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 301–400 of 1,108
Enrichment of clinical trials in MCI due to AD using markers of amyloid and neurodegeneration
Wolz, R., Schwarz, A. J., Gray, K. R., Yu, P., Hill, D., & Initiative, A. D. N. (2016) · Neurology · doi:10.1212/wnl.0000000000003126 · Cited by 46
Yoo, S., Son, G., Bae, J., Kim, S. Y., Yoo, Y. K., Park, D., Baek, S. Y., Chang, K., Suh, Y., Lee, Y., et al. (2020) · Scientific Reports · doi:10.1038/s41598-020-68148-2 · Cited by 44
Defining and predicting transdiagnostic categories of neurodegenerative disease
Cornblath, E. J., Robinson, J. L., Irwin, D. J., Lee, E. B., Lee, V. M. ‐., Trojanowski, J. Q., & Bassett, D. S. (2020) · Nature Biomedical Engineering · doi:10.1038/s41551-020-0593-y · Cited by 48
Concordance of Clinical Alzheimer Diagnosis and Neuropathological Features at Autopsy
Gauthreaux, K., Bonnett, T. A., Besser, L. M., Brenowitz, W. D., Teylan, M., Mock, C., Chen, Y.-C., Chan, K. C. G., Keene, C. D., Zhou, X.-H., et al. (2020) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/nlaa014 · Cited by 44
“Beach et al (6) found that sensitivity ranged from 70.”
BackgroundInfluentialSelf-citationA Review of Application of Aβ42/40 Ratio in Diagnosis and Prognosis of Alzheimer’s Disease
Xu, C., Zhao, L., & Dong, C. (2022) · Journal of Alzheimer s Disease · doi:10.3233/jad-220673 · Cited by 46
“Beach et al. [63] discovered that approximately 20% of the pathological phenotypes of the brain of clinical AD patients did not support their prenatal diagnosis, and inconsistent cases were usually identified as Lewy body dementia, FTD, corticobasal degeneration, and progressive supranuclear palsy…”
Screening for dementia - is it a no brainer?
Fox, C., Lafortune, L., Boustani, M. A., Dening, T., Rait, G., & Brayne, C. (2013) · International Journal of Clinical Practice · doi:10.1111/ijcp.12239 · Cited by 44
Witte, M. M., Foster, N. L., Fleisher, A., Williams, M., Quaid, K. A., Wasserman, M. R., Hunt, G., Roberts, J. S., Rabinovici, G. D., Levenson, J. L., et al. (2015) · Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring · doi:10.1016/j.dadm.2015.06.006 · Cited by 44
“Postmortem neuropathology studies indicate that even dementia experts often have difficulty in making an accurate clinical diagnosis of AD [12,23].”
BackgroundSensitivity and Specificity of Diagnostic Accuracy in Alzheimer’s Disease
Gaugler, J. E., Kane, R. L., Johnston, J. A., & Sarsour, K. (2013) · American Journal of Alzheimer s Disease & Other Dementias® · doi:10.1177/1533317513488910 · Cited by 50
“Alternatively, the use of pathological diagnosis as a gold standard is challenging since a proportion of older persons that fulfill predetermined criteria for AD (which themselves have been subjected to recent revision)(56) do not present with clinical symptoms while alive.(55) In addition, AD often co-occurs with oth…”
BackgroundInfluentialA broader view of dementia: multiple co-pathologies are the norm
Coulthard, E. J., & Love, S. (2018) · Brain · doi:10.1093/brain/awy153 · Cited by 45
Shaw, L. M. J., Hansson, O., Manuilova, E., Masters, C. L., Doecke, J. D., Li, Q.-X., Rutz, S., Widmann, M., Leinenbach, A., & Blennow, K. (2019) · Clinical Biochemistry · doi:10.1016/j.clinbiochem.2019.05.006 · Cited by 45
Sánchez, D., Castilla-Marti, M., Marquié, M., Valero, S., Moreno–Grau, S., Rodríguez‐Gómez, O., Piferrer, A., Martínez, G., Martínez, J., de Rojas, I., et al. (2020) · Scientific Reports · doi:10.1038/s41598-020-58399-4 · Cited by 45
Diabetes Mellitus Increases Risk of Incident Dementia in APOE ɛ 4 Carriers: A Meta-Analysis
Li, L., Cavuoto, M. G., Biddiscombe, K. J., & Pike, K. E. (2020) · Journal of Alzheimer s Disease · doi:10.3233/jad-191068 · Cited by 44
“Given the reasonable accuracy rates for clinical criteria diagnoses [57], the lack of neuroimaging data for the other studies did not affect our judgement of risk of bias.”
