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Longitudinal tau aggregation, atrophy, and cognitive decline in Alzheimer's disease
Singleton EH, Mattsson-Carlgren N, Pichet Binette A, Stomrud E, Strandberg O, Palmqvist S, Ossenkoppele R, Hansson O.. Alzheimer's & dementia : the journal of the Alzheimer's Association, 2025-07-01
Topic: Amyloid, tau and blood-test diagnosis
Introduction The independent contributions of baseline and longitudinal tau positron emission tomography (PET) and magnetic resonance imaging (MRI) to cognitive decline remain unclear. Methods We included n = 761 amyloid-positive individuals from the Swedish BioFINDER-2 study with [ 18 F]RO948-tau-PET, 3-Tesla structural-MRI, and cognition (n = 322 with longitudinal imaging data). Linear-mixed-models with random-intercepts and -slopes or linear-regressions were adjusted for age, sex, education, diagnosis, and other-imaging-modality. Results Tau-PET showed stronger associations with cognitive decline than MRI, showing the strongest associations in a neocortical-composite-region with a cognitive composite (β = -0.25 ± 0.02, p < 0.001) for baseline and longitudinal tau-PET (β = -0.62 ± 0.05, p < 0.001). Baseline tau-PET explained the largest proportion of cognitive decline (54.0%-94.0%), with modest mediation effects for longitudinal tau-PET or MRI pathways (2.0%-15.0%). Simulated reductions of tau-PET-slopes (up to 100%) were associated with marginally altered cognitive trajectories. Discussion The strong associations between baseline tau-PET and longitudinal cognition, with marginal contributions of longitudinal tau-PET and MRI, emphasize the importance of baseline tau aggregates for prognostics and treatments in Alzheimer's disease (AD). Highlights Baseline and longitudinal regional tau-PET uptake were more closely associated than structural MRI with longitudinal cognitive decline. Baseline tau-PET was a stronger determinant of longitudinal cognitive decline than longitudinal tau-PET. Simulated reductions of tau-PET accumulation showed limited alterations of cognitive trajectories, with potential implications for tau-targeting therapies.
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APA 7th
Singleton, E. H., Mattsson-Carlgren, N., Pichet Binette, A., Stomrud, E., Strandberg, O., Palmqvist, S., et al. (2025). Longitudinal tau aggregation, atrophy, and cognitive decline in Alzheimer's disease. Alzheimer's & dementia : the journal of the Alzheimer's Association. https://doi.org/10.1002/alz.70435
Vancouver
Singleton EH, Mattsson-Carlgren N, Pichet Binette A, Stomrud E, Strandberg O, Palmqvist S, et al. Longitudinal tau aggregation, atrophy, and cognitive decline in Alzheimer's disease. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2025. doi:10.1002/alz.70435. PMID: 40629696.
BibTeX
@article{singleton2025-40629696,
author = {Singleton, E. H. and Mattsson-Carlgren, N. and Pichet Binette, A. and Stomrud, E. and Strandberg, O. and Palmqvist, S. and Ossenkoppele, R. and Hansson, O.},
title = {{Longitudinal tau aggregation, atrophy, and cognitive decline in Alzheimer's disease}},
journal = {Alzheimer's \& dementia : the journal of the Alzheimer's Association},
year = {2025},
doi = {10.1002/alz.70435},
pmid = {40629696},
url = {https://doi.org/10.1002/alz.70435}
}
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Key findings
- Results Tau-PET showed stronger associations with cognitive decline than MRI, showing the strongest associations in a neocortical-composite-region with a cognitive composite (β = -0.25 ± 0.02, p < 0.001) for baseline and longitudinal tau-PET (β = -0.62 ± 0.05, p < 0.001).
- Simulated reductions of tau-PET-slopes (up to 100%) were associated with marginally altered cognitive trajectories.
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Study details
- Study designlongitudinal study
- Participants761
- Effect size54.0%; 94.0%; 2.0%
- Evidence strengthModerate
How this study scored 76/100
Published in a leading specialty journal, and it is a longitudinal study following the same people over time. Scored zero for 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 44 of the 58 points we could judge it on, which is 76 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Alzheimer's & dementia : the journal of the Alzheimer's Association) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| 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 | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 2 / 4 | 761 participants |
| Effect reported | 2 / 3 | Effect reported as a number, without an interval or test |
| 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 40629696) |
| Free to read | 2 / 2 | Free to read |
| Points | 44 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 44 of the 58 points we could judge it on is 76 out of 100. |
| Total | 76 / 100 | — |
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