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Cognitive Trajectories from Preclinical Alzheimer's Disease to Dementia

Öhman, Fredrik ; Raket, Lars Lau LU orcid and Schöll, Michael LU (2026) In Advanced Science
Abstract

Alzheimer's disease (AD) is marked by progressive cognitive decline, highlighting the importance of cognitive assessment in both clinical practice and research. This study investigates the temporal dynamics of cognitive decline and the differential sensitivity of cognitive measures across the AD spectrum. Cognitive measures, functional assessments, and amyloid-beta (Aβ) and tau positron emission tomography (PET) scans from the Alzheimer's Disease Neuroimaging Initiative (ADNI) are analyzed using a latent-time disease progression model. Data from 1,447 participants across cognitively normal, mild cognitive impairment, and dementia stages are positioned along an estimated AD timeline. The model estimates a ∼20-year progression from... (More)

Alzheimer's disease (AD) is marked by progressive cognitive decline, highlighting the importance of cognitive assessment in both clinical practice and research. This study investigates the temporal dynamics of cognitive decline and the differential sensitivity of cognitive measures across the AD spectrum. Cognitive measures, functional assessments, and amyloid-beta (Aβ) and tau positron emission tomography (PET) scans from the Alzheimer's Disease Neuroimaging Initiative (ADNI) are analyzed using a latent-time disease progression model. Data from 1,447 participants across cognitively normal, mild cognitive impairment, and dementia stages are positioned along an estimated AD timeline. The model estimates a ∼20-year progression from initial Aβ PET positivity to late-stage dementia. Cognitive trajectories reveal that cognitive measures deviate at different time points, with varying levels of abnormality across the disease continuum. These findings demonstrate that cognitive measures differ markedly in their sensitivity across the AD continuum. Characterizing when specific measures become abnormal provides a framework for stage-appropriate test selection in clinical practice, improving clinical interpretation while informing the choice of cognitive endpoints and inclusion criteria in clinical trials.

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author
; and
author collaboration
organization
publishing date
type
Contribution to journal
publication status
epub
subject
keywords
alzheimer's disease, biomarkers, clinical assessment, clinical trials, cognition, preclinical
in
Advanced Science
publisher
John Wiley & Sons Inc.
external identifiers
  • scopus:105035613932
  • pmid:41910174
ISSN
2198-3844
DOI
10.1002/advs.202518124
language
English
LU publication?
yes
id
066b6e8e-ac15-433a-9995-116b1e274b6d
date added to LUP
2026-05-27 10:52:10
date last changed
2026-09-18 01:51:10
@article{066b6e8e-ac15-433a-9995-116b1e274b6d,
  abstract     = {{<p>Alzheimer's disease (AD) is marked by progressive cognitive decline, highlighting the importance of cognitive assessment in both clinical practice and research. This study investigates the temporal dynamics of cognitive decline and the differential sensitivity of cognitive measures across the AD spectrum. Cognitive measures, functional assessments, and amyloid-beta (Aβ) and tau positron emission tomography (PET) scans from the Alzheimer's Disease Neuroimaging Initiative (ADNI) are analyzed using a latent-time disease progression model. Data from 1,447 participants across cognitively normal, mild cognitive impairment, and dementia stages are positioned along an estimated AD timeline. The model estimates a ∼20-year progression from initial Aβ PET positivity to late-stage dementia. Cognitive trajectories reveal that cognitive measures deviate at different time points, with varying levels of abnormality across the disease continuum. These findings demonstrate that cognitive measures differ markedly in their sensitivity across the AD continuum. Characterizing when specific measures become abnormal provides a framework for stage-appropriate test selection in clinical practice, improving clinical interpretation while informing the choice of cognitive endpoints and inclusion criteria in clinical trials.</p>}},
  author       = {{Öhman, Fredrik and Raket, Lars Lau and Schöll, Michael}},
  issn         = {{2198-3844}},
  keywords     = {{alzheimer's disease; biomarkers; clinical assessment; clinical trials; cognition; preclinical}},
  language     = {{eng}},
  publisher    = {{John Wiley & Sons Inc.}},
  series       = {{Advanced Science}},
  title        = {{Cognitive Trajectories from Preclinical Alzheimer's Disease to Dementia}},
  url          = {{http://dx.doi.org/10.1002/advs.202518124}},
  doi          = {{10.1002/advs.202518124}},
  year         = {{2026}},
}