The DOI matches its Crossref record; 56 of the 56 references it cites were found in a registry or an index; 21 of the 46 sources its claims cite were checked for support.
Accuracy of the Clinical Diagnosis of Alzheimer Disease at National Institute on Aging Alzheimer Disease Centers, 2005–2010
Open accessAbstract
The neuropathologic examination is considered to provide the gold standard for Alzheimer disease (AD). To determine the accuracy of currently used clinical diagnostic methods, clinical and neuropathologic data from the National Alzheimer's Coordinating Center, which gathers information from the network of National Institute on Aging (NIA)-sponsored Alzheimer Disease Centers (ADCs), were collected as part of the National Alzheimer's Coordinating Center Uniform Data Set (UDS) between 2005 and 2010. A database search initially included all 1198 subjects with at least one UDS clinical assessment and who had died and been autopsied; 279 were excluded as being not demented or because critical data fields were missing. The final subject number was 919. Sensitivity and specificity were determined based on "probable" and "possible" AD levels of clinical confidence and 4 levels of neuropathologic confidence based on varying neuritic plaque densities and Braak neurofibrillary stages. Sensitivity ranged from 70.9% to 87.3%; specificity ranged from 44.3% to 70.8%. Sensitivity was generally increased with more permissive clinical criteria and specificity was increased with more restrictive criteria, whereas the opposite was true for neuropathologic criteria. When a clinical diagnosis was not confirmed by minimum levels of AD histopathology, the most frequent primary neuropathologic diagnoses were tangle-only dementia or argyrophilic grain disease, frontotemporal lobar degeneration, cerebrovascular disease, Lewy body disease and hippocampal sclerosis. When dementia was not clinically diagnosed as AD, 39% of these cases met or exceeded minimum threshold levels of AD histopathology. Neurologists of the NIA-ADCs had higher predictive accuracy when they diagnosed AD in subjects with dementia than when they diagnosed dementing diseases other than AD. The misdiagnosis rate should be considered when estimating subject numbers for AD studies, including clinical trials and epidemiologic studies.
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Claims the paper makes
25 Own result · 11 Partly supported · 10 Own interpretation · 10 No basis given · 8 No full text of the sources · 4 Sources not found · 3 Own method · 1 Supported · 1 Supported so far · 1 Not supported · accuracy not yet measured
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“the last diagnostic accuracy studies utilizing a complete ADC dataset were performed in 1998 and 1999 (4, 23)”
§ Accuracy of the Clinical Diagnosis of Alzheimer Disease at National Institute on Aging Alzheimer's Disease Centers, 2005–2010 > Introduction
What the sources say
- Partly supportedcites [4] sourceExperimental — accuracy not yet measured
The Subjects section describes a diagnostic study using patients from 26 Alzheimer's disease centers, and the Results report diagnostic sensitivity and specificity. The Results also say complete information was available for only 2,188 of 3,177 patients. This 1998 paper does not establish that its dataset was complete or that the last such studies were performed in 1998 and 1999. (LLM, conf=0.83)
- Not checked — no full text of the sourcecites [23] 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.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Because of 25 possible combinations of CERAD neuritic plaque density and Braak neurofibrillary stage, NIA-Reagan provides instructions for classification of only 3 (32, 38).”
§ Accuracy of the Clinical Diagnosis of Alzheimer Disease at National Institute on Aging Alzheimer's Disease Centers, 2005–2010 > Discussion
What the sources say
- Partly supportedcites [32] sourceExperimental — accuracy not yet measured
The Introduction (page unavailable) describes three NIA-Reagan likelihood categories and says off-diagonal plaque–tangle pairings are not clearly addressed. It does not support the count of 25 possible combinations: it describes four CERAD tiers and Braak stages 0–VI. The three categories also cover ranges of Braak stages, rather than just three individual combinations. (LLM, conf=0.88)
- Not checked — no full text of the sourcecites [38] 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.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“These findings suggest that phenotype is not rigidly linked to etiology and may be moldable to a large extent by an individual's genetic and epigenetic background and/or total environmental exposure.”
§ Accuracy of the Clinical Diagnosis of Alzheimer Disease at National Institute on Aging Alzheimer's Disease Centers, 2005–2010 > Discussion
What the sources say
- Partly supportedcites [44] sourceExperimental — accuracy not yet measured
The introductory passage following the Abstract conclusion says GRN-associated frontotemporal lobar degeneration is clinically heterogeneous even among relatives with the same mutation, and identifies nonmendelian genetic risk factors. This supports the suggestion that phenotype is not rigidly determined by the causal mutation, but the paper does not establish a large effect of epigenetic background or environmental exposure. Page numbers are unavailable in our copy. (LLM, conf=0.86)
- Not checked — no full text of the sourcecites [45] Larner, 2009, Genotype-phenotype relationships of presenilin-1 mutations in Alzheimer's disease: An update, J Alzheimer Dis source
- Partly supportedcites [46] sourceExperimental — accuracy not yet measured
The Comment section (page unavailable) reports marked clinical heterogeneity among family members likely to share a single disease-causing mutation, supporting the point that this disease’s phenotype is not fixed by its apparent etiology. The paper does not attribute that variation to genetic or epigenetic background or environmental exposure, nor establish how extensively those factors mold phenotype. (LLM, conf=0.86)
- Partly supportedcites [47] Wszolek, 2009, Frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17), Orphanet J Rare Dis sourceExperimental — accuracy not yet measured
The Abstract and Genetic counseling sections (pages not supplied) report that the FTDP-17 phenotype can vary even among people with the same mutation, supporting the point that phenotype is not rigidly determined by etiology. Unresolved questions suggests that genetic modifiers and environmental factors may influence its expression, but does not mention epigenetic background, total environmental exposure, or influence 'to a large extent.' (LLM, conf=0.86)
hedgedconditional- 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.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Correlation studies between molecular genetics and neuropathology also indicate that for several autosomal dominant dementias, the presenting clinical phenotype may vary widely, from various dementia subtypes to parkinsonism to motor neuron disease-like, even among individuals with the same causative mutation (44-47).”
§ Accuracy of the Clinical Diagnosis of Alzheimer Disease at National Institute on Aging Alzheimer's Disease Centers, 2005–2010 > Discussion
What the sources say
- Partly supportedcites [44] sourceExperimental — accuracy not yet measured
The introductory passage following the Abstract conclusion (page unavailable) says GRN-associated frontotemporal lobar degeneration is clinically heterogeneous even among family members with the same mutation. The Results report dementia and parkinsonian diagnoses, but describe motor neuron disease as uncommon and concomitant, not a typical presenting phenotype. This paper addresses GRN-associated disease, so it does not by itself establish the claim across several autosomal dominant dementias. (LLM, conf=0.86)
- Not checked — no full text of the sourcecites [45] Larner, 2009, Genotype-phenotype relationships of presenilin-1 mutations in Alzheimer's disease: An update, J Alzheimer Dis source
- Partly supportedcites [46] sourceExperimental — accuracy not yet measured
The Results (Clinical features) and Comment describe markedly different presentations—including FTD, ALS and Parkinsonism—within one family with autosomal dominant FTD/ALS. But the Genetics section identifies a shared chromosome 9p21 haplotype, not a causative mutation, and the paper does not establish this pattern across several autosomal dominant dementias. (LLM, conf=0.88)
- Partly supportedcites [47] Wszolek, 2009, Frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17), Orphanet J Rare Dis sourceExperimental — accuracy not yet measured
The Abstract says FTDP-17 phenotypes vary even within families carrying the same mutation. The Clinical description (Phenotype-genotype correlations; Symptoms and signs) describes dementia-predominant and parkinsonism-predominant presentations and motor neuron dysfunction. The paper addresses FTDP-17, not several autosomal dominant dementias, and does not establish motor neuron disease-like illness as a presenting phenotype. (LLM, conf=0.85)
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The new NIA criteria use the same combination of NPs and Braak stage as the minimum lesion density necessary for attributing the cause of dementia to AD (39, 40).”
§ Accuracy of the Clinical Diagnosis of Alzheimer Disease at National Institute on Aging Alzheimer's Disease Centers, 2005–2010 > Discussion
What the sources say
- Partly supportedcites [39] sourceExperimental — accuracy not yet measured
The Classification section defines moderate or frequent neuritic plaques and Braak stages III–VI as scores used by the new criteria. But it requires a third measure, Aβ plaque score, to classify AD neuropathologic change; the Reporting section says an intermediate or high overall level, rather than the stated two-measure combination alone, is an adequate explanation of dementia. Our copy provides no page numbers for these passages. (LLM, conf=0.87)
- Partly supportedcites [40] sourceExperimental — accuracy not yet measured
The Classification section says the new criteria use Braak stage and neuritic-plaque score, but also require an Aβ-plaque score as part of the ABC score. The Reporting section says intermediate or high AD neuropathologic change can adequately explain dementia; the passages do not establish moderate or frequent neuritic plaques plus Braak stage III–VI as the minimum sufficient combination. (LLM, conf=0.86)
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.
- Partly supported
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“When optimizing for sensitivity and specificity, the best result was 70.9% sensitivity and 70.8% specificity. This was achieved when the clinical diagnosis was defined as probable AD and the neuropathological diagnosis as moderate or frequent neuritic plaques with Braak stage III-VI.”
§ Accuracy of the Clinical Diagnosis of Alzheimer Disease at National Institute on Aging Alzheimer's Disease Centers, 2005–2010 > Results > Diagnostic Classification Comparison
plaincorrelational- 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.
A result the paper reports from its own data — 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 median scores for neuritic plaque density and Braak stage were significantly different, with progressively lower scores moving from probable AD through possible AD and not AD groups.”
§ Accuracy of the Clinical Diagnosis of Alzheimer Disease at National Institute on Aging Alzheimer's Disease Centers, 2005–2010 > Results > Subject Characteristics
plaincorrelational- 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.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“here, we found that when non-demented controls were not included, 33% of subjects were not classifiable.”
