOEU). This multicenter, observational, prospective study enrolled 40 consecutive nondemented adults diagnosed with LOEU, together with 43 age- and sex-matched healthy controls. All patients completed neuropsychological tests, core CSF AD biomarkers assessment (Aβ_1-42, total tau, and phosphorylated tau), and follow-up for a mean of 3 years to verify cognitive decline. Despite age and baseline cognitive performance were similar to healthy controls, patients with LOEU had significant prevalence of CSF pathological Aβ_1-42 (<500 pg/mL; 37.5%), 7.5% displaying an AD-like CSF pattern. Moreover, 17.5% of patients with LOEU converted to AD dementia, versus none among healthy controls (p < 0.005). Patients with LOEU with pathological Aβ_1-42 had a hazard ratio 3.4 (CI 0.665–17.73) for progression to AD dementia at follow-up. Patients with LOEU have a high prevalence of abnormal CSF Aβ_1-42 and progression to AD dementia compared with healthy controls, and therefore should be monitored for cognitive decline.