A conceptual framework for research on subjective cognitive decline in preclinical Alzheimer's disease
Open accessAbstract
There is increasing evidence that subjective cognitive decline (SCD) in individuals with unimpaired performance on cognitive tests may represent the first symptomatic manifestation of Alzheimer's disease (AD). The research on SCD in early AD, however, is limited by the absence of common standards. The working group of the Subjective Cognitive Decline Initiative (SCD‐I) addressed this deficiency by reaching consensus on terminology and on a conceptual framework for research on SCD in AD. In this publication, research criteria for SCD in pre‐mild cognitive impairment (MCI) are presented. In addition, a list of core features proposed for reporting in SCD studies is provided, which will enable comparability of research across different settings. Finally, a set of features is presented, which in accordance with current knowledge, increases the likelihood of the presence of preclinical AD in individuals with SCD. This list is referred to as SCD plus .
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SCD is postulated to manifest at a relatively late phase of preclinical AD.
“SCD is postulated to manifest at a relatively late phase of preclinical AD and is associated with increased risks of AD biomarker abnormalities and future cognitive decline and dementia [2, 4, 6]”
From Neuroimaging advances regarding subjective cognitive decline in preclinical Alzheimer's disease (2020) · cites this paper as [4]
Section 3 says SCD can occur during preclinical AD, and the Introduction discusses subjective decline as a possible indicator of early effects of AD pathology. The paper does not establish that SCD manifests specifically at a relatively late phase of preclinical AD; the Introduction also describes its potential value at a very early disease stage. Page numbers were not available in our copy. (LLM, conf=0.82)
Experimental — accuracy not yet measuredSCD is regarded as the first clinical manifestation in the AD continuum.
“Subjective cognitive decline (SCD), the first clinical manifestation in the AD continuum, is self-experienced decline in cognitive function without evidence of objective cognitive impairment [3–5].”
From Neuroimaging advances regarding subjective cognitive decline in preclinical Alzheimer's disease (2020) · cites this paper as [4]
The Introduction describes SCD as a possible indicator of the first effects of AD pathology on cognition, and section 3 says it may be a symptomatic indicator of preclinical AD. But the paper does not establish SCD as the first clinical manifestation in the AD continuum: section 3 says SCD is not present in every case of preclinical AD and can have causes other than AD. Page numbers are not available in our copy. (LLM, conf=0.86)
Experimental — accuracy not yet measuredSubjective cognitive decline is one of the earliest warning signs of dementia and may be a way to identify people who are at high risk of developing Alzheimer's or other dementias, as well as MCI.
“Subjective cognitive decline is one of the earliest warning signs of dementia and may be a way to identify people who are at high risk of developing Alzheimer's or other dementias, as well as MCI.”
From 2024 Alzheimer's disease facts and figures (2024) · cites this paper as [274]
The Introduction (page unavailable) describes subjective cognitive decline as potentially informative at a very early stage of Alzheimer’s disease and associates it with increased risk of future cognitive decline and Alzheimer’s dementia. It also places subjective decline before MCI, but does not establish that it identifies people at high risk of developing other dementias. (LLM, conf=0.86)
Experimental — accuracy not yet measuredFor some people, subjective cognitive decline is normal aging, but for others, these symptoms can be a warning sign of future Alzheimer's disease.
“For some people, this is normal aging, but for others, these symptoms can be a warning sign of future Alzheimer's disease.[246][247][248][249][250]”
From 2023 Alzheimer's disease facts and figures (2023) · cites this paper as [248]
In 2014, the SCD-I proposed a consensus terminology and conceptual framework for research on SCD related to AD, including SCD-plus features.
“In 2014, a consensus terminology and a conceptual framework for research on SCD related to AD was proposed by the Subjective Cognitive Decline Initiative (SCD-I) [4].”
From Neuroimaging advances regarding subjective cognitive decline in preclinical Alzheimer's disease (2020) · cites this paper as [4]
SCD is a heterogeneous concept that can be induced by many conditions other than AD, including normal aging, psychiatric conditions, other neurological and medical disorders, substance abuse and certain medications.
“Although SCD is a heterogeneous concept that can be induced by many conditions other than AD [4], including normal aging, psychiatric conditions (e.g., depression), other neurological and medical disorders (e.g., frontal temporal dementia and dementia with Lewy bodies), substance abuse and certain medications”
From Neuroimaging advances regarding subjective cognitive decline in preclinical Alzheimer's disease (2020) · cites this paper as [4]
SCD is associated with increased risks of AD biomarker abnormalities and future cognitive decline and dementia.
