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 601–700 of 1,108
Apolipoprotein E genotypes and longevity across dementia disorders
Skillbäck, T. B., Lautner, R., Mattsson, N., Schott, J. M., Skoog, I. G., Nägga, K., Kilander, L., Wimo, A. B., Winblad, B. G., Eriksdotter, M., et al. (2018) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2018.02.003 · Cited by 14
“Another limitation is that the majority of patients were diagnosed only clinically, which is known to introduce a high misdiagnosis rate, with low-specificity figures (44%–71%) for AD, and a large proportion (39%) of clinically diagnosed FTD, DLB, and VaD patients showing AD pathology at autopsy [48].”
BackgroundLilamand, M., Hourrègue, C., & Paquet, C. (2020) · Revue Neurologique · doi:10.1016/j.neurol.2019.12.006 · Cited by 13
Schwaber, E. J., Thompson, A. C., Smilnak, G., Stinnett, S. S., Whitson, H. E., & Lad, E. M. (2020) · Journal of Alzheimer s Disease · doi:10.3233/jad-200111 · Cited by 12
Serrano, G. E., Intorcia, A. J., Carew, J., Chiarolanza, G., Hidalgo, J. A., Sue, L. I., Dugger, B. N., Saxon‐LaBelle, M., Filon, J. R., Scroggins, A., et al. (2015) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0000000000000235 · Cited by 13
“When diagnosing AD, using the most commonly used combination of the clinical and neuropathologic definitions of AD, sensitivity and specificity are both only approximately 70% (3).”
BackgroundMethodSelf-citationHadjichrysanthou, C., Initiative, A. D. N., McRae‐McKee, K., Evans, S., de Wolf, F., & Anderson, R. M. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-180101 · Cited by 13
“For AD in particular, it has been shown that a high proportion, which can be up to 30%, of subjects diagnosed with probable AD, may not actually display AD-typical neuropathological changes at autopsy [12, 13].”
BackgroundNadebaum, D. P., Krishnadas, N., Poon, A. M. T., Kalff, V., Lichtenstein, M., Villemagne, V. L., Jones, G. R., & Rowe, C. C. (2020) · Internal Medicine Journal · doi:10.1111/imj.14890 · Cited by 13
Drug Discovery to Drug Development of BACE1 Inhibitor as Antialzheimer’s: A Review
Mehendale-Munj, S., & Patil, P. B. (2022) · Current Topics in Medicinal Chemistry · doi:10.2174/1568026623666221228140450 · Cited by 12
Evaluating the updated LATE‐NC staging criteria using data from NACC
Woodworth, D. C., Nguyen, K. M., Sordo, L., Scambray, K. A., Head, E., Kawas, C. H., Corrada, M. M., Nelson, P. T., & Sajjadi, S. A. (2024) · Alzheimer s & Dementia · doi:10.1002/alz.14262 · Cited by 14
“While strongly related, clinical AD is not always related to underlying ADNC, 19 but is the most common pheno-typeofbothADNCandLATE-NC.”
InfluentialWang, X., Li, F., Gao, Q., Jiang, Z., Abudusaimaiti, X., Yao, J., & Zhu, H. (2022) · Journal of Alzheimer s Disease · doi:10.3233/jad-215394 · Cited by 14
“Researchers reported that the overall accuracy of clinical diagnosis, biomarkers, neuroimaging, and genetic testing in diagnosing AD are never 100% accurate when confirmed by autopsy validation [17–21].”
Dragović, I. R., Popović, N., Ždralević, M., Radulović, L., Vuković, T., Marzano, F., Tullo, A., & Radunović, M. (2022) · Journal of Alzheimer s Disease · doi:10.3233/jad-220676 · Cited by 17
“Currently accepted biomarkers have relatively low specificity [4] and enable diagnosis sometimes even a few decades after the cascade of the pathophysiological processes has been initiated [5].”