Dobson, R., Patterson, K., Malik, R., Mandal, U., Asif, H., Humphreys, R. A., Payne, M., O-charoenrat, E., Huzzey, L., Clare, A., et al. (2024) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp-2024-333468 · Cited by 44
“19 Accurate diagnosis, which requires biomarker support would reduce the number ultimately being eligible for therapies.”
BackgroundWang, Y., Liu, S., Spiteri, A. G., Huynh, A. L. H., Chu, C., Masters, C. L., Goudey, B., Pan, Y., & Jin, L. (2024) · Alzheimer s Research & Therapy · doi:10.1186/s13195-024-01540-6 · Cited by 48
“Accurate differential diagnosis is important for clinicians to offer the most suitable care options to the patients [91].”
BackgroundGault, L. M., Lenz, R. A., Ritchie, C. W., Meier, A., Othman, A. A., Tang, Q., Berry, S. M., Pritchett, Y., & Robieson, W. (2016) · Alzheimer s Research & Therapy · doi:10.1186/s13195-016-0210-1 · Cited by 44
“Based on neuropathological analysis of patients meeting diagnostic criteria for AD [30, 31] and on recent clinical trial results showing that approximately 30 % of subjects selected with these criteria have negative positron emission tomography scans for amyloid [32, 33], we expect that some subjects in this trial wou…”
BackgroundMcHugh, D. J., Root, J. C., Nelson, C. J., & Morris, M. J. (2018) · Cancer · doi:10.1002/cncr.31153 · Cited by 43
“Although the authors acknowledge that there may be some decrease in diagnostic accuracy in relying on clinical diagnoses rather than autopsy results, they reference 2 studies that reported adequate sensitivity and specificity in relying on clinical diagnoses.(58,59) In both studies, however, clinical diagnoses were ma…”
ResultPre‐analytical protocol for measuring Alzheimer's disease biomarkers in fresh CSF
Hansson, O., Rutz, S., Zetterberg, H., Bauer, E., Hähl, T., Manuilova, E., Mert, M. C., Wahl, S., Blennow, K., & Stomrud, E. (2020) · Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring · doi:10.1002/dad2.12137 · Cited by 43
“Several criteria must be achieved before implementing AD CSF biomarkers in routine clinical practice: (1) development/validation of reliable assays for measuring biomarkers; (2) determination of criteria to guide appropriate use of these biomarkers; and (3) establishment of a pre-analytical protocol for measuring biom…”
BackgroundMethodBoccardi, M., Dodich, A., Albanese, E., Gayet‐Ageron, A., Festari, C., Ashton, N. J., Bischof, G. N., Chiotis, K., Leuzy, A., Wolters, E. E., et al. (2021) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-020-05120-2 · Cited by 44
Neuropathology of the Alzheimer's continuum: an update
Jellinger, K. A. (2020) · Free Neuropathology · doi:10.17879/freeneuropathology-2020-3050 · Cited by 52
Leuzy, A., Mattsson, N., Cullen, N. C., Stomrud, E., Palmqvist, S., Joie, R. L., Iaccarino, L., Zetterberg, H., Rabinovici, G. D., Blennow, K., et al. (2023) · Alzheimer s & Dementia · doi:10.1002/alz.12897 · Cited by 46
“ences in how the assays are run as well as variability in kit components between assay lots),8,11 and (3) biological/patient-related (i.”
Acoustic Speech Analysis in Alzheimer's Disease: A Systematic Review and Meta-Analysis
Saeedi, S., Hetjens, S., Grimm, M., & Latoszek, B. B. V. (2024) · The Journal of Prevention of Alzheimer s Disease · doi:10.14283/jpad.2024.132 · Cited by 43
“Some studies have shown that a significant proportion of individuals with a clinical diagnosis of AD may not have evidence of AD neuropathology on biomarker testing (9, 10).”
