Evidence map›Paper›PMID 39985404›Full record

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

SCD-plus features and AD biomarkers in cognitively unimpaired samples: A meta-analytic approach for nine cohort studies.

Elizabeth Kuhn, Hannah M Klinger, Rebecca E Amariglio, Michael Wagner, Frank Jessen, Emrah Düzel, Michael T Heneka, Gael Chételat, Dorene M Rentz, Reisa A Sperling and 17 more

Abstract readMeta-Analysis
In one paragraph

Synthesis 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 9 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
9citing 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

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

  1. Pooled it
  2. Sex specificity of resistance to caTAUstrophe.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. 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

27 authors.

Elizabeth KuhnGerman Center for Neurodegenerative Diseases (DZNE) Bonn, Bonn, Germany.ORCID 0000-0002-3744-1155
Hannah M KlingerDepartment of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA.ORCID 0009-0006-5633-2954
Rebecca E AmariglioDepartment of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA.
Michael WagnerGerman Center for Neurodegenerative Diseases (DZNE) Bonn, Bonn, Germany.
Frank JessenGerman Center for Neurodegenerative Diseases (DZNE) Bonn, Bonn, Germany.
Emrah DüzelGerman Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany.
Michael T HenekaLuxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Belvaux, Esch-sur-Alzette, Luxembourg.
Gael ChételatNormandie Univ, UNICAEN, INSERM, U1237, Physiopathology and Imaging of Neurological Disorders (PhIND), Neuropresage Team, Cyceron, Caen cedex, France.ORCID 0000-0002-4889-7932
Dorene M RentzHarvard Medical School, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Reisa A SperlingDepartment of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA.
Jarith L EbenauAlzheimer Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc, Amsterdam, The Netherlands.
Elke ButterbrodDepartment of Clinical, Neuro and Developmental Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Wiesje M Van Der FlierAlzheimer Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc, Amsterdam, The Netherlands.ORCID 0000-0001-8766-6224
Sietske A M SikkesAlzheimer Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc, Amsterdam, The Netherlands.
Charlotte E TeunnissenNeurochemistry Laboratory, Department of Laboratory Medicine, Amsterdam Neuroscience, Amsterdam University Medical Center, Vrije Universiteit, Amsterdam, The Netherlands.ORCID 0000-0002-4061-0837
Argonde C Van HartenAlzheimer Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc, Amsterdam, The Netherlands.ORCID 0000-0002-1477-8724
Elsmarieke M Van De GiessenDepartment of Radiology and Nuclear Medicine, Amsterdam University Medical Center, Vrije Universiteit, Amsterdam, The Netherlands.ORCID 0000-0001-9956-4233
Lorena RamiHospital Clinic. Fundació Clinic, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain.ORCID 0000-0002-7411-1921
Adria TortHospital Clinic. Fundació Clinic, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain.ORCID 0000-0002-5646-0482
Gonzalo Sánchez BenavidesBarcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona, Spain.ORCID 0000-0003-3454-800X
Katherine A GiffordVanderbilt Memory and Alzheimer's Center, Department of Neurology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.ORCID 0000-0001-6232-9408
Carol Van HulleDepartment of Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Rachel F BuckleyDepartment of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA.ORCID 0000-0002-5356-5537
Alzheimer's Disease Neuroimaging Initiative
Australian Imaging Biomarkers and Lifestyle flagship study of ageing, A4 Study Team
DELCODE Study
Harvard Aging Brain Study

