Journal Article

Differences in baseline cognitive performance between participants with early‐onset and late‐onset Alzheimer's disease: Comparison of LEADS and ADNI

Aisen, Paul, Grant, Ian, Wolk, David A., Lagarde, Julien, Rabinovici, Gil D., Rogalski, Emily, Dickerson, Bradford C., Eloyan, Ani, Dage, Jeffrey L., Gao, Sujuan, Apostolova, Liana G., Duara, Ranjan, Day, Gregory S., Riddle, Meghan, Thangarajah, Maryanne, Nudelman, Kelly, Mendez, Mario F., Carrillo, Maria C., Reman, Rema, Onyike, Chiadi U., Graff‐Radford, Neill R., Polsinelli, Angelina J., Womack, Kyle, Masdeu, Joseph C., Musiek, Erik, Salloway, Steven, Hammers, Dustin B., Honig, Lawrence S., La Joie, Renaud, Kirby, Kala, Jones, David T., Clark, David, Sha, Sharon J., Johnson, Erik C. B., Wingo, Thomas S., Atri, Alireza, Beckett, Laurel, Taurone, Alexander, Turner, Raymond Scott

2025

Overview

INTRODUCTION Early‐onset Alzheimer's disease (EOAD) and late‐onset Alzheimer's disease (LOAD) share similar amyloid etiology, but evidence from smaller‐scale studies suggests that they manifest differently clinically. Current analyses sought to contrast the cognitive profiles of EOAD and LOAD. METHODS Z‐score cognitive‐domain composites for 311 amyloid‐positive sporadic EOAD and 314 amyloid‐positive LOAD participants were calculated from baseline data from age‐appropriate control cohorts. Z‐score composites were compared between AD groups for each domain. RESULTS After controlling for cognitive status, EOAD displayed worse visuospatial, executive functioning, and processing speed/attention skills relative to LOAD, and LOAD displayed worse language, episodic immediate memory, and episodic delayed memory. DISCUSSION Sporadic EOAD possesses distinct cognitive profiles relative to LOAD. Clinicians should be alert for non‐amnestic impairments in younger patients to ensure proper identification and intervention using disease‐modifying treatments. Highlights Both early‐onset Alzheimer's disease (EOAD) and late‐onset Alzheimer's disease (LOAD) participants displayed widespread cognitive impairments relative to their same‐aged peers. Cognitive impairments were more severe for EOAD than for LOAD participants in visuospatial and executive domains. Memory and language impairments were more severe for LOAD than for EOAD participants Results were comparable after removing clinical phenotypes of posterior cortical atrophy (PCA), primary progressive aphasia (lv‐PPA), and frontal‐variant AD.

• Publisher: John Wiley & Sons, Inc,John Wiley and Sons Inc
• Subject: Age / Age groups / Age of Onset / Aged / Alzheimer Disease - psychology / Alzheimer's disease / amnestic / Aphasia / Atrophy / Biomarkers / Cognition / Cognition - physiology / Cognitive ability / Cognitive impairment / Delayed memory / Dementia / Disease / early‐onset / Etiology / Executive Function / Family medical history / Female / Humans / Language disorders / late‐onset / Longitudinal studies / Magnetic resonance imaging / Male / Medical imaging / Memory / Middle Aged / Mild cognitive impairment / Mutation / Neuroimaging / Neuropsychological Tests - statistics & numerical data / Neuropsychology / non‐amnestic / Patients / Phenotypes / Spatial memory / Treatment methods / Visual memory