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Longitudinal tau aggregation, atrophy, and cognitive decline in Alzheimer's disease

Singleton, Ellen LU ; Mattsson-Carlgren, Niklas LU orcid ; Pichet Binette, Alexa LU ; Stomrud, Erik LU orcid ; Strandberg, Olof LU ; Palmqvist, Sebastian LU orcid ; Ossenkoppele, Rik LU and Hansson, Oskar LU orcid (2025) In Alzheimer's and Dementia 21(7).
Abstract

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 [18F]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... (More)

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 [18F]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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author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Alzheimer's disease, clinical trials, cognition, longitudinal, MRI, tau-PET
in
Alzheimer's and Dementia
volume
21
issue
7
article number
e70435
publisher
Wiley
external identifiers
  • pmid:40629696
  • scopus:105010156250
ISSN
1552-5260
DOI
10.1002/alz.70435
language
English
LU publication?
yes
additional info
Publisher Copyright: © 2025 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.
id
26d11a55-4024-47ba-b0d4-0d6974b42f29
date added to LUP
2025-12-11 15:25:12
date last changed
2025-12-12 03:22:51
@article{26d11a55-4024-47ba-b0d4-0d6974b42f29,
  abstract     = {{<p>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 [<sup>18</sup>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 &lt; 0.001) for baseline and longitudinal tau-PET (β = −0.62 ± 0.05, p &lt; 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.</p>}},
  author       = {{Singleton, Ellen and Mattsson-Carlgren, Niklas and Pichet Binette, Alexa and Stomrud, Erik and Strandberg, Olof and Palmqvist, Sebastian and Ossenkoppele, Rik and Hansson, Oskar}},
  issn         = {{1552-5260}},
  keywords     = {{Alzheimer's disease; clinical trials; cognition; longitudinal; MRI; tau-PET}},
  language     = {{eng}},
  number       = {{7}},
  publisher    = {{Wiley}},
  series       = {{Alzheimer's and Dementia}},
  title        = {{Longitudinal tau aggregation, atrophy, and cognitive decline in Alzheimer's disease}},
  url          = {{http://dx.doi.org/10.1002/alz.70435}},
  doi          = {{10.1002/alz.70435}},
  volume       = {{21}},
  year         = {{2025}},
}