§ Accuracy of the Clinical Diagnosis of Alzheimer Disease at National Institute on Aging Alzheimer's Disease Centers, 2005–2010 > Discussion
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.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Of these, 107 cases met a minimum histopathological threshold for AD, i.e. neuritic plaque density of moderate or frequent in combination with any Braak neurofibrillary tangle stage between III and VI, inclusive, despite their negative clinical diagnoses.”
§ Accuracy of the Clinical Diagnosis of Alzheimer Disease at National Institute on Aging Alzheimer's Disease Centers, 2005–2010 > Results > Analysis of Mismatched Clinical and Neuropathological Diagnoses
plainn = 107- 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.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Neurologists of the NIA-ADCs had higher predictive accuracy when they diagnosed AD in demented subjects than when they diagnosed dementing diseases other than AD.”
§ Accuracy of the Clinical Diagnosis of Alzheimer Disease at National Institute on Aging Alzheimer's Disease Centers, 2005–2010 > Abstract
plaincorrelational- 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. 27
- Probably not a substantial claim. 25
- The quote only partly states this claim. 1
At least one cited source doesn’t support this claim or points to a different paper, and none confirmed it — see the verdicts below.
In the paper
“However, one study has reported no evident selection bias between autopsied and non-autopsied subjects among an incident community-diagnosed dementia series, suggesting that dementia case composition may not be substantially different in different settings (48).”
§ Accuracy of the Clinical Diagnosis of Alzheimer Disease at National Institute on Aging Alzheimer's Disease Centers, 2005–2010 > Discussion
What the sources say
- Disputedcites [48] sourceExperimental — accuracy not yet measured
Split into 2 atoms — 0 confirmed, 1 partially supported, 1 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Checked by a reasoning model — may be wrong.
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether 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.
- Disputed
Every source the paper cites for this claim was checked and supports it.
In the paper
“The shortcomings of the NIA-Reagan criteria have been recognized and a revised set of criteria are currently in press (39, 40).”
§ Accuracy of the Clinical Diagnosis of Alzheimer Disease at National Institute on Aging Alzheimer's Disease Centers, 2005–2010 > Discussion
What the sources say
- Supportedcites [39] source
The Abstract identifies the NIA-Reagan criteria as the 1997 criteria and says advances in knowledge prompted an update. The “Revised Neuropathologic criteria for Alzheimer’s disease” section explains a limitation of those criteria and presents revised criteria; the Summary states that the committee’s goal was to update them. This supports the substance of the claim, though the paper does not establish the citing document’s time-specific phrase “currently in press.” (LLM, conf=0.90)
- Supportedcites [40] source
The Introduction identifies the 1997 NIA-Reagan guidelines as the criteria being updated and revised, and the Abstract describes major revisions to the previous criteria. The References list the revised neuropathologic guidelines as “in press” (reference 29). Our copy provides no page numbers for these passages. (LLM, conf=0.88)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“In a recent multivariate analysis, approximately two-thirds of the variation in cognitive ability of elderly subjects was accounted for by variation in CERAD neuritic plaque density and Braak stage (41).”
§ Accuracy of the Clinical Diagnosis of Alzheimer Disease at National Institute on Aging Alzheimer's Disease Centers, 2005–2010 > Discussion
What the sources say
- Partly supportedcites [41] sourceExperimental — accuracy not yet measured
The Results section (page not provided) says that more than two-thirds of MMSE-score variability in the elderly autopsy cohort was associated with Alzheimer-type pathology, specifically neurofibrillary tangles and neuritic plaques. It does not attribute that figure to CERAD neuritic plaque density and Braak stage as the two measures in the claim; the Discussion describes its findings as compatible with Braak staging. (LLM, conf=0.89)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Partly supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“There is also relatively close agreement with the last 2 prior assessments of diagnostic accuracy using the total NIA-ADC dataset: Mayeux et al estimated a sensitivity of 93% and a specificity of 55% (4) and Tsuang et al reported a sensitivity of 84% and a specificity of 50% (23).”
§ Accuracy of the Clinical Diagnosis of Alzheimer Disease at National Institute on Aging Alzheimer's Disease Centers, 2005–2010 > Discussion
What the sources say
- Supportedcites [4] source
The Results report 93% sensitivity and 55% specificity for the clinical diagnosis of Alzheimer’s disease, matching the figures attributed to Mayeux et al. The Subjects section describes patients referred to 26 Alzheimer’s disease centers. The separate figures attributed to Tsuang et al. are not part of this citation’s claim. (LLM, conf=0.93)
- Not checked — no full text of the sourcecites [23] source
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether 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.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Due to the idiosyncratic assignment of these categories from case to case (32), we instead stratified by all relevant combinations of the deterministic histopathological scores, consisting of the CERAD-defined neuritic plaque density score (29) and the Braak neurofibrillary tangle stage (33).”
§ Accuracy of the Clinical Diagnosis of Alzheimer Disease at National Institute on Aging Alzheimer's Disease Centers, 2005–2010 > Materials and Methods > Analysis Strategy
What the sources say
- Partly supportedcites [32] sourceExperimental — accuracy not yet measured
The Results report relatively low consistency in NIA-Reagan category assignments for cases outside the guidelines, supporting the concern behind the citing authors’ choice. But they also report high consistency for cases that match the guidelines, so the source does not support describing assignments as idiosyncratic across cases generally. The decision to stratify by CERAD and Braak scores is the citing authors’ own method, not a finding attributed to this source. (LLM, conf=0.83)
plaindirect- 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.
Probably not a substantial claim.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“because measures of all biomarkers studied to date have considerable overlap with those found other types of dementia (as well the cognitively normal elderly population), it remains difficult to determine whether or not cognitive impairment is due to AD or another more dominant and concurrent process.”
§ Accuracy of the Clinical Diagnosis of Alzheimer Disease at National Institute on Aging Alzheimer's Disease Centers, 2005–2010 > Introduction
What the sources say
- Partly supportedcites [1] sourceExperimental — accuracy not yet measured
The section ‘Biomarker abnormalities precede clinical symptoms’ (page not provided) reports amyloid-biomarker abnormalities in 20–40% of cognitively normal elderly people, and ‘AD clinical features and pathological changes’ notes that dementia in older patients often has multiple underlying pathologies. The ‘Biomarkers of neurodegeneration’ section also says CSF tau is not specific to AD. These passages support diagnostic ambiguity, but not the broader assertion that all biomarkers studied have considerable overlap with both other dementias and cognitively normal elderly people. (LLM, conf=0.84)
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.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“In the revision of the 1997 criteria, combinations of plaque and tangle pathologies considered sufficient to cause dementia and qualify for the neuropathological diagnosis of AD are explicitly stated (40, 41).”
§ Accuracy of the Clinical Diagnosis of Alzheimer Disease at National Institute on Aging Alzheimer's Disease Centers, 2005–2010 > Discussion
What the sources say
- Supportedcites [40] source
The Classification section defines an ABC score combining amyloid plaques, neurofibrillary tangles, and neuritic plaques. The Reporting section states that, in individuals with cognitive impairment, intermediate or high levels are an adequate explanation for dementia and warrant a final diagnosis of Alzheimer’s disease. (LLM, conf=0.90)
- Could not verifycites [41] sourceExperimental — accuracy not yet measured
The Neuropathology section describes how the study counted plaques and tangles, but does not state what combinations qualify for an AD diagnosis or are sufficient to cause dementia. Searches for the 1997 criteria, their revision, and diagnostic thresholds found no passage addressing that claim in our copy; the other relevant matches were in the References section. (LLM, conf=0.72)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“New clinical diagnostic consensus criteria have now been finalized under the auspices of the NIA and Alzheimer's Association (52), with novel features including recognition of a preclinical stage of AD and the incorporation of imaging and laboratory-based cerebrospinal fluid biomarkers.”
§ Accuracy of the Clinical Diagnosis of Alzheimer Disease at National Institute on Aging Alzheimer's Disease Centers, 2005–2010 > Discussion
What the sources say
- Partly supportedcites [52] 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.
plainconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Amyloid staging may be of immediate clinical diagnostic utility when used to guide amyloid imaging as the progression of amyloid plaques beyond the cortex appears to be a useful marker of higher Braak tangle stage and of the presence of dementia (49, 50).”
§ Accuracy of the Clinical Diagnosis of Alzheimer Disease at National Institute on Aging Alzheimer's Disease Centers, 2005–2010 > Discussion
What the sources say
- Not checked — no full text of the sourcecites [49] Thal, 2002, Phases of A beta-deposition in the human brain and its relevance for the development of AD, Neurology source
- Partly supportedcites [50] Beach, 2012, Striatal amyloid plaque density predicts Braak neurofibrillary stage and clinicopathological Alzheimer's disease: Implications for amyloid imaging, J Alzheimer Dis 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.
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A result the paper reports from its own data — 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 most frequent primary neuropathological diagnoses in these cases were frontotemporal lobar degeneration (60 cases), followed by Lewy body disease (39 cases), Creutzfeldt-Jakob disease (20 cases) and progressive supranuclear palsy (18 cases).”
§ Accuracy of the Clinical Diagnosis of Alzheimer Disease at National Institute on Aging Alzheimer's Disease Centers, 2005–2010 > Results > Analysis of Mismatched Clinical and Neuropathological Diagnoses
plainn = 164- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether 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 result the paper reports from its own data — 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 mean age of the “not AD” group was significantly lower than that of the probable or possible AD groups (72.8, 81.2 and 83.2 years, respectively).”
§ Accuracy of the Clinical Diagnosis of Alzheimer Disease at National Institute on Aging Alzheimer's Disease Centers, 2005–2010 > Results > Subject Characteristics
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Sensitivity ranged from 70.9% to 87.3%; specificity ranged from 44.3% to 70.8%.”
- Also stated in: § Diagnostic Classification Comparison · plain
“Sensitivity ranged from 70.9% to 87.3% and specificity ranged from 44.3% to 70.8%.”