Retinal imaging in animal models: Searching for biomarkers of neurodegeneration
Batista, A., Guimarães, P., Serranho, P., Nunes, A., Martins, J., Moreira, P. I., Ambrósio, A. F., Morgado, M., Castelo-Branco, M. S., & Bernardes, R. (2023) · Frontiers in Ophthalmology · doi:10.3389/fopht.2023.1156605 · Cited by 13
Couch, E., Ashford, M. T., Zhang, W., et al. (2023) · Alzheimer Disease & Associated Disorders · doi:10.1097/wad.0000000000000569 · Cited by 12
Barrado, L. G., Coart, E., & Burzykowski, T. (2016) · Biometrics · doi:10.1111/biom.12583 · Cited by 12
“Reports about the accuracy of the diagnosis are available in the literature (Wollman and Prohovnik, 2004; Beach et al., 2012). Using this information might be instrumental in obtaining more reliable estimates of biomarker accuracy and in mitigating issues of identifiability. This is possible within the Bayesian framew…”
BackgroundMethodInfluentialvan Waalwijk van Doorn, L. J. C., Gispert, J. D., Kuiperij, H. B., Claassen, J. A. H. R., Arighi, A., Baldeiras, I., Blennow, K., Bozzali, M., Castelo-Branco, M., Cavedo, E., et al. (2017) · Journal of Alzheimer’s Disease · doi:10.3233/jad-160668 · Cited by 13
“[2].”
Faull, M., Ching, S., Jarmolowicz, A. I., Beilby, J. P., & Panegyres, P. K. (2014) · Europe PMC (PubMed Central) · Cited by 12
Swan, A., Waddell, B., Holloway, G. J. T., Bak, T. H., Colville, S., Khan, Z. H., & Pal, S. (2015) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000369551 · Cited by 12
Calderón‐Garcidueñas, L., Chávez, V. S. J., Vacaseydel-Aceves, N., Calderón-Sánchez, R., Escobedo, E. H. M., Frías, C., Giacometto, M., Velásquez, L., Félix-Villarreal, R., Martin, J. D., et al. (2016) · Frontiers in Pharmacology · doi:10.3389/fphar.2016.00232 · Cited by 12
“…of mild cognitive impairment (MCI) or dementia (Driscoll et al., 2006; Twamley et al., 2006; Grober et al., 2008; Howieson et al., 2008; Price et al., 2009; Riley et al., 2011; Sperling et al., 2011; Beach et al., 2012; Monsell et al., 2014; Hassenstab et al., 2015; Pettigrew et al., 2015).”
BackgroundMiller, A.-M., Balasa, M., Blennow, K., Gardiner, M., Rutkowska, A., Scheltens, P., Teunissen, C. E., Visser, P. J., Winblad, B. G., Waldemar, G., et al. (2017) · Journal of Alzheimer s Disease · doi:10.3233/jad-170502 · Cited by 12
Predicting Alzheimer’s disease progression trajectory and clinical subtypes using machine learningPreprint
Satone, V. K., Kaur, R., Dadu, A., Leonard, H. L., Iwaki, H., Makarious, M. B., Sargent, L. J., Initiative, A. D. N., Daneshmand, A., Scholz, S. W., et al. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/792432 · Cited by 11
“3% as compared to the neuropathologic assessments, which are considered the gold standard for AD identification [41].”
BackgroundWill PET Amyloid Imaging Lead to Overdiagnosis of Alzheimer Dementia?
Dubroff, J. G., & Nasrallah, I. M. (2015) · Academic Radiology · doi:10.1016/j.acra.2015.02.005 · Cited by 12
Rennert, L., & Xie, S. X. (2019) · Statistics in Medicine · doi:10.1002/sim.8185 · Cited by 11
Drage, R., Escudero, J., Parra, M. A., Scally, B., Anghinah, R., de Araújo, A. V. L., Basile, L., & Abásolo, D. (2022) · Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC) · doi:10.1109/embc48229.2022.9871497 · Cited by 11
“Clinical diagnostic accuracy is reported to be approximately 79% on average and is highly dependent on the study of test results by specialists [3].”
BackgroundHok‐A‐Hin, Y. S., Bolsewig, K., Ruiters, D. N., Lleó, A., Alcolea, D. A., Lemstra, A. W., van der Flier, W. M., Teunissen, C. E., & del Campo, M. (2023) · Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring · doi:10.1002/dad2.12456 · Cited by 10
“3,4 Furthermore, biological therapies targeting distinct pathological mechanisms of AD have recently become available in the United States.”
Qin, T., Wang, L., Xu, H., Liu, C., Shao, Y., Li, F., Wang, Y., Jiang, J., & Lin, H. (2023) · Cerebral Cortex · doi:10.1093/cercor/bhad460 · Cited by 12
Alzheimer’s Disease Biomarkers — Timing Is Everything
Mayeux, R. P. (2024) · New England Journal of Medicine · doi:10.1056/nejme2400102 · Cited by 11
Gaugler, J. E., Hovater, M. K., Roth, D. L., Johnston, J. A., Kane, R. L., & Sarsour, K. (2013) · Aging & Mental Health · doi:10.1080/13607863.2013.814100 · Cited by 11
“ADCs operate as tertiary referral centers (Beach et al., 2012).”