Neuroligin-1 in brain and CSF of neurodegenerative disorders: investigation for synaptic biomarkers
Camporesi, E., Lashley, T., Gobom, J., Lantero‐Rodriguez, J., Hansson, O., Zetterberg, H., Blennow, K., & Becker, B. (2021) · Acta Neuropathologica Communications · doi:10.1186/s40478-021-01119-4 · Cited by 43
“The MMSE test, together with other neuropsychological tests, is a very useful tool to assess the patient’s cognitive status, but because of comorbidities and overlap between symptoms a definitive diagnosis is challenging [59].”
MethodInitiative, A. D. N., Ramanan, V. K., Lesnick, T. G., Przybelski, S. A., Heckman, M. G., Knopman, D. S., Graff‐Radford, J., Lowe, V. J., Machulda, M. M., Mielke, M. M., et al. (2021) · Acta Neuropathologica Communications · doi:10.1186/s40478-021-01154-1 · Cited by 40
“Case–control GWAS designs have been fruitful in identifying non-APOE risk variants for AD dementia, but may not be ideal to discover disease-specific resilience factors given the discrepancies between clinically diagnosed probable AD dementia versus biologically defined AD [5] as well as the heterogeneity amongst cont…”
BackgroundBacterial pneumonia and subsequent dementia risk: A nationwide cohort study
Chu, C., Liang, C., Tsai, S., Bai, Y., Su, T., Chen, T., & Chen, M. (2022) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2022.04.002 · Cited by 41
Visuospatial dysfunction in Alzheimer's disease and behavioural variant frontotemporal dementia
Salimi, S., Irish, M., Foxe, D., Hodges, J. R., Piguet, O., & Burrell, J. R. (2019) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2019.04.019 · Cited by 40
Iaccarino, L., Sala, A., Caminiti, S. P., Presotto, L., Perani, D., & Initiative, F. T. A. D. N. (2020) · Journal of Alzheimer s Disease · doi:10.3233/jad-190954 · Cited by 40
“Since ADNI enrollment criteria are based on the 1984 NINCDS/ADRDA clinical criteria for AD [27], known to yield some mismatch against definite neuropathological diagnosis [28], we set additional and more stringent inclusion criteria to select our clinical sample.”
MethodKokkinou, M., Beishon, L., Smailagic, N., Noel-Storr, A. H., Hyde, C., Ukoumunne, O. C., Worrall, R., Hayen, A., Desai, M., Ashok, A. H., et al. (2021) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd010945.pub2 · Cited by 43
Sierra, A., Balasa, M., Olives, J., Antonell, A., Iranzo, Á., Castellvı́, M., Bosch, B., Grau‐Rivera, O., Fernández‐Villullas, G., Rami, L., et al. (2015) · Neurodegenerative Diseases · doi:10.1159/000439258 · Cited by 42
Micro-, Meso- and Macro-Dynamics of the Brain
Buzsáki, G., Christen, Y., & Publishing, S. I. (2016) · Research and perspectives in neurosciences · doi:10.1007/978-3-319-28802-4 · Cited by 44
Cox Regression Model with Doubly Truncated Data
Rennert, L., & Xie, S. X. (2017) · Biometrics · doi:10.1111/biom.12809 · Cited by 40
Nanoconstructs as a versatile tool for detection and diagnosis of Alzheimer biomarkers
Gopalan, D., Pandey, A. P., Alex, A. T., Kalthur, G., Pandey, S., Udupa, N., & Mutalik, S. (2020) · Nanotechnology · doi:10.1088/1361-6528/abcdcb · Cited by 42
“3%, respectively, compared to post-mortem histopathology [3].”
Longitudinal memory profiles in behavioral-variant frontotemporal dementia and Alzheimer’s disease
Schubert, S., Leyton, C. E., Hodges, J. R., & Piguet, O. (2016) · Journal of Alzheimer's Disease · doi:10.3233/jad-150802 · Cited by 37
“Ascertainment of brain pathology in life in dementia remains diffi-cult, even in highly-specialized dementia clinics [31].”
