ATN-classification and clinical progression in subjective cognitive decline: the SCIENCe project

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.