“SCD is postulated to manifest at a relatively late phase of preclinical AD and is associated with increased risks of AD biomarker abnormalities and future cognitive decline and dementia [2, 4, 6]”
From Neuroimaging advances regarding subjective cognitive decline in preclinical Alzheimer's disease (2020) · cites this paper as [4]
Quantitative EEG (qEEG) has been proven as a reliable clinical tool for the diagnosis and study of brain diseases and cortical disorders.
“In recent years, the quantitative EEG (qEEG) has been proven as a reliable clinical tool for the diagnosis and study of brain diseases and cortical disorders such as Huntington’s disease [16], autism spectrum disorders [17], epilepsy [18], and dementia due to Parkinson ‘s disease [19].”
From Alzheimer's Disease and Frontotemporal Dementia: A Robust Classification Method of EEG Signals and a Comparison of Validation Methods (2021) · cites this paper as [17]
The Introduction discusses biomarkers and subjective cognitive decline in preclinical Alzheimer’s disease, not qEEG as a reliable clinical diagnostic tool. A References entry names a study of quantitative EEG correlates of cognitive deterioration in older adults, but the paper’s text does not establish the claimed reliability or address qEEG diagnosis across brain diseases and cortical disorders (searched: quantitative EEG, clinical reliability, and electrophysiological imaging). (LLM, conf=0.76)
Experimental — accuracy not yet measured
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2019 Alzheimer’s disease facts and figures.
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2020 Alzheimer's disease facts and figures
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2018 Alzheimer's disease facts and figures
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Self-citationDefeating Alzheimer's disease and other dementias: a priority for European science and society
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Self-citationThe characterisation of subjective cognitive decline
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Self-citationAlzheimer’s Disease: Past, Present, and Future
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Strategic roadmap for an early diagnosis of Alzheimer's disease based on biomarkers
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Self-citationImplementation of subjective cognitive decline criteria in research studies
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Plasma Amyloid as Prescreener for the Earliest <scp>A</scp> lzheimer Pathological Changes
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Glial activation and inflammation along the Alzheimer’s disease continuum
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Subjective Cognitive Impairment and Affective Symptoms: A Systematic Review
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Self-citationNeuroimaging advances regarding subjective cognitive decline in preclinical Alzheimer's disease
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Self-citationTowards a future where Alzheimer’s disease pathology is stopped before the onset of dementia
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Self-citationATN classification and clinical progression in subjective cognitive decline: The SCIENCe project
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Mediterranean Diet, Alzheimer Disease Biomarkers, and Brain Atrophy in Old Age
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Unbiased estimates of cerebrospinal fluid β-amyloid 1–42 cutoffs in a large memory clinic population
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Self-citationCortical Thinning in Individuals with Subjective Memory Impairment
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Self-citationCorrelates of Subjective Cognitive Decline in Lesbian, Gay, Bisexual, and Transgender Older Adults
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Brain amyloid and vascular risk are related to distinct white matter hyperintensity patterns
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Altered gut microbiota in adults with subjective cognitive decline: the SILCODE study
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Subregional volume reduction of the cholinergic forebrain in subjective cognitive decline (SCD)
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Self-citationWhite matter degeneration in subjective cognitive decline: a diffusion tensor imaging study
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Self-citationAmyloid PET and cognitive decline in cognitively normal individuals: the SCIENCe project
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Personalized risk for clinical progression in cognitively normal subjects-the ABIDE project
