Evidence map›Paper›PMID 40741702›Full record

ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2025

Change points for dynamic biomarkers in the Alzheimer's disease pathological cascade: A 30-year cohort study.

Yuto Uchida, Kei Nishimaki, Anja Soldan, Corinne Pettigrew, Sara Grace Ho, Abhay Moghekar, Mei-Cheng Wang, Michael I Miller, Marilyn Albert, Kenichi Oishi

Abstract read
In one paragraph

Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

16 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Review
  6. Observational
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Review
  13. Article
  14. Article
  15. Article
  16. Change points for dynamic biomarkers in the Alzheimer's disease pathological cascade: A 30-year cohort study.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Yuto UchidaDepartment of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.ORCID 0000-0002-6521-0784
Kei NishimakiDepartment of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Anja SoldanDepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Corinne PettigrewDepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Sara Grace HoDepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Abhay MoghekarDepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Mei-Cheng WangDepartment of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
Michael I MillerDepartment of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland, USA.
Marilyn AlbertDepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Kenichi OishiDepartment of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.ORCID 0000-0002-1200-8611

Funding

Project 2 MeasurementU19AG033655 · NIA · JOHNS HOPKINS UNIVERSITY · PI Abhay Moghekar · 2014 to 2026
$51.5M
Research Education ComponentP30AG066507 · NIA · JOHNS HOPKINS UNIVERSITY · PI JUAN TRONCOSO · 2020 to 2026
$29.3M
X-LINKED ADRENOLEUKODYSTROPHYP41RR015241 · NCRR · HUGO W. MOSER RES INST KENNEDY KRIEGER · PI CALABRESI, PETER A · 2001 to 2011
$18.5M
TRD 4: Platforms for multi-modal and multi-scale imaging dataP41EB031771 · NIBIB · HUGO W. MOSER RES INST KENNEDY KRIEGER · PI Hanzhang Lu, Peter CM Van Zijl · 2021 to 2026
$9.9M
Quantification of microstructures in the entorhinal-hippocampus pathway as a sensitive biomarker for neurodegeneration during the preclinical stage of Alzheimer's diseaseK99AG088363 · NIA · JOHNS HOPKINS UNIVERSITY · PI UCHIDA, YUTO · 2024 to 2025
$195k
Alzheimer's Association NIAP24-1268927NCRR NIH HHS P41 RR015241NIA NIH HHS K99 AG088363NIA NIH HHS P30 AG066507NIA NIH HHS U19 AG033655NIBIB NIH HHS P41 EB031771NIH HHS K99AG088363NIH HHS P30AG066507NIH HHS P41RR015241NIH HHS U19AG033655
6 · The paper itself

Abstract

introductionThis study aimed to delineate trajectories of biomarkers-amyloid beta (Aβ), phosphorylated tau, neurodegeneration, and inflammation-and to identify change points along these trajectories.

methodsLongitudinal data were collected over 30 years from 349 cognitively unimpaired individuals enrolled in the Biomarkers for Older Controls at Risk for Dementia study. Piecewise regression models were used to identify change points in cerebrospinal fluid biomarkers, brain magnetic resonance imaging volumes, and a composite measure of global cognition.

resultsEighty-two participants progressed to mild cognitive impairment or dementia during the follow-up period. Change points were identified in years prior to clinical symptom onset: Aβ at -17.1 years, phosphorylated tau at -15.8 years, neurofilament light chain and whole-brain white matter at -11.6 years, and total ventricles at -9.7 years.

conclusionThese findings support the temporal sequence proposed by the dynamic biomarker model of Alzheimer's disease and underscore the significance of white matter degeneration as an early marker for disease progression in the pathological cascade. HIGHLIGHTS: Data were collected from 349 participants in Biomarkers for Older Controls at Risk for Dementia, a 30-year cohort study. Eighty-two participants progressed to mild cognitive impairment or dementia over an average of 11 to 12 years. Core cerebrospinal fluid biomarkers for Alzheimer's disease began to accelerate 15 to 20 years before clinical onset. Magnetic resonance imaging volumes accelerated with variations across brain structures. Volumetric changes in the white matter and ventricles preceded the hippocampus.

Indexed as

Alzheimer DiseaseBiomarkersCognitive DysfunctionAgedAged, 80 and overAmyloid beta-PeptidesBrainCohort StudiesDisease ProgressionFemaleHumansLongitudinal StudiesMagnetic Resonance ImagingMaleNeurofilament Proteinstau ProteinsAmyloid beta-PeptidesBiomarkersNeurofilament Proteinstau ProteinsAlzheimer's diseaseamyloidcerebrospinal fluidcognitive declineglial fibrillary acidic proteinlongitudinal studymagnetic resonance imagingmild cognitive impairmentneurofilament light chaintau

Identifiers

PMID40741702
PMCPMC12311614

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.