Histopathology and Florbetaben PET in Patients Incorrectly Diagnosed with Alzheimer’s Disease
Sabbagh, M. N., Schäuble, B., Anand, K., Richards, D., Murayama, S., Akatsu, H., Takao, M., Rowe, C. C., Masters, C. L., Barthel, H., et al. (2016) · Journal of Alzheimer s Disease · doi:10.3233/jad-160821 · Cited by 11
“Establishing the in vivo diagnosis of Alzheimer’s disease (AD) or other dementias relies on clinical criteria, although their accuracy can be limited [1].”
Dolci, G. A. M., Damanti, S., Scortichini, V., Galli, A., Rossi, P. D., Abbate, C., Arosio, B., Mari, D., Arighi, A., Fumagalli, G., et al. (2017) · Frontiers in Medicine · doi:10.3389/fmed.2017.00203 · Cited by 12
Fighting the Cause of Alzheimer’s and GNE Myopathy
Devi, S., Yadav, R., Chanana, P., & Arya, R. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00669 · Cited by 12
“The clinical diagnosis of AD is about 70–90% accurate relative to the pathological diagnosis (Beach et al., 2012).”
BackgroundNeuroimaging and Neurolaw: Drawing the Future of Aging
Tigano, V., Cascini, G. L., Sánchez‐Castañeda, C., Péran, P., & Sabatini, U. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00217 · Cited by 15
Perani, D., Iaccarino, L., Jacobs, A. H., IMBI Brain Imaging Working Group, Lammertsma, A. A., Nordberg, A. K., Windhorst, A. D., Gerhard, A., Winkeler, A., Jacobs, A. H., et al. (2019) · Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring · doi:10.1016/j.dadm.2019.02.004 · Cited by 11
The role of pragmatics in the diagnosis of dementia
Cummings, L. (2020) · East Asian Pragmatics · doi:10.1558/eap.39716 · Cited by 9
Heterogeneity of Alzheimer’s disease identified by neuropsychological test profiling
Nguyen, T. T. T., Lee, H., Huang, L., Hu, C., Yeh, C.-Y., Yang, W. V., & Lin, M. (2023) · PLoS ONE · doi:10.1371/journal.pone.0292527 · Cited by 13
“As AD dementia remains primarily a clinical diagnosis and the sensitivity and specificity of the NIA-AA diagnostic criteria have been shown to be 71%, we believe that the likelihood of misdiagnosis remains a concern but has been minimized as best as we could [55].”
BackgroundRequired improvements for cerebrospinal fluid-based biomarker tests of Alzheimer’s disease
Gaetani, L., Chiasserini, D., Paoletti, F. P., Bellomo, G., & Parnetti, L. (2023) · Expert Review of Molecular Diagnostics · doi:10.1080/14737159.2023.2276918 · Cited by 10
“Clinical evaluation has several limitations in sensitivity and, above all, specificity [81].”
BackgroundPredictors and outcomes of fluctuations in the clinical dementia rating scale
Wilks, H., Benzinger, T. L. S., Schindler, S. E., Cruchaga, C., Morris, J. C., & Hassenstab, J. J. (2024) · Alzheimer s & Dementia · doi:10.1002/alz.13679 · Cited by 11
A Comprehensive Review of Therapeutic Compounds from Plants forNeurodegenerative Diseases
Panneerselvam, D. S., Kanakaraja, A., Sakthivelu, M., Gopinath, S. C. B., & Pachaiappan, R. (2024) · Current Medicinal Chemistry · doi:10.2174/0109298673272435231204072922 · Cited by 11
Quispialaya, K. M., Therriault, J., Aliaga, A., Tissot, C., Servaes, S., Rahmouni, N., Karikari, T. K., Benedet, A. L., Ashton, N. J., Macedo, A. C., et al. (2024) · European Journal of Neurology · doi:10.1111/ene.16255 · Cited by 12
Windon, C., Gatsonis, C. A., Carrillo, M. C., Romanoff, J., Hanna, L., Glavin, E. E., Gareen, I. F., Gutman, R., Hillner, B. E., March, A., et al. (2025) · Alzheimer s & Dementia · doi:10.1002/alz.70504 · Cited by 11
New behavioural variant FTD criteria and clinical practice
Pasquier, F. (2013) · Revue Neurologique · doi:10.1016/j.neurol.2013.08.002 · Cited by 10
The Translational Journey of Brain β-Amyloid Imaging
Rabinovici, G. D. (2015) · JAMA Neurology · doi:10.1001/jamaneurol.2014.4143 · Cited by 10
Teipel, S. J., Spottke, A. E., Boecker, H., Daamen, M., Graf, E., Sahlmann, J., Buchert, R., Mohnike, W., Mohnike, K., Kurth, J., et al. (2023) · Alzheimer s & Dementia Translational Research & Clinical Interventions · doi:10.1002/trc2.12383 · Cited by 10
Development and Evaluation of an Explainable Diagnostic AI for Alzheimer's Disease
Yilmaz, D. (2023) · International Conference on Artificial Intelligence Science and Applications in Industry and Society (CAISAIS) · doi:10.1109/caisais59399.2023.10270042 · Cited by 12
“Research regarding biomarkers may have an impact on diagnosis, but currently, all studied biomarkers for AD have overlapping associations with other types of dementia [4].”
