35 ATN classification in subjective cognitive decline Cognitive decline We used linear mixed models to assess the association between ATN classification and cognitive test performance. Figure 3 shows the observed raw neuropsychological test scores and trajectories over time, Table 4 shows estimated baseline cognitive tests scores and annual change by ATN profile. There were a few modest associations between ATN profile and baseline cognitive test performance. By contrast, we found significant interactions of ATN profile with time for a large number of tests. Participants in A+T+N- and A+T+N+ showed a steeper decline over time than A-T-N- on all memory tests. Other A+ profiles also showed a steeper decline on tests for memory, attention, and executive function (A+T-N- on VAT-A and TMT-B; A+T+N- on TMT-A, TMT-B and Stroop III). A-T+N+ was the only A- profile associated with steeper decline over time, namely on two memory tests (RAVLT immediate and delayed recall). Supplemental Table e-4 and Figure e-2 (data available from Dryad: https://doi. org/10.5061/dryad.bg79cnp71) show the results of the additional analyses based on three clustered ATN categories. There was a main effect of ATN category on RAVLT delayed recall, implying that participants classified in the Alzheimer’s continuum had a lower baseline memory performance than participants with normal AD biomarkers. There were no associations with baseline score for any of the other cognitive tests. Participants in the Alzheimer’s continuum showed a steeper decline over time in tests for memory, attention, language and executive functioning compared to the normal AD biomarker category. Participants with non-AD pathologic change only showed a steeper decline over time on RAVLT delayed recall. In the control group without SCD, only one participant (A+T+N+) progressed to dementia, precluding any formal testing. In the control group, we found no significant associations between ATN profiles and (cross-sectional or longitudinal) cognitive test score (Supplemental Table e-5, data available from Dryad). 2
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