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Tau-PET and in vivo Braak-staging as prognostic markers of future cognitive decline in cognitively normal to demented individuals
Biel D, Brendel M, Rubinski A, Buerger K, Janowitz D, Dichgans M, Franzmeier N, Alzheimer’s Disease Neuroimaging Initiative (ADNI).. Alzheimer's research & therapy, 2021-08-12
Topic: Brain proteins, microglia and lab models
Background To systematically examine the clinical utility of tau-PET and Braak-staging as prognostic markers of future cognitive decline in older adults with and without cognitive impairment. Methods In this longitudinal study, we included 396 cognitively normal to dementia subjects with 18 F-Florbetapir/ 18 F-Florbetaben-amyloid-PET, 18 F-Flortaucipir-tau-PET and ~ 2-year cognitive follow-up. Annual change rates in global cognition (i.e., MMSE, ADAS13) and episodic memory were calculated via linear-mixed models. We determined global amyloid-PET (Centiloid) plus global and Braak-stage-specific tau-PET SUVRs, which were stratified as positive( + )/negative( - ) at pre-established cut-offs, classifying subjects as Braak 0 /Braak I+ /Braak I-IV+ /Braak I-VI+ /Braak atypical+ . In bootstrapped linear regression, we assessed the predictive accuracy of global tau-PET SUVRs vs. Centiloid on subsequent cognitive decline. To test for independent tau vs. amyloid effects, analyses were further controlled for the contrary PET-tracer. Using ANCOVAs, we tested whether more advanced Braak-stage predicted accelerated future cognitive decline. All models were controlled for age, sex, education, diagnosis, and baseline cognition. Lastly, we determined Braak-stage-specific conversion risk to mild cognitive impairment (MCI) or dementia. Results Baseline global tau-PET SUVRs explained more variance (partial R 2 ) in future cognitive decline than Centiloid across all cognitive tests (Cohen's d ~ 2, all tests p Conclusion Tau-PET and Braak-staging are highly predictive markers of future cognitive decline and may be promising single-modality estimates for prognostication of patient-specific progression risk in clinical settings.
Key findings
- Results Baseline global tau-PET SUVRs explained more variance (partial R 2 ) in future cognitive decline than Centiloid across all cognitive tests (Cohen's d ~ 2, all tests p < 0.001) and diagnostic groups.
Why it matters
Tau-PET and Braak-staging were highly predictive of future cognitive decline in this group of 396 people followed for about 2 years. The authors describe tau-PET as a promising marker, but this is a prognostic tool for predicting decline, not a treatment or cure.
Study details
- Study designlongitudinal study
- Participants396
- Evidence strengthModerate
How this study scored 65/100
Published in a peer-reviewed journal, and it is a longitudinal study following the same people over time. Scored zero for effect reported and randomised / blinded because the record does not state it. We have no data on senior author's track record, so that was left out: it earned 62 of the 96 points we could judge it on, which is 65 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Alzheimer's research & therapy) |
| Journal's citation record | 1 / 4 | Alzheimer s Research & Therapy: journal h-index 146 (OpenAlex, 2026-10-29) |
| Study design | 7 / 12 | A longitudinal study following the same people over time |
| 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 | 3 / 5 | 2021 — within 6 year(s) of the newest study here |
| Sample size | 2 / 4 | 396 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 156 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 22.3 citations a year over 7 year(s) since 2021 |
| Impact for its field and year | 4 / 6 | Cited 13.7× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 16 other studies in this library |
| Still being cited | 3 / 4 | Cited 99 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | 1 / 3 | Ludwig-Maximilians-Universität München: institution h-index 1,224 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 5 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 34384484) |
| Free to read | 2 / 2 | Free to read |
| Points | 62 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 62 of the 96 points we could judge it on is 65 out of 100. |
| Total | 65 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1186/s13195-021-00880-x
- PubMed: 34384484
- Original source →
- Free full text: Alzheimer s Research & Therapy →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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 names 7 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
APA 7th
Biel, D., Brendel, M., Rubinski, A., Buerger, K., Janowitz, D., Dichgans, M., et al. (2021). Tau-PET and in vivo Braak-staging as prognostic markers of future cognitive decline in cognitively normal to demented individuals. Alzheimer's research & therapy. https://doi.org/10.1186/s13195-021-00880-x
Vancouver
Biel D, Brendel M, Rubinski A, Buerger K, Janowitz D, Dichgans M, et al. Tau-PET and in vivo Braak-staging as prognostic markers of future cognitive decline in cognitively normal to demented individuals. Alzheimer's research & therapy. 2021. doi:10.1186/s13195-021-00880-x. PMID: 34384484.
BibTeX
@article{biel2021-34384484,
author = {Biel, D. and Brendel, M. and Rubinski, A. and Buerger, K. and Janowitz, D. and Dichgans, M. and Franzmeier, N.},
title = {{Tau-PET and in vivo Braak-staging as prognostic markers of future cognitive decline in cognitively normal to demented individuals}},
journal = {Alzheimer's research \& therapy},
year = {2021},
doi = {10.1186/s13195-021-00880-x},
pmid = {34384484},
url = {https://doi.org/10.1186/s13195-021-00880-x}
}
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