31 ATN classification in subjective cognitive decline Figure 1. Distribution of the ATN biomarker profiles in subjective cognitive decline Pie chart illustrates the distribution of the 8-profile and 3-category ATN classification. AD = Alzheimer’s disease. Risk of dementia Table 2 shows that after 3±2 years of follow-up, 16 (21%) participants in A+ profiles showed incident dementia (AD n=14; non-AD n=2), compared to 2 (1%) participants in A-T-N- (non-AD n=2) . The Supplemental e-Box, available from Dryad , provides a case description of the two participants in respectively A-T+N- and A-T+N+ that progressed to AD dementia and two participants in A-T-N- that progressed to dementia. Both A- participants that progressed to AD dementia became A+T+N+ on follow-up. The participants who initially were A-T-N- progressed to primary progressive aphasia and to possible FTD. Cox proportional hazard analyses showed that compared to A-T-N-, participants in the A+ profiles were at increased risk of dementia with an incremental increase in hazard rate (A+T-N- HR 9.7 (1.6-59.3), A+T+N- HR 20.2 (3.7-110.2) and A+T+N+ HR 62.3 (9.5-408.4); Figure 2). Within the A- profiles, participants in A-T+N+ were at increased risk of dementia (HR 18.5 (1.6-211.4)), but participants in A-T+N- and A-T-N+ were not. When we repeated the analyses with clinical progression to MCI or dementia as outcome, a similar pattern emerged, although the Hazard Ratios were lower, caused by a higher number of participants progressing to MCI in the reference profile. 2
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