- Also stated in: § Discussion · plain
“We found that sensitivity for AD diagnosis ranged from 70.9% to 87.3% whereas specificity ranged from 44.3% to 70.8%.”
§ Accuracy of the Clinical Diagnosis of Alzheimer Disease at National Institute on Aging Alzheimer's Disease Centers, 2005–2010 > Abstract
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.
- Also stated in: § Diagnostic Classification Comparison · plain
A result the paper reports from its own data — 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 PPV for the clinical diagnosis of AD ranged from 46.0% to 83.3%, with the best result achieved when the clinical diagnosis was defined by probable AD and the neuropathological diagnosis as moderate or frequent neuritic plaques with Braak stage III-VI (the prevalence of subjects at or above this histopathological threshold was 67.2%).”
§ Accuracy of the Clinical Diagnosis of Alzheimer Disease at National Institute on Aging Alzheimer's Disease Centers, 2005–2010 > Results > Diagnostic Classification Comparison
plaincorrelational- 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 result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“For the set of minimum neuropathological criteria that are perhaps most commonly used to define AD (i.e. CERAD neuritic plaque density of ‘moderate” or “frequent” and Braak stage III-VI), the sensitivity and specificity of the clinical diagnosis of “probable AD” were each approximately 71%, whereas for “combined “probable” and possible AD” sensitivity was about 83% with specificity about 55%.”
§ Accuracy of the Clinical Diagnosis of Alzheimer Disease at National Institute on Aging Alzheimer's Disease Centers, 2005–2010 > Discussion
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 result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Sensitivity was generally increased with more permissive clinical criteria and specificity was increased with more restrictive criteria, whereas the opposite was true for neuropathological criteria.”
- Also stated in: § Diagnostic Classification Comparison · plain
“In general, sensitivity was increased with more permissive clinical criteria and specificity was increased with more restrictive clinical criteria, whereas the opposite was true for neuropathological criteria.”
§ Accuracy of the Clinical Diagnosis of Alzheimer Disease at National Institute on Aging Alzheimer's Disease Centers, 2005–2010 > Abstract
plaindirect- 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.
- Also stated in: § Diagnostic Classification Comparison · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Of the 526 subjects diagnosed as clinically probable AD, 438 were confirmed as neuropathological AD, as defined above, and 88 did not meet neuropathological criteria.”
§ Accuracy of the Clinical Diagnosis of Alzheimer Disease at National Institute on Aging Alzheimer's Disease Centers, 2005–2010 > Results > Analysis of Mismatched Clinical and Neuropathological Diagnoses
plainn = 526- 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 result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“A small number of cases received primary neuropathological diagnoses of progressive supranuclear palsy (3 cases), corticobasal degeneration (2 cases) and neuroaxonal dystrophy/Hallervorden-Spatz-like disease (2 cases); there were several other miscellaneous neuropathological diagnoses (1 case each) (Table 4).”
§ Accuracy of the Clinical Diagnosis of Alzheimer Disease at National Institute on Aging Alzheimer's Disease Centers, 2005–2010 > Results > Analysis of Mismatched Clinical and Neuropathological Diagnoses
plainn = 3- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether 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 result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“When a clinical diagnosis was not confirmed by minimum levels of AD histopathology, the most frequent primary neuropathological diagnoses were tangle-only dementia or argyrophilic grain disease, frontotemporal lobar degeneration, cerebrovascular”
§ Accuracy of the Clinical Diagnosis of Alzheimer Disease at National Institute on Aging Alzheimer's Disease Centers, 2005–2010 > Abstract
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.
The quote only partly states this claim.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Many cases had contributing neuropathological diagnoses in addition to their primary diagnosis; the most frequent contributing diagnoses were similar to the most frequent primary diagnoses.”
§ Accuracy of the Clinical Diagnosis of Alzheimer Disease at National Institute on Aging Alzheimer's Disease Centers, 2005–2010 > Results > Analysis of Mismatched Clinical and Neuropathological Diagnoses
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether 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 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
“While not formally analyzed here, we did note a high rate of multiple neuropathological diagnoses in demented subjects whereas clinicians rarely assign more than one diagnosis.”
§ Accuracy of the Clinical Diagnosis of Alzheimer Disease at National Institute on Aging Alzheimer's Disease Centers, 2005–2010 > Discussion
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether 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.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The excluded subjects significantly differed from the 919 included subjects in terms of age, gender distribution and AD-related histopathological scores, but not in the mean interval last clinical assessment and death.”
§ Accuracy of the Clinical Diagnosis of Alzheimer Disease at National Institute on Aging Alzheimer's Disease Centers, 2005–2010 > Results > Subject Characteristics
plainn = 919- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether 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 claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“there have been several changes in neuropathological diagnostic criteria, including the “Khachaturian criteria” of 1985 (27), the “Tierney” criteria of 1988 (28), The Consortium to Establish a Registry for Alzheimer's Disease (CERAD) criteria in 1991 (29), and the National Institute on Aging (NIA)-Reagan criteria in 1997 (30).”
§ Accuracy of the Clinical Diagnosis of Alzheimer Disease at National Institute on Aging Alzheimer's Disease Centers, 2005–2010 > Introduction
What the sources say
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.
Probably not a substantial claim.
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
“The neuropathological examination is considered to provide the gold standard for Alzheimer disease (AD).”
- Also stated in: § Introduction · boosted
“it is generally accepted that histological examination is the best indicator of AD diagnosis.”
§ Accuracy of the Clinical Diagnosis of Alzheimer Disease at National Institute on Aging Alzheimer's Disease Centers, 2005–2010 > Abstract
boosted- 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.
Probably not a substantial claim.
- Also stated in: § Introduction · boosted
In the paper
“For the neuropathological diagnosis of AD, the NIA-Reagan criteria (30) are the most current guidelines”
§ Accuracy of the Clinical Diagnosis of Alzheimer Disease at National Institute on Aging Alzheimer's Disease Centers, 2005–2010 > Materials and Methods > Analysis Strategy
What the sources say
- Not checked — no full text of the sourcecites [30] source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
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
“In most studies, sensitivity is relatively high while specificity is low and many studies have reported only sensitivity or positive predictive value, which has led to a false impression that the clinical diagnosis of AD is extremely accurate.”
§ Accuracy of the Clinical Diagnosis of Alzheimer Disease at National Institute on Aging Alzheimer's Disease Centers, 2005–2010 > Discussion
plaindirect- 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: fails — The paper may give no reason why it holds.
Probably not a substantial claim. 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
“For example, with an estimated response rate to a trial medication of 50%, a 20% misdiagnosis rate would lower the actual response rate to 40% (if non-AD dementia subjects do not respond to the medication), which would require an approximate doubling of subject recruitment to maintain statistical power.”
§ Accuracy of the Clinical Diagnosis of Alzheimer Disease at National Institute on Aging Alzheimer's Disease Centers, 2005–2010 > Discussion
hedgeddirect- 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 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
“While the clinical diagnosis of AD often is validated by neuropathological examination, a clinical diagnosis of a non-AD dementia is often not verified by neuropathology.”
§ Accuracy of the Clinical Diagnosis of Alzheimer Disease at National Institute on Aging Alzheimer's Disease Centers, 2005–2010 > Discussion
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
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
“it is important, for current research and clinical usage, to obtain more appropriate figures.”
§ Accuracy of the Clinical Diagnosis of Alzheimer Disease at National Institute on Aging Alzheimer's Disease Centers, 2005–2010 > Introduction
plain- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence.
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
“Because many studies have reported only sensitivity or positive predictive value, a general impression has arisen that the clinical diagnosis of AD is extremely accurate.”
§ Accuracy of the Clinical Diagnosis of Alzheimer Disease at National Institute on Aging Alzheimer's Disease Centers, 2005–2010 > Introduction
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence.
In the paper
“The data analyzed in this study have been collected as part of the NACC Uniform Data Set (UDS) since 2005 (31) and thus represent the most current research practices.”
§ Accuracy of the Clinical Diagnosis of Alzheimer Disease at National Institute on Aging Alzheimer's Disease Centers, 2005–2010 > Introduction
What the sources say
- Not checked — no full text of the sourcecites [31] 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.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The 3 groups did not significantly differ in the mean interval between last clinical assessment and death.”
§ Accuracy of the Clinical Diagnosis of Alzheimer Disease at National Institute on Aging Alzheimer's Disease Centers, 2005–2010 > Results > Subject Characteristics
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Sensitivity estimates have ranged between 41% and 100% (median of 87%), while specificity has ranged between 37% and 100% (median of 58%).”
§ Accuracy of the Clinical Diagnosis of Alzheimer Disease at National Institute on Aging Alzheimer's Disease Centers, 2005–2010 > Introduction
What the sources say
- Not matchedcites 2-25
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
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.
- Not matched
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
“Thus, a large fraction of subjects are not classifiable by NIA-Reagan criteria and the neuropathologist is left to make an arbitrary assignment.”
§ Accuracy of the Clinical Diagnosis of Alzheimer Disease at National Institute on Aging Alzheimer's Disease Centers, 2005–2010 > Discussion
plaindirect- 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.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The gender distribution was generally skewed towards more males but did not significantly differ among groups.”
§ Accuracy of the Clinical Diagnosis of Alzheimer Disease at National Institute on Aging Alzheimer's Disease Centers, 2005–2010 > Results > Subject Characteristics
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. 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
“These, however, do not give entirely specific guidelines for making the diagnosis, but rather set probability levels, given threshold levels of histopathological severity (CERAD neuritic plaque density and Braak neurofibrillary stage) for when dementia may be due to AD.”
§ Accuracy of the Clinical Diagnosis of Alzheimer Disease at National Institute on Aging Alzheimer's Disease Centers, 2005–2010 > Discussion
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.
Probably not a substantial claim. 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
“However, even a modest level of diagnostic misclassification could have a significant effect on clinical trial calculations for minimum subject number and thus should be considered in clinical trial planning.”
