Different rates of cognitive decline in autosomal dominant and late-onset Alzheimer disease

Abstract

As prevention trials advance with autosomal dominant Alzheimer disease (ADAD) participants, understanding the similarities and differences between ADAD and “sporadic” late-onset AD (LOAD) is critical to determine generalizability of findings between these cohorts. Cognitive trajectories of ADAD mutation carriers (MCs) and autopsy-confirmed LOAD individuals were compared to address this question. Longitudinal rates of change on cognitive measures were compared in ADAD MCs (n = 310) and autopsy-confirmed LOAD participants (n = 163) before and after symptom onset (estimated/observed). LOAD participants declined more rapidly in the presymptomatic (preclinical) period and performed more poorly at symptom onset than ADAD participants on a cognitive composite. After symptom onset, however, the younger ADAD MCs declined more rapidly. The similar but not identical cognitive trajectories (declining but at different rates) for ADAD and LOAD suggest common AD pathologies but with some differences.

RAS ID

42660

Document Type

Journal Article

Date of Publication

10-1-2022

Volume

18

Issue

10

Funding Information

National Institute on Aging (NIA)

German Center for Neurodegenerative Diseases (DZNE)

Raul Carrea Institute for Neurological Research (FLENI)

Japan Agency for Medical Research and Development, AMED

NIHR UCL/UCLH Biomedical Research Centre

MRC Dementias Platform UK (MR/L023784/1 and MR/009076/1)

School

School of Medical and Health Sciences

Copyright

subscription content

Publisher

Wiley

Comments

Buckles, V. D., Xiong, C., Bateman, R. J., Hassenstab, J., Allegri, R., Berman, S. B., ... & Dominantly Inherited Alzheimer's Network. (2022). Different rates of cognitive decline in autosomal dominant and late‐onset Alzheimer disease. Alzheimer's & Dementia, 18(10), 1754-1764. https://doi.org/10.1002/alz.12505

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Link to publisher version (DOI)

10.1002/alz.12505