BackgroundCerebrospinal fluid biomarkers for the differential diagnosis of Alzheimer’s disease
Magalhaes, C. A., Figueiró, M., Fraga, V. G., Mateo, E. C. C., Toledo, A. A. S. F., Ferriani, M. D. G. C., Caramelli, P., & Gomes, K. B. (2015) · Jornal Brasileiro de Patologia e Medicina Laboratorial · doi:10.5935/1676-2444.20150059 · Cited by 10
“The biomarkers were measured using the INNOTEST hTAU Ag, INNOTEST PHOSPHO-TAU (181P), and INNOTEST β-Amyloid (1-42) (Innogenetics, Bélgica) kits by enzyme-linked immunosorbent assay (ELISA) technique, the manufacturer’s instructions were strictly followed.”
MethodSzalárdy, L., Zádori, D., Klivènyi, P., & Vécsei, L. (2016) · Journal of Alzheimer s Disease · doi:10.3233/jad-160037 · Cited by 10
“…corresponding sensitivities and specificities of 70.9–76.6% and 59.5–70.8%, respectively (the values depended on the applied minimum threshold levels of histopathological severity, with morepermissiveneuropathologicaldefinitionsresult-inginhigherpredictivevalueandspecificity,and lowersensitivity)[39].”
InfluentialWeidman, D. A., ZAMRINI, E. Y., Sabbagh, M. N., Jacobson, S. A., Burke, A. D., Belden, C. M., Powell, J. J., Bhalla, N., Roontiva, A., Kuang, X., et al. (2017) · Neurocase · doi:10.1080/13554794.2017.1290806 · Cited by 11
Predictors of Life Expectancy in Autopsy-Confirmed Alzheimer’s Disease1
Schaffert, J., LoBue, C., Hynan, L. S., Hart, J., Rossetti, H., Carlew, A. R., Lacritz, L., White, C. L., & Cullum, C. M. (2022) · Journal of Alzheimer s Disease · doi:10.3233/jad-215200 · Cited by 12
“Another potentially significant limitation of most studies has been the reliance upon clinical diagnoses of AD, which are about 80% accurate in specialized dementia centers when compared to autopsy classification [14].”
Applying the IWG Research Criteria in Clinical Practice
Molinuevo, J. L., & Rami, L. (2013) · Medical Clinics of North America · doi:10.1016/j.mcna.2012.12.018 · Cited by 11
MRI biomarkers — a precision medicine tool in neurology?
McMillan, C. T. (2016) · Nature Reviews Neurology · doi:10.1038/nrneurol.2016.51 · Cited by 10
Li, M., Li, Y., Schindler, S. E., Yen, D. P., Sutcliffe, S., Babulal, G. M., Benzinger, T. L. S., Lenze, E. J., & Bateman, R. J. (2023) · Alzheimer s & Dementia · doi:10.1002/alz.13125 · Cited by 9
“expert assessment: in a study evaluating the clinical diagnostic accuracy of AD dementia compared with different neuropathological criteria at 30 National Institute on Aging Alzheimer’s Disease Centers (ADCs), sensitivity ranged from 71% to 87% and specificity ranged from 44% to 71% [48].”
MethodKurihara, M., Kondo, S., Ohse, K., Nojima, H., Kikkawa-Saito, E., & Iwata, A. (2024) · Journal of Alzheimer s Disease · doi:10.3233/jad-240185 · Cited by 8
“Clinical diagnosis is not sufficiently specific [1] and biological confirmation via biomarkers is important [2, 3].”
