Evidence map›Paper›PMID 30842300›Full record

ArticleNeurology2019

ATN profiles among cognitively normal individuals and longitudinal cognitive outcomes.

Anja Soldan, Corinne Pettigrew, Anne M Fagan, Suzanne E Schindler, Abhay Moghekar, Christopher Fowler, Qiao-Xin Li, Steven J Collins, Cynthia Carlsson, Sanjay Asthana and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neurology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
73citing papers in PubMed, 1 pooled it
–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

73 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Trial
  3. Article
  4. Article
  5. HSV-1 as a Potential Driver of Alzheimer's Disease.Pathogens (Basel, Switzerland) · 2025
    Review
  6. Article
  7. Review
  8. Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. Article
  14. Review
  15. Article
  16. Article
  17. Article
  18. Review
  19. Data-Driven Thresholding Statistically Biases ATN Profiling across Cohort Datasets.The journal of prevention of Alzheimer's disease · 2024
    Article
  20. Article

13 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors.

Anja SoldanFrom the Department of Neurology (A.S., C.P., A.M., M.A.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Neurology (A.M.F., S.E.S., J.C.M.), Washington University School of Medicine, St. Louis, MO; Florey Institute of Neuroscience and Mental Health (C.F., Q.-X.L., S.J.C., C.L.M.), the University of Melbourne, Australia; Geriatric Research Education and Clinical Center (C.C., S.A., S.J.), Wm. S. Middleton Memorial VA Hospital and Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison; and Center on Aging and Health and Department of Epidemiology (A.L.G.), Johns Hopkins Bloomberg School of Public Health, Baltimore, MD. asoldan1@jhmi.edu.
Corinne PettigrewFrom the Department of Neurology (A.S., C.P., A.M., M.A.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Neurology (A.M.F., S.E.S., J.C.M.), Washington University School of Medicine, St. Louis, MO; Florey Institute of Neuroscience and Mental Health (C.F., Q.-X.L., S.J.C., C.L.M.), the University of Melbourne, Australia; Geriatric Research Education and Clinical Center (C.C., S.A., S.J.), Wm. S. Middleton Memorial VA Hospital and Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison; and Center on Aging and Health and Department of Epidemiology (A.L.G.), Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.ORCID 0000-0003-4264-275X
Anne M FaganFrom the Department of Neurology (A.S., C.P., A.M., M.A.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Neurology (A.M.F., S.E.S., J.C.M.), Washington University School of Medicine, St. Louis, MO; Florey Institute of Neuroscience and Mental Health (C.F., Q.-X.L., S.J.C., C.L.M.), the University of Melbourne, Australia; Geriatric Research Education and Clinical Center (C.C., S.A., S.J.), Wm. S. Middleton Memorial VA Hospital and Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison; and Center on Aging and Health and Department of Epidemiology (A.L.G.), Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.
Suzanne E SchindlerFrom the Department of Neurology (A.S., C.P., A.M., M.A.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Neurology (A.M.F., S.E.S., J.C.M.), Washington University School of Medicine, St. Louis, MO; Florey Institute of Neuroscience and Mental Health (C.F., Q.-X.L., S.J.C., C.L.M.), the University of Melbourne, Australia; Geriatric Research Education and Clinical Center (C.C., S.A., S.J.), Wm. S. Middleton Memorial VA Hospital and Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison; and Center on Aging and Health and Department of Epidemiology (A.L.G.), Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.
Abhay MoghekarFrom the Department of Neurology (A.S., C.P., A.M., M.A.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Neurology (A.M.F., S.E.S., J.C.M.), Washington University School of Medicine, St. Louis, MO; Florey Institute of Neuroscience and Mental Health (C.F., Q.-X.L., S.J.C., C.L.M.), the University of Melbourne, Australia; Geriatric Research Education and Clinical Center (C.C., S.A., S.J.), Wm. S. Middleton Memorial VA Hospital and Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison; and Center on Aging and Health and Department of Epidemiology (A.L.G.), Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.
Christopher FowlerFrom the Department of Neurology (A.S., C.P., A.M., M.A.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Neurology (A.M.F., S.E.S., J.C.M.), Washington University School of Medicine, St. Louis, MO; Florey Institute of Neuroscience and Mental Health (C.F., Q.-X.L., S.J.C., C.L.M.), the University of Melbourne, Australia; Geriatric Research Education and Clinical Center (C.C., S.A., S.J.), Wm. S. Middleton Memorial VA Hospital and Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison; and Center on Aging and Health and Department of Epidemiology (A.L.G.), Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.
Qiao-Xin LiFrom the Department of Neurology (A.S., C.P., A.M., M.A.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Neurology (A.M.F., S.E.S., J.C.M.), Washington University School of Medicine, St. Louis, MO; Florey Institute of Neuroscience and Mental Health (C.F., Q.-X.L., S.J.C., C.L.M.), the University of Melbourne, Australia; Geriatric Research Education and Clinical Center (C.C., S.A., S.J.), Wm. S. Middleton Memorial VA Hospital and Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison; and Center on Aging and Health and Department of Epidemiology (A.L.G.), Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.
