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.

Keywords: Alzheimer disease; autosomal dominant Alzheimer disease; cognitive; comorbidities; late-onset Alzheimer disease.

Figure 1:. Conceptual model of clinically significant phases

The conceptual analytic model depicting three clinical time points: preclinical phase when EYO is negative, symptom onset when EYO=0, and disease progression when EYO is positive. EYO = Estimated Years to/from Onset.

Figure 2:. Individual and group cognitive performance

Figure displays individual performance (spaghetti plots) and group mean rates of change (solid lines, unadjusted) over time for the global cognitive composite. [Note: The large majority of DIAN participants do not know, nor do they wish to learn, their mutation status. To reduce the possibility of unintended disclosure that a DIAN individual may be a mutation carrier, data points from the few participants who are more than 20 years younger than their estimated age at symptomatic onset are not displayed in Figure 2, although all data were used in the analyses.]