Soluble amyloid precursor proteins and secretases as Alzheimer's disease biomarkers
Perneczky, R., Alexopoulos, P., & Kurz, A. (2013) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2013.10.001 · Cited by 42
Apostolova, L. G., Haider, J. M., Goukasian, N., Rabinovici, G. D., Chételat, G., Ringman, J. M., Kremen, S. A., Grill, J. D., Restrepo, L., Mendez, M. F., et al. (2016) · Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring · doi:10.1016/j.dadm.2016.12.001 · Cited by 39
“The major drawbacks cited by insurance carriers are (1) imperfect specificity [2], (2) ethical concern that cognitively normal individualsmight be inappropriately scanned (i.”
BackgroundResultInfluentialLi, W., Shen, Y., Tian, D., Bu, X., Zeng, F., Liu, Y.-H., Chen, Y., Yao, X., Li, H.-Y., Chen, D., et al. (2019) · Journal of Alzheimer s Disease · doi:10.3233/jad-190056 · Cited by 39
“However, based on our present study, the amyloid-positive rate of patients with typical AD symptoms was merely 77.36%, which was consistent with previous studies that the prevalence of amyloid positivity ranging from 65 % to 91.2% [31–35].”
InfluentialBrain Tau Imaging: Food and Drug Administration Approval of 18F-Flortaucipir Injection
Mattay, V. S., Fotenos, A. F., Ganley, C. J., & Marzella, L. (2020) · Journal of Nuclear Medicine · doi:10.2967/jnumed.120.252254 · Cited by 40
“The accuracy of a clinical diagnosis of AD by dementia experts is modest (2), and a definitive diagnosis of AD can be established only by demonstrating the presence of b-amyloid plaques and tau-neurofibrillary tangles (NFTs) in the brain (3).”
BackgroundDimethylarginines, Homocysteine Metabolism, and Cerebrospinal Fluid Markers for Alzheimer's Disease
Arlt, S., Schwedhelm, E., Kölsch, H., Jahn, H., Linnebank, M., Smulders, Y. M., Jessen, F., Böger, R. H., & Popp, J. (2012) · Journal of Alzheimer s Disease · doi:10.3233/jad-2012-112138 · Cited by 39
“The diagnostic accuracy of clinical AD is reduced compared to neuropathological diagnosis with a sensitivity of 71–87% and a specificity of 44 to 71% [38].”
Neuropsychological Markers of Cognitive Decline in Persons With Alzheimer Disease Neuropathology
Hassenstab, J. J., Monsell, S. E., Mock, C., Roe, C. M., Cairns, N. J., Morris, J. C., & Kukull, W. A. (2015) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0000000000000254 · Cited by 40
Self-citationPolsinelli, A. J., Logan, P. E., Lane, K. A., Manchella, M. K., Nemes, S., Sanjay, A. B., Gao, S., & Apostolova, L. G. (2022) · Alzheimer s & Dementia · doi:10.1002/alz.12831 · Cited by 40
Avelar‐Pereira, B., Belloy, M. E., O'Hara, R. M., Hosseini, S. M. H., & Initiative, A. D. N. (2022) · Molecular Psychiatry · doi:10.1038/s41380-022-01886-z · Cited by 42
Dugger, B. N., Clark, C. M., Serrano, G. E., Mariner, M., Bedell, B. J., Coleman, R. E., Doraiswamy, P. M., Lu, M., Fleisher, A., Reiman, E. M., et al. (2013) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0000000000000028 · Cited by 37
Self-citationKnight, M. J., Wearn, A. R., Coulthard, E. J., & Kauppinen, R. A. (2018) · Journal of Magnetic Resonance Imaging · doi:10.1002/jmri.26195 · Cited by 38
Usefulness of Biomarkers in the Diagnosis and Prognosis of Early-Onset Cognitive Impairment
Balasa, M., Sánchez‐Valle, R., Antonell, A., Bosch, B., Olives, J., Rami, L., Castellvı́, M., Molinuevo, J. L., & Lladó, A. (2014) · Journal of Alzheimer s Disease · doi:10.3233/jad-132195 · Cited by 39
“Clinicopathological studies have shown that the sensitivity and specificity of the classical clinical criteria for AD diagnosis are around 85% and 70%, respectively [16].”