Funding

The Alzheimer's Clinical Trial Consortium - Down Syndrome Network (ACTC- DSN)U24AG057437 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI Paul S. Aisen, RONALD C PETERSEN · 2018 to 2026
$198.4M
Alzheimer's Disease Neuroimaging Initiative - SupplementU01AG024904 · NIA · NORTHERN CALIFORNIA INSTITUTE RES &EDUC · PI WEINER, MICHAEL W · 2004 to 2015
$121.0M
RECRUITMENT COREU19AG010483 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI FELDMAN, HOWARD · 2013 to 2020
$80.6M
University of Wisconsin Institute for Clinical and Translational ResearchUL1TR002373 · NCATS · UNIVERSITY OF WISCONSIN-MADISON · PI ELIZABETH S BURNSIDE, Allan R. Brasier · 2017 to 2026
$75.9M
Vascular factors, physical activity, and inflammation as modulators of neurodegenerative and cognitive trajectories (Project 2)P01AG036694 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI Rachel Frances Buckley, Keith A. Johnson · 2010 to 2026
$50.2M
The Vanderbilt Institute for Clinical and Translational Research (VICTR)UL1TR000445 · NCATS · VANDERBILT UNIVERSITY MEDICAL CENTER · PI BERNARD, GORDON RAPHAEL · 2012 to 2016
$41.4M
Wisconsin Registry for Alzheimer's Prevention: Sex Differences in DNA MethylationR01AG027161 · NIA · UNIVERSITY OF WISCONSIN-MADISON · PI Nathaniel Ark Chin, Sterling C Johnson · 2007 to 2026
$35.6M
Institutional Clinical and Translational Science AwardUL1TR000427 · NCATS · UNIVERSITY OF WISCONSIN-MADISON · PI DREZNER, MARC KENNETH · 2012 to 2016
$32.2M
Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) Open-Label Extension StudyR01AG063689 · NIA · BRIGHAM AND WOMEN'S HOSPITAL · PI AISEN, PAUL S., SPERLING, REISA A. · 2019 to 2024
$30.8M
Vanderbilt Memory & Aging ProjectR01AG034962 · NIA · VANDERBILT UNIVERSITY MEDICAL CENTER · PI JEFFERSON, ANGELA L. · 2011 to 2025
$24.1M
Wisconsin Registry for Alzheimer's PreventionRF1AG027161 · NIA · UNIVERSITY OF WISCONSIN-MADISON · PI JOHNSON, STERLING C · 2018 to 2018
$18.8M
Subjective Cognitive Decline in OIder AdultsR01AG062826 · NIA · VANDERBILT UNIVERSITY MEDICAL CENTER · PI GIFFORD, KATHERINE A., JEFFERSON, ANGELA L. · 2020 to 2024
$4.1M
AbbVieAgence Nationale de la Recherche (ANR LONGVIE 2007)Albert Einstein College of MedicineAlzheimer's Association IIRG-08-88733Alzheimer's Drug Discovery FoundationAlzheimer's Therapeutic Research Institute, University of Southern CaliforniaAraclon BiotechAssociation France Alzheimer et maladies apparentées (AAP 2013)Austin HealthAVIDBioClinica, Inc.BiogenBrigham and Women's HospitalBristol-Myers Squibb CompanyCereSpir, Inc.CIHRCogstateCommonwealth Scientific and Industrial Research Organisation (CSIRO)Davis Alzheimer Prevention ProgramDeutsches Zentrum für Neurodegenerative Erkrankungen BN012Dioraphte and the Noaber FoundationEdith Cowan UniversityEisai Inc.Elan Pharmaceuticals, Inc.Eli Lilly and CompanyEuroImmunEuropean Union, FSE+F. Hoffmann-La Roche Ltd and Genentech, Inc.Florey Institute, The University of MelbourneFondation Philippe ChatrierFondation Plan Alzheimer (Alzheimer Plan 2008-2012)Foundation for Neurologic DiseaseFoundation for the National Institutes of HealthFujirebioGE HealthcareGHR FoundationHelmholtz Artificial Intelligence Cooperation Unit ZT-I-PF-5-163INSERMInstituto de Salud Carlos III CP23/00039IXICO Ltd.Janssen Alzheimer Immunotherapy Research & Development, LLCJohnson & Johnson Pharmaceutical Research & Development LLCLaboratory for Neuro Imaging, University of Southern CaliforniaLumosityLundbeckMerck & Co., Inc.Meso Scale Diagnostics, LLCNational Ageing Research InstituteNational Institutes of Health/National Institute on Aging (NIH/NIA) DP2AG082342National Institutes of Health/National Institute on Aging (NIH/NIA) K23-AG045966National Institutes of Health/National Institute on Aging (NIH/NIA) P01AG036694National Institutes of Health/National Institute on Aging (NIH/NIA) R00-AG061238National Institutes of Health/National Institute on Aging (NIH/NIA) R01-AG027161National Institutes of Health/National Institute on Aging (NIH/NIA) R01-AG062826National Institutes of Health/National Institute on Aging (NIH/NIA) R01-AG063689National Institutes of Health/National Institute on Aging (NIH/NIA) R01-AG079142National Institutes of Health/National Institute on Aging (NIH/NIA) U01AG024904National Institutes of Health/National Institute on Aging (NIH/NIA) U19AG010483National Institutes of Health/National Institute on Aging (NIH/NIA) U24AG057437NCATS NIH HHS UL1 TR000427NCATS NIH HHS UL1 TR000445NCATS NIH HHS UL1 TR002373NeuroRx ResearchNeurotrack TechnologiesNIA NIH HHS DP2 AG082342NIA NIH HHS DP2AG082342NIA NIH HHS K23 AG045966NIA NIH HHS K99 AG061238NIA NIH HHS P01 AG036694NIA NIH HHS R00 AG061238NIA NIH HHS R01 AG027161NIA NIH HHS R01 AG034962NIA NIH HHS R01 AG062826NIA NIH HHS R01 AG063689NIA NIH HHS R01 AG079142NIA NIH HHS RF1 AG027161NIA NIH HHS U01 AG024904NIA NIH HHS U19 AG010483NIA NIH HHS U24 AG057437NIBIB NIH HHSNIH-NCATS UL1TR000427Northern California Institute for Research and EducationNovartis Pharmaceuticals CorporationPasman ChairPfizer Inc.PHRCN 2011-A01493-38PHRCN 2012-12-006-0347Piramal ImagingRégion Basse NormandieServierTakeda Pharmaceutical CompanyTransition TherapeuticsUniversity Caen NormandyU.S. Department of Defense W81XWH-12-2-0012
6 · The paper itself

