Objective: To investigate the relationship between the ATN-model and risk of dementia and cognitive decline in individuals with subjective cognitive decline (SCD).

Methods: We classified 693 participants with SCD (60±9yr, 41%F, MMSE 28±2) from the Amsterdam Dementia Cohort and SCIENCe project according to the ATN-model, as determined by amyloid PET or CSF Abeta (A), CSF p-tau (T) and MRI-based medial temporal lobe atrophy (N). All underwent extensive neuropsychological assessment. For 342 participants follow-up was available (3±2yr). As a control population, we included 124 participants without SCD.

Results: 56% (n=385) participants had normal AD biomarkers (A-T-N-), 27% (n=186) had non-AD pathologic change (A-T-N+, A-T+N-, A-T+N+), 18% (n=122) fell within the Alzheimer’s continuum (A+T-N-, A+T-N+, A+T+N-, A+T+N+). ATN profiles were unevenly distributed, with A-T+N+, A+T-N+ and A+T+N+ containing very few participants. Cox regression showed that compared to A-T-N-, participants in A+ profiles had a higher risk of dementia with a dose-response pattern for number of biomarkers affected. Linear mixed models showed participants in A+ profiles showed a steeper decline on tests addressing memory, attention, language, and executive functions. In the control group, there was no association between ATN and cognition.

Conclusions: Among individuals presenting with SCD at a memory clinic, those with a biomarker profile A-T+N+, A+T-N-, A+T+N- and A+T+N+ were at increased risk of dementia, and showed steeper cognitive decline compared to A-T-N- individuals. These results suggest a future where biomarker results could be used for individualized risk profiling in cognitively normal individuals presenting at a memory clinic.