The DOI matches its Crossref record; 117 of the 119 references it cites were found in a registry or an index; 3 of the 67 sources its claims cite were checked for support.
Clinical diagnosis of Alzheimer’s disease: Recommendations of the International Working Group
Open accessAbstract
In 2018, the National Institute of Aging and the Alzheimer Association proposed a purely biological definition of Alzheimer’s disease (AD) relying on biomarkers. While the intended use of the framework was for research purposes, it has engendered debate and challenges regarding its application in everyday clinical practice. For instance, cognitively unimpaired individuals may have biomarker evidence of both amyloid and tau pathology, but may never develop clinical manifestations in their lifetime. Furthermore, a positive AD pattern may be observed in other brain diseases where AD pathology is present as co‐pathology. In this presentation, the international Working Group (IWG) presents what we consider to be the current limitations of biomarkers in the diagnosis of AD, and on the basis of this evidence we propose recommendations for how biomarkers should and should not be used for diagnosis of AD in a clinical setting. We recommend that AD diagnosis be restricted to the occurrence of positive biomarkers together with specific AD phenotypes, whereas biomarker positive cognitively unimpaired individuals should be considered only at‐risk for progression to AD.
Overview
AI snapshot
Written from the paper’s full text.
TL;DR
The International Working Group argues that a purely biological ATN definition of Alzheimer’s disease is not ready for clinical diagnosis and recommends restricting Alzheimer’s disease diagnosis to people with both a specific Alzheimer’s disease clinical phenotype and positive amyloid and tau biomarkers. Biomarker-positive cognitively unimpaired individuals should be considered at-risk for progression, not clinically diagnosed with Alzheimer’s disease.
Key findings
- The IWG recommends a clinical–biological diagnosis: a specific Alzheimer’s disease phenotype plus amyloid-positive and tau-positive biomarker evidence; biomarker-positive cognitively unimpaired people should be classified as at-risk, not as having Alzheimer’s disease.
- A purely biological definition has low predictive accuracy: cognitively unimpaired biomarker-positive individuals often do not progress, and best current estimates of lifetime dementia risk range from 5% to 42%.
- Alzheimer’s pathology is commonly mixed: pure Alzheimer’s disease pathology is found in 3–30% of neuropathological series of people with dementia of the Alzheimer type, and 50–60% of Alzheimer’s-type dementia is estimated to be attributable to copathologies such as α-synucleinopathy, vascular pathology, non-Alzheimer’s tauopathies, and TDP-43 pathology.
- Practical biomarker limitations include artificial thresholds, limited generalisability, and accessibility; Cochrane reviews could not recommend routine CSF or amyloid PET use in clinical practice, plasma biomarkers are not currently recommended, and biomarker investigation in cognitively unimpaired individuals is not recommended.
Methods
- Design: a Personal View and consensus recommendations from the International Working Group, not a primary empirical study.
- Data or sample: no new primary sample is reported; the paper synthesises prior diagnostic frameworks, biomarker literature, neuropathology evidence, Cochrane reviews, and cohort findings.
- Analysis: narrative evidence synthesis leading to expert recommendations, including proposed diagnostic criteria, biomarker measures, and a risk-stratification proposal for cognitively unimpaired biomarker-positive individuals.
Limitations
- The paper states that a purely biological definition risks confusion between Alzheimer’s disease lesions and Alzheimer’s disease, has low predictive accuracy, is complicated by copathologies, and faces uncertain pathogenesis, threshold, generalisability, accessibility, and ethical problems.
- The paper states that current individualised prediction models do not work sufficiently well in cognitively unimpaired people compared with people in the prodromal stage, and that disclosing individual patient-level risk would be premature and is to be avoided.
- Evident from the text: as a Personal View, the recommendations are expert consensus rather than a systematic review or meta-analysis; the proposed risk stratification is a starting point for research and requires validation studies on large cohorts with long follow-up, as the paper itself notes.
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Claims the paper makes
33 Not checked yet · 13 Own interpretation · 1 Partly supported · 1 No basis given · accuracy not yet measured
In the paper
“For instance, cognitively unimpaired individuals can have biomarker evidence of both amyloid β and tau pathology but will often not develop clinical manifestations in their lifetime.”
- Also stated in: § Difficulty in classifying cognitively unimpaired biomarker-positive individuals · hedged
“Cognitively unimpaired individuals with biomarker positivity will not invariably experience subsequent cognitive decline; the best current estimates of lifetime dementia risk range from 5% to 42%.33”
§ Clinical diagnosis of Alzheimer’s disease: recommendations of the International Working Group > Abstract
What the sources say
- Not checked yetcites [33] Brookmeyer, 2018, Estimation of lifetime risks of Alzheimer's disease dementia using biomarkers for preclinical disease, Alzheimers Dement source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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- Also stated in: § Difficulty in classifying cognitively unimpaired biomarker-positive individuals · hedged
In the paper
“current individualised prediction models do not work sufficiently well in cognitively unimpaired people compared with people who are in the prodromal stage of Alzheimer’s disease.62”
§ Clinical diagnosis of Alzheimer’s disease: recommendations of the International Working Group > Limitations of a purely biological definition of Alzheimer’s disease > Difficulty in classifying cognitively unimpaired biomarker-positive individuals
What the sources say
- Not checked yetcites [62] van Maurik, 2019, Personalized risk for clinical progression in cognitively normal subjects-the ABIDE project, Alzheimers Res Ther source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“In 2018, the US National Institute on Aging and the Alzheimer’s Association proposed a purely biological definition of Alzheimer’s disease that relies on biomarkers.”
- Also stated in: § Introduction · plain
“In 2018, the US National Institute on Aging (NIA) and the Alzheimer’s Association (AA) proposed the amyloid β, tau, neurodegeneration (ATN) research framework for the definition and diagnosis of Alzheimer’s disease (for a glossary of terms, see panel 1).1”
§ Clinical diagnosis of Alzheimer’s disease: recommendations of the International Working Group > Abstract
What the sources say
- Not checked yetcites [1] Jack, 2018, NIA–AA research framework: toward a biological definition of Alzheimer's disease, Alzheimers Dement source
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § Introduction · plain
In the paper
“However, the follow-up of cognitively unimpaired biomarker-positive individuals suggests that the majority of these individuals do not progress over time (panel 2).”
§ Clinical diagnosis of Alzheimer’s disease: recommendations of the International Working Group > Limitations of a purely biological definition of Alzheimer’s disease > Uncertainty about the pathogenesis model of Alzheimer’s disease
What the sources say
- Not checked yetcites panel 2
hedged- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The relationship between the coexistence of tau and amyloid β pathology on the one hand, and the development of cognitive decline and neurodegeneration on the other hand, remain uncertain at an individual level.”
§ Clinical diagnosis of Alzheimer’s disease: recommendations of the International Working Group > Limitations of a purely biological definition of Alzheimer’s disease > Uncertainty about the pathogenesis model of Alzheimer’s disease
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Several studies (panel 2) indicate that the presence of both tau and amyloid β positivity is insufficient to definitively predict the occurrence of symptoms (mild cognitive impairment or dementia) in individuals without clinical impairment.”
