Relationship between age and severity of cognitive impairment at diagnosis for early-onset and late-onset Alzheimer's disease: Comparison of LEADS and ADNI.

Relationship between age and severity of cognitive impairment at diagnosis for early-onset and late-onset Alzheimer's disease: Comparison of LEADS and ADNI. Alzheimer's & dementia : the journal of the Alzheimer's Association Hammers, D. B., Eloyan, A., Thangarajah, M., Taurone, A., Gao, S., Beckett, L., Kirby, K., Dage, J. L., Nudelman, K., Aisen, P., Reman, R., Vemuri, P., La Joie, R., Touroutoglou, A., Atri, A., Clark, D., Day, G. S., Duara, R., Graff-Radford, N. R., Honig, L. S., Jones, D. T., Masdeu, J. C., Mendez, M. F., Womack, K., Musiek, E., Onyike, C. U., Riddle, M., Grant, I., Rogalski, E., Johnson, E. C., Salloway, S., Sha, S. J., Turner, R. S., Wingo, T. S., Wolk, D. A., Carrillo, M. C., Dickerson, B. C., Rabinovici, G. D., Apostolova, L. G. 2026; 22 (2): e71160

Abstract

Recent work has identified unique cognitive profiles for early-onset Alzheimer's disease (EOAD) relative to late-onset Alzheimer's disease (LOAD), however, examination has been limited in determining whether the association between age and cognitive severity at presentation also differs across conditions.A series of linear spline regression models was conducted across baseline cognitive data from 325 EOAD and 314 LOAD participants, after accounting for education, sex, and apolipoprotein e4 status.Significant differences existed in the relationship between baseline age and cognitive performance between EOAD and LOAD samples for Processing Speed/Attention, Executive Functioning, and Episodic Immediate Memory. Younger participants from both EOAD and LOAD groups performed disproportionately worse on non-amnestic cognitive domains, with this occurring to a greater extent in EOAD than LOAD.In the age of disease-modifying treatments, results highlight the importance of assessing for cognitive declines in individuals starting much earlier than age 65.Early-onset Alzheimer's disease (EOAD) and late-onset Alzheimer's disease (LOAD) participants each displayed cognitive impairments relative to same-aged peers across most domains. Both groups displayed positive relationships between impairment among non-amnestic cognitive domains and baseline age. This relationship displayed a significantly greater effect in EOAD than LOAD, with domains of Processing Speed/Attention and Executive Functioning skills being the most pronounced. Of those participants developing AD, age displayed a disproportionate impact on their symptom onset.

View details for DOI 10.1002/alz.71160

View details for PubMedID 41614286

View details for PubMedCentralID PMC12856522