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Self-citationGray Matter Network Disruptions and Regional Amyloid Beta in Cognitively Normal Adults
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Self-citationThe Role of Chronic Stress as a Trigger for the Alzheimer Disease Continuum
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Diminution of context association memory structure in subjects with subjective cognitive decline
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Federated learning for cognitive impairment detection using speech data
Blazquez-Folch, J., Limones Andrade, M., Calm, B., Auñón García, J. M., Alegret, M., Muñoz, N., Cano, A., Fernández, V., García-Gutiérrez, F., De Rojas, I., et al. (2025) · Frontiers in Artificial Intelligence · doi:10.3389/frai.2025.1662859 · Cited by 2 · see citing works
- Authors
- Jessen, F., Amariglio, R. E., van Boxtel, M., Breteler, M., Ceccaldi, M., Chételat, G., Dubois, B., Dufouil, C., Ellis, K. A., van der Flier, W. M., Glodzik, L., van Harten, A. C., de Leon, M. J., McHugh, P., Mielke, M. M., Molinuevo, J. L., Mosconi, L., Osorio, R. S., Perrotin, A., Petersen, R. C., Rabin, L. A., Rami, L., Reisberg, B., Rentz, D. M., Sachdev, P. S., de la Sayette, V., Saykin, A. J., Scheltens, P., Shulman, M. B., Slavin, M. J., Sperling, R. A., Stewart, R., Uspenskaya, O., Vellas, B., Visser, P. J., Wagner, M., & Subjective Cognitive Decline Initiative (SCD‐I) Working Group
- Affiliations
- University of Bonn (DE)
- Brigham and Women's Hospital (US)
- Department of Psychiatry and Neuropsychology School for Mental Health and Neuroscience (MHeNS), Maastricht University Maastricht The Netherlands
- German Center for Neurodegenerative Diseases (DE)
- Institut de Neurosciences des Systèmes (FR)
- Inserm (FR)
- Université Pierre-et-Marie-Curie (FR)
- Université de Bordeaux (FR)
- The University of Melbourne (AU)
- Alzheimer Center Department of Neurology, Neuroscience Campus Amsterdam VU University Medical Centre Amsterdam The Netherlands
- NYU Langone Health (US)
- Department of Psychiatry New York University Langone Medical Center New York NY USA
- Mayo Clinic (US)
- Alzheimer's Disease and Other Cognitive Disorders Unit IDIBAPS, Hospital Clinic Barcelona Spain
- The Graduate Center, CUNY (US)
- Hospital Clínic de Barcelona (ES)
- UNSW Sydney (AU)
- INSERM, U1077 Caen France
- Indiana University School of Medicine (US)
- Amsterdam Neuroscience (NL)
- King's College London (GB)
- Pitié-Salpêtrière Hospital (FR)
- Université Toulouse III - Paul Sabatier (FR)
- Maastricht University (NL)
- Corresponding author
- Jessen, Frank
- ORCID
- Jessen, Frank
- Amariglio, Rebecca E.
- Breteler, Monique
- Ceccaldi, Mathieu
- Chételat, Gaël
- Dubois, Bruno
- Dufouil, Carole
- Ellis, Kathryn A.
- Glodzik, Lidia
- Mielke, Michelle M.
- Mosconi, Lisa
- Osorio, Ricardo S.
- Perrotin, Audrey
- Petersen, Ronald C.
- Rami, Lorena
- Reisberg, Barry
- Rentz, Dorene M.
- Sachdev, Perminder S.
- Saykin, Andrew J.
- Scheltens, Philip
- Shulman, Melanie B.
- Sperling, Reisa A.
- Stewart, Robert
- Vellas, Bruno
- Visser, Pieter Jelle
- Wagner, Michael
- Venue
- Alzheimer's & Dementia
- Publisher
- Wiley
- Published
- 2014-05-02
- Volume
- 10
- Issue
- 6
- Pages
- 844-852
- ISSN
- 1552-5260 (ISSN-L)
- 1552-5279
- PMC
- PMC4317324
- OpenAlex
- W2048505725
- Cited by
- 3,014
- References
- 63
- Citations by year
- 2026: 313 · 2025: 357 · 2024: 408 · 2023: 324 · 2022: 308 · 2021: 343 · 2020: 266 · 2019: 216 · 2018: 174 · 2017: 137 · 2016: 81 · 2015: 71 · 2014: 12
- FWCI
- 13.81
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Alzheimer s & Dementia (publishedVersion)
- PubMed (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Research Publications (Maastricht University) (submittedVersion, other-oa)
- Research Portal (King's College London) (submittedVersion)
- DZNE Pub (submittedVersion)
- Pure Amsterdam UMC (submittedVersion)
- IUScholarWorks (Indiana University) (submittedVersion)
- Research Publications (Maastricht University) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- PMC
- Funders
- National Institutes of Health (UL1TR001108)
- National Institute on Aging (P30AG010133, R01AG022374, P30AG008051, K23AG044431, R01AG019771)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cancer-related cognitive impairment studies
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- subjective cognitive decline, preclinical Alzheimer's disease
- MeSH terms
- Alzheimer Disease, Cognition Disorders, Female, Humans, Male, Neuropsychological Tests, Terminology as Topic, Psychiatric Status Rating Scales, Age of Onset, Disease Progression, Prodromal Symptoms
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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