§ Accuracy of the Clinical Diagnosis of Alzheimer Disease at National Institute on Aging Alzheimer's Disease Centers, 2005–2010 > Discussion
hedgedconditional- 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.
Probably not a substantial claim. It may state two separate claims as one.
In the paper
“In a recent examination of NACC data, Nelson et al estimated that 18% of subjects with dementia fell outside of the NIA-Reagan guidelines (34);”
§ Accuracy of the Clinical Diagnosis of Alzheimer Disease at National Institute on Aging Alzheimer's Disease Centers, 2005–2010 > Discussion
What the sources say
- Not checked — no full text of the sourcecites [34] source
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
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
“It is likely that, just as some subjects with 90% coronary artery stenosis suffer myocardial infarctions and some do not, individual subjects will vary in their ability to withstand a given lesion density (perhaps due to “cognitive reserve”), differences in genetic background or differences in environmental exposures.”
§ Accuracy of the Clinical Diagnosis of Alzheimer Disease at National Institute on Aging Alzheimer's Disease Centers, 2005–2010 > Discussion
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence. 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
“For selecting subjects for clinical trials, the relatively high sensitivity is somewhat reassuring because it means that a relatively small percentage of non-AD subjects will be included in clinical trials.”
§ Accuracy of the Clinical Diagnosis of Alzheimer Disease at National Institute on Aging Alzheimer's Disease Centers, 2005–2010 > Discussion
hedgeddirect- 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: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds.
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
“Because ADCs are tertiary referral centers, diagnostic accuracy rates may differ from those that may be achieved in secondary or primary care settings.”
§ Accuracy of the Clinical Diagnosis of Alzheimer Disease at National Institute on Aging Alzheimer's Disease Centers, 2005–2010 > Discussion
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Rests on an assumption: Patients with a more complex clinical syndrome are more likely to be referred to a tertiary care center.
- Rests on an assumption: The greater level of neurological expertise at tertiary care centers contributes to more accurate diagnoses.
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
“Thus there are “low,” “intermediate” and “high” probability designations for classifying autopsy subjects although definitive recommendations on which of these 3 levels should be attained to justify the conclusion that dementia is due primarily to AD have not been defined.”
§ Accuracy of the Clinical Diagnosis of Alzheimer Disease at National Institute on Aging Alzheimer's Disease Centers, 2005–2010 > Discussion
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Although neuropathological consensus criteria for AD have changed several times over the last 3 decades, the clinical criteria have remained virtually unchanged since the NINCDS-ADRDA-sponsored criteria published in 1984 (6).”
§ Accuracy of the Clinical Diagnosis of Alzheimer Disease at National Institute on Aging Alzheimer's Disease Centers, 2005–2010 > Discussion
What the sources say
- Not checked — no full text of the sourcecites [6] McKeel, 2004, Neuropathologic criteria for diagnosing Alzheimer disease in persons with pure dementia of Alzheimer type, J Neuropathol Exp Neurol source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“AD has generally been attributed to be the neuropathological cause in between 65% and 75% of dementia cases (42, 43).”
§ Accuracy of the Clinical Diagnosis of Alzheimer Disease at National Institute on Aging Alzheimer's Disease Centers, 2005–2010 > Discussion
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The paper relies on this without support.
Biopsy has long been contraindicated for AD due to a high risk/benefit ratio.
“For many disorders this is possible during life through biopsy but biopsy has long been contraindicated for AD due to a high risk/benefit ratio.”
The paper relies on this without support.
The consensus of expert opinion has required that the clinically documented presence of dementia be part of the definition of AD.
“Indeed, until the present time the consensus of expert opinion has required that the clinically documented presence of dementia be part of the definition of AD.”
The paper relies on this without support.
It has been the common practice for both clinical and neuropathological diagnostic definitions of AD to require the presence of dementia.
“Subjects without dementia were excluded because it has been the common practice for both clinical and neuropathological diagnostic definitions of AD to require the presence of dementia.”
The paper relies on this without support.
Non-demented subjects are not generally classified as AD.
“Therefore, non-demented subjects are not generally classified as AD.”
The paper relies on this without support.
The available body of knowledge does not allow neuropathologists to be dogmatic about exactly how much plaque and tangle pathology is necessary to cause dementia.
“We feel that our approach here has been cautious as the available body of knowledge does not allow neuropathologists to be dogmatic about exactly how much plaque and tangle pathology is necessary to cause dementia.”
The paper relies on this without support.
The clinical methods for diagnosing AD have not changed substantially since the introduction of NINDS-ADRDA criteria in 1984.
“whereas the clinical methods for diagnosing AD have not changed substantially since the introduction of the National Institute of Neurological Disorders and Stroke-Alzheimer's Disease and Related Disorders Association (NINDS-ADRDA) criteria in 1984 (26)”
The paper relies on this without support.
A large fraction of cognitively unimpaired elderly possesses sparse neuritic plaques and/or Braak stages 0-II.
“Lowering the lesion density threshold further (e.g. allowing sparse neuritic plaques and/or Braak stages 0-II) seemed counterintuitive because a large fraction of cognitively unimpaired elderly possesses such attributes.”
The paper relies on this without support.
Patients with a more complex clinical syndrome are more likely to be referred to a tertiary care center.
“For example, patients with a more complex clinical syndrome are more likely to be referred to a tertiary care center.”
The paper relies on this without support.
The greater level of neurological expertise at tertiary care centers contributes to more accurate diagnoses.
“On the other hand, the greater level of neurological expertise at these centers would presumably contribute to more accurate diagnoses.”
The paper relies on this without support.
Large reported autopsy series are only done in tertiary care settings.
“Because large reported autopsy series are only done in tertiary care settings, it is not possible to know for certain whether such differences exist.”
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 source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“while physicians struggle with accurate and reliable diagnostics even when multimodality is present, as proven by histopathological correlation42.”
From Fusion of medical imaging and electronic health records using deep learning: a systematic review and implementation guidelines (2020) · cites this paper as [42]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“common causes of dementias outside of AD such as vascular dementia (VD), Lewy body dementia (LBD), and frontotemporal dementia (FTD) widen the differential diagnosis of neurodegenerative conditions and contribute to variability in diagnostic sensitivity and specificity12.”
From Multimodal deep learning for Alzheimer's disease dementia assessment (2022) · cites this paper as [12]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Beach et al (6) found that sensitivity ranged from 70.9% to 87.3% and specificity from 44.3% to 70.8%.”
From Concordance of Clinical Alzheimer Diagnosis and Neuropathological Features at Autopsy (2020) · cites this paper as [6]
Citations
Cites
McKhann, G., Drachman, D., Folstein, M., Katzman, R., Price, D., & Stadlan, E. M. (1984) · Neurology · doi:10.1212/wnl.34.7.939 · Cited by 27,915 · cited 3×
“For the clinical diagnosis of AD, NINDSADRDA criteria (26) were stratified by considering ‘‘probable AD’’ alone as well as ‘‘probable’’ plus ‘‘possible AD.”
MethodInfluentialNeuropathological stageing of Alzheimer-related changes.
Braak, H., & Braak, E. (1991) · Acta Neuropathologica · doi:10.1007/bf00308809 · Cited by 16,123 · cited 1×
“’’ Because of the idiosyncratic assignment of these categories from case to case (32), we instead stratified all relevant combinations of the deterministic histopathologic scores, consisting of the CERAD-defined neuritic plaque density score (29) and the Braak neurofibrillary tangle stage (33).”
BackgroundSperling, R. A., Aisen, P. S., Beckett, L. A., Bennett, D. A., Craft, S., Fagan, A. M., Iwatsubo, T., Jack, C. R., Kaye, J., Montine, T. J., et al. (2011) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2011.03.003 · Cited by 7,155 · cited 1×
“New clinical diagnostic consensus criteria have now been finalized under the auspices of the NIA and Alzheimer’s Association (52), with novel features including recognition of a preclinical stage of AD and the incorporation of imaging and laboratory-based cerebrospinal fluid biomarkers.”
BackgroundMirra, S. S., Heyman, A., McKeel, D., Sumi, S. M., Crain, B. J., Brownlee, L. M., Vogel, F. S., Hughes, J. P., Belle, G. V., Berg, L., et al. (1991) · Neurology · doi:10.1212/wnl.41.4.479 · Cited by 4,961 · cited 2×
“’’ Because of the idiosyncratic assignment of these categories from case to case (32), we instead stratified all relevant combinations of the deterministic histopathologic scores, consisting of the CERAD-defined neuritic plaque density score (29) and the Braak neurofibrillary tangle stage (33).”
BackgroundHypothetical model of dynamic biomarkers of the Alzheimer's pathological cascade
Jack, C. R., Knopman, D. S., Jagust, W. J., Shaw, L. M., Aisen, P. S., Weiner, M. W., Petersen, R. C., & Trojanowski, J. Q. (2010) · The Lancet Neurology · doi:10.1016/s1474-4422(09)70299-6 · Cited by 4,806 · cited 1×
“The emergence of new biomarkers may have a major impact on clinical diagnostic practice (1); however, because measures of all biomarkers studied to date have considerable overlap with those found in other types of dementia (as well the cognitively normal elderly population), it remains difficult to determine whether c…”
BackgroundPhases of Aβ-deposition in the human brain and its relevance for the development of AD
Thal, D. R., Rüb, U., Orantes, M., & Braak, H. (2002) · Neurology · doi:10.1212/wnl.58.12.1791 · Cited by 3,490 · cited 1×
“Amyloid staging may be of immediate clinical diagnostic utility when used to guide amyloid imaging as the progression of amyloid plaques beyond the cortex appears to be a useful marker of higher Braak tangle stage and of the presence of dementia (49, 50).”