Steven J CollinsFrom the Department of Neurology (A.S., C.P., A.M., M.A.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Neurology (A.M.F., S.E.S., J.C.M.), Washington University School of Medicine, St. Louis, MO; Florey Institute of Neuroscience and Mental Health (C.F., Q.-X.L., S.J.C., C.L.M.), the University of Melbourne, Australia; Geriatric Research Education and Clinical Center (C.C., S.A., S.J.), Wm. S. Middleton Memorial VA Hospital and Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison; and Center on Aging and Health and Department of Epidemiology (A.L.G.), Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.
Cynthia CarlssonFrom the Department of Neurology (A.S., C.P., A.M., M.A.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Neurology (A.M.F., S.E.S., J.C.M.), Washington University School of Medicine, St. Louis, MO; Florey Institute of Neuroscience and Mental Health (C.F., Q.-X.L., S.J.C., C.L.M.), the University of Melbourne, Australia; Geriatric Research Education and Clinical Center (C.C., S.A., S.J.), Wm. S. Middleton Memorial VA Hospital and Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison; and Center on Aging and Health and Department of Epidemiology (A.L.G.), Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.
Sanjay AsthanaFrom the Department of Neurology (A.S., C.P., A.M., M.A.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Neurology (A.M.F., S.E.S., J.C.M.), Washington University School of Medicine, St. Louis, MO; Florey Institute of Neuroscience and Mental Health (C.F., Q.-X.L., S.J.C., C.L.M.), the University of Melbourne, Australia; Geriatric Research Education and Clinical Center (C.C., S.A., S.J.), Wm. S. Middleton Memorial VA Hospital and Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison; and Center on Aging and Health and Department of Epidemiology (A.L.G.), Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.
Colin L MastersFrom the Department of Neurology (A.S., C.P., A.M., M.A.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Neurology (A.M.F., S.E.S., J.C.M.), Washington University School of Medicine, St. Louis, MO; Florey Institute of Neuroscience and Mental Health (C.F., Q.-X.L., S.J.C., C.L.M.), the University of Melbourne, Australia; Geriatric Research Education and Clinical Center (C.C., S.A., S.J.), Wm. S. Middleton Memorial VA Hospital and Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison; and Center on Aging and Health and Department of Epidemiology (A.L.G.), Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.
Sterling JohnsonFrom the Department of Neurology (A.S., C.P., A.M., M.A.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Neurology (A.M.F., S.E.S., J.C.M.), Washington University School of Medicine, St. Louis, MO; Florey Institute of Neuroscience and Mental Health (C.F., Q.-X.L., S.J.C., C.L.M.), the University of Melbourne, Australia; Geriatric Research Education and Clinical Center (C.C., S.A., S.J.), Wm. S. Middleton Memorial VA Hospital and Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison; and Center on Aging and Health and Department of Epidemiology (A.L.G.), Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.
John C MorrisFrom the Department of Neurology (A.S., C.P., A.M., M.A.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Neurology (A.M.F., S.E.S., J.C.M.), Washington University School of Medicine, St. Louis, MO; Florey Institute of Neuroscience and Mental Health (C.F., Q.-X.L., S.J.C., C.L.M.), the University of Melbourne, Australia; Geriatric Research Education and Clinical Center (C.C., S.A., S.J.), Wm. S. Middleton Memorial VA Hospital and Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison; and Center on Aging and Health and Department of Epidemiology (A.L.G.), Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.
Marilyn AlbertFrom the Department of Neurology (A.S., C.P., A.M., M.A.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Neurology (A.M.F., S.E.S., J.C.M.), Washington University School of Medicine, St. Louis, MO; Florey Institute of Neuroscience and Mental Health (C.F., Q.-X.L., S.J.C., C.L.M.), the University of Melbourne, Australia; Geriatric Research Education and Clinical Center (C.C., S.A., S.J.), Wm. S. Middleton Memorial VA Hospital and Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison; and Center on Aging and Health and Department of Epidemiology (A.L.G.), Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.
Alden L GrossFrom the Department of Neurology (A.S., C.P., A.M., M.A.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Neurology (A.M.F., S.E.S., J.C.M.), Washington University School of Medicine, St. Louis, MO; Florey Institute of Neuroscience and Mental Health (C.F., Q.-X.L., S.J.C., C.L.M.), the University of Melbourne, Australia; Geriatric Research Education and Clinical Center (C.C., S.A., S.J.), Wm. S. Middleton Memorial VA Hospital and Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison; and Center on Aging and Health and Department of Epidemiology (A.L.G.), Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.

