Late-Onset Epilepsy Differs From Alzheimer Disease

TOPLINEPatients with late-onset temporal lobe epilepsy (LO-TLE) and normal cerebrospinal fluid (CSF) biomarkers demonstrated preserved attention despite deficits in other cognitive domains, contrasting sharply with the marked attentional impairment observed in mild cognitive impairment (MCI) due to Alzheimer disease (MCI-AD). METHODOLOGYA cross-sectional study compared cognitive performance and CSF biomarkers in patients with LO-TLE (n = 18; mean age, 64.33 years), MCI-AD (n = 24; mean age, 60.75 years), and age and sex-matched healthy controls (HC, n = 17; mean age, 60.88 years).Patients with LO-TLE had epilepsy onset after age 50 years, normal structural MRI or nonspecific findings, and CSF biomarkers within normal ranges for beta-amyloid: (Aβ)1–42 >600 pg/mL, Aβ1–42/Aβ1–40 ratio >0.069, phosphorylated-tau181(p-tau181 <56.5 pg/mL, and total tau (t-tau) <400 pg/mL.Patients with MCI-AD had AD-specific CSF bio marker alterations and absence of any history of seizures or epilepsy.Comprehensive neuropsychological assessment covered five cognitive domains: episodic memory, short-term memory, language, executive functions, and attention.CSF biomarkers (Aβ1–42, Aβ1–42/Aβ1–40 ratio, p-tau181, t-tau, phosphorylated-to-total tau ratio [p/t-tau], and neurofilament light chain [NfL]) were measured using automated immunoassays.TAKEAWAYPatients with LO-TLE showed significantly lower t-tau (F (1,40) = 46.07, PFDR < 0.001) and p-tau181 (F (1,40) = 91.41, false discovery rate-adjusted P value (PFDR)< 0.001), and lower NfL levels (F (1,40) = 39.26, PFDR < 0.001) compared with patients with MCI-AD.Attention performance was preserved in LO-TLE patients compared with HC, whereas MCI-AD patients demonstrated significant attentional deficits.Both LO-TLE and MCI-AD groups showed impairments in episodic memory, short-term memory, language, and executive functions compared with HC.In LO-TLE, a higher p/t-tau ratio was associated with better global cognition and short-term memory, and higher t-tau was associated with worse executive function; no significant biomarker-cognition correlations were found in MCI-AD.IN PRACTICE"LO-TLE patients with normal CSF biomarkers showed a distinct cognitive profile compared with MCI-AD, particularly characterized by preserved attention in contrast to the marked attentional decline observed in MCI-AD. This dissociation may provide a useful clinical clue for differentiating these conditions in routine assessment," the authors of the study wrote.SOURCEThe study was led by Alessia Casarini, University of Modena and Reggio Emilia in Modena, Italy. It was published online on August 4, 2026, in Neurology.LIMITATIONSThe cohort included only patients with normal Alzheimer disease CSF biomarkers, which limited generalizability. Behavioral and psychiatric assessments were not included. Left-sided temporal lobe epilepsy was more common than right-sided disease, limiting lateralization analyses.DISCLOSURESThe study was supported by grants from the Lega Italiana Contro l'Epilessia (LICE) Foundation. One author reported research support from the Ministry of Health, and one reported speaker or consultancy fees from Angelini. Full disclosures are available in the original article.This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.