§ Clinical diagnosis of Alzheimer’s disease: recommendations of the International Working Group > Limitations of a purely biological definition of Alzheimer’s disease > Low predictive accuracy
What the sources say
- Not checked yetcites panel 2
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Pure Alzheimer’s disease pathology is the exception rather than the rule (found in 3–30% of neuropathological series of people with dementia of the Alzheimer type, depending on age40) at post-mortem examination.”
§ Clinical diagnosis of Alzheimer’s disease: recommendations of the International Working Group > Limitations of a purely biological definition of Alzheimer’s disease > Presence of other pathologies
What the sources say
- Not checked yetcites [40] Robinson, 2018, Neurodegenerative disease concomitant proteinopathies are prevalent, age-related and APOE4-associated, Brain source
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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None of the sources cited for this claim have been checked yet.
In the paper
“50–60% of Alzheimer’s-type dementia (dementia defined clinically as Alzheimer’s disease) is estimated to be attributable to these copathologies.40,42–45”
§ Clinical diagnosis of Alzheimer’s disease: recommendations of the International Working Group > Limitations of a purely biological definition of Alzheimer’s disease > Presence of other pathologies
What the sources say
- Not checked yetcites [40] Robinson, 2018, Neurodegenerative disease concomitant proteinopathies are prevalent, age-related and APOE4-associated, Brain source
- Not checked yetcites [42] Yokota, 2018, Neuropathological comorbidity associated with argyrophilic grain disease, Neuropathology source
- Not checked yetcites [43] Ossenkoppele, 2020, Assessment of demographic, genetic, and imaging variables associated with brain resilience and cognitive resilience to pathological tau in patients with Alzheimer disease, JAMA Neurol source
- Not checked yetcites [44] Karanth, 2020, Prevalence and clinical phenotype of quadruple misfolded proteins in older adults, JAMA Neurol source
- Not checked yetcites [45] Nelson, 2019, Limbic-predominant age-related TDP-43 encephalopathy (LATE): consensus working group report, Brain source
hedgeddirect- Asserted: passes — The authors put it forward as true.
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- Based: passes — The paper gives a reason why it holds.
In the paper
“Furthermore, a positive Alzheimer’s disease pattern of biomarkers can be observed in other brain diseases in which Alzheimer’s disease pathology is present as a comorbidity.”
- Also stated in: § Presence of other pathologies · hedged
“Another challenge with using a biomarker-only diagnosis of Alzheimer’s disease is that the in-vivo presence of biomarkers of Alzheimer’s disease lesions could certify Alzheimer’s disease as the primary diagnosis, because such lesions are commonly found in people who have other neurodegenerative diseases, most often dementia with Lewy bodies.40”
§ Clinical diagnosis of Alzheimer’s disease: recommendations of the International Working Group > Abstract
What the sources say
- Not checked yetcites [40] Robinson, 2018, Neurodegenerative disease concomitant proteinopathies are prevalent, age-related and APOE4-associated, Brain source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § Presence of other pathologies · hedged
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Unfortunately, biomarkers are currently unavailable for the pathological changes that underlie the non-Alzheimer’s neurodegenerative diseases often found in people with dementia, and disentangling Alzheimer’s disease from other neurodegenerative diseases continues to depend on phenotype or postmortem examination.”
§ Clinical diagnosis of Alzheimer’s disease: recommendations of the International Working Group > Limitations of a purely biological definition of Alzheimer’s disease > Presence of other pathologies
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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- Rests on an assumption: Biomarkers are currently unavailable for the pathological changes that underlie the non-Alzheimer’s neurodegenerative diseases often found in people with dementia.
- It may state two separate claims as one. 19
- Probably not a substantial claim. 7
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The positivity of both amyloid and tau biomarkers is required because an amnestic phenotype with only amyloid positivity is not specific to Alzheimer’s disease and is seen in other neurodegenerative diseases with amyloid copathology (including LATE and dementia with Lewy bodies1,40,41,100) or in patients with cerebral amyloid angiopathy and amnestic vascular cognitive impairment101 (appendix p 2).”
§ Clinical diagnosis of Alzheimer’s disease: recommendations of the International Working Group > IWG recommendations for clinical diagnosis of Alzheimer’s disease
What the sources say
- Partly supportedcites [1] Jack, 2018, NIA–AA research framework: toward a biological definition of Alzheimer's disease, Alzheimers Dement sourceExperimental — accuracy not yet measured
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
- Partly supportedcites [40] Robinson, 2018, Neurodegenerative disease concomitant proteinopathies are prevalent, age-related and APOE4-associated, Brain sourceExperimental — accuracy not yet measured
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
- Partly supportedcites [41] McKeith, 2017, Diagnosis and management of dementia with Lewy bodies: fourth consensus report of the DLB Consortium, Neurology sourceExperimental — accuracy not yet measured
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
plaindirect- Asserted: passes — The authors put it forward as true.
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- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
None of the sources cited for this claim have been checked yet.
In the paper
“Most of all, this binary threshold does not reflect the reality of amyloid β and tau pathology, which is continuous and present at a minimal extent in almost all people older than 70 years,17 with important discrepancies between pathology burden and clinical symptoms at intermediate extents (panel 2).”
§ Clinical diagnosis of Alzheimer’s disease: recommendations of the International Working Group > Limitations of a purely biological definition of Alzheimer’s disease > Biomarker thresholds
What the sources say
- Not checked yetcites [17] Braak, 2011, Stages of the pathologic process in Alzheimer disease: age categories from 1 to 100 years, J Neuropathol Exp Neurol source
- Not checked yetcites panel 2
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The clear-cut separation between negative and positive patients in relation to a given biomarker is somewhat artificial and differs between sites and studies.”
§ Clinical diagnosis of Alzheimer’s disease: recommendations of the International Working Group > Limitations of a purely biological definition of Alzheimer’s disease > Biomarker thresholds
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In summary, amyloid β and tau biomarkers are not sufficient to confidently predict progression to prodromal Alzheimer’s disease or Alzheimer’s disease dementia, or to define a person’s position on the Alzheimer’s disease continuum, without clinical input.”
§ Clinical diagnosis of Alzheimer’s disease: recommendations of the International Working Group > Limitations of a purely biological definition of Alzheimer’s disease > Uncertainty about the pathogenesis model of Alzheimer’s disease
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Cognitively unimpaired individuals with biomarker positivity will not invariably experience subsequent cognitive decline; the best current estimates of lifetime dementia risk range from 5% to 42%.33”
§ Clinical diagnosis of Alzheimer’s disease: recommendations of the International Working Group > Limitations of a purely biological definition of Alzheimer’s disease > Difficulty in classifying cognitively unimpaired biomarker-positive individuals
What the sources say
- Not checked yetcites [33] Brookmeyer, 2018, Estimation of lifetime risks of Alzheimer's disease dementia using biomarkers for preclinical disease, Alzheimers Dement source
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
In the paper
“For physicians, Alzheimer’s disease equates with Alzheimer’s disease neuropathological changes, whereas for patients, Alzheimer’s disease equates with dementia, dependency, and death.”