BackgroundHyman, B. T., Phelps, C. H., Beach, T. G., Bigio, E. H., Cairns, N. J., Carrillo, M. C., Dickson, D. W., Duyckaerts, C., Frosch, M. P., Masliah, E., et al. (2012) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2011.10.007 · Cited by 3,092
Self-citationMontine, T. J., Phelps, C. H., Beach, T. G., Bigio, E. H., Cairns, N. J., Dickson, D. W., Duyckaerts, C., Frosch, M. P., Masliah, E., Mirra, S. S., et al. (2012) · Acta Neuropathologica · doi:10.1007/s00401-011-0910-3 · Cited by 2,894 · cited 3×
“The new NIA criteria use this same combination of NPs and Braak stage as the minimum lesion density necessary for attributing the cause of dementia to AD (39, 40).”
BackgroundMethodSelf-citationDiagnosis of Alzheimer's Disease
Khachaturian, Z. S. (1985) · Archives of Neurology · doi:10.1001/archneur.1985.04060100083029 · Cited by 2,499
Practice parameter: Management of dementia (an evidence-based review) [RETIRED]
Doody, R. S., Stevens, J. E., Beck, C., Dubinsky, R., Kaye, J. A., Gwyther, L. P., Mohs, R. C., Thal, L. J., Whitehouse, P. J., DeKosky, S. T., et al. (2001) · Neurology · doi:10.1212/wnl.56.9.1154 · Cited by 1,708
Cited by
Sorted by citations
Items 201–300 of 1,108
In-depth insights into Alzheimer’s disease by using explainable machine learning approach
Bogdanovic, B., Eftimov, T., & Simjanoska, M. (2022) · Scientific Reports · doi:10.1038/s41598-022-10202-2 · Cited by 77
“…researches provide contemporary view about differentiating clinically diagnosed AD dementia from other neurodegenerative disorders using plasma P-tau217 32 , improvements in neuropathological diagnosing the disease 33 and possible approach for a drug development against its progression 34 .”
BackgroundCecchi, M., Moore, D. K., Sadowsky, C., Solomon, P. R., Doraiswamy, P. M., Smith, C. D., Jicha, G. A., Budson, A. E., Arnold, S. E., & Fadem, K. C. (2015) · Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring · doi:10.1016/j.dadm.2015.08.004 · Cited by 74
“Despite the emergence of putative biomarkers for Alzheimer’s disease (AD) [1], clinical diagnostic accuracy is suboptimal [2].”
BackgroundFantoni, E. R., Chalkidou, A., O’ Brien, J. T., Farrar, G., & Hammers, A. (2018) · Journal of Alzheimer’s Disease · doi:10.3233/jad-171093 · Cited by 68
“Also, concordance between diagnostic change after aPET and extent of mismatch between clinical diagnosis and final neuropathological diagnosis [72] indicates overall high diagnostic performance of aPET.”
BackgroundClarke, N., Foltz, P. W., & Garrard, P. (2020) · Cortex · doi:10.1016/j.cortex.2020.05.001 · Cited by 70
“Clinical diagnosis is often difficult; for those diagnosed with AD in life, sensitivity to post-mortem thresholds for disease have been found to range from between 70.9% and 87.3%, and specificity between 44.3% and 70.8% (Beach, Monsell, Phillips, & Kukull, 2012).”
BackgroundInfluentialSugarman, M. A., Zetterberg, H., Blennow, K., Tripodis, Y., McKee, A. C., Stein, T. D., Martin, B. M., Palmisano, J. N., Steinberg, E. G., Simkin, I., et al. (2020) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2020.05.011 · Cited by 68
“Approximately 17% of individuals who receive a clinical diagnosis of AD dementia do not have AD neuropathologic changes at autopsy (Beach et al., 2012).”
Backgroundd’Abramo, C., D'adamio, L., & Giliberto, L. (2020) · Journal of Personalized Medicine · doi:10.3390/jpm10030116 · Cited by 71
Dukart, J., Sambataro, F., Bertolino, A., & Initiative, A. D. N. (2015) · Journal of Alzheimer s Disease · doi:10.3233/jad-150570 · Cited by 68
“The known limited accuracy of clinical diagnoses may lead to the inclusion of other dementias in the AD groups or of preclinical AD as healthy controls [29, 30].”
Modifiable, Non-Modifiable, and Clinical Factors Associated with Progression of Alzheimer’s Disease
Loeffler, D. A. (2021) · Journal of Alzheimer s Disease · doi:10.3233/jad-201182 · Cited by 71
“A review of cases from the National Alzheimer’s Coordinating Center, using neuropathological confirmation of AD as the gold standard, found that diagnostic sensitivity for AD ranged from 70.9% to 87.3% and diagnostic speci-ficity ranged from 44.3% to 70.8% [433].”
InfluentialHajjar, I. M., Okafor, M. O., Choi, J. D., Moore, E., Abrol, A., Calhoun, V. D., & Goldstein, F. C. (2023) · Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring · doi:10.1002/dad2.12393 · Cited by 74
Mouton‐Liger, F., Wallon, D., Troussière, A., Yatimi, R., Dumurgier, J., Magnin, É., Sayette, V. D. L., Duron, E., Philippi, N., Beaufils, É., et al. (2013) · Journal of Neurology · doi:10.1007/s00415-013-7160-3 · Cited by 67
“In living patients, comparable rates were found in clinical trials using new imaging biomarkers such as Pittsburg compound B (PIB) [3, 25].”
ResultEarly vs late age at onset frontotemporal dementia and frontotemporal lobar degeneration
Seo, S. W., Thibodeau, M., Perry, D. C., Hua, A. Y., Sidhu, M., Sible, I. J., Vargas, J. N. S., Gaus, S. E., Rabinovici, G. D., Rankin, K. D., et al. (2018) · Neurology · doi:10.1212/wnl.0000000000005163 · Cited by 67
Imaging Biomarkers Associated With Cognitive Decline: A Review
McConathy, J., & Sheline, Y. I. (2014) · Biological Psychiatry · doi:10.1016/j.biopsych.2014.08.024 · Cited by 68
Sassi, C., Guerreiro, R. J., Gibbs, J. R., Ding, J., Lupton, M. K., Troakes, C., Al‐Sarraj, S., Niblock, M., Gallo, J., Adnan, J., et al. (2014) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2014.06.002 · Cited by 68
“The overlapping clinical and neuropathologic features between AD and other neurodegenerative dementias (frontotemporal dementia [FTD], corticobasal degeneration [CBD], progressive supranuclear palsy [PSP], and Creutzfeldt-Jakob disease [CJD]) lead to a misdiagnosis in 17%e30% of AD cases (Beach et al., 2012).”
Analysis of 50 Neurodegenerative Genes in Clinically Diagnosed Early-Onset Alzheimer’s Disease
Giau, V. V., Senanarong, V., Bagyinszky, E., An, S. S. A., & Kim, S. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20061514 · Cited by 64
Wilks, H., Aschenbrenner, A. J., Gordon, B. A., Balota, D. A., Fagan, A. M., Musiek, E. S., Balls-Berry, J., Benzinger, T. L. S., Cruchaga, C., Morris, J. C., et al. (2021) · Journal of Clinical and Experimental Neuropsychology · doi:10.1080/13803395.2021.2009447 · Cited by 60
“Most individuals with a CDR of .5 present with the clinical phenotype of AD in our sample (Morris et al., 2001), but there are cases where the etiology is uncertain, or when the clinical classification of an AD phenotype is incorrect (Beach et al., 2012).”
BackgroundTesting for Alzheimer Disease Biomarkers and Disclosing Results Across the Disease Continuum
Largent, E. A., Grill, J. D., O’Brien, K. S., Wolk, D. A., Harkins, K. A., & Karlawish, J. H. (2023) · Neurology · doi:10.1212/wnl.0000000000206891 · Cited by 64
“Even at the dementia stage, etiologic misdiagnosis is common.(21) AD biomarker results can thus provide valuable diagnostic and prognostic information and assist cognitively impaired adults and their families in future planning.”
BackgroundHigh‐resolution metabolomic profiling of Alzheimer’s disease in plasma
Niedzwiecki, M. M., Walker, D. I., Howell, J. C., Watts, K. D., Jones, D. P., Miller, G. W., & Hu, W. T. (2019) · Annals of Clinical and Translational Neurology · doi:10.1002/acn3.50956 · Cited by 65
“At the same time, “-omics” studies in AD research suffer from non-standardized sample handling, over-training in a single small cohort, and limited accuracy of the clinical AD diagnosis, with at least 17% of clinically-probable AD found to have no AD neuropathology on autopsy.(6,9) Along with inter-individual variabil…”
BackgroundSánchez, D., Castilla-Marti, M., Rodríguez‐Gómez, O., Valero, S., Piferrer, A., Martínez, G., Martínez, J., Serra, J., Moreno–Grau, S., Hernández‐Olasagarre, B., et al. (2018) · Scientific Reports · doi:10.1038/s41598-018-34577-3 · Cited by 64
Blood Amyloid-β Oligomerization as a Biomarker of Alzheimer’s Disease: A Blinded Validation Study
Youn, Y. C., Lee, B. S., Kim, G. J., Ryu, J. S., Lim, K., Lee, R., Suh, J., Park, Y. H., Pyun, J., Ryu, N., et al. (2020) · Journal of Alzheimer s Disease · doi:10.3233/jad-200061 · Cited by 65
Prevalence of Traumatic Brain Injury in Early Versus Late-Onset Alzheimer’s Disease
Mendez, M. F., Paholpak, P., Lin, A., Zhang, J. Y., & Teng, E. (2015) · Journal of Alzheimer s Disease · doi:10.3233/jad-143207 · Cited by 62
“3% [33].”
