Evidence map›Paper›PMID 39956674›Full record

ArticleThe journal of prevention of Alzheimer's disease2025

Characterizing and validating 12-month reliable cognitive change in Early-Onset Alzheimer's Disease for use in clinical trials.

Dustin B Hammers, Jane Musema, Ani Eloyan, Maryanne Thangarajah, Alexander Taurone, Renaud La Joie, Alexandra Touroutoglou, Prashanthi Vemuri, Joel Kramer, Paul Aisen and 29 more

Abstract readValidation Study
PubMed Full text at PMC Publisher
In one paragraph

Article in The journal of prevention of Alzheimer's disease, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed.

  1. Article
  2. Review
  3. Metabotropic glutamate receptor 5 is associated with plasma GFAP dependent on age.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
  4. Cognitive dispersion profiles and prediction of cognitive change in early-onset dementias: Results from LEADS.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
  5. Everyday functioning in young onset dementia: differences between diagnostic groups.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Article
  6. 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

39 authors.

Dustin B HammersDepartment of Neurology, Indiana University School of Medicine, Indianapolis, IN 46202, USA. Electronic address: HammersD@iu.edu.
Jane MusemaDepartment of Neurology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Ani EloyanDepartment of Biostatistics, Center for Statistical Sciences, Brown University, Providence, Rhode Island 02912, USA.
Maryanne ThangarajahDepartment of Biostatistics, Center for Statistical Sciences, Brown University, Providence, Rhode Island 02912, USA.
Alexander TauroneDepartment of Biostatistics, Center for Statistical Sciences, Brown University, Providence, Rhode Island 02912, USA.
Renaud La JoieDepartment of Neurology, University of California - San Francisco, San Francisco, California 94143, USA.
Alexandra TouroutoglouDepartment of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA.
Prashanthi VemuriDepartment of Neurology, Mayo Clinic, Rochester, Minnesota 55905, USA.
Joel KramerDepartment of Neurology, University of California - San Francisco, San Francisco, California 94143, USA.
Paul AisenAlzheimer's Therapeutic Research Institute, University of Southern California, San Diego, California 92121, USA.
Jeffrey L DageDepartment of Neurology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Kelly N NudelmanDepartment of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.
Kala KirbyDepartment of Neurology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Alireza AtriBanner Sun Health Research Institute, Sun City, Arizona 85351, USA.
David ClarkDepartment of Neurology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Gregory S DayDepartment of Neurology, Mayo Clinic, Jacksonville, Florida 32224, USA.
Ranjan DuaraWien Center for Alzheimer's Disease and Memory Disorders, Mount Sinai Medical Center, Miami, Florida 33140, USA.
Neill R Graff-RadfordDepartment of Neurology, Mayo Clinic, Jacksonville, Florida 32224, USA.
Ian GrantDepartment of Psychiatry and Behavioral Sciences, Mesulam Center for Cognitive Neurology and Alzheimer's Disease, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
Lawrence S HonigTaub Institute and Department of Neurology, Columbia University Irving Medical Center, New York, New York 10032, USA.
Erik C B JohnsonDepartment of Neurology and Human Genetics, Emory University School of Medicine, Atlanta, Georgia 30307, USA.
David T JonesDepartment of Neurology, Mayo Clinic, Rochester, Minnesota 55905, USA.
Joseph C MasdeuNantz National Alzheimer Center, Houston Methodist and Weill Cornell Medicine, Houston, Texas 77030, USA.
Mario F MendezDepartment of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, California 90095, USA.
Kyle WomackDepartment of Neurology, Washington University in St. Louis, St. Louis, Missouri 63130, USA.
Erik MusiekDepartment of Neurology, Washington University in St. Louis, St. Louis, Missouri 63130, USA.
Chiadi U OnyikeDepartment of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Meghan RiddleDepartment of Neurology, Alpert Medical School, Brown University, Providence, Rhode Island 02912, USA.
Emily RogalskiHealthy Aging & Alzheimer's Research Care Center, Department of Neurology, University of Chicago, Chicago, Illinois 60637, USA.
Steven SallowayDepartment of Neurology, Alpert Medical School, Brown University, Providence, Rhode Island 02912, USA.
Sharon J ShaDepartment of Neurology & Neurological Sciences, Stanford University, Palo Alto, California 94304, USA.
Raymond Scott TurnerDepartment of Neurology, Georgetown University, Washington D.C. 20057, USA.
Thomas S WingoDepartment of Neurology, UC Davis Alzheimer's Disease Research Center, University of California - Davis, Davis, California 95816, USA.
David A WolkDepartment of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Maria C CarrilloMedical & Scientific Relations Division, Alzheimer's Association, Chicago, Illinois 60603, USA.
Gil D RabinoviciDepartment of Neurology, University of California - San Francisco, San Francisco, California 94143, USA.
Bradford C DickersonDepartment of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA.
Liana G ApostolovaDepartment of Neurology, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA; Department of Radiology and Imaging Sciences, Center for Neuroimaging, Indiana University School of Medicine Indianapolis, Indianapolis, Indiana, 46202, USA.
LEADS ConsortiumDepartment of Neurology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.