§ Clinical diagnosis of Alzheimer’s disease: recommendations of the International Working Group > Limitations of a purely biological definition of Alzheimer’s disease > Ethical concerns
What the sources say
- Not checked yetcites [12] Frisoni, 2019, Re-aligning scientific and lay narratives of Alzheimer's disease, Lancet Neurol source
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“CSF investigation is prioritised because it provides simultaneous information on the two types of biomarkers (amyloid β and tau) and is less expensive than amyloid PET, tau PET, or both.”
§ Clinical diagnosis of Alzheimer’s disease: recommendations of the International Working Group > IWG recommendations for clinical diagnosis of Alzheimer’s disease
plaindirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. It may state two separate claims as one.
In the paper
“However, this increased sensitivity in the detection of cognitive decline comes at the expense of a reduced specificity, and numerous other causes than neurodegeneration or Alzheimer’s disease can be responsible for the observed changes, such as metabolic disorders, psychiatric disorders, or sleep apnoea.72”
§ Clinical diagnosis of Alzheimer’s disease: recommendations of the International Working Group > Limitations of a purely biological definition of Alzheimer’s disease > Biomarker thresholds
What the sources say
- Not checked yetcites [72] Chipi, 2019, Biomarker-based signature of alzheimer's disease in pre-MCI individuals, Brain Sci source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“Biomarker thresholds also depend on their intended use (eg, to identify the first signs of amyloid β pathology, or to predict the occurrence of clinical symptoms) and no consensus on the context of use (eg, in asymptomatic vs symptomatic individuals; in people who complain about subjective cognitive decline vs non-complainers) is currently available.1”
§ Clinical diagnosis of Alzheimer’s disease: recommendations of the International Working Group > Limitations of a purely biological definition of Alzheimer’s disease > Biomarker thresholds
What the sources say
- Not checked yetcites [1] Jack, 2018, NIA–AA research framework: toward a biological definition of Alzheimer's disease, Alzheimers Dement source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“In both situations, pathophysiological Alzheimer’s disease biomarkers can be positive.111”
§ Clinical diagnosis of Alzheimer’s disease: recommendations of the International Working Group > IWG recommendations for clinical diagnosis of Alzheimer’s disease
What the sources say
- Not checked yetcites [111] Niemantsverdriet, 2018, Added diagnostic value of cerebrospinal fluid biomarkers for differential dementia diagnosis in an autopsy-confirmed cohort, J Alzheimers Dis source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“As shown in panel 2, the effect of biomarker positivity on clinical progression remains weak to moderate and was established using selected volunteers from research cohorts.”
§ Clinical diagnosis of Alzheimer’s disease: recommendations of the International Working Group > Limitations of a purely biological definition of Alzheimer’s disease > Generalisability and accessibility in clinical practice
What the sources say
- Not checked yetcites panel 2
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“This deep difference in use and understanding of the term can adversely affect the therapeutic alliance.12”
§ Clinical diagnosis of Alzheimer’s disease: recommendations of the International Working Group > Limitations of a purely biological definition of Alzheimer’s disease > Ethical concerns
What the sources say
- Not checked yetcites [12] Frisoni, 2019, Re-aligning scientific and lay narratives of Alzheimer's disease, Lancet Neurol source
plainconditional- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim.
None of the sources cited for this claim have been checked yet.
In the paper
“The current in-vivo detection of tau positivity using 18F-flortaucipir PET seems to correspond only to widespread tau pathology in the brain (ie, Braak stages ≥IV),69 whereas CSF phosphorylated tau elevation can reflect earlier stages of tauopathy.70”
§ Clinical diagnosis of Alzheimer’s disease: recommendations of the International Working Group > Limitations of a purely biological definition of Alzheimer’s disease > Biomarker thresholds
What the sources say
- Not checked yetcites [69] Fleisher, 2020, Positron emission tomography imaging with [18F]flortaucipir and postmortem assessment of Alzheimer disease neuropathologic changes, JAMA Neurol source
- Not checked yetcites [70] Mattsson-Carlgren, 2020, Aβ deposition is associated with increases in soluble and phosphorylated tau that precede a positive tau PET in Alzheimer's disease, Sci Adv source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“If a person decides to receive the results and the results are positive, they should be counselled that they are at risk for subsequent clinical progression to prodromal Alzheimer’s disease or Alzheimer’s disease dementia, but are not clinically diagnosed as having Alzheimer’s disease.”
§ Clinical diagnosis of Alzheimer’s disease: recommendations of the International Working Group > IWG recommendations for clinical diagnosis of Alzheimer’s disease
plaincorrelational- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim.
In the paper
“As underscored by the Cochrane reviews, the prognostic value of a diagnosis based on biomarkers remains limited, first because there is a high variability of decline rate among individuals with biomarker-positive Alzheimer’s disease,79 and second because non-Alzheimer’s disease neurodegenerative diseases contribute to cognitive decline.”
§ Clinical diagnosis of Alzheimer’s disease: recommendations of the International Working Group > Limitations of a purely biological definition of Alzheimer’s disease > Generalisability and accessibility in clinical practice
What the sources say
- Not checked yetcites [79] Jang, 2019, Prediction of fast decline in amyloid positive mild cognitive impairment patients using multimodal biomarkers, Neuroimage Clin source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In symptomatic patients, the identification of the specific clinical phenotype (interfering or not with independence in everyday activities) is a major step in diagnosis, because it expresses the brain dysfunction that the biomarkers are signalling.”
§ Clinical diagnosis of Alzheimer’s disease: recommendations of the International Working Group > Limitations of a purely biological definition of Alzheimer’s disease > Difficulty in classifying cognitively unimpaired biomarker-positive individuals
plaindirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim.
None of the sources cited for this claim have been checked yet.
In the paper
“Subjective cognitive decline might be a risk factor of clinical progression,24 but the ability of subjective cognitive decline to predict progression to objective cognitive decline (ie, mild cognitive decline, or dementia, or both) remains low (OR 1·5–3·081).”
§ Clinical diagnosis of Alzheimer’s disease: recommendations of the International Working Group > Limitations of a purely biological definition of Alzheimer’s disease > Generalisability and accessibility in clinical practice
What the sources say
- Not checked yetcites [24] Ebenau, 2020, ATN classification and clinical progression in subjective cognitive decline: the SCIENCe project, Neurology source
- Not checked yetcites [81] Slot, 2019, Subjective cognitive decline and rates of incident Alzheimer's disease and non-Alzheimer's disease dementia, Alzheimers Dement source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“However, an isolated amnestic syndrome of the hippocampal type with only tau biomarker positivity can occur in primary age-related tauopathy37,38 or in atypical presentations of mixed 3 repeat or 4 repeat tau frontotemporal lobar degeneration100,102 (appendix p 2).”