Mallik, A. K., Drzezga, A. E., & Minoshima, S. (2016) · Seminars in Nuclear Medicine · doi:10.1053/j.semnuclmed.2016.09.005 · Cited by 64
Towards clinical application of tau PET tracers for diagnosing dementia due to Alzheimer's disease
Ossenkoppele, R., & Hansson, O. (2021) · Alzheimer's & Dementia · doi:10.1002/alz.12356 · Cited by 62
Amyloid imaging, Risk Disclosure and Alzheimer’s Disease: Ethical and Practical Issues
Roberts, J. S., Dunn, L. B., & Rabinovici, G. D. (2013) · Neurodegenerative Disease Management · doi:10.2217/nmt.13.25 · Cited by 64
Chien, Y.-W., Hong, S.-Y., Cheah, W.-T., Yao, L.-H., Chang, Y., & Fu, L. (2019) · Scientific Reports · doi:10.1038/s41598-019-56020-x · Cited by 61
Mathys, J., Gholamrezaee, M., Henry, H., von Gunten, A., & Popp, J. (2017) · Experimental Gerontology · doi:10.1016/j.exger.2017.10.013 · Cited by 51
“Diagnosis of AD based on clinical and neuropsychological features (McKhann et al., 2011) has limited accuracy in discriminating between cognitive impairment due to AD pathology and cognitive impairment of other causes (Beach et al., 2012).”
Regional hypometabolism in the 3xTg mouse model of Alzheimer's disease
Adlimoghaddam, A., Snow, W. M., Stortz, G., Perez, C., Djordjevic, J., Goertzen, A. L., Ko, J. H., & Albensi, B. C. (2019) · Neurobiology of Disease · doi:10.1016/j.nbd.2019.03.008 · Cited by 61
Clinical impact of [18F]flutemetamol PET among memory clinic patients with an unclear diagnosis
Leuzy, A., Savitcheva, I., Chiotis, K., Lilja, J., Andersen, P., Bogdanović, N., Jelić, V., & Nordberg, A. K. (2019) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-019-04297-5 · Cited by 60
Comparison of symptomatic and asymptomatic persons with primary age-related tauopathy
Besser, L. M., Crary, J. F., Mock, C., & Kukull, W. A. (2017) · Neurology · doi:10.1212/wnl.0000000000004521 · Cited by 59
“Unauthorized reproduction of this article is prohibited. respects are indistinguishable from AD NFTs.11 However, individuals with PART usually display milder cognitive symptoms than patients with AD.9 Some evidence suggests that subjective memory complaints are common in PART12 and that PART dementia is more common in…”
BackgroundInfluentialSelf-citationSelvackadunco, S., Langford, K., Shah, Z., Hurley, S. M., Bódi, I., King, A., Aarsland, D., Troakes, C., & Al‐Sarraj, S. (2019) · Journal of Neural Transmission · doi:10.1007/s00702-018-01967-w · Cited by 63
Medical costs of Alzheimer's disease misdiagnosis among US Medicare beneficiaries
Hunter, C. A., Kirson, N. Y., Desai, U. S., Cummings, A. K. G., Faries, D. E., & Birnbaum, H. G. (2015) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2015.06.1889 · Cited by 58
“The application of neuropathologic and neuroimaging techniques has revealed a substantial rate of misdiagnosis for multiple types of dementia in both clinical and research settings, even when using strict diagnostic criteria [10–12].”
Jutkowitz, E., MacLehose, R. F., Gaugler, J. E., Dowd, B. E., Kuntz, K. M., & Kane, R. L. (2016) · The Journals of Gerontology Series A · doi:10.1093/gerona/glw079 · Cited by 58
Koenig, L. N., Day, G. S., Salter, A. R., Keefe, S., Marple, L. M., Long, J. M., LaMontagne, P., Massoumzadeh, P., Snider, B. J., Kanthamneni, M., et al. (2020) · NeuroImage Clinical · doi:10.1016/j.nicl.2020.102248 · Cited by 62
“To appear in: NeuroImage: Clinical Received date: 12 December 2019 Revised date: 12 March 2020 Accepted date: 15 March 2020 Please cite this article as: Lauren N. Koenig , Gregory S. Day , Amber Salter , Sarah Keefe , Laura M. Marple , Justin Long , Pamela LaMontagne , Parinaz Massoumazada , B. Joy Snider , Manasa Kan…”
Lessons Learnt from the Second Generation of Anti-Amyloid Monoclonal Antibodies Clinical Trials
Kwan, A. T. H., Arfaie, S., Therriault, J., Rosa‐Neto, P., & Gauthier, S. G. (2020) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000511506 · Cited by 59
Blood Pressure and Vascular Cognitive Impairment
Levine, D. A., Springer, M. V., & Brodtmann, A. G. (2022) · Stroke · doi:10.1161/strokeaha.121.036140 · Cited by 63
Fluid biomarkers in Alzheimer's disease
Simrén, J., Elmgren, A., Blennow, K., & Zetterberg, H. (2023) · Advances in Clinical Chemistry · doi:10.1016/bs.acc.2022.09.006 · Cited by 58
Kang, J. H., Korecka, M., Lee, E. B., Cousins, K. A. Q., Tropea, T. F., Chen-Plotkin, A. A., Irwin, D. J., Wolk, D., Brylska, M., Wan, Y., et al. (2023) · Clinical Chemistry · doi:10.1093/clinchem/hvad139 · Cited by 64
Certified normal: Alzheimer's disease biomarkers and normative estimates of cognitive functioning
Hassenstab, J. J., Chasse, R., Grabow, P., Benzinger, T. L. S., Fagan, A. M., Xiong, C., Jasielec, M. S., Grant, E., & Morris, J. C. (2016) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2016.03.014 · Cited by 58
“In addition, clinical diagnosis, even from National Institute on Aging funded Alzheimer’s Disease Centers, is inaccurate in 15% or more of cases, when compared to the gold standard of neuropathologic diagnosis (Beach et al., 2012).”
ResultBlanken, A. E., Hurtz, S., Zarow, C., Biado, K., Honarpisheh, H., Somme, J. H., Brook, J. K., Tung, S., Kraft, E., Lo, D. C. W., et al. (2017) · NeuroImage Clinical · doi:10.1016/j.nicl.2017.04.020 · Cited by 57
“In the hands of highly trained dementia specialists, the accuracy of bedside clinical diagnosis is still suboptimal, reaching 70.9% to 87.3% sensitivity and 44.3% to 70.8% specificity (Beach et al., 2012; Shim et al., 2013).”
InfluentialBeyond amyloid: Getting real about nonamyloid targets in Alzheimer's disease
Herrup, K., Carrillo, M. C., Schenk, D., Cacace, A. M., DeSanti, S., Fremeau, R. T., Bhat, R. V., Glicksman, M. A., May, P. C., Swerdlow, R. H., et al. (2013) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2013.01.017 · Cited by 55
“Using this gold standard, a recent study conducted by National Alzheimer’s Coordinating Center showed that the median sensitivity of clinical diagnosis was about 87% and the median specificity was only about 58% [8].”
ResultAssociation of plasma P-tau181 with memory decline in non-demented adults
Therriault, J., Benedet, A. L., Pascoal, T. A., Lussier, F. Z., Tissot, C., Karikari, T. K., Ashton, N. J., Chamoun, M., Bezgin, G., Mathotaarachchi, S., et al. (2021) · Brain Communications · doi:10.1093/braincomms/fcab136 · Cited by 56
Advances in Deep Neuropathological Phenotyping of Alzheimer Disease: Past, Present, and Future
Shakir, M., & Dugger, B. N. (2022) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/nlab122 · Cited by 58
Gardner, R. C., Langa, K. M., & Yaffe, K. S. (2017) · PLoS Medicine · doi:10.1371/journal.pmed.1002246 · Cited by 60
Ceccaldi, M. P., Jonveaux, T., Verger, A., Krolak‐Salmon, P., Houzard, C., Godefroy, O., Shields, T., Perrotin, A., Gismondi, R., Bullich, S., et al. (2017) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2017.09.009 · Cited by 56
“As many as 39% of patients diagnosed with non-AD dementia show histopathological features of AD on postmortem examination, while up to 25% of patients with a clinical diagnosis of AD have no amyloid pathology at autopsy [2].”
Lee, J. S., Kim, C., Shin, J., Cho, H., Shin, D.-S., Kim, N., Kim, H. J., Kim, Y., Lockhart, S. N., Na, D. L., et al. (2018) · Scientific Reports · doi:10.1038/s41598-018-22277-x · Cited by 58
“Considering the discrepancy in diagnosis for AD between clinical and neuropathological data 27 , and a certain portion of clinically diagnosed AD patients may show negative amyloid positron emission tomography scan 28 , we cannot exclude the possibility that our classification meth-ods might have…”
BackgroundAge‐stratified longitudinal study of Alzheimer's and vascular dementia patients
Jørgensen, I. F., Aguayo‐Orozco, A., Lademann, M., & Brunak, S. (2020) · Alzheimer s & Dementia · doi:10.1002/alz.12091 · Cited by 54
A deep ensemble hippocampal CNN model for brain age estimation applied to Alzheimer’s diagnosis
Poloni, K. M., & Ferrari, R. J. (2022) · Expert Systems with Applications · doi:10.1016/j.eswa.2022.116622 · Cited by 55
Blood-Based ATN Biomarkers of Alzheimer’s Disease: A Meta-Analysis
Koychev, I. G., Jansen, K., Dette, A., Shi, L., & Holling, H. (2020) · Journal of Alzheimer s Disease · doi:10.3233/jad-200900 · Cited by 59
Singh, S. G., Das, D., Barman, U., & Saikia, M. J. (2024) · Diagnostics · doi:10.3390/diagnostics14161759 · Cited by 60
“Also generalizing characteristics from various data modalities is difficult [24,25].”
BackgroundMethodDickerson, B. C., Atri, A., Clevenger, C. K., Karlawish, J. H., Knopman, D. S., Lin, P., Norman, M., Onyike, C. U., Sano, M., Scanland, S., et al. (2024) · Alzheimer s & Dementia · doi:10.1002/alz.14337 · Cited by 62
“13 Therefore, it is not uncommon, in older individuals and those with multiple comorbidities, that a cognitive–behavioral syndrome has a “mixed etiology,” which when causing dementia-level impairment is called mixed etiology dementia.”
