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
21 of 46 cited sources checked · 4 supported · 1 flagged · 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
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- 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
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- 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)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- 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)
Strength:hedged· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes- 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)
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- 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
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA 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
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA 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
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA 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
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA 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
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
- 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.
Strength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt 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)
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably 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)
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably 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
Strength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt 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)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably 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)
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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)
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably 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.
Strength:plain· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably 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.
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably 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
Strength:plain· not yet calibratedn = 164Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt 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
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably 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
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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
Strength:plain· not yet calibratedn = 3Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt 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
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesThe 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
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt 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
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt 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
Strength:plain· not yet calibratedn = 919Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt 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
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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
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- 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
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably 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
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✗ Based: failsProbably 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
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✗ Based: failsProbably 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
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✗ Checkable: fails✓ Load-bearing: passes✓ Based: passesProbably 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
Tests✓ Asserted: passes✗ Checkable: fails✓ Load-bearing: passes✓ Based: passesProbably 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
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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
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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.
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- 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
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably 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
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably 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
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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
Tests✓ Asserted: passes✗ Checkable: fails✓ Load-bearing: passes✓ Based: passesProbably 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
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✗ Based: failsProbably 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
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably 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
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably 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
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably 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
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably 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
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Items 101–200 of 1,108
Chronic Traumatic Encephalopathy: Historical Origins and Current Perspective
Montenigro, P. H., Stein, T. D., Cantu, R. C., & Stern, R. A. (2015) · Annual Review of Clinical Psychology · doi:10.1146/annurev-clinpsy-032814-112814 · Cited by 133
Hu, Y., Kirmess, K. M., Meyer, M. R., Rabinovici, G. D., Gatsonis, C., Siegel, B. A., Whitmer, R. A., Apgar, C., Hanna, L., Kanekiyo, M., et al. (2022) · JAMA Network Open · doi:10.1001/jamanetworkopen.2022.8392 · Cited by 120
Leptin Dysfunction and Alzheimer’s Disease: Evidence from Cellular, Animal, and Human Studies
McGuire, M. J., & Ishii, M. (2016) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-015-0282-7 · Cited by 129
“In one study investigating the accuracy of the clinical diagnosis of AD at National Institute on Aging Alzheimer Disease Centers, the sensitivity in diagnosing AD ranged from 70.9 to 87.3 % while the specificity ranged from 44.3 to 70.8 % (Beach et al. 2012).”
InfluentialBullich, S., Seibyl, J. P., Catafau, A. M., Jovalekic, A., Koglin, N., Barthel, H., Sabri, O., & Santi, S. D. (2017) · NeuroImage Clinical · doi:10.1016/j.nicl.2017.04.025 · Cited by 123
“It has been reported that up to one-third of people clinically diagnosed with mild to moderate AD do not meet criteria for significant Aβ accumulation in the cerebral cortex (Beach et al., 2012; Monsell et al., 2015) while also some cognitively normal subjects may have elevated Aβ deposition in the brain.”
Research Criteria for the Behavioral Variant of Alzheimer Disease
Ossenkoppele, R., Singleton, E. H., Groot, C., Dijkstra, A. A., Eikelboom, W. S., Seeley, W. W., Miller, B. L., Laforce, R. J., Scheltens, P., Papma, J. M., et al. (2021) · JAMA Neurology · doi:10.1001/jamaneurol.2021.4417 · Cited by 134
Schaffert, J., LoBue, C., White, C. L., Chiang, H.-S., Didehbani, N., Lacritz, L., Rossetti, H., Dieppa, M., Hart, J., & Cullum, C. M. (2018) · Neuropsychology · doi:10.1037/neu0000423 · Cited by 120
Ashton, N. J., Leuzy, A., Karikari, T. K., Mattsson-Carlgren, N., Dodich, A., Boccardi, M., Corre, J., Drzezga, A., Nordberg, A., Ossenkoppele, R., et al. (2021) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-021-05253-y · Cited by 142
den Haan, J., Janssen, S. F., van de Kreeke, J. A., et al. (2017) · Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring · doi:10.1016/j.dadm.2017.10.005 · Cited by 122
“Clinical amyloid-PET studies show that a clinical diagnosis of AD is not confirmed by amyloid PET in 5%–38% of the cases [30–33] and neuropathological research reported a mismatch of clinical and neuropathological diagnosis of at least 17% [34].”