§ Clinical diagnosis of Alzheimer’s disease: recommendations of the International Working Group > IWG recommendations for clinical diagnosis of Alzheimer’s disease
What the sources say
- Not checked yetcites [37] Toledo, 2015, Alzheimer's disease cerebrospinal fluid biomarker in cognitively normal subjects, Brain source
- Not checked yetcites [38] Bell, 2019, Neuropathologic, genetic, and longitudinal cognitive profiles in primary age-related tauopathy (PART) and Alzheimer's disease, Alzheimers Dement source
- Not checked yetcites [100] Villain, 2019, Alzheimer's disease including focal presentations, Semin Neurol source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“Subjective memory complaints and subjective cognitive decline, if isolated and not supported by objective cognitive impairment, are not specific enough to be considered part of the Alzheimer’s disease phenotype.109”
§ Clinical diagnosis of Alzheimer’s disease: recommendations of the International Working Group > IWG recommendations for clinical diagnosis of Alzheimer’s disease
What the sources say
- Not checked yetcites [109] Jessen, 2020, Prediction of dementia of Alzheimer type by different types of subjective cognitive decline, Alzheimers Dement source
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“individuals included in such longitudinal cohorts are usually recruited by advertisement and do not represent the variety of individuals to whom the biomarker investigations would be applied in clinical practice.”
§ Clinical diagnosis of Alzheimer’s disease: recommendations of the International Working Group > Limitations of a purely biological definition of Alzheimer’s disease > Generalisability and accessibility in clinical practice
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In clinical practice, such an extension to earlier thresholds in amyloid or tau biomarkers might lengthen the duration of the asymptomatic stages and decrease the lifetime probability of clinical progression.”
§ Clinical diagnosis of Alzheimer’s disease: recommendations of the International Working Group > Limitations of a purely biological definition of Alzheimer’s disease > Biomarker thresholds
hedgedconditional- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Overall, evidence for the use of biomarkers in clinical practice remains highly disputed and suffers from a dearth of evidence-based data to recommend biomarker assessments for cognitively unimpaired individuals.”
§ Clinical diagnosis of Alzheimer’s disease: recommendations of the International Working Group > Limitations of a purely biological definition of Alzheimer’s disease > Generalisability and accessibility in clinical practice
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Although the definition of Alzheimer’s disease based exclusively on biological markers has gained substantial traction in research settings, emerging studies suggest that the biomarker definition is not ready for application in clinical settings and for diagnosis of individuals without cognitive impairment.”
§ Clinical diagnosis of Alzheimer’s disease: recommendations of the International Working Group > Conclusion
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper relies on this without support.
A specific clinical phenotype of Alzheimer’s disease can be reliably identified in clinical practice.
“It requires the presence of both a specific clinical phenotype of Alzheimer’s disease (phenotype positive) and biomarker evidence of Alzheimer’s disease pathology (amyloid-positive and tau positive).”
The paper relies on this without support.
Biomarkers are currently unavailable for the pathological changes that underlie the non-Alzheimer’s neurodegenerative diseases often found in people with dementia.
“Unfortunately, biomarkers are currently unavailable for the pathological changes that underlie the non-Alzheimer’s neurodegenerative diseases often found in people with dementia, and disentangling Alzheimer’s disease from other neurodegenerative diseases continues to depend on phenotype or postmortem examination.”
The paper relies on this without support.
In some complex cases, only post-mortem evaluation will provide definitive information about whether Alzheimer's disease is the primary pathology or a copathology.
“In some complex cases, only post-mortem evaluation will provide definitive information.”
The paper relies on this without support.
Biomarker investigations can be limited by the availability, cost, and health-care payment coverage of biomarkers across countries, centres, and clinical situations.
“Biomarker investigations can also be limited by the availability, cost, and health-care payment coverage of biomarkers across countries, centres, and clinical situations.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Disease onset can occur at < 65 (familial early-onset) or > 65 years of age (sporadic late-onset), with the latter afflicting more than 95% of patients [87, 213]”
From Microglia and monocytes in inflammatory CNS disease: integrating phenotype and function (2022) · cites this paper as [87]
Experimental — accuracy not yet measuredIn the citing paper
“In 2021, new recommendations for the clinical diagnosis of AD were proposed by the International working group, highlighting that the diagnosis of AD should be restricted to people who have positive biomarkers together with specific AD phenotypes. Cognitively unimpaired individuals who are only positive to biomarkers should be considered at-risk for progression to AD [10].”
From Role of Oxidative Damage in Alzheimer’s Disease and Neurodegeneration: From Pathogenic Mechanisms to Biomarker Discovery (2021) · cites this paper as [10]
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BackgroundSelf-citationClinicopathological correlations in corticobasal degeneration
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“Other phenotypes, including the behavioural/dysexecutive variant 70,71 , the cortico-basal variant 72,73 , and the other variants of primary progressive aphasia 69,74 (Supplementary Figure 1), are less commonly related to AD pathology (uncommon AD phenotypes).”
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“Such modelling is in its early stages but exemplified through the example of age adjusted polygenic hazard scores 33 .”
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BackgroundJack, C. R., Wiste, H. J., Therneau, T. M., Weigand, S. D., Knopman, D. S., Mielke, M. M., Lowe, V. J., Vemuri, P., Machulda, M. M., Schwarz, C. G., et al. (2019) · JAMA · doi:10.1001/jama.2019.7437 · Cited by 324 · cited 4×
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Self-citationClinicopathological correlations in behavioural variant frontotemporal dementia
Perry, D. C., Brown, J. A., Possin, K. L., Datta, S., Trujillo, A., Radke, A., Karydas, A., Kornak, J., Sias, A. C., Rabinovici, G. D., et al. (2017) · Brain · doi:10.1093/brain/awx254 · Cited by 309 · cited 3×
“Other phenotypes, including the behavioural/dysexecutive variant 70,71 , the cortico-basal variant 72,73 , and the other variants of primary progressive aphasia 69,74 (Supplementary Figure 1), are less commonly related to AD pathology (uncommon AD phenotypes).”
BackgroundSelf-citationSubjective memory complaints in elders: depression, anxiety, or cognitive decline?
Balash, Y., Mordechovich, M., Shabtai, H., Giladi, N., Gurevich, T., & Korczyn, A. D. (2012) · Acta Neurologica Scandinavica · doi:10.1111/ane.12038 · Cited by 290 · cited 1×
“SCD may result from many factors besides aging: anxiety, depression, fatigue, sleep disorders, attention deficits, and drug side effects amongst others 57 .”