Alzheimer's disease diagnostic criteria: practical applications
Cummings, J. L. (2012) · Alzheimer s Research & Therapy · doi:10.1186/alzrt138 · Cited by 54
“When applied by expert clinicians, these criteria have an 80% positive predictive value and a 60% negative predictive value for the accurate clinical diagnosis of AD when compared with postmortem examination [4].”
BackgroundMotsinger‐Reif, A. A., Zhu, H., Kling, M. A., Matson, W. R., Sharma, S., Fiehn, O., Reif, D. M., Appleby, D. H., Doraiswamy, P. M., Trojanowski, J. Q., et al. (2013) · Acta Neuropathologica Communications · doi:10.1186/2051-5960-1-28 · Cited by 54
“A recent clinico-pathologic comparison study of more than 900 patients diagnosed at major centers in the United States found that 17-30% of clinical diagnoses were inconsistent with autopsy diagnoses [1].”
BackgroundFluid and imaging biomarkers for Alzheimer's disease: Where we stand and where to head to
Henriques, A. D., Benedet, A. L., Camargos, E. F., Rosa‐Neto, P., & Nóbrega, O. D. T. (2018) · Experimental Gerontology · doi:10.1016/j.exger.2018.01.002 · Cited by 56
Palermo, G., Mazzucchi, S., Vecchia, A. D., Siciliano, G., Bonuccelli, U., Azuar, C., Ceravolo, R., Lista, S., Hampel, H. J., & Baldacci, F. (2020) · Molecular Neurobiology · doi:10.1007/s12035-020-02035-9 · Cited by 55
Khoonsari, P. E., Shevchenko, G., Herman, S., Remnestål, J., Giedraitis, V., Brundin, R., Gunnarsson, M. D., Kilander, L., Zetterberg, H., Nilsson, P., et al. (2019) · Journal of Alzheimer s Disease · doi:10.3233/jad-180855 · Cited by 51
An anti-amyloid therapy works for Alzheimer’s disease: why has it taken so long and what is next?
Hardy, J., & Mummery, C. J. (2023) · Brain · doi:10.1093/brain/awad049 · Cited by 55
“brains collected by the NIH Alzheimer Centres estimated a diagnostic accuracy rate for Alzheimer’s disease in dementia series of ∼70% with genetic analyses of clinical cases giving similar accuracy estimates.(8,9)”
MethodInsights into the use of biomarkers in clinical trials in Alzheimer's disease
Pascoal, T. A., Aguzzoli, C. S., Lussier, F. Z., Crivelli, L., Suemoto, C. K., Fortea, J., Rosa‐Neto, P., Zimmer, E. R., Ferreira, P. C. L., & Bellaver, B. (2024) · EBioMedicine · doi:10.1016/j.ebiom.2024.105322 · Cited by 60
“42 – 45 Most recent clinical trials used only A β biomarkers to enrich their populations, 16 – 18 whereas Donanemab trials were enriched with participants who had an A+/T+ biomarker pro fi le.”
Differentiating the Frontal Presentation of Alzheimer's Disease with FDG-PET
Woodward, M. C., Rowe, C. C., Jones, G. R., Villemagne, V. L., & Varos, T. A. (2015) · Journal of Alzheimer s Disease · doi:10.3233/jad-141110 · Cited by 53
Alzheimer's disease: Only prevention makes sense
Viña, J., & Sanz‐Ros, J. (2018) · European Journal of Clinical Investigation · doi:10.1111/eci.13005 · Cited by 55
A novel Alzheimer’s disease detection approach using GAN-based brain slice image enhancement
Bai, T., Du, M., Li, Z., Ren, L., Ruan, L., Yang, Y., Qian, G., Meng, Z., Zhao, L., & Deen, M. J. (2022) · Neurocomputing · doi:10.1016/j.neucom.2022.04.012 · Cited by 52
“The investigation by Beach et al. [9] showed that sensitivity of AD diagnostic ranged from 70.9 % to 87.3 % and specificity ranged from 44.3 % to 70.8 % .”
InfluentialWeiner, M. W., Harvey, D. J., Landau, S. M., Veitch, D. P., Neylan, T. C., Grafman, J. H., Aisen, P. S. S., Petersen, R. C., Jack, C. R., Tosun, D., et al. (2022) · Alzheimer s & Dementia · doi:10.1002/alz.12712 · Cited by 54
“MCI, n (%) 2 (3) 16 (20) 9 (21) 24 (25)”
Donaghy, P. C., Carrarini, C., Ferreira, D., Habich, A., Aarsland, D., Babiloni, C., Bayram, E., Kane, J. P. M., Lewis, S. J. G., Pilotto, A., et al. (2023) · Alzheimer s & Dementia · doi:10.1002/alz.13105 · Cited by 55
“REM-sleep behavior disorder Pooled proportion (95%CI) 60% (41-76) 4% (1-10) 8% (4-18) <0.”
Kaerst, L., Kuhlmann, A., Wedekind, D., Stoeck, K., Lange, P., & Zerr, I. (2013) · Journal of Alzheimer s Disease · doi:10.3233/jad-130995 · Cited by 53
“[23] collected clinical and neuropathological data from the National Alzheimer’s Coordinating Center, comprising 919 patients, seeking to determine the accuracy of currently used clinical diagnostic methods.”
BackgroundNayate, A. P., Dubroff, J. G., Schmitt, J. E., Nasrallah, I. M., Kishore, R., Mankoff, D. A., Pryma, D. A., & Initiative, A. D. N. (2015) · American Journal of Neuroradiology · doi:10.3174/ajnr.a4281 · Cited by 52
Cai, K., Xu, H., Guan, H., Zhu, W., Jiang, J., Cui, Y. J., Zhang, J., Liu, T., & Wen, W. X. (2017) · PLoS ONE · doi:10.1371/journal.pone.0170875 · Cited by 51
Polygenic Risk Score Analysis of Alzheimer's Disease in Cases without APOE4 or APOE2 Alleles
Escott‐Price, V., Myers, A., Huentelman, M. J., Shoai, M., & Hardy, J. (2019) · The Journal of Prevention of Alzheimer s Disease · doi:10.14283/jpad.2018.46 · Cited by 54
“We believe this is likely to be because of poor diagnostic accuracy among those labeled as AD in the absence of an E4 allele: this interpretation is consistent with post mortem follow up of AD clinical trials, which suggested a diagnostic inaccuracy of up to 25% (6, 7).”
Metabolomics of Neurodegenerative Diseases
Botas, A., Campbell, H. M., Han, X., & Maletić‐Savatić, M. (2015) · International review of neurobiology · doi:10.1016/bs.irn.2015.05.006 · Cited by 52
Immune and myodegenerative pathomechanisms in inclusion body myositis
Keller, C. W., Schmidt, J., & Lünemann, J. D. (2017) · Annals of Clinical and Translational Neurology · doi:10.1002/acn3.419 · Cited by 57
Sacuiu, S. F. (2016) · Handbook of clinical neurology · doi:10.1016/b978-0-12-802973-2.00008-2 · Cited by 57
Coexistence of Multiple Sclerosis and Alzheimer's disease: A review
Luczynski, P., Laule, C., Hsiung, G. R., Moore, G. R. W., & Tremlett, H. L. (2018) · Multiple Sclerosis and Related Disorders · doi:10.1016/j.msard.2018.10.109 · Cited by 52
Identification of genetic heterogeneity of Alzheimer's disease across age
Lo, M., Kauppi, K., Fan, C.-C., Sanyal, N., Reas, E. T., Sundar, V. S., Lee, W., Desikan, R. S., McEvoy, L. K., & Chen, C. (2019) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2019.02.022 · Cited by 53
“First, the previous study showed that the positive predictive value of AD based on the clinical diagnosis was 83%(Beach et al., 2012), which indicates that 17% of AD cases might be misdiagnosed.”
Ruchinskas, R. A. (2019) · The Clinical Neuropsychologist · doi:10.1080/13854046.2019.1585574 · Cited by 52
Rossano, S. M., Johnson, A. S., Smith, A. P., Ziaggi, G., Roetman, A. E., Guzman, D., Okafor, A., Klein, J., Tomljanovic, Z., Stern, Y., et al. (2024) · Alzheimer s & Dementia · doi:10.1002/alz.13699 · Cited by 54
“58 Participants who were amyloid-negative but tau-positive were similar to amyloid-positive and tau-positive participants in terms of age, cortical thickness, memory-biomarker associations, and more.”
Application of the National Institute on Aging-Alzheimer's Association AD criteria to ADNI
Lowe, V. J., Peller, P. J., Weigand, S. D., Quintero, C. M., Tosakulwong, N., Vemuri, P., Senjem, M. L., Jordan, L. G., Jack, C. R., Knopman, D. S., et al. (2013) · Neurology · doi:10.1212/wnl.0b013e318295d6cf · Cited by 50
Suspected non-Alzheimer's pathology – Is it non-Alzheimer's or non-amyloid?
Dani, M., Brooks, D. J., & Edison, P. (2017) · Ageing Research Reviews · doi:10.1016/j.arr.2017.02.003 · Cited by 50
Carswell, C. J., Win, Z., Muckle, K., Kennedy, A. M., Waldman, A. D., Dawe, G., Barwick, T. D., Khan, S., Malhotra, P., & Perry, R. J. (2017) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp-2017-316194 · Cited by 50
Bayram, E., Shan, G., & Cummings, J. L. (2019) · Journal of Alzheimer s Disease · doi:10.3233/jad-181285 · Cited by 49
The impact of demographic, clinical, genetic, and imaging variables on tau PET status
Ossenkoppele, R., Leuzy, A., Cho, H., Sudre, C. H., Strandberg, O. T., Smith, R. A., Palmqvist, S., Mattsson, N., Olsson, T., Jögi, J., et al. (2020) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-020-05099-w · Cited by 53
Bensaïdane, M. R., Beauregard, J., Poulin, S. P., Buteau, F.-A., Guimond, J. V., Bergeron, D., Verret, L., Fortin, M., Houde, M., Bouchard, R. W., et al. (2016) · Journal of Alzheimer s Disease · doi:10.3233/jad-151180 · Cited by 50
“Indeed, trained physicians can diagnose “probable AD” with a sensitivity and specificity of only 71% when compared to pathology, and up to 39% of patients diagnosed with non-AD dementia show postmortem AD-histopathologicalfeatures[4].”