BackgroundGrundman, M., Pontecorvo, M. J., Salloway, S., Doraiswamy, P. M., Fleisher, A., Sadowsky, C., Nair, A. K., Siderowf, A. D., Lu, M., Arora, A., et al. (2012) · Alzheimer Disease & Associated Disorders · doi:10.1097/wad.0b013e318279d02a · Cited by 123
Gallagher, D., Kiss, A., Lanctot, K., & Herrmann, N. (2018) · The American Journal of Geriatric Psychiatry · doi:10.1016/j.jagp.2018.05.002 · Cited by 122
“Accuracy of clinical diagnoses of AD in the NACC dataset have previously been validated according to neuropathological criteria (19).”
MethodMild to moderate Alzheimer dementia with insufficient neuropathological changes
Serrano‐Pozo, A., Qian, J., Monsell, S. E., Blacker, D., Gómez‐Isla, T., Betensky, R. A., Growdon, J. H., Johnson, K. A., Frosch, M. P., Sperling, R. A., et al. (2014) · Annals of Neurology · doi:10.1002/ana.24125 · Cited by 120
Self-citationByun, M. S., Kim, S. E., Park, J., Yi, D., Choe, Y. M., Sohn, B. K., Choi, H. J., Baek, H., Han, J., Woo, J. I., et al. (2015) · PLoS ONE · doi:10.1371/journal.pone.0142756 · Cited by 121
“Clinical diagnosis of Alzheimer’s disease (AD) has generally relied on symptom-oriented criteria [1], which are both variable and insufficiently accurate [2, 3].”
BackgroundAPP/Aβ structural diversity and Alzheimer's disease pathogenesis
Roher, A. E., Kokjohn, T. A., Clarke, S. G., Sierks, M. R., Maarouf, C. L., Serrano, G. E., Sabbagh, M., & Beach, T. G. (2017) · Neurochemistry International · doi:10.1016/j.neuint.2017.08.007 · Cited by 126
“…the interpretation of previous clinical trials is the observation that a large fraction of elderly dementia cases, even those with clinical manifestations of AD do not harbor conventionally defined AD neuropathology based on densities and distributions of plaques and tangles (Beach et al., 2012).”
Self-citationGenome-wide association studies for Alzheimer’s disease: bigger is not always better
Escott-Price, V., & Hardy, J. (2022) · Brain Communications · doi:10.1093/braincomms/fcac125 · Cited by 119
“The fi rst is that the diagnostic accuracy for Alzheimer ’ s disease is poor: of the order of 80% in clinic-basedseries based both on neuropathological criteria 2 and on genetic analysis 3 and this is certain to be worse in the case of the proxy cases used in the larger and more recent GWAS.”
MethodThe application of retinal fundus camera imaging in dementia: A systematic review
McGrory, S., Cameron, J. R., Pellegrini, E., Warren, C., Doubal, F., Deary, I. J., Dhillon, B., Wardlaw, J. M., Trucco, E., & MacGillivray, T. (2016) · Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring · doi:10.1016/j.dadm.2016.11.001 · Cited by 119
Upcoming Candidate Cerebrospinal Fluid Biomarkers of Alzheimer’s Disease
Fagan, A. M., & Perrin, R. J. (2012) · Biomarkers in Medicine · doi:10.2217/bmm.12.42 · Cited by 118
Ansart, M., Epelbaum, S., Bassignana, G., Bône, A., Bottani, S., Cattai, T., Couronné, R., Faouzi, J., Koval, I., Louis, M., et al. (2021) · Medical Image Analysis · doi:10.1016/j.media.2020.101848 · Cited by 116
Alzheimer's disease including focal presentations
Villain, N., & Dubois, B. (2019) · Seminars in Neurology · doi:10.1055/s-0039-1681041 · Cited by 113
Aβ-amyloid and Tau Imaging in Dementia
Villemagne, V. L., Doré, V., Bourgeat, P., Burnham, S. C., Laws, S., Salvado, O., Masters, C. L., & Rowe, C. C. (2017) · Seminars in Nuclear Medicine · doi:10.1053/j.semnuclmed.2016.09.006 · Cited by 110
Staging of Alzheimer’s disease: past, present, and future perspectives
Therriault, J., Zimmer, E. R., Benedet, A. L., Pascoal, T. A., Gauthier, S. G., & Rosa‐Neto, P. (2022) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2022.05.008 · Cited by 123
Diagnostic impact of [18F]flutemetamol PET in early-onset dementia
Zwan, M. D., Bouwman, F. H., Konijnenberg, E., van der Flier, W. M., Lammertsma, A. A., Verhey, F. R. J., Aalten, P., van Berckel, B. N. M., & Scheltens, P. (2017) · Alzheimer's Research & Therapy · doi:10.1186/s13195-016-0228-4