BackgroundThe impact of amyloid‐beta and tau on prospective cognitive decline in older individuals
Sperling, R. A., Mormino, E. C., Schultz, A. P., Betensky, R. A., Papp, K. V., Amariglio, R. E., Hanseeuw, B. J., Buckley, R., Chhatwal, J., Hedden, T., et al. (2019) · Annals of Neurology · doi:10.1002/ana.25395 · Cited by 286
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Self-citationDubois, B., Epelbaum, S., Nyasse, F., Bakardjian, H., Gagliardi, G. P., Uspenskaya, O., Houot, M., Lista, S., Cacciamani, F., Potier, M., et al. (2018) · The Lancet Neurology · doi:10.1016/s1474-4422(18)30029-2 · Cited by 253
Self-citationSmailagic, N., Vacante, M., Hyde, C., Martin, S., Ukoumunne, O. C., & Sachpekidis, C. (2015) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd010632.pub2 · Cited by 235
Ritchie, C. W., Smailagic, N., Noel-Storr, A. H., Ukoumunne, O. C., Ladds, E. C., & Martin, S. (2017) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd010803.pub2 · Cited by 217
Raj, A., LoCastro, E., Kuceyeski, A. F., Tosun, D., Relkin, N. R., & Weiner, M. W. (2015) · Cell Reports · doi:10.1016/j.celrep.2014.12.034 · Cited by 210 · cited 1×
“***** In apparent contradiction of the widely accepted disease model where the accumulation of brain amyloid lesions triggers the fast spreading of tau lesions outside the medial temporal lobes 103 .”
BackgroundBurnham, S. C., Bourgeat, P., Doré, V., Savage, G., Brown, B., Laws, S., Maruff, P., Salvado, O., Ames, D., Martins, R. N., et al. (2016) · The Lancet Neurology · doi:10.1016/s1474-4422(16)30125-9 · Cited by 207 · cited 1×
“…to an overall cognitive decline although a majority of (A+) subjects remain cognitively stable over time even after several years 42,55,83,84,94–99 83,84 , even more in case of (SCD) 55 ; - Longitudinal tau PET studies showed no or only minimal acceleration of tau tracer uptake in the…”
BackgroundSelf-citationParnetti, L., Chipi, E., Salvadori, N., D’Andrea, K., & Eusebi, P. (2019) · Alzheimer s Research & Therapy · doi:10.1186/s13195-018-0459-7 · Cited by 206
Prevalence and clinical phenotype of quadruple misfolded proteins in older adults
Karanth, S., Nelson, P. T., Katsumata, Y., Kryscio, R. J., Schmitt, F. A., Fardo, D. W., Cykowski, M. D., Jicha, G. A., Van Eldik, L. J., & Abner, E. L. (2020) · JAMA Neurology · doi:10.1001/jamaneurol.2020.1741 · Cited by 206
Prevalence of amyloid‐β pathology in distinct variants of primary progressive aphasia
Bergeron, D., Gorno‐Tempini, M. L., Rabinovici, G. D., Santos‐Santos, M. A., Seeley, W., Miller, B. L., Pijnenburg, Y., Keulen, M. A., Groot, C., van Berckel, B. N. M., et al. (2018) · Annals of Neurology · doi:10.1002/ana.25333 · Cited by 203 · cited 4×
“Other phenotypes, including the behavioural/dysexecutive variant 70,71 , the cortico-basal variant 72,73 , and the other variants of primary progressive aphasia 69,74 (Supplementary Figure 1), are less commonly related to AD pathology (uncommon AD phenotypes).”
BackgroundInfluentialSelf-citationATN classification and clinical progression in subjective cognitive decline: The SCIENCe project
Ebenau, J. L., Timmers, T., Wesselman, L. M. P., Verberk, I. M. W., Verfaillie, S. C. J., Slot, R. E. R., van Harten, A. C., Teunissen, C. E., Barkhof, F., van den Bosch, K. A., et al. (2020) · Neurology · doi:10.1212/wnl.0000000000009724 · Cited by 191 · cited 8×
“SMC and SCD, when isolated and not supported by objective cognitive impairment, are not specific enough to be considered as part of the AD phenotype 85 .”
BackgroundInfluentialThe genes associated with early-onset Alzheimer’s disease
Dai, M.-H., Zheng, H., Zeng, L.-D., & Zhang, Y. (2017) · Oncotarget · doi:10.18632/oncotarget.23738 · Cited by 178 · cited 1×
“…a risk stratification of biomarkers is proposed (Panel 3) distinguishing an absolute risk group (carriers of autosomal dominant monogenic mutations for AD) 82 , a high-risk group 42 , and an undefined risk group, to be further clarified in the future as additional evidence accrues 55,83,84 .”
BackgroundHamelin, L., Lagarde, J., Dorothée, G., Potier, M. C., Corlier, F., Kuhnast, B., Caillé, F., Dubois, B., Fillon, L., Chupin, M., et al. (2018) · Brain · doi:10.1093/brain/awy079 · Cited by 177 · cited 1×
“Alzheimer’s disease can be associated with other brain pathologies, including synucleinopathy 28 , vascular pathology, non-AD tauopathies, and TDP-43 pathology 12–15 .”
BackgroundSelf-citationBrookmeyer, R., & Abdalla, N. (2018) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2018.03.005 · Cited by 176
Ritchie, C. W., Smailagic, N., Noel-Storr, A. H., Takwoingi, Y., Flicker, L. A., Mason, S., & McShane, R. H. (2014) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd008782.pub4 · Cited by 167
The Myth of Alzheimer's: What You Aren't Being Told About Today's Most Dreaded Diagnosis
Whitehouse, P. J., & George, D. R. (2008) · Cited by 164
Ossenkoppele, R., Lyoo, C. H., Jester-Broms, J., Sudre, C. H., Cho, H., Ryu, Y. H., Choi, J. Y., Smith, R., Strandberg, O., Palmqvist, S., et al. (2020) · JAMA Neurology · doi:10.1001/jamaneurol.2019.5154 · Cited by 161
Potentially reversible conditions in 1000 consecutive memory clinic patients
Hejl, A. (2002) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.73.4.390 · Cited by 153 · cited 1×
“They represent up to 20-30% of new patients in some specialty memory clinics 59–61 and in some of these cases, biomarker investigations may have been performed.”
BackgroundSubjective cognitive decline: self and informant comparisons
Caselli, R. J., Chen, K., Locke, D. E. C., Lee, W., Roontiva, A., Bandy, D., Fleisher, A. S., & Reiman, E. M. (2014) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2013.01.003 · Cited by 145 · cited 1×
“In cognitively unimpaired individuals, self-reported complaints and complaints reported by an informant should be clearly distinguished as the latter are more at-risk of progression 86 and merit a closer follow-up with regular clinical and neuropsychological evaluations.”
BackgroundAlzheimer's disease cerebrospinal fluid biomarker in cognitively normal subjects
Toledo, J. B., Zetterberg, H., van Harten, A. C., Glodzik, L., Martinez-Lage, P., Bocchio-Chiavetto, L., Rami, L., Hansson, O., Sperling, R., Engelborghs, S., et al. (2015) · Brain · doi:10.1093/brain/awv199 · Cited by 136 · cited 2×
“On the other hand, an isolated amnestic syndrome of the hippocampal type with only tau biomarker positivity can be encountered in primary age-related tauopathy (PART) 77,78 or in atypical presentations of mixed 3R/4R frontotemporal lobar degeneration (FTLD) tau 75,79 (Supplementary Figure 1).”