BackgroundEratne, D., Li, Q.-X., Lewis, C. C., Dang, C., Kang, M. J., Grewal, J. K., Loi, S. M., Walterfang, M., Evans, A. H., Malpas, C. B., et al. (2024) · Journal of Neurology · doi:10.1007/s00415-024-12732-3 · Cited by 12
“This is likely a reflection of the real-world clinically heterogenous clinical cohort and ranges, that many non-AD disorders have A+T− and other abnormal CSF profiles [35, 36], as well as the recognised challenges (and inaccuracies) of in vivo clinical diagnosis [13, 24, 25, 29, 30].”
Wang, M., Chen, K., Huang, Y., Chen, S., Wang, R., Zhang, Y., Hu, H.-Y., Ma, L.-Z., Liu, W., Wang, J., et al. (2025) · Translational Psychiatry · doi:10.1038/s41398-025-03345-z · Cited by 10
“When compared to brain histology, experienced clinicians ’ diagnoses of “ probable AD ” have a sensitivity and speci fi city of only 71% [2].”
Unravelling the plasma proteome: Pioneering biomarkers for differential dementia diagnosis
Gezegen, H., Alaylıoğlu, M., Şahin, E., Swann, O., Veleva, E., Güven, G., Yaman, Ü., Salih, D. A. M., Bılgıç, B., Hanağası, H. A., et al. (2025) · Alzheimer s & Dementia · doi:10.1002/alz.70162 · Cited by 10
Blood-based biomarkers for Alzheimer’s disease: influence of kidney function
Gaetani, L., Bellomo, G., Nardi, G., Toja, A., Streva, C., Giombetti, E., Torrigiani, E. G., Paoletti, F. P., Villa, A., Tozzi, A., et al. (2026) · Alzheimer s Research & Therapy · doi:10.1186/s13195-026-01970-4 · Cited by 10
“Fluid biomarkers improve the accuracy in the diagnosis of Alzheimer’s disease (AD) [1–3].”
Alzheimer’s Disease Prediction Model Using Demographics and Categorical Data
Khan, A., & Usman, M. (2019) · International Journal of Online and Biomedical Engineering (iJOE) · doi:10.3991/ijoe.v15i15.11472 · Cited by 10
Ramanan, V. K., Heckman, M. G., Przybelski, S. A., Lesnick, T. G., Lowe, V. J., Graff‐Radford, J., Mielke, M. M., Jack, C. R., Knopman, D. S., Petersen, R. C., et al. (2022) · Journal of Alzheimer s Disease · doi:10.3233/jad-220164 · Cited by 9
“Up to 10–20% of cases of clinically probable AD dementia do not meet criteria for biologically defined AD (i.e., they are not amyloid-and tau-positive) [42].”
Salloway, S., & Sperling, R. A. (2015) · JAMA Neurology · doi:10.1001/jamaneurol.2015.1804 · Cited by 9
Albin, R. L., Fisher‐Hubbard, A., Shanmugasundaram, K., Koeppe, R. A., Burke, J. F., Camelo-Piragua, S. I., Lieberman, A. P., Giordani, B., & Frey, K. A. (2015) · Annals of Neurology · doi:10.1002/ana.24481 · Cited by 9
“using the NACC data set to compare clinical and neuropathological diagnoses.(17) Our limited evaluation of FDG-PET classifications suggests that this method is less precise than combined amyloid and dopamine terminal PET imaging.”
MethodMiller, M. C., Orwat, D., Rahimighazikalayeh, G., & Mintzer, J. E. (2018) · International Psychogeriatrics · doi:10.1017/s1041610218001151 · Cited by 10
“An analysis of a National Institute on Aging database has found AD diagnostic sensitivity to be between 70.9% to 87.3%, and specificity between 44.3% and 70.8% compared with autopsy diagnosis (Beach et al., 2012).”
MethodInfluentialSmilnak, G., Deans, J. R., Doraiswamy, P. M., Stinnett, S. S., Whitson, H. E., & Lad, E. M. (2019) · PLoS ONE · doi:10.1371/journal.pone.0223199 · Cited by 9
Stereoscopic Depth Perception and Visuospatial Dysfunction in Alzheimer’s Disease
Kim, N.-G., & Lee, H. (2021) · Healthcare · doi:10.3390/healthcare9020157 · Cited by 10
Thorlacius-Ussing, G., Bruun, M., Gjerum, L., Frederiksen, K. S., Rhodius‐Meester, H. F. M., van der Flier, W. M., Waldemar, G., & Hasselbalch, S. G. (2021) · Journal of Alzheimer s Disease · doi:10.3233/jad-210278 · Cited by 9
“Up to 17% of patients fulfilling clinical criteria for AD do not have evidence of AD pathology on postmortem examination [37].”