Funding

Project 2 MeasurementU19AG033655 · NIA · JOHNS HOPKINS UNIVERSITY · PI JUAN TRONCOSO · 2014 to 2026
$51.5M
The natural history of AB accumulation in preclinical ADP01AG026276 · NIA · WASHINGTON UNIVERSITY · PI MORRIS, JOHN · 2005 to 2025
$49.5M
Wisconsin Alzheimer's Disease Research CenterP30AG062715 · NIA · UNIVERSITY OF WISCONSIN-MADISON · PI Sanjay Asthana · 2019 to 2026
$34.5M
Research Education ComponentP30AG066507 · NIA · JOHNS HOPKINS UNIVERSITY · PI Jinchong Xu · 2020 to 2026
$29.3M
Wisconsin Alzheimer's Disease Research CenterP50AG033514 · NIA · UNIVERSITY OF WISCONSIN-MADISON · PI JOHNSON, JEFFREY A · 2009 to 2018
$16.2M
Democratising Machine Learning for researchers working in Alzheimer's spaceR01AG058676 · NIA · UNIVERSITY OF MELBOURNE · PI MASTERS, COLIN · 2018 to 2022
$10.9M
Preclinical AD ConsortiumRF1AG059869 · NIA · JOHNS HOPKINS UNIVERSITY · PI ALBERT, MARILYN S. · 2018 to 2018
$7.7M
STAGING PRECLINICAL AD WITH CSF BIOMARKERSK23AG053426 · NIA · WASHINGTON UNIVERSITY · PI SCHINDLER, SUZANNE ELIZABETH · 2017 to 2020
$654k
NIA NIH HHS K23 AG053426NIA NIH HHS P01 AG026276NIA NIH HHS P30 AG062715NIA NIH HHS P30 AG066507NIA NIH HHS P50 AG033514NIA NIH HHS R01 AG058676NIA NIH HHS RF1 AG059869NIA NIH HHS U19 AG033655
6 · The paper itself

Abstract

objectiveTo examine the long-term cognitive trajectories of individuals with normal cognition at baseline and distinct amyloid/tau/neurodegeneration (ATN) profiles.

methodsPooling data across 4 cohort studies, 814 cognitively normal participants (mean baseline age = 59.6 years) were classified into 8 ATN groups using baseline CSF levels of β-amyloid 1-42 as a measure of amyloid (A), phosphorylated tau 181 as a measure of tau (T), and total tau as a measure of neurodegeneration (N). Cognitive performance was measured using a previously validated global factor score and with the Mini-Mental State Examination. We compared the cognitive trajectories across groups using growth curve models (mean follow-up time = 7 years).

resultsUsing different model formulations and cut points for determining biomarker abnormality, only the group with abnormal levels of amyloid, tau, and neurodegeneration (A+T+N+) showed consistently greater cognitive decline than the group with normal levels of all biomarkers (A-T-N-). Replicating prior findings using the 2011 National Institute on Aging-Alzheimer's Association/suspected non-Alzheimer disease pathophysiology schema, only individuals with abnormal levels of both amyloid and phosphorylated tau 181 or total tau (stage 2) showed greater cognitive decline than those with normal biomarker levels (stage 0).

conclusionThe results are consistent with the hypothesis that both elevated brain amyloid and neurofibrillary tangles are necessary to observe accelerated neurodegeneration, which in turn leads to cognitive decline.

Indexed as

CognitionAgedAlzheimer DiseaseAmyloid beta-PeptidesCohort StudiesDisease ProgressionFemaleHumansLongitudinal StudiesMaleMiddle AgedPeptide FragmentsPhosphoproteinstau ProteinsAmyloid beta-Peptidesamyloid beta-protein (1-42)MAPT protein, humanPeptide FragmentsPhosphoproteinstau Proteins

Identifiers

PMID30842300
PMCPMC6448449

What OpenQuestion holds

Textmetadata
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 OpenQuestion graph.