Incentives and Barriers to Research Participation and Brain Donation Among African Americans
Schnieders, T. C., Danner, D. D., McGuire, C., Reynolds, F., & Abner, E. L. (2013) · American Journal of Alzheimer s Disease & Other Dementias® · doi:10.1177/1533317513488922 · Cited by 39
“On the individual level, although clinical researchers’ ability to identify AD is high, 80% to 90%,(16) it is important to investigate the clinical assessments and brain tissue because a definitive diagnosis of AD can only be made at autopsy.(17)”
BackgroundHernández, M., Ramon-Julvez, U., & Ferraz, F. M. (2022) · PLoS ONE · doi:10.1371/journal.pone.0264695 · Cited by 40
“8 in the identification of probable AD individuals [8].”
Bun, S., Ito, D., Tezuka, T., Kubota, M., Ueda, R., Takahata, K., Moriguchi, S., Kurose, S., Momota, Y., Suzuki, N., et al. (2023) · Alzheimer s Research & Therapy · doi:10.1186/s13195-023-01296-5 · Cited by 39
“However, the accuracy of the clinical diagnosis may be inadequate [2] when referenced to the gold standard neuropathological findings, including amyloid β (Aβ) plaques and intracellular accumulation of the hyperphosphorylated protein tau as neurofibrillary tangles in the brain [3].”
BackgroundGrundman, M., Johnson, K. A., Lu, M., Siderowf, A. D., Dell’Agnello, G., Arora, A., Skovronsky, D., Mintun, M. A., Pontecorvo, M. J., & for the 18F-AV-45-A17 Study Group (2016) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000441139 · Cited by 38
Michaud, T. L., Siahpush, M., Farazi, P. A., Kim, J., Yu, F., Su, D., & Murman, D. L. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-180278 · Cited by 40
“…[15], we did not examine the weight change one-year after the onset of dementia as what has been done in the previous study [18] because: 1) weight loss may precede at least a decade before dementia diagnosis [34, 47]; and 2) there are some misdiagnosis issues embedded in dementia studies [48].”
CSF level of β-amyloid peptide predicts mortality in Alzheimer’s disease
Boumenir, A., Cognat, E., Sabia, S., Hourrègue, C., Lilamand, M., Dugravot, A., Bouaziz-Amar, É., Laplanche, J., Hugon, J., Singh‐Manoux, A., et al. (2019) · Alzheimer s Research & Therapy · doi:10.1186/s13195-019-0481-4 · Cited by 38
Cerebrospinal Fluid Mitochondrial DNA in Rapid and Slow Progressive Forms of Alzheimer’s Disease
Podlesniy, P., Llorens, F., Puigròs, M., Serra, N., Falla, D. S., Schmidt, C., Hermann, P., Zerr, I., & Trullás, R. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21176298 · Cited by 38
“These observations are consistent with previous evidence indicating that purely clinical diagnostic criteria for AD have poor accuracy, with specificity and sensitivity values between 70–80% when compared with neuropathology [18,27].”
ResultKarikari, T. K. (2022) · Journal of Alzheimer s Disease · doi:10.3233/jad-215730 · Cited by 37
“agrees with autopsy-verified AD by 30% [42]).”
Kryscio, R. J., Abner, E. L., Lin, Y., Cooper, G. E., Fardo, D. W., Jicha, G. A., Nelson, P. T., Smith, C. D., Eldik, L. J. V., Wan, L., et al. (2013) · Journal of Alzheimer s Disease · doi:10.3233/jad-122146 · Cited by 39
Llano, D. A., Devanarayan, P., & Devanarayan, V. (2019) · Alzheimer Disease & Associated Disorders · doi:10.1097/wad.0000000000000328 · Cited by 35
[11C]Martinostat PET analysis reveals reduced HDAC I availability in Alzheimer’s disease
Pascoal, T. A., Chamoun, M., Lax, E., Wey, H.-Y., Shin, M., Ng, K. P., Kang, M. S., Mathotaarachchi, S., Benedet, A. L., Therriault, J., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-30653-5 · Cited by 43
Clinical use of biomarkers in the era of Alzheimer's disease treatments
VandeVrede, L. A., & Schindler, S. E. (2024) · Alzheimer s & Dementia · doi:10.1002/alz.14201 · Cited by 40
Pan, C., Korff, A., Galasko, D. R., Ginghină, C., Peskind, E. R., Li, G., Quinn, J. F., Montine, T. J., Cain, K. C., Shi, M. Y., et al. (2015) · Journal of Alzheimer s Disease · doi:10.3233/jad-143099 · Cited by 36
“8% compared 435 to the “gold” standard of postmortem neuropathologic 436 evaluation [2], it is not surprising that autopsy-based 437 studies generally report higher sensitivity and speci438”