Funding

National Centralized Repository for Alzheimer's Disease and Related Dementias (NCRAD)U24AG021886 · NIA · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI TATIANA M. FOROUD · 2002 to 2026
$119.8M
NATIONAL ALZHEIMERS COORDINATING CENTER (NACC)U01AG016976 · NIA · UNIVERSITY OF WASHINGTON · PI KUKULL, WALTER ANTHONY · 1999 to 2020
$72.8M
Early Onset AD Consortium - the LEAD Study (LEADS)U01AG057195 · NIA · INDIANA UNIVERSITY INDIANAPOLIS · PI APOSTOLOVA, LIANA G, CARRILLO, MARIA C · 2018 to 2023
$70.3M
WASHINGTON UNIVERSITY ALZHEIMERS DISEASE RESEARCH CENTERP50AG005681 · NIA · WASHINGTON UNIVERSITY · PI MORRIS, JOHN · 1985 to 2019
$52.1M
Satellite Diagnostic and Treatment Clinic CoreP50AG008702 · NIA · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI DE JAGER, PHILIP L · 1989 to 2019
$46.3M
'T V ASSESSMENT - MEMORY DISORDERED PATIENTS'P50AG005146 · NIA · JOHNS HOPKINS UNIVERSITY · PI HUGANIR, RICHARD L · 1985 to 2019
$37.6M
Research Education ComponentP30AG010133 · NIA · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI SAYKIN, ANDREW J · 1991 to 2020
$37.3M
Research Education ComponentP30AG062422 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Serggio Carlo Lanata · 2019 to 2026
$36.9M
Research Education ComponentP30AG062421 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI Christine S Ritchie · 2019 to 2026
$36.5M
UPenn ADCC Biomarker CoreP30AG010124 · NIA · UNIVERSITY OF PENNSYLVANIA · PI XIE, SHARON XIANGWEN · 1991 to 2020
$35.1M
Neuropathology CoreP30AG013854 · NIA · NORTHWESTERN UNIVERSITY AT CHICAGO · PI BIGIO, EILEEN H. · 1996 to 2020
$28.9M
PrPSc SPECIFIC INTERACTION WITH NOVEL PrP-Fc FUSION PROTEINSP50AG023501 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MILLER, BRUCE L · 2004 to 2018
$27.1M
NIA NIH HHS K23 AG080071NIA NIH HHS P30 AG010124NIA NIH HHS P30 AG010133NIA NIH HHS P30 AG013854NIA NIH HHS P30 AG062421NIA NIH HHS P30 AG062422NIA NIH HHS P30 AG066506NIA NIH HHS P30 AG072972NIA NIH HHS P30 AG072976NIA NIH HHS P30 AG072979NIA NIH HHS P30 AG072980NIA NIH HHS P50 AG005146NIA NIH HHS P50 AG005681NIA NIH HHS P50 AG008702NIA NIH HHS P50 AG023501NIA NIH HHS P50 AG025688NIA NIH HHS P50 AG047366NIA NIH HHS R56 AG057195NIA NIH HHS U01 AG016976NIA NIH HHS U01 AG057195NIA NIH HHS U24 AG021886
6 · The paper itself

Abstract

backgroundAs literature suggests that Early-Onset Alzheimer's Disease (EOAD) and late-onset AD may differ in important ways, need exists for randomized clinical trials for treatments tailored to EOAD. Accurately measuring reliable cognitive change in individual patients with EOAD will have great value for these trials.

objectivesThe current study sought to characterize and validate 12-month reliable change from the Longitudinal Early-Onset Alzheimer's Disease Study (LEADS) neuropsychological battery.

designStandardized regression-based (SRB) prediction equations were developed from age-matched cognitively intact participants within LEADS, and applied to clinically impaired participants from LEADS.

settingParticipants were recruited from outpatient academic medical centers.

participantsParticipants were enrolled in LEADS and diagnosed with amyloid-positive EOAD (n = 189) and amyloid-negative early-onset cognitive impairment not related to AD (EOnonAD; n = 43). MEASUREMENT: 12-month reliable change (Z-scores) was compared between groups across cognitive domain composites, and distributions of individual participant trajectories were examined. Prediction of Z-scores by common AD biomarkers was also considered.

resultsBoth EOAD and EOnonAD displayed significantly lower 12-month follow-up scores than were predicted based on SRB equations, with declines more pronounced for EOAD across several domains. AD biomarkers of cerebral β-amyloid, tau, and EOAD-specific atrophy were predictive of 12-month change scores.

conclusionsThe current results support including EOAD patients in longitudinal clinical trials, and generate evidence of validation for using 12-month reliable cognitive change as a clinical outcome metric in clinical trials in EOAD cohorts like LEADS. Doing so will enhance the success of EOAD trials and permit a better understanding of individual responses to treatment.

Indexed as

Alzheimer DiseaseCognitionCognitive DysfunctionNeuropsychological TestsAgedAge of OnsetFemaleHumansLongitudinal StudiesMaleMiddle AgedReproducibility of ResultsCognitionEarly-onset Alzheimer's disease, memoryLongitudinalNon-Amnestic

Identifiers

PMID39956674
PMCPMC11954665

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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.