BackgroundResultSelf-citationDetermining clinically meaningful decline in preclinical Alzheimer disease
Insel, P. S., Weiner, M., Mackin, R. S., Mormino, E., Lim, Y. Y., Stomrud, E., Palmqvist, S., Masters, C. L., Maruff, P. T., Hansson, O., et al. (2019) · Neurology · doi:10.1212/wnl.0000000000007831 · Cited by 128 · cited 1×
“…bias from these data is strong, especially in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort with many individuals lost to follow-up 54 , and the risk of selection bias is even stronger since individuals included in these longitudinal cohorts were usually selected by advertisement…”
BackgroundPredicting progression from normal cognition to mild cognitive impairment for individuals at 5 years
Albert, M., Zhu, Y., Moghekar, A., Mori, S., Miller, M. I., Soldan, A., Pettigrew, C., Selnes, O., Li, S., & Wang, M.-C. (2018) · Brain · doi:10.1093/brain/awx365 · Cited by 118
The implications of different approaches to define AT(N) in Alzheimer disease
Mattsson-Carlgren, N., Leuzy, A., Janelidze, S., Palmqvist, S., Stomrud, E., Strandberg, O., Smith, R., & Hansson, O. (2020) · Neurology · doi:10.1212/wnl.0000000000009485 · Cited by 114 · cited 1×
“On the other hand, an isolated amnestic syndrome of the hippocampal type with only tau biomarker positivity can be encountered in primary age-related tauopathy (PART) 77,78 or in atypical presentations of mixed 3R/4R frontotemporal lobar degeneration (FTLD) tau 75,79 (Supplementary Figure 1).”
BackgroundAlzheimer's disease including focal presentations
Villain, N., & Dubois, B. (2019) · Seminars in Neurology · doi:10.1055/s-0039-1681041 · Cited by 113 · cited 2×
“On the other hand, an isolated amnestic syndrome of the hippocampal type with only tau biomarker positivity can be encountered in primary age-related tauopathy (PART) 77,78 or in atypical presentations of mixed 3R/4R frontotemporal lobar degeneration (FTLD) tau 75,79 (Supplementary Figure 1).”
BackgroundSelf-citationBell, W. R., An, Y., Kageyama, Y., English, C., Rudow, G. L., Pletnikova, O., Thambisetty, M., O'Brien, R., Moghekar, A. R., Albert, M. S., et al. (2019) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2018.07.215 · Cited by 111 · cited 3×
“On the other hand, an isolated amnestic syndrome of the hippocampal type with only tau biomarker positivity can be encountered in primary age-related tauopathy (PART) 77,78 or in atypical presentations of mixed 3R/4R frontotemporal lobar degeneration (FTLD) tau 75,79 (Supplementary Figure 1).”
BackgroundResultPrevalence, incidence and duration of Braak's stages in the general population: can we know?
Duyckaerts, C., & Hauw, J.-J. (1997) · Neurobiology of Aging · doi:10.1016/s0197-4580(97)00047-x · Cited by 109 · cited 2×
“ Neurofibrillary tangles in the medial temporal regions are found in almost all cognitively unimpaired individual over 70 years old 18,41”
BackgroundIdentifying Changepoints in Biomarkers During the Preclinical Phase of Alzheimer’s Disease
Laurent Younes, B., Albert, M., Moghekar, A., Soldan, A., Pettigrew, C. A., & Miller, M. I. (2019) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2019.00074 · Cited by 93 · cited 3×
“…a risk stratification of biomarkers is proposed (Panel 3) distinguishing an absolute risk group (carriers of autosomal dominant monogenic mutations for AD) 82 , a high-risk group 42 , and an undefined risk group, to be further clarified in the future as additional evidence accrues 55,83,84 .”
BackgroundSadikki, H., Fayossé, A., Cognat, E., Sabia, S., Engelborghs, S., Wallon, D., Alexopoulos, P., Blennow, K., Zetterberg, H., Parnetti, L., et al. (2019) · PLoS Medicine · doi:10.1371/journal.pmed.1003289 · Cited by 87
Self-citationOn the reconceptualization of Alzheimer’s disease
Schermer, M., & Richard, E. (2018) · Bioethics · doi:10.1111/bioe.12516 · Cited by 77
Antonell, A., Tort‐Merino, A., Ríos, J., Balasa, M., Borrego‐Écija, S., Auge, J. M., Muñoz‐García, C., Bosch, B., Falgàs, N., Rami, L., et al. (2019) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2019.09.001 · Cited by 76 · cited 1×
“…are low CSF A 42, increased CSF A 40/42 ratio (which is, if possible, preferred to low CSF Aβ42), or increased tracer retention in amyloid PET; for tau pathology, we recommend high CSF p-tau (not total tau [t-tau] due to its lack of specificity 80 ) or increased ligand retention in tau PET.”
BackgroundSelf-citationSubjective cognitive decline and β-amyloid burden predict cognitive change in healthy elderly
Vogel, J. W., Doležalová, M. V., Joie, R. L., Marks, S. M., Schwimmer, H., Landau, S. M., & Jagust, W. J. (2017) · Neurology · doi:10.1212/wnl.0000000000004627 · Cited by 75
Iacono, D., Resnick, S. M., O’Brien, R., Zonderman, A. B., An, Y., Pletnikova, O., Rudow, G., Crain, B., & Troncoso, J. C. (2014) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0000000000000052 · Cited by 73
Mozersky, J. T., Sankar, P. L., Harkins, K. A., Hachey, S. M., & Karlawish, J. H. (2017) · JAMA Neurology · doi:10.1001/jamaneurol.2017.2954 · Cited by 72 · cited 1×
“Recent experience with the Sokrates study underscores some of the uncertainties (e.g. inability to make an accurate short-or medium-term prediction about cognitive decline for an individual), which are inherent in revealing amyloid PET results alone to cognitively unimpaired individuals 62 .”
BackgroundYu, J., Li, J., Suckling, J., Feng, L., Pan, A., Wang, Y., Song, B., Zhu, S., Li, D., Wang, H.-F., et al. (2019) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2019.05.006 · Cited by 72 · cited 3×
“…to an overall cognitive decline although a majority of (A+) subjects remain cognitively stable over time even after several years 42,55,83,84,94–99 83,84 , even more in case of (SCD) 55 ; - Longitudinal tau PET studies showed no or only minimal acceleration of tau tracer uptake in the following 1…”
BackgroundLiebsch, F., Kulic, L., Teunissen, C., Shobo, A., Ulku, I., Engelschalt, V., Hancock, M. A., van der Flier, W. M., Kunach, P., Rosa-Neto, P., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-10152-w · Cited by 68 · cited 1×
“In CSF, a positive amyloid measure despite a negative amyloid PET or the use of novel biomarkers (for instance, CSF A 34/42 ratio 39 ) might also prove to be reliable biomarkers of early amyloid deposition stages 39,40 .”