Circulating microRNAs as novel biomarkers of Alzheimer's disease
Zendjabil, M. (2018) · Clinica Chimica Acta · doi:10.1016/j.cca.2018.05.039 · Cited by 38
Shaping a data-driven era in dementia care pathway through computational neurology approaches
Wong‐Lin, K., McClean, P. L., McCombe, N., Kaur, D., Sánchez‐Bornot, J. M., Gillespie, P., Todd, S., Finn, D. P., Joshi, A., Kane, J. P. M., et al. (2020) · BMC Medicine · doi:10.1186/s12916-020-01841-1 · Cited by 38
Ashraf, G., McGuinness, M. B., Khan, M. A., Obtinalla, C., Hadoux, X., & van Wijngaarden, P. (2023) · Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring · doi:10.1002/dad2.12421 · Cited by 42
Biofluid biomarkers in Alzheimer’s disease and other neurodegenerative dementias
Zetterberg, H., & Bendlin, B. B. (2026) · Nature · doi:10.1038/s41586-025-10018-w · Cited by 45
“However, most patients evaluated in memory clinics do not have pure AD but often have other accompanying pathophysiological processes 5 (Box 1).”
Beach, T., Schneider, J., Sue, L., Serrano, G., Dugger, B., Monsell, S. E., & Kukull, W. (2014) · Journal of Neuropathology and Experimental Neurology · doi:10.1097/nen.0000000000000114 · Cited by 37
Self-citationLaforce, R. J., Rosa‐Neto, P., Soucy, J., Rabinovici, G. D., Dubois, B., & Gauthier, S. G. (2016) · Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques · doi:10.1017/cjn.2015.401 · Cited by 34
“The clinical diagnosis of AD has only moderate sensitivity and specificity when compared with the pathological cause of dementia as determined at autopsy.(51) Misdiagnosis rates are even higher in complex, atypical patients with an uncertain diagnosis, approaching 30%.”
John, S. E., Gurnani, A. S., Bussell, C. A., Saurman, J. L., Griffin, J. W., & Gavett, B. E. (2016) · Neuropsychology · doi:10.1037/neu0000315 · Cited by 36
“Of note, when other dementia syndromes and neurodegenerative disorders are clinically misdiagnosed as cases of AD, 39% of those misdiagnosed cases possess or exceed the minimum AD histopathological threshold used for diagnosis, suggesting simultaneous pathology (Beach et al., 2012).”
BackgroundCost-effectiveness of cerebrospinal biomarkers for the diagnosis of Alzheimer’s disease
Lee, S. A. W., Sposato, L. A., Hachinski, V., & Cipriano, L. E. (2017) · Alzheimer s Research & Therapy · doi:10.1186/s13195-017-0243-0 · Cited by 38
“Clinical diagnosis of AD has a relatively low and highly uncertain diagnostic accuracy [12, 13].”
Gnjidic, D., Agogo, G. O., Ramsey, C. M., Moga, D. C., & Allore, H. G. (2018) · The Journals of Gerontology Series A · doi:10.1093/gerona/gly078 · Cited by 42
Rapp, T., Andrieu, S., Chartier, F., Deberdt, W. G., Reed, C. C., Belger, M. A., & Vellas, B. J. (2017) · Value in Health · doi:10.1016/j.jval.2017.09.019 · Cited by 35
Hadjichrysanthou, C., Ower, A. K., de Wolf, F., Anderson, R. M., & Initiative, A. D. N. (2018) · PLoS ONE · doi:10.1371/journal.pone.0190615 · Cited by 36
Hornberger, J. C., Bae, J. P., Watson, I., Johnston, J., & Happich, M. (2016) · Current Medical Research and Opinion · doi:10.1080/03007995.2016.1277197 · Cited by 35
Analysis of neurodegenerative Mendelian genes in clinically diagnosed Alzheimer Disease
Fernández, M. V., Kim, J. H., Budde, J., Black, K., Medvedeva, A., Saef, B. A., Deming, Y. K., Del‐Aguila, J. L., Ibáñez, L., Dube, U., et al. (2017) · PLoS Genetics · doi:10.1371/journal.pgen.1007045 · Cited by 35
Evidence-based Interpretation of Amyloid-β PET Results
Bergeron, D., Ossenkoppele, R., & Laforce, R. J. (2018) · Alzheimer Disease & Associated Disorders · doi:10.1097/wad.0000000000000239 · Cited by 33
Impact of Amyloid PET Imaging in the Memory Clinic: A Systematic Review and Meta-Analysis
Shea, Y. F., Barker, W., Greig-Gusto, M. T., Loewenstein, D., Duara, R., & DeKosky, S. T. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-180239 · Cited by 35
“These examinations revealed some major limitations in accuracy of the clinical diagnosis of AD; compared with postmortem examination, a clinical diagnosis of probable AD had sensitivity and specificity of 70.9% and 70.8%, respectively [2].”
