ArticleMolecular psychiatry2025
Blood biomarkers confirm subjective cognitive decline (SCD) as a distinct molecular and clinical stage within the NIA-AA framework of Alzheimer´s disease.
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Article in Molecular psychiatry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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21citing papers in PubMed, 1 pooled it
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Neuroinflammatory markers sTREM2 and YKL-40 in association with Alzheimer's disease pathology: a systematic review and meta-analysis.Molecular psychiatry · 2026Pooled it
- Dementia risk factors and biomarkers in subjective cognitive decline: real world evidence from the monza brain health service.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026Article
- Comparative Prognostic Performance of Hippocampal Volume and Plasma Biomarkers in Amyloid-Negative Subjective Cognitive Decline: A Four-Year Follow-up.Journal of clinical neurology (Seoul, Korea) · 2026Article
- Cognitive heterogeneity in mild cognitive impairment due to Alzheimer's disease pathology.Neural regeneration research · 2026Article
- Joint trajectories of brain atrophy, white matter hyperintensities and cognition quantify brain maintenance.Nature communications · 2026Article
- Uncovering Frailty in Burning Mouth Syndrome: Insights From a SUNFRAIL+ Based Multidimensional Assessment.Journal of oral rehabilitation · 2026Article
- Plasma p-tau217 best captures early longitudinal cognitive changes in subjective cognitive decline compared with p-tau181 and NfL.Journal of neurology · 2026Article
- Plasma pTau181 is associated with subjective cognitive concerns but not objective cognitive decline or structural brain integrity measures in midlife.GeroScience · 2026Article
- Association of plasma biomarkers with amyloid and tau PET in pre-dementia stages.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Association between MRI indicators of the glymphatic system and cognition in high-risk populations for Alzheimer's disease.The journal of prevention of Alzheimer's disease · 2026Article
- Associations of plasma biomarkers with longitudinal co-pathologies in Alzheimer's disease and cerebral small vessel disease comorbidity.The journal of prevention of Alzheimer's disease · 2026Article
- Screen, Sample, Stratify: Biomarkers and Machine Learning Compress Dementia Pathways.Biomedicines · 2026Article
- Plasma p-tau181 as a Marker of Conversion to Alzheimer's Disease Dementia and Worsening in Cognitive Functions in Subjective Cognitive Decline and Mild Cognitive Impairment: A Longitudinal Study.Annals of clinical and translational neurology · 2025Article
- Adaptive Frequency-Optimized Wavelet Networks for Early Detection of Subjective Cognitive Decline via Resting-State fMRI.Brain and behavior · 2025Article
- Italian intersocietal recommendations for restructuring the diagnostic-therapeutic pathway for the implementation and appropriate use of anti-amyloid monoclonal antibodies in Alzheimer's disease.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025Review
- Clinical definition, biological characterization, and detection guidelines of subjective cognitive decline due to Alzheimer's disease and related dementia: A position paper from ISTAART SCD PIA.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Gut microbial metabolites and the brain-gut axis in Alzheimer's disease: A review.Biomolecules & biomedicine · 2025Review
- Association between insecticide exposomics and cognitive function in older adults: an observational study based on NHANES 2011-2014.Frontiers in public health · 2025Observational
- Event-related potential markers of subjective cognitive decline and mild cognitive impairment during a sustained visuo-attentive task.NeuroImage. Clinical · 2025Article
- Subjective cognitive decline-a neglected but preventable public health concern: development and validation of a risk prediction model for subjective cognitive decline in older adults: a cross-sectional survey study from Anhui Province in eastern China.Frontiers in public health · 2025Article
Corrections and comments
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Authors and funding
46 authors.
David MengelDivision Translational Genomics of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research and Center of Neurology, University of Tübingen, Hoppe-Seyler-Str. 3, 72076, Tübingen, Germany.ORCID http://orcid.org/0000-0002-4133-7182
Ester SoterDivision Translational Genomics of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research and Center of Neurology, University of Tübingen, Hoppe-Seyler-Str. 3, 72076, Tübingen, Germany.
Julia Maren OttDivision Translational Genomics of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research and Center of Neurology, University of Tübingen, Hoppe-Seyler-Str. 3, 72076, Tübingen, Germany.
Madeleine WackerDivision Translational Genomics of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research and Center of Neurology, University of Tübingen, Hoppe-Seyler-Str. 3, 72076, Tübingen, Germany.
Alejandra LeyvaDivision Translational Genomics of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research and Center of Neurology, University of Tübingen, Hoppe-Seyler-Str. 3, 72076, Tübingen, Germany.