Abstract

introductionSpecific features of subjective cognitive decline (SCD-plus) have been proposed to indicate an increased risk of preclinical Alzheimer's disease (AD). However, few studies have examined how these features relate to AD biomarkers in cognitively unimpaired (CU) older adults.

methodsMeta-analyses were performed using cross-sectional data from nine cohorts (n = 7219, mean age (SD): 71.17 (5.9), 56.5% female) to determine associations of SCD-plus features with positron emission tomography (PET)- or cerebrospinal fluid (CSF)-derived amyloid beta (Aβ) and tau biomarkers.

resultsParticipants with preclinical AD (community-based only) were more likely to fulfill SCD-plus features. The presence of self-reported memory decline, associated concern/worry, and a higher number of fulfilled features were all associated with high Aβ levels. Only the latter was associated with abnormal tau. DISCUSSION: Simultaneous endorsement of multiple SCD-plus features is a robust indicator of abnormal AD biomarkers in CU older adults, whereas isolated SCD features seem only sensitive to elevated Aβ, supporting their value as early behavioral markers of preclinical AD. HIGHLIGHTS: About two-tenths of our sample had abnormal amyloid beta (Aβ) levels with evidence of subjective cognitive decline (SCD). Preclinical AD subsamples (community-based) had a higher percentage of participants meeting SCD-plus features. Self-reported memory decline and concern/worry were the sole features associated with high Aβ, but not tau, burden. A higher number of fulfilled SCD-plus features are linked to high Aβ and tau burden. Use of multiple SCD-plus features may help identify early stages of biological AD.

Indexed as

Alzheimer DiseaseCognitive DysfunctionAgedAmyloid beta-PeptidesBiomarkersCohort StudiesCross-Sectional StudiesFemaleHumansMalePositron-Emission Tomographytau ProteinsAmyloid beta-PeptidesBiomarkerstau ProteinsAlzheimer's diseaseamyloid pathologycerebrospinal fluidmeta‐analysispositron emission tomographySCD‐Initiativesubjective cognitive declinetau burden

Identifiers

PMID39985404
PMCPMC12079645

What Socratic holds

Textmetadata
LicenceCC BY
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.