Falgàs, N., Sánchez-Valle, R., Bargalló, N., Balasa, M., Fernández-Villullas, G., Bosch, B., Olives, J., Tort-Merino, A., Antonell, A., Muñoz-García, C., et al. (2019) · NeuroImage: Clinical · doi:10.1016/j.nicl.2019.101927 · Cited by 47
“We consider this fact to be a significant caveat since trying to establish AD diagnosis without biological confirmation of the disease can lead to higher rates of misdiagnosis (Beach et al., 2012).”
BackgroundWhat does heritability of Alzheimer’s disease represent?
Baker, E. A., Leonenko, G., Schmidt, K. M., Hill, M., Myers, A., Shoai, M., de Rojas, I., Tesi, N., Holstege, H. H., van der Flier, W. M., et al. (2023) · PLoS ONE · doi:10.1371/journal.pone.0281440 · Cited by 55
“This is expected as a pathologically/amyloid confirmed diagnosis is more accurate than a clinical diagnosis of AD which may contain up to 30% of misdiagnosed individuals [4, 5].”
BackgroundNeuroimaging biomarkers in Alzheimer’s disease and other dementias
Villemagne, V. L., & Chételat, G. (2016) · Ageing Research Reviews · doi:10.1016/j.arr.2016.01.004 · Cited by 55
The Dynamics of Dementia Communication
Wray, A. (2020) · doi:10.1093/oso/9780190917807.001.0001 · Cited by 51
Advances in Brain Amyloid Imaging
Krishnadas, N., Villemagne, V. L., Doré, V., & Rowe, C. C. (2021) · Seminars in Nuclear Medicine · doi:10.1053/j.semnuclmed.2020.12.005 · Cited by 48
Katsumata, Y., Shade, L. M. P., Hohman, T. J., Schneider, J. A., Bennett, D. A., Farfel, J. M., Kukull, W. A., Fardo, D. W., & Nelson, P. T. (2022) · Neurobiology of Disease · doi:10.1016/j.nbd.2022.105880 · Cited by 45
“More specifically, previous studies revealed that the clinical diagnosis of AD dementia was imperfectly predictive of ADNC (Beach et al., 2012), and only ~20% of dementia cases are “pure” ADNC at autopsy (Karanth et al., 2021; Shim et al., 2013).”
Self-citationThe future of human cerebral cartography: a novel approach
Frackowiak, R. S. J., & Markram, H. (2015) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2014.0171 · Cited by 49
“B 370 : 20140171 recent major pathological reviews, diagnoses of Alzheimer’s disease in life are no better than 60–70% accurate [67,68].”
BackgroundA Review of Biomarkers for Neurodegenerative Disease: Will They Swing Us Across the Valley?
Beach, T. G. (2017) · Neurology and Therapy · doi:10.1007/s40120-017-0072-x · Cited by 50
Self-citationHippocampal Sclerosis, Argyrophilic Grain Disease, and Primary Age-Related Tauopathy
Jicha, G. A., & Nelson, P. T. (2019) · CONTINUUM Lifelong Learning in Neurology · doi:10.1212/con.0000000000000697 · Cited by 51
Blennow, K., & Zetterberg, H. (2019) · Progress in molecular biology and translational science · doi:10.1016/bs.pmbts.2019.07.006 · Cited by 46
Cure, S., Abrams, K. R., Belger, M. A., Dell’Agnello, G., & Happich, M. (2014) · Journal of Alzheimer s Disease · doi:10.3233/jad-131559 · Cited by 47
“However, despite these rigorous criteria and detailed examinations, 10% to 20% of patients clinically diagnosed with AD do not have AD pathology [9] and up to 40% have neuropathological findings of AD though clinically diagnosed not to have it [10].”
Agogo, G. O., Ramsey, C. M., Gnjidic, D., Moga, D. C., & Allore, H. G. (2018) · International Psychogeriatrics · doi:10.1017/s1041610218000017 · Cited by 47
“…were deemed to have dementia if they met the standard criteria for dementia of the Alzheimer’s type or for other non-Alzheimer’s dementing disorders based on comprehensive neuropsychiatric battery or cognitive assessment with a trained ADC clinician (Mirra et al., 1991; Beach et al., 2012).”
MethodAli, M., Erabadda, B., Chen, Y., Xu, Y., Gong, K., Liu, M., Binette, A. P., Timsina, J., Western, D., Yang, C., et al. (2025) · Nature Medicine · doi:10.1038/s41591-025-03833-1 · Cited by 58
“This reliance on clinical assessments may introduce some diagnostic misclassification, potentially reducing power and underestimating the extent of molecular overlap across NDs 67 .”
Gurnani, A. S., & Gavett, B. E. (2016) · Neuropsychology Review · doi:10.1007/s11065-016-9334-0 · Cited by 46
“Autopsy studies suggest that misdiagnosis occurs in 12–23% of individuals with a clinical diagnosis of AD (Beach et al. 2012; Gaugler et al. 2013).”
BackgroundTremblay, C., François, A., Delay, C., Freland, L., Vandal, M., Bennett, D. A., & Calon, F. (2017) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/nlw109 · Cited by 49
“MCI-NAP individuals could represent a mix of several different types of amyloidunrelated pathologies that may resemble AD clinically, in line with the fact that a non-negligible minority of patients do not meet neuropathologic criteria for AD histopathology (126, 128).”
ResultVarikasuvu, S. R., Bukke, S., Dutt, N., et al. (2017) · Journal of Trace Elements in Medicine and Biology · doi:10.1016/j.jtemb.2017.04.005 · Cited by 46
Effectiveness of Florbetapir PET Imaging in Changing Patient Management
Pontecorvo, M. J., Siderowf, A. D., Dubois, B., Doraiswamy, P. M., Frisoni, G. B., Grundman, M., Nobili, F. M., Sadowsky, C., Salloway, S., Arora, A., et al. (2017) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000478007 · Cited by 46
The role of biomarkers and imaging in the clinical diagnosis of dementia
Bayer, A. J. (2018) · Age and Ageing · doi:10.1093/ageing/afy004 · Cited by 45
“Even in expert hands, clinical diagnosis of Alzheimer’s disease (AD) dementia will be wrong in about 20% of cases [2].”
Multi-scale graph-based grading for Alzheimer’s disease prediction
Hett, K., Ta, V., Oğuz, İ., Manjón, J. V., & Pierrick Coupé, A. (2020) · Medical Image Analysis · doi:10.1016/j.media.2020.101850 · Cited by 48
“…the diagnoses provided by ADNI were established using a set of cognitive-scores and functional performances, which results in diagnosis error ( Beach et al., 2012; Matias-Guiu et al., 2017 ) since AD can only be diagnosed for sure after a postmortem analysis revealing the two cerebral…”
Cognitive heterogeneity in probable Alzheimer disease
Qiu, Y., Jacobs, D. M., Messer, K. S., Salmon, D. P., & Feldman, H. (2019) · Neurology · doi:10.1212/wnl.0000000000007967 · Cited by 52
Genetic architecture of common non-Alzheimer’s disease dementias
Guerreiro, R. J., Gibbons, E., Tábuas‐Pereira, M., Kun‐Rodrigues, C., Cordeiro, G., & Brás, J. (2020) · Neurobiology of Disease · doi:10.1016/j.nbd.2020.104946 · Cited by 48
Degenhardt, E. K., Witte, M. M., Case, M. G., Yu, P., Henley, D. B., Hochstetler, H. M., D’Souza, D. N., & Trzepacz, P. T. (2016) · Psychosomatics · doi:10.1016/j.psym.2015.12.002 · Cited by 48
Metadata
- Authors
- Beach, T. G., Monsell, S. E., Phillips, L. E., & Kukull, W.
- Affiliations
- Banner Sun Health Research Institute (US)
- University of Washington (US)
- Corresponding author
- Beach, Thomas G.
- Venue
- Journal of Neuropathology & Experimental Neurology
- Publisher
- Oxford University Press (OUP)
- Published
- 2012-04
- Volume
- 71
- Issue
- 4
- Pages
- 266-273
- ISSN
- 0022-3069 (ISSN-L)
- 1554-6578
- PMC
- PMC3331862
- OpenAlex
- W1974300727
- Semantic Scholar
- 59ed18597d0cb2e750fc7f3c928871aedf079d0a
- Cited by
- 1,103
- References
- 56
- Citations by year
- 2026: 71 · 2025: 94 · 2024: 94 · 2023: 92 · 2022: 91 · 2021: 84 · 2020: 117 · 2019: 90 · 2018: 74 · 2017: 69 · 2016: 66 · 2015: 71 · 2014: 34 · 2013: 46 · 2012: 9
- FWCI
- 36.35
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuropathology & Experimental Neurology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Michael J. Fox Foundation for Parkinson's Research (P30 AG19610)
- Arizona Department of Health Services (P30 AG19610, U01 AG016976)
- National Alzheimer's Coordinating Center (U01AG016976)
- Arizona Biomedical Research Commission (P30 AG19610)
- National Institute on Aging (U01AG016976, P30AG019610, U19AG010483)
- 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
- Social Sciences › Psychology › Applied Psychology › Psychological Testing and Assessment
- Keywords
- Alzheimer's disease, diagnostic accuracy, neuropathologic diagnosis, sensitivity and specificity, neuritic plaques, misdiagnosis, dementia, Lewy body disease, frontotemporal lobar degeneration, argyrophilic grain disease, hippocampal sclerosis, cerebrovascular disease
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Female, Humans, Male, Middle Aged, United States, Databases, Factual, National Institute on Aging (U.S.)
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