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ATN classification and clinical progression in subjective cognitive decline: The SCIENCe project
Ebenau JL, Timmers T, Wesselman LMP, Verberk IMW, Verfaillie SCJ, Slot RER, van Harten AC, Teunissen CE et al.. Neurology, 2020-06-10
Topic: Risk, prevention and care in population studies
Objective To 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). Methods We 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. Results Fifty-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. 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.
Key findings
- Results Fifty-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+).
- 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.
- 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.
Why it matters
Among people with subjective cognitive decline at a memory clinic, those with abnormal amyloid biomarkers had a higher risk of dementia and steeper cognitive decline. This describes risk prediction and does not show a treatment, cure, or prevention.
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Study details
- Participants385
- Evidence strengthModerate
How this study scored 64/100
Published in a leading specialty journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Neurology) |
| Journal's citation record | 4 / 4 | Neurology: journal h-index 525 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 2 / 5 | 2020 — within 10 year(s) of the newest study here |
| Sample size | 2 / 4 | 385 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 5 / 7 | Cited 193 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 24.1 citations a year over 8 year(s) since 2020 |
| Impact for its field and year | 4 / 6 | Cited 16.0× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 15 other studies in this library |
| Still being cited | 3 / 4 | Cited 92 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Wiesje M. van der Flier: h-index 132 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University College London: institution h-index 2,029 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 5 institution(s) in 3 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 32522798) |
| Free to read | 2 / 2 | Free to read |
| Total | 64 / 100 | — |
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Read the original
- DOI: 10.1212/wnl.0000000000009724
- PubMed: 32522798
- Original source →
- Free full text: PubMed Central →
Full text: free to read — PubMed Central lists this copy as free to read: the link above (checked 10 Oct 2026).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Ebenau, J. L., Timmers, T., Wesselman, L. M. P., Verberk, I. M. W., Verfaillie, S. C. J., Slot, R. E. R., et al. (2020). ATN classification and clinical progression in subjective cognitive decline: The SCIENCe project. Neurology. https://doi.org/10.1212/wnl.0000000000009724
Vancouver
Ebenau JL, Timmers T, Wesselman LMP, Verberk IMW, Verfaillie SCJ, Slot RER, et al. ATN classification and clinical progression in subjective cognitive decline: The SCIENCe project. Neurology. 2020. doi:10.1212/wnl.0000000000009724. PMID: 32522798.
BibTeX
@article{ebenau2020-32522798,
author = {Ebenau, J. L. and Timmers, T. and Wesselman, L. M. P. and Verberk, I. M. W. and Verfaillie, S. C. J. and Slot, R. E. R. and van Harten, A. C. and Teunissen, C. E. and others},
title = {{ATN classification and clinical progression in subjective cognitive decline: The SCIENCe project}},
journal = {Neurology},
year = {2020},
doi = {10.1212/wnl.0000000000009724},
pmid = {32522798},
url = {https://doi.org/10.1212/wnl.0000000000009724}
}
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