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

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.

Automated summary

As prevention trials progress with ADAD participants, it is important to understand similarities and differences with sporadic LOAD to ensure generalizability of findings. Cognitive trajectories of ADAD MCs were compared to autopsy-confirmed LOAD individuals, showing differences in rates of decline between the two groups. While both groups showed declining cognitive performance, ADAD MCs declined more rapidly post-symptom onset, indicating common AD pathologies but with some distinct differences.