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

Jarith L. Ebenau*, Tessa Timmers, Linda M. P. Wesselman, Inge M. W. Verberk, Sander C. J. Verfaillie, Rosalinde E. R. Slot, Argonde C. van Harten, Charlotte E. Teunissen, Frederik Barkhof, Karlijn A. van den Bosch, Mardou van Leeuwenstijn, Jori Tomassen, Anouk den Braber, Pieter Jelle Visser, Niels D. Prins, Sietske A. M. Sikkes, Philip Scheltens, Bart N. M. van Berckel, Wiesje M. van der Flier

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

73 Citations (Web of Science)


ObjectiveTo investigate the relationship between the ATN classification system (amyloid, tau, neurodegeneration) and risk of dementia and cognitive decline in individuals with subjective cognitive decline (SCD).MethodsWe classified 693 participants with SCD (60 ± 9 years, 41% women, Mini-Mental State Examination score 28 ± 2) from the Amsterdam Dementia Cohort and Subjective Cognitive Impairment Cohort (SCIENCe) project according to the ATN model, as determined by amyloid PET or CSF β-amyloid (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 ± 2 years). As a control population, we included 124 participants without SCD.ResultsFifty-six (n = 385) participants had normal Alzheimer disease (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 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.ConclusionsAmong 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.

Original languageEnglish
Pages (from-to)46-58
Number of pages13
Issue number1
Publication statusPublished - 7 Jul 2020


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