BackgroundZhang, S., Smailagic, N., Hyde, C., Noel-Storr, A. H., Takwoingi, Y., McShane, R., & Feng, J. (2014) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd010386.pub2 · Cited by 66
Vig, P. J. S., Lu, D., Paul, A. M., et al. (2018) · Brain Sciences · doi:10.3390/brainsci9010001 · Cited by 63
Martínez, G., Vernooij, R. W. M., Padilla, P. F., Zamora, J., Bonfill, X., & Flicker, L. A. (2017) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd012216.pub2 · Cited by 62
Endosomal recycling reconciles the Alzheimer's disease paradox
Small, S. A., & Petsko, G. A. (2020) · Science Translational Medicine · doi:10.1126/scitranslmed.abb1717 · Cited by 60 · cited 1×
“Besides the dominating amyloid cascade model, additional pathogenesis models have been advanced, including the role of endosomal recycling deficiency 21 , of immunity, of lipid metabolism and endocytosis deficiency 22 , of vascular dysfunction 23 , etc.”
BackgroundMartínez, G., Vernooij, R. W. M., Padilla, P. F., Zamora, J., Flicker, L. A., & Bonfill, X. (2017) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd012884 · Cited by 56
Timmers, T., Ossenkoppele, R., Wolters, E. E., Verfaillie, S. C. J., Visser, D., Golla, S. S. V., Barkhof, F., Scheltens, P., Boellaard, R., van der Flier, W. M., et al. (2019) · Alzheimer s Research & Therapy · doi:10.1186/s13195-019-0510-3 · Cited by 55
Personalized risk for clinical progression in cognitively normal subjects-the ABIDE project
Initiative, F. T. A. D. N., van Maurik, I. S., Slot, R. E. R., Verfaillie, S. C. J., Zwan, M. D., Bouwman, F. H., Prins, N. D., Teunissen, C. E., Scheltens, P., Barkhof, F., et al. (2019) · Alzheimer's Research & Therapy · doi:10.1186/s13195-019-0487-y · Cited by 47
Jang, H., Park, J., Woo, S., Kim, S., Kim, H. J., Na, D. L., Lockhart, S. N., Kim, Y., Kim, K. W., Cho, S. H., et al. (2019) · NeuroImage Clinical · doi:10.1016/j.nicl.2019.101941 · Cited by 46 · cited 1×
“As underscored by the Cochrane reviews, the prognostic value of biomarker diagnosis remains limited by the fact that 1) there is a high variability of decline rate amongst biomarker-positive AD patients 53 and 2) non-AD neurodegenerative diseases contribute to cognitive decline.”
BackgroundMartínez, G., Vernooij, R. W. M., Padilla, P. F., Zamora, J., Flicker, L. A., & Bonfill, X. (2017) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd012883 · Cited by 44
Re-aligning scientific and lay narratives of Alzheimer's disease
Frisoni, G. B., Ritchie, C., Carrera, E., Nilsson, P., Ousset, P.-J., Molinuevo, J. L., Dubois, B., Scheltens, P., & Minoshima, S. (2019) · The Lancet Neurology · doi:10.1016/s1474-4422(19)30323-0 · Cited by 39 · cited 3×
“These 2016 consensus meeting and 2018 criteria 1,7 have engendered significant debate about applying a biomarker-based disease diagnosis, with clinical symptoms and phenotype being used only for staging 9,10 .”
BackgroundSelf-citationNeuropathological comorbidity associated with argyrophilic grain disease
Yokota, O., Miki, T., Ikeda, C., Nagao, S., Takenoshita, S., Ishizu, H., Haraguchi, T., Kuroda, S., Terada, S., & Yamada, N. (2018) · Neuropathology · doi:10.1111/neup.12429 · Cited by 38
Prediction of dementia of Alzheimer type by different types of subjective cognitive decline
Jessen, F., Kleineidam, L., Wolfsgruber, S., Bickel, H., Brettschneider, C., Fuchs, A., Kaduszkiewicz, H., König, H., Mallon, T., Mamone, S., et al. (2020) · Alzheimer's & Dementia · doi:10.1002/alz.12163 · Cited by 37 · cited 1×
“SMC and SCD, when isolated and not supported by objective cognitive impairment, are not specific enough to be considered as part of the AD phenotype 85 .”
BackgroundElevated medial temporal lobe and pervasive brain tau‐PET signal in normal participants
Lowe, V. J., Bruinsma, T. J., Min, H.-K. P., Lundt, E. S., Fang, P., Senjem, M. L., Boeve, B. F., Josephs, K. A., Pandey, M. K., Murray, M. E., et al. (2018) · Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring · doi:10.1016/j.dadm.2018.01.005 · Cited by 32
Toward common mechanisms for risk factors in Alzheimer's syndrome
Medina, M., Khachaturian, Z. S., Rossor, M. N., Ávila, J., & Cedazo-Mı́nguez, Á. (2017) · Alzheimer s & Dementia Translational Research & Clinical Interventions · doi:10.1016/j.trci.2017.08.009 · Cited by 30 · cited 1×
“…pathways (genetic protection and risk factors regarding tau binding proteins and amyloid precursor protein metabolism; protection and risk factors related to immunity, endocytosis, and lipid metabolism 26–30 ; newly described brain cellular senescence mechanisms 31 ), and co-pathology.”
BackgroundSwanson, C. J., Zhang, Y., Dhadda, S., Wang, J., Kaplow, J. M., Lai, R. Y. K., Lannfelt, L., Kramer, L. D., & Luthman, J. (2018) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2018.07.009 · Cited by 28
Biomarker-based signature of alzheimer's disease in pre-MCI individuals
Chipi, E., Salvadori, N., Farotti, L., & Parnetti, L. (2019) · Brain Sciences · doi:10.3390/brainsci9090213 · Cited by 27 · cited 1×
“However, this increased sensitivity in the detection of cognitive decline comes at the expense of a reduced specificity, and numerous other etiologies can be responsible for the observed changes, such as personality traits, psychiatric disorders, and sleep apnea amongst others 46 .”
BackgroundEpelbaum, S., Paquet, C., Hugon, J., Dumurgier, J., Wallon, D., Hannequin, D., Jonveaux, T., Besozzi, A., Pouponneau, S., Hommet, C., et al. (2019) · BMJ Open · doi:10.1136/bmjopen-2019-029663 · Cited by 24
Self-citationVerity, R., Kirk, A., O’Connell, M. E., Karunanayake, C. P., & Morgan, D. (2017) · Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques · doi:10.1017/cjn.2017.267 · Cited by 22 · cited 1×
“They represent up to 20-30% of new patients in some specialty memory clinics 59–61 and in some of these cases, biomarker investigations may have been performed.”
BackgroundNiemantsverdriet, E., Feyen, B. F. E., Le Bastard, N., Martin, J.-J., Goeman, J., De Deyn, P. P., Bjerke, M., & Engelborghs, S. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-170927 · Cited by 19 · cited 1×
“In both situations, pathophysiological AD biomarkers can be positive 87 .”