Oliver PetersGerman Center for Neurodegenerative Diseases (DZNE), Robert-Rössle-Straße 10, 13125, Berlin, Germany.
Julian Hellmann-RegenGerman Center for Neurodegenerative Diseases (DZNE), Robert-Rössle-Straße 10, 13125, Berlin, Germany.ORCID http://orcid.org/0000-0003-0411-9204
Luisa-Sophie SchneiderGerman Center for Neurodegenerative Diseases (DZNE), Robert-Rössle-Straße 10, 13125, Berlin, Germany.ORCID http://orcid.org/0000-0001-5822-1744
Xiao WangCharité - Universitätsmedizin Berlin, Department of Psychiatry and Neurosciences, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charitéplatz 1, 10117, Berlin, Germany.
Josef PrillerGerman Center for Neurodegenerative Diseases (DZNE), Robert-Rössle-Straße 10, 13125, Berlin, Germany.
Eike SpruthGerman Center for Neurodegenerative Diseases (DZNE), Robert-Rössle-Straße 10, 13125, Berlin, Germany.
Slawek AltensteinGerman Center for Neurodegenerative Diseases (DZNE), Robert-Rössle-Straße 10, 13125, Berlin, Germany.
Anja SchneiderGerman Center for Neurodegenerative Diseases (DZNE), Sigmund-Freud-Straße 27, 53127, Bonn, Germany.ORCID http://orcid.org/0000-0001-9540-8700
Klaus FliessbachGerman Center for Neurodegenerative Diseases (DZNE), Sigmund-Freud-Straße 27, 53127, Bonn, Germany.
Jens WiltfangGerman Center for Neurodegenerative Diseases (DZNE), Von-Siebold-Straße 3a, 37075, Göttingen, Germany.ORCID http://orcid.org/0000-0003-1492-5330
Niels HansenDepartment of Psychiatry and Psychotherapy, University Medical Center Göttingen, University of Göttingen, Von-Siebold-Straße 3a, 37075, Göttingen, Germany.ORCID http://orcid.org/0000-0001-5785-9594
Ayda RostamzadehDepartment of Psychiatry, Faculty of Medicine and University Hospital Cologne, University of Cologne, Kerpener Str. 62, 50937, Cologne, Germany.
Emra DüzelGerman Center for Neurodegenerative Diseases (DZNE), Leipziger Str. 44, 39120, Magdeburg, Germany.
Wenzel GlanzGerman Center for Neurodegenerative Diseases (DZNE), Leipziger Str. 44, 39120, Magdeburg, Germany.
Enise I IncesoyGerman Center for Neurodegenerative Diseases (DZNE), Leipziger Str. 44, 39120, Magdeburg, Germany.
Katharina BuergerGerman Center for Neurodegenerative Diseases (DZNE), Feodor-Lynen-Str. 17, 81377, Munich, Germany.
Daniel JanowitzGerman Center for Neurodegenerative Diseases (DZNE), Feodor-Lynen-Str. 17, 81377, Munich, Germany.
Michael EwersGerman Center for Neurodegenerative Diseases (DZNE), Feodor-Lynen-Str. 17, 81377, Munich, Germany.ORCID http://orcid.org/0000-0001-5231-1714
Robert PerneczkyGerman Center for Neurodegenerative Diseases (DZNE), Feodor-Lynen-Str. 17, 81377, Munich, Germany.ORCID http://orcid.org/0000-0003-1981-7435
Boris RauchmannDepartment of Psychiatry and Psychotherapy, University Hospital, LMU, Nussbaumstraße 7, 80336, Munich, Germany.
Stefan TeipelGerman Center for Neurodegenerative Diseases (DZNE), Gehlsheimer Straße 20, 18147, Rostock, Germany.
Ingo KilimannGerman Center for Neurodegenerative Diseases (DZNE), Gehlsheimer Straße 20, 18147, Rostock, Germany.
Christoph LaskeGerman Center for Neurodegenerative Diseases (DZNE), University of Tübingen, Otfried-Müller-Straße 27, 72076, Tübingen, Germany.
Sebastian SodenkampGerman Center for Neurodegenerative Diseases (DZNE), University of Tübingen, Otfried-Müller-Straße 27, 72076, Tübingen, Germany.
Annika SpottkeGerman Center for Neurodegenerative Diseases (DZNE), Sigmund-Freud-Straße 27, 53127, Bonn, Germany.
Johanna BrustkernGerman Center for Neurodegenerative Diseases (DZNE), Sigmund-Freud-Straße 27, 53127, Bonn, Germany.