InfluentialJang, H., Soroski, T., Rizzo, M., Barral, O., Harisinghani, A., Newton‐Mason, S. M., Granby, S., Vasco, T. D. C., Lewis, C., Tutt, P., et al. (2021) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2021.716670 · Cited by 42
Retinal Biomarkers for Alzheimer Disease: The Facts and the Future
Yuan, A., & Lee, C. S. (2022) · Asia-Pacific Journal of Ophthalmology · doi:10.1097/apo.0000000000000505 · Cited by 39
A History of Senile Plaques: From Alzheimer to Amyloid Imaging
Beach, T. G. (2022) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/nlac030 · Cited by 37
Self-citationAPOE ε4 is associated with earlier symptom onset in LOAD but later symptom onset in EOAD
Polsinelli, A. J., Lane, K. A., Manchella, M. K., Logan, P. E., Gao, S., & Apostolova, L. G. (2023) · Alzheimer s & Dementia · doi:10.1002/alz.12955 · Cited by 34
New horizons in the diagnosis and management of Alzheimer’s Disease in older adults
Dolphin, H., Dyer, A. H., Morrison, L., Shenkin, S. D., Welsh, T. J., & Kennelly, S. (2024) · Age and Ageing · doi:10.1093/ageing/afae005 · Cited by 33
“It has since been estimated that up to one-third of those diagnosed based on these criteria have no evidence of underlying ad neuro-pathology when examined post-mortem [33].”
BackgroundAlcohol Use Disorder and Dementia: A Review
Zahr, N. M. (2024) · Alcohol research · doi:10.35946/arcr.v44.1.03 · Cited by 42
“64,65 Vascular dementia, the second most diagnosed subtype (up to 20% of cases), often coexists with and is incorrectly diagnosed as Alzheimer’s disease.”
BackgroundPahlke, S. C., Kahale, L. A., Mahinrad, S., Sousa‐Pinto, B., Vieira, R. J., McAteer, M. B., Claessen, T., Contador, J., Hofmann, A., Kuchenbecker, L. A., et al. (2025) · Alzheimer s & Dementia · doi:10.1002/alz.70828 · Cited by 42
Fischer, C. E., Qian, W., Schweizer, T. A., Ismail, Z., Smith, E. E., Millikin, C. P., & Muñoz, D. G. (2017) · Alzheimer s & Dementia Translational Research & Clinical Interventions · doi:10.1016/j.trci.2017.06.001 · Cited by 33
“On the basis of the analyses of data from the National Alzheimer’s Coordinating Center (NACC) database, it has been estimated that sensitivity rates for an AD diagnosis are in the range of 71% to 87% whereas specificity rates range from 44% to 71%, leaving much to be desired [6].”
