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Tau PET positivity predicts clinically relevant cognitive decline driven by Alzheimer's disease compared to comorbid cases; proof of concept in the ADNI study
Ioannou K, Bucci M, Tzortzakakis A, Savitcheva I, Nordberg A, Chiotis K, Alzheimer’s Disease Neuroimaging Initiative.. Molecular psychiatry, 2024-08-23
Topic: Amyloid, tau and blood-test diagnosis
β-amyloid (Aβ) pathology is not always coupled with Alzheimer's disease (AD) relevant cognitive decline. We assessed the accuracy of tau PET to identify Aβ(+) individuals who show prospective disease progression. 396 cognitively unimpaired and impaired individuals with baseline Aβ and tau PET and a follow-up of ≥ 2 years were selected from the Alzheimer's Disease Neuroimaging Initiative dataset. The participants were dichotomously grouped based on either clinical conversion (i.e., change of diagnosis) or cognitive deterioration (fast (FDs) vs. slow decliners (SDs)) using data-driven clustering of the individual annual rates of cognitive decline. To assess cognitive decline in individuals with isolated Aβ(+) or absence of both Aβ and tau (T) pathologies, we investigated the prevalence of non-AD comorbidities and FDG PET hypometabolism patterns suggestive of AD. Baseline tau PET uptake was higher in Aβ(+)FDs than in Aβ(-)FD/SDs and Aβ(+)SDs, independently of baseline cognitive status. Baseline tau PET uptake identified MCI Aβ(+) Converters and Aβ(+)FDs with an area under the curve of 0.85 and 0.87 (composite temporal region of interest) respectively, and was linearly related to the annual rate of cognitive decline in Aβ(+) individuals. The T(+) individuals constituted largely a subgroup of those being Aβ(+) and those clustered as FDs. The most common biomarker profiles in FDs (n = 70) were Aβ(+)T(+) (n = 34, 49%) and Aβ(+)T(-) (n = 19, 27%). Baseline Aβ load was higher in Aβ(+)T(+)FDs (M = 83.03 ± 31.42CL) than in Aβ(+)T(-)FDs (M = 63.67 ± 26.75CL) (p-value = 0.038). Depression diagnosis was more prevalent in Aβ(+)T(-)FDs compared to Aβ(+)T(+)FDs (47% vs. 15%, p-value = 0.021), as were FDG PET hypometabolism pattern not suggestive of AD (86% vs. 50%, p-value = 0.039). Our findings suggest that high tau PET uptake is coupled with both Aβ pathology and accelerated cognitive decline. In cases of isolated Aβ(+), cognitive decline may be associated with changes within the AD spectrum in a multi-morbidity context, i.e., mixed AD.
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APA 7th
Ioannou, K., Bucci, M., Tzortzakakis, A., Savitcheva, I., Nordberg, A., Chiotis, K., et al. (2025). Tau PET positivity predicts clinically relevant cognitive decline driven by Alzheimer's disease compared to comorbid cases; proof of concept in the ADNI study. Molecular psychiatry. https://doi.org/10.1038/s41380-024-02672-9
Vancouver
Ioannou K, Bucci M, Tzortzakakis A, Savitcheva I, Nordberg A, Chiotis K, et al. Tau PET positivity predicts clinically relevant cognitive decline driven by Alzheimer's disease compared to comorbid cases; proof of concept in the ADNI study. Molecular psychiatry. 2025. doi:10.1038/s41380-024-02672-9. PMID: 39179903.
BibTeX
@article{ioannou2025-39179903,
author = {Ioannou, K. and Bucci, M. and Tzortzakakis, A. and Savitcheva, I. and Nordberg, A. and Chiotis, K. and {Alzheimer’s Disease Neuroimaging Initiative}},
title = {{Tau PET positivity predicts clinically relevant cognitive decline driven by Alzheimer's disease compared to comorbid cases; proof of concept in the ADNI study}},
journal = {Molecular psychiatry},
year = {2025},
doi = {10.1038/s41380-024-02672-9},
pmid = {39179903},
url = {https://doi.org/10.1038/s41380-024-02672-9}
}
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.
Key findings
- Depression diagnosis was more prevalent in Aβ(+)T(-)FDs compared to Aβ(+)T(+)FDs (47% vs. 15%, p-value = 0.021), as were FDG PET hypometabolism pattern not suggestive of AD (86% vs. 50%, p-value = 0.039).
- Our findings suggest that high tau PET uptake is coupled with both Aβ pathology and accelerated cognitive decline.
- In cases of isolated Aβ(+), cognitive decline may be associated with changes within the AD spectrum in a multi-morbidity context, i.e., mixed AD.
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Study details
- Participants70
- Evidence strengthLow
How this study scored 55/100
Published in a leading specialty journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 32 of the 58 points we could judge it on, which is 55 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Molecular psychiatry) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 1 / 4 | 70 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 | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 39179903) |
| Free to read | 2 / 2 | Free to read |
| Points | 32 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 32 of the 58 points we could judge it on is 55 out of 100. |
| Total | 55 / 100 | — |
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