Frederic BrosseronGerman Center for Neurodegenerative Diseases (DZNE), Sigmund-Freud-Straße 27, 53127, Bonn, Germany.ORCID http://orcid.org/0000-0003-3137-7516
Michael WagnerGerman Center for Neurodegenerative Diseases (DZNE), Sigmund-Freud-Straße 27, 53127, Bonn, Germany.
Melina StarkGerman Center for Neurodegenerative Diseases (DZNE), Sigmund-Freud-Straße 27, 53127, Bonn, Germany.
Luca KleineidamGerman Center for Neurodegenerative Diseases (DZNE), Sigmund-Freud-Straße 27, 53127, Bonn, Germany.ORCID http://orcid.org/0009-0006-3309-6856
Kai ShaoGerman Center for Neurodegenerative Diseases (DZNE), Sigmund-Freud-Straße 27, 53127, Bonn, Germany.
Falk LüsebrinkGerman Center for Neurodegenerative Diseases (DZNE), Gehlsheimer Straße 20, 18147, Rostock, Germany.
Renat YakupovGerman Center for Neurodegenerative Diseases (DZNE), Gehlsheimer Straße 20, 18147, Rostock, Germany.ORCID http://orcid.org/0000-0002-3868-284X
Matthias SchmidGerman Center for Neurodegenerative Diseases (DZNE), Sigmund-Freud-Straße 27, 53127, Bonn, Germany.
Stefan HetzerBerlin Center for Advanced Neuroimaging, Charité - Universitätsmedizin Berlin, Philippstraße 13, 10115, Berlin, Germany.
Peter DechentMR-Research in Neurosciences, Department of Cognitive Neurology, Georg-August-University Göttingen, Von-Siebold-Straße 3a, 37075, Göttingen, Germany.
Klaus SchefflerDepartment for Biomedical Magnetic Resonance, University of Tübingen, Hoppe-Seyler-Str. 3, 72076, Tübingen, Germany.
David BerronGerman Center for Neurodegenerative Diseases (DZNE), Leipziger Str. 44, 39120, Magdeburg, Germany.ORCID http://orcid.org/0000-0003-1558-1883
Frank JessenGerman Center for Neurodegenerative Diseases (DZNE), Sigmund-Freud-Straße 27, 53127, Bonn, Germany.
Matthis SynofzikDivision Translational Genomics of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research and Center of Neurology, University of Tübingen, Hoppe-Seyler-Str. 3, 72076, Tübingen, Germany. matthis.synofzik@uni-tuebingen.de.ORCID http://orcid.org/0000-0002-2280-7273
DELCODE study group
Funding
Deutsches Zentrum für Neurodegenerative Erkrankungen (German Center for Neurodegenerative Diseases) BN012
Abstract
Subjective cognitive decline (SCD) is proposed as an indicator of transitional disease stage 2 in the Alzheimer's disease (AD) continuum. However, molecular and particularly longitudinal fluid biomarker data for this stage are still limited. This study aimed to determine whether blood-based biomarkers in amyloid-positive individuals with SCD (A + SCD) support the notion of stage 2 as a distinct stage between stages 1 and 3 of AD and to identify those at high risk for clinical progression. In a prospective multicenter study (DELCODE) involving 457 participants across the AD continuum, we analyzed plasma phospho-tau 181 (p181) and neurofilament light chain (NfL) and assessed their association with longitudinal cognition, hippocampal atrophy, and AD clinical stage transition. The results showed that baseline plasma p181 levels were elevated and increased more rapidly in A + SCD individuals compared to amyloid-positive cognitively unimpaired (A + CU) individuals (stage 1). NfL levels rose across A + CU, A + SCD, and amyloid-positive mild cognitive impairment (A + MCI, stage 3). In A + SCD, but not in A + CU, higher p181 levels predicted cognitive decline (PACC5) and transition to MCI. In conclusion, plasma p181 provides molecular biomarker evidence supporting A + SCD as a pre-dementia AD stage (stage 2) distinct from A + CU (stage 1) and helps identify individuals at risk for cognitive decline early in the AD continuum.
Indexed as
Alzheimer DiseaseCognitive DysfunctionAgedAged, 80 and overAmyloid beta-PeptidesAtrophyBiomarkersCognitionDisease ProgressionFemaleHippocampusHumansLongitudinal StudiesMaleMiddle AgedNeurofilament ProteinsAmyloid beta-PeptidesBiomarkersneurofilament protein LNeurofilament Proteinstau Proteins
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