MethodFour subgroups based on tau levels in Alzheimer’s disease observed in two independent cohorts
ADNI, Duits, F. H., Wesenhagen, K. E. J., Ekblad, L. L., Wolters, E. E., Willemse, E. A. J., Scheltens, P., van der Flier, W. M., Teunissen, C. E., Visser, P. J., et al. (2021) · Alzheimer s Research & Therapy · doi:10.1186/s13195-020-00713-3 · Cited by 34
Complete Evaluation of Dementia: PET and MRI Correlation and Diagnosis for the Neuroradiologist
Oldan, J. D., Jewells, V. L., Pieper, B., & Wong, T. Z. (2021) · American Journal of Neuroradiology · doi:10.3174/ajnr.a7079 · Cited by 34
“itors delay cognitive decline, and there is the need for institutionalization and improved end-of-life planning.(1) Molecular imaging modalities demonstrate elevated amyloid-”
BackgroundBalasa, M., Gelpi, E., Martín, I., Antonell, A., Rey, M. J., Grau‐Rivera, O., Molinuevo, J. L., Sánchez‐Valle, R., Lladó, A., & Catalan collaborative Study Group for FTLD (2015) · Neuropathology and Applied Neurobiology · doi:10.1111/nan.12194 · Cited by 32
Tian, Y., Lu, Y., Cao, Y., Dang, C., Wang, N., Tian, K., Luo, Q., Guo, E., Luo, S., Wang, L., et al. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.919614 · Cited by 32
“For decades, the conventional diagnosis for AD relies on deposits of amyloid beta (Aβ)-tau interaction and accumulation of neurofibrillary tangles in focal brain biopsy (Beach et al., 2012).”
BackgroundBhole, R. P., Chikhale, R. V., & Rathi, K. M. (2023) · IBRO Neuroscience Reports · doi:10.1016/j.ibneur.2023.11.003 · Cited by 34
Valizadeh, G., Elahi, R., Hasankhani, Z., Rad, H. S., & Shalbaf, A. (2024) · Archives of Computational Methods in Engineering · doi:10.1007/s11831-024-10176-6 · Cited by 35
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“Furthermore, numerous elderly individuals who appeared cognitively normal near the time of death have been found to harbour AD-related brain changes at autopsy, such as A β plaques and tau tangles [22].”
Higher Working Memory Predicts Slower Functional Decline in Autopsy-Confirmed Alzheimer's Disease
Pillai, J. A., Bonner‐Jackson, A., Walker, E., Mourany, L., & Cummings, J. L. (2014) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000362715 · Cited by 34
Suppa, P., Anker, U., Spies, L., Bopp-Kistler, I., Rüegger‐Frey, B., Klaghofer, R., Gocke, C., Hampel, H. J., Beck, S., & Buchert, R. (2015) · Journal of Alzheimer s Disease · doi:10.3233/jad-141446 · Cited by 31
“8% [40].”
Applicability of digital analysis and imaging technology in neuropathology assessment
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“11 23–27 Apart from research promises, WSI analysis offers the potential to directly benefit clinical applications.”
InfluentialPerrotte, M., Page, A. Y. L., Fournet, M., Sayec, M. L., Rassart, É., Fülöp, T., & Ramassamy, C. (2018) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2018.10.452 · Cited by 33
Kamalian, A., khodadadifar, T., Saberi, A., Masoudi, M., Camilleri, J. A., Eickhoff, C. R., Zarei, M., Pasquini, L., Laird, A. R., Fox, P. T., et al. (2022) · Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring · doi:10.1002/dad2.12318 · Cited by 31
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“A multicentre post-mortem study [1] yielded a sensitivity and specificity of only 71% each for a clinical diagnosis of ‘probable Alzheimer’s disease (AD)’ and of 83% and 55% for ‘possible AD’, respectively, when the clinical diagnosis was based on the 1984 criteria of McKhann et al.”
BackgroundMethodInfluentialChaudhry, A., Houlden, H., & Rizig, M. (2020) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2020.116886 · Cited by 33
“One study found that AD clinical diagnosis based on McKhann 1984 criteria was wrong in ~20% of cases, with mismatched cases commonly exhibiting LBD, FTD, CBD, or PSP neuropathology (Beach, 2012).”
BackgroundStage, E., Svaldi, D. O., Phillips, M. L., Canela, V. H., Duran, T., Goukasian, N., Risacher, S. L., Saykin, A. J., Apostolova, L. G., & Initiative, A. D. N. (2020) · Alzheimer s Research & Therapy · doi:10.1186/s13195-020-00647-w · Cited by 30
New insights into the role of fibroblast growth factors in Alzheimer’s disease
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“The diagnosis of AD is mainly based on neuropsychological and physical examination, and it is further confirmed with imaging studies and laboratory-based AD-associated cerebrospinal fluid (CSF) biomarkers [8].”
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“In particular, one study [35] has shown that a clinical diagnosis of probable AD has sensitivity between 70.”
BackgroundWei, H., Masurkar, A. V., & Razavian, N. (2023) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2023.1149036 · Cited by 30
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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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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