BackgroundGenetic Comparison of Symptomatic and Asymptomatic Persons With Alzheimer Disease Neuropathology
Monsell, S. E., Mock, C., Fardo, D. W., Bertelsen, S. E., Cairns, N. J., Roe, C. M., Ellingson, S. R., Morris, J. C., Goate, A., & Kukull, W. A. (2016) · Alzheimer Disease & Associated Disorders · doi:10.1097/wad.0000000000000179 · Cited by 18
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“10.”
BackgroundSelf-citationCerebral Amyloid Angiopathy: Report of Two Cases
Pala, E. E., Bayol, Ü., Türelik, Ö., et al. (2012) · Turkiye Klinikleri Journal of Neurology · Cited by 1
Cited by
Sorted by citations
Revised criteria for diagnosis and staging of Alzheimer's disease: Alzheimer's Association Workgroup
Jack, C. R., Andrews, J. S., Beach, T. G., Buracchio, T., Dunn, B., Graf, A., Hansson, O., Ho, C., Jagust, W., McDade, E., et al. (2024) · Alzheimer's & Dementia · doi:10.1002/alz.13859 · Cited by 2,803
“158,159 Differentphenotypesoftenoverlapwithin an individual, and the severity of impairment within each domain can be variable.”
Alzheimer’s Disease: Epidemiology and Clinical Progression
Tahami Monfared, A. A., Byrnes, M. J., White, L. A., & Zhang, Q. (2022) · Neurology and Therapy · doi:10.1007/s40120-022-00338-8 · Cited by 629
“However, the International Working Group recommended against widespread biomarker testing of cognitively unimpaired individuals [21].”
BackgroundHansson, O., Edelmayer, R. M., Boxer, A. L., Carrillo, M. C., Mielke, M. M., Rabinovici, G. D., Salloway, S., Sperling, R., Zetterberg, H., & Teunissen, C. E. (2022) · Alzheimer's & Dementia · doi:10.1002/alz.12756 · Cited by 607
“Further, the CSF criteria also suggest using AD biomarkers in patients with SCD at increased risk of AD, but there is an ongoing debate on the clinical use of biomarkers in patients without objective cognitive impairment such as in SCD. 93 Naturally, patients with cognitive symp-tomsshouldundergorelevantclinicalassess…”
BackgroundSelf-citationOssenkoppele, R., Pichet Binette, A., Groot, C., Smith, R., Strandberg, O., Palmqvist, S., Stomrud, E., Tideman, P., Ohlsson, T., Jögi, J., et al. (2022) · Nature Medicine · doi:10.1038/s41591-022-02049-x · Cited by 496
Self-citationAlzheimer Disease as a Clinical-Biological Construct—An International Working Group Recommendation
Dubois, B., Villain, N., Schneider, L., Fox, N., Campbell, N., Galasko, D., Kivipelto, M., Jessen, F., Hanseeuw, B., Boada, M., et al. (2024) · JAMA Neurology · doi:10.1001/jamaneurol.2024.3770 · Cited by 426
Self-citation
Metadata
- Authors
- Dubois, B., Villain, N., Frisoni, G. B., Rabinovici, G. D., Sabbagh, M., Cappa, S., Bejanin, A., Bombois, S., Epelbaum, S., Teichmann, M., Habert, M.-O., Nordberg, A., Blennow, K., Galasko, D., Stern, Y., Rowe, C. C., Salloway, S., Schneider, L. S., Cummings, J. L., & Feldman, H. H.
- Affiliations
- Sorbonne Université (FR)
- University of Geneva (CH)
- University of California, San Francisco (US)
- Cleveland Clinic (US)
- Istituto Universitario di Studi Superiori di Pavia (IT)
- Universitat Autònoma de Barcelona (ES)
- Inserm (FR)
- Institut national de recherche en sciences et technologies du numérique (FR)
- Centre National de la Recherche Scientifique (FR)
- Karolinska University Hospital (SE)
- Sahlgrenska University Hospital (SE)
- University of California San Diego (US)
- Columbia University (US)
- The University of Melbourne (AU)
- Brown University (US)
- University of Southern California (US)
- Corresponding author
- Dubois, Bruno
- ORCID
- Dubois, Bruno
- Villain, Nicolas
- Frisoni, Giovanni B
- Rabinovici, Gil D
- Cappa, Stefano
- Bejanin, Alexandre
- Bombois, Stéphanie
- Epelbaum, Stéphane
- Teichmann, Marc
- Habert, Marie-Odile
- Nordberg, Agneta
- Blennow, Kaj
- Galasko, Douglas
- Stern, Yaakov
- Rowe, Christopher C
- Salloway, Stephen
- Schneider, Lon S
- Cummings, Jeffrey L
- Feldman, Howard H
- Venue
- The Lancet Neurology
- Publisher
- Elsevier BV
- Published
- 2021-06
- Volume
- 20
- Issue
- 6
- Pages
- 484-496
- ISSN
- 1474-4422 (ISSN-L)
- PMC
- PMC8339877
- OpenAlex
- W3159530258
- Semantic Scholar
- dc5f525087f24d7c6a95d667de138557d460fc7e
- Cited by
- 1,051
- References
- 119
- Citations by year
- 2026: 146 · 2025: 272 · 2024: 237 · 2023: 209 · 2022: 153 · 2021: 33
- FWCI
- 28.16
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (am, 171 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- The Lancet Neurology (acceptedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- HAL (submittedVersion, other-oa)
- HAL (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Oskar-Bordeaux (Universite de Bordeaux) (submittedVersion)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- Funders
- National Institutes of Health
- Merck
- Rainwater Charitable Foundation
- U.S. Department of Defense
- Novartis
- National Health and Medical Research Council
- National Institute on Aging
- Roche
- Eisai
- National Institute of General Medical Sciences
- Medtronic
- Adamas Pharmaceuticals
- Johnson and Johnson
- UCB Pharma
- Abbott Laboratories
- American College of Radiology
- Alzheimer's Drug Discovery Foundation
- ACADIA Pharmaceuticals
- Eli Lilly and Company
- Avid Radiopharmaceuticals
- Genentech
- Merz Pharmaceuticals
- Biogen
- Sorbonne Université
- Alzheimer's Association
- GE Healthcare
- National Institute of Neurological Disorders and Stroke
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Oncology › Cancer-related cognitive impairment studies
- Keywords
- Alzheimer's disease, diagnosis, biomarkers, amyloid-beta, tau pathology, NIA-AA criteria, cognitively unimpaired individuals, prodromal Alzheimer's disease, at-risk individuals, comorbidities, diagnostic recommendations
- MeSH terms
- Alzheimer Disease, Humans, Phenotype, Biomarkers, Amyloid beta-Peptides, tau Proteins, Disease Progression, Cognitive Dysfunction
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.
A language model drew the claims from the paper on 2026-10-10, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-10 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
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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