BackgroundDastgheib, Z. A., Lithgow, B., & Moussavi, Z. (2022) · Medical & Biological Engineering & Computing · doi:10.1007/s11517-022-02507-1 · Cited by 9
“Currently, brain autopsy is the only way to confirm a dementia type based on the underlying neuropathology [10].”
BackgroundHampsey, E., Meszaros, M., Skirrow, C., Strawbridge, R., Taylor, R. H., Chok, L., Aarsland, D., Al‐Chalabi, A., Chaudhuri, К. R., Weston, J., et al. (2022) · BMJ Open · doi:10.1136/bmjopen-2022-061193 · Cited by 12
Morrow, C. B., Leoutsakos, J., Yan, H., Onyike, C. U., & Kamath, V. J. (2023) · Journal of Alzheimer s Disease Reports · doi:10.3233/adr-230034 · Cited by 12
“However, diagnostic reliability in NACC has been validated in previous studies, suggesting that the clinical diagnoses are largely accurate [43].”
Prevalence of hippocampal sclerosis in a clinicopathologically characterized cohort
Malek‐Ahmadi, M. H., Kahlon, V., Adler, C. H., Obradov, A., Thind, K., Shill, H. A., Sue, L. I., Caviness, J. N., Jacobson, S. A., & Sabbagh, M. N. (2013) · Clinical and Experimental Medical Sciences · doi:10.12988/cems.2013.13026 · Cited by 9
“Nakashima-Yasuda et al [23] report that TDP-43 binding was present in 7.2% of PD cases and 19% of PDD cases, while Beach et al [5] report that 7 of 12 cases with HS pathology demonstrated clinical parkinsonian symptoms.”
InfluentialAlexopoulos, P., & Kurz, A. (2015) · Psychopathology · doi:10.1159/000441327 · Cited by 10
Rubí, S., Noguera, A., Tarongí, S., Oporto, M., García, A., Vico, H., Espino, A., Picado, M. J., Mas, A., Peña, C., et al. (2017) · Revista Española de Medicina Nuclear e Imagen Molecular · doi:10.1016/j.remn.2017.05.003 · Cited by 9
Cerebrospinal fluid collection: An informative animation video for patients and caregivers
Mofrad, R. B., Visser, L. N. C., Fruijtier, A. D., et al. (2019) · Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring · doi:10.1016/j.dadm.2019.04.005 · Cited by 9
Burkhart, M. C., Lee, L. Y., Vaghari, D., Toh, A. Q., Chong, E. J. Y., Chen, C., Peter Tiňo, B., & Kourtzi, Z. (2024) · Scientific Reports · doi:10.1038/s41598-024-60914-w · Cited by 12
Davies‐Jenkins, C. W., Workman, C. I., Hupfeld, K. E., Zöllner, H. J., Leoutsakos, J., Kraut, M. A., Barker, P. B., Smith, G. S., & Oeltzschner, G. (2024) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2024.06.003 · Cited by 8
Zilioli, A., Rosenberg, A., Mohanty, R., Matton, A., Granberg, T., Hagman, G., Lötjönen, J. M. P., Kivipelto, M., & Westman, E. (2024) · Journal of Neurology · doi:10.1007/s00415-024-12853-9 · Cited by 9
Dino, F., Pressman, P., Cohen, K. B., Dubljević, V., Jarrold, W., Foltz, P. W., DeCamp, M., Mahoor, M. H., & Hunter, L. (2025) · Journal of Medical Ethics · doi:10.1136/jme-2024-110252 · Cited by 8
Liu, S., Bush, W. S., Akinyemi, R., Byrd, G. S., Caban‐Holt, A., Rajabli, F., Reitz, C., Kunkle, B. W., Tosto, G., Vance, J. M., et al. (2025) · PLoS Genetics · doi:10.1371/journal.pgen.1011701 · Cited by 9
“Clinical diagnosis have inherent misdiagnosis rates [83] that can affect heritability estimates.”
Fully Connected Multi-Kernel Convolutional Neural Network Based on Alzheimer’s Disease Diagnosis
Deng, L., Initiative, A. D. N., & Wang, Y. (2023) · Journal of Alzheimer s Disease · doi:10.3233/jad-220519 · Cited by 8
“Clinic pathological studies have shown that the diagnostic sensitivity of clinicians is between 70.9% and 87.3%, and the specificity is between 44.3% and 70.8% [10].”
InfluentialFletcher, J. R. (2023) · Journal of Aging Studies · doi:10.1016/j.jaging.2023.101155 · Cited by 8
Momota, Y., Bun, S., Hirano, J., Kamiya, K., Ueda, R., Iwabuchi, Y., Takahata, K., Yamamoto, Y., Tezuka, T., Kubota, M., et al. (2024) · Scientific Reports · doi:10.1038/s41598-024-58223-3 · Cited by 8
“Notably, it surpassed the accuracy of the physicians’ clinical diagnosis of AD, which is approximately 70% 3 .”
Kim, K., Jang, Y. J., Shin, J., Park, M. J., Kim, H., Seong, J., & Jeon, H. J. (2024) · Alzheimer s Research & Therapy · doi:10.1186/s13195-024-01562-0 · Cited by 9
“The sensitivity and specificity of clinical diagnosis of Alzheimer’s dementia using the neuropathologic diagnosis were only around 70–80% [50].”
MethodA Multi-Label Deep Learning Model for Detailed Classification of Alzheimer's Disease
Yang, M., Zhao, Y., Yu, H., Chen, S., Gao, G., Li, D., Wu, X., Huang, L., & Ye, S. (2025) · Actas Españolas de Psiquiatría · doi:10.62641/aep.v53i1.1728 · Cited by 7
Microfluidic and Computational Tools for Neurodegeneration Studies
Gomez, K., Yarmey, V. R., Mane, H., & San‐Miguel, A. (2025) · Annual Review of Chemical and Biomolecular Engineering · doi:10.1146/annurev-chembioeng-082223-054547 · Cited by 8
Adapting to Dementia in Society: A Challenge for Our Lifetimes and a Charge for Public Health
D’Alton, S., Hunter, S., Whitehouse, P. J., Brayne, C., & George, D. R. (2014) · Journal of Alzheimer s Disease · doi:10.3233/jad-140213 · Cited by 8
“Given the preponderance of vascular lesions and hippocampal sclerosis in AD, it seems reasonable to conclude that these lesions contribute to the difficulty in predicting underlying neuropathology in clinical AD and to the poor rate of concordance between clinical AD and plaque and tangle pathology [65].”
BackgroundPatient and Caregiver Assessment of the Benefits From the Clinical Use of Amyloid PET Imaging
Mustafa, R., Brosch, J. R., Rabinovici, G. D., Dickerson, B. C., Carrillo, M. C., Glazier, B. S., Gao, S., Tierney, M., Fargo, K. N., Austrom, M. G., et al. (2017) · Alzheimer Disease & Associated Disorders · doi:10.1097/wad.0000000000000220 · Cited by 8
Ye, L., Gao, P.-R., Zhang, Y.-B., Cheng, H.-R., Tao, Q., Wu, Z., & Li, H. (2021) · Clinical Interventions in Aging · doi:10.2147/cia.s294756 · Cited by 8
“recognized as toxic senile plaques formed by extracellular β-amyloid deposition and neurofibrillary tangles (NFTs) formed with intracellular accumulation of hyperphosphorylated tau in the brain.(1) In most ante-mortem cases, the diagnosis of AD”
BackgroundAssessing Genetic Overlap and Causality Between Blood Plasma Proteins and Alzheimer’s Disease
Handy, Á., Initiative, O. B. O. T. A. D. N., Lord, J., Green, R., Xu, J., Aarsland, D., Velayudhan, L., Hye, A., Dobson, R., & Proitsi, P. (2021) · Journal of Alzheimer s Disease · doi:10.3233/jad-210462 · Cited by 9
“Clinical manifestation is heterogenous [77, 78] and in-life diagnosis can be inaccurate [79, 80] implying that adding endophenotype measures closer to causal biology (e.”
Vizcarra, J. C., Teich, A. F., Dugger, B. N., & Gutman, D. A. (2023) · Free Neuropathology · doi:10.17879/freeneuropathology-2023-4696 · Cited by 8
Novel autoimmune response in a tauopathy mouse model
Nogueras‐Ortiz, C. J., Jesús‐Cortés, H. D., Vaquer‐Alicea, J., & Vega, I. E. (2014) · Frontiers in Neuroscience · doi:10.3389/fnins.2013.00277 · Cited by 8
“However, approximately 10% of the cases can be unrecognized by most experienced physicians and related neurodegenerative disorders could be misidentified as AD (Beach et al., 2012).”
BackgroundSex-related biomarkers in cardiovascular and neurodegenerative disorders.
Pietraforte, D., Straface, E., Piscopo, P., Vona, R., & Confaloni, A. (2016) · Annali dell Istituto Superiore di Sanità · doi:10.4415/ann_16_02_15 · Cited by 8
A Common Variant in the MC1R Gene (p.V92M) is associated with Alzheimer’s Disease Risk
Tell‐Martí, G., Puig‐Butillé, J. A., Potrony, M., Plana, E., Bádenas, C., Antonell, A., Sánchez‐Valle, R., Molinuevo, J. L., Lleó, A., Alcolea, D. A., et al. (2017) · Journal of Alzheimer s Disease · doi:10.3233/jad-161113 · Cited by 8
“Clinicopathological studies have shown that the sensitivity and specificity of the classical clinical criteria for AD diagnosis are roughly 85% and 70%, respectively [32].”
BackgroundDiagnosis in vascular dementia, applying ‘Cochrane diagnosis rules’ to ‘dementia diagnostic tools’
Quinn, T. J., & McCleery, J. M. (2017) · Clinical Science · doi:10.1042/cs20170025 · Cited by 8
Early-Onset Alzheimer Disease (EOAD) With Aphasia: A Case Report
Borges, M. K., Lopes, T. N., Biella, M. M., de Siqueira, A. S. S., Mauer, S., & Aprahamian, I. (2018) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2018.00469 · Cited by 8
“the young age and atypical presentation, diagnostic accuracy is particularly low in EOAD and the diagnosis is often delayed (20).”
BackgroundAmyloid PET and Changes in Clinical Management for Patients With Cognitive Impairment
Jack, C. R., & Petersen, R. C. (2019) · JAMA · doi:10.1001/jama.2019.1998 · Cited by 8
Triviño‐Ibáñez, E. M., Sánchez-Vañó, R., Sopena‐Novales, P., Romero-Fábrega, J. C., Rodrı́guez-Fernández, A., Pardo, C. C., Lozano, M. D., & Gómez-Río, M. M. (2019) · Medicine · doi:10.1097/md.0000000000016509 · Cited by 8
“The clinical diagnosis suffers from limitations in the actual clinic context.([24]) The use of consensual criteria improves this setting, but, even for dementia (not only for MCI), the misdiagnosed rate is high.”
BackgroundAccuracy of the Early Diagnosis of Parkinson's Disease
Beach, T. G., Adler, C. H., Shill, H. A., et al. (2023) · Movement Disorders · doi:10.1002/mds.29556 · Cited by 7
Self-citationJovalekic, A., Bullich, S., Roé-Vellvé, N., Kolinger, G. D., Howard, L. R., Elsholz, F., Lagos‐Quintana, M., Blanco-Rodriguez, B., Pérez-Martínez, E., Gismondi, R., et al. (2024) · Pharmaceuticals · doi:10.3390/ph17121648 · Cited by 7
“This shift in diagnostic guidelines re fl ects the growing understanding that AD, when de fi ned by clinical phenotype alone, may not fully capture the underlying pathological processes [22].”
InfluentialRuling in, ruling out: the clinical utility of plasma biomarkers in diagnosis of Alzheimer’s disease
Wisch, J. K., & Ances, B. M. (2025) · Journal of Clinical Investigation · doi:10.1172/jci198725 · Cited by 7
“In specialized memory centers, clinical diagnosis rates based on patient history and cognitive testing alone range from 70% to 87% sensitivity and 44% to 71% specificity (6), suggesting diagnostic accuracies of 50%–75% compared with assessment at autopsy.”
Bayahya, A. Y., Banjar, H. R., Talabay, O., & Alamri, S. H. (2025) · Scientific Reports · doi:10.1038/s41598-025-27914-w · Cited by 9
“This threshold achievement is particularly significant for clinical implementation, as inadequate sensitivity in control populations can lead to false positive diagnoses, unnecessary patient distress, and inappropriate clinical interventions 96 .”
Recent advances in Alzheimer’s disease: From molecular mechanisms to therapeutic strategies
Rudman, M. D., Ulrich, J. D., & Holtzman, D. M. (2026) · Cell · doi:10.1016/j.cell.2026.06.006 · Cited by 12
Functional nanoassemblies for the diagnosis and therapy of Alzheimer's diseases
Zhang, L., Sun, H., Chen, Y., Wei, M., Lee, J., Li, F., & Ling, D. (2021) · Wiley Interdisciplinary Reviews Nanomedicine and Nanobiotechnology · doi:10.1002/wnan.1696 · Cited by 8
Nachum, R., Jackson, K., Duric, Z., & Gerber, L. (2021) · Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC) · doi:10.1109/embc46164.2021.9630492 · Cited by 7
Regulatory Agencies and PET/CT Imaging in the Clinic
Herscovitch, P. (2022) · Current Cardiology Reports · doi:10.1007/s11886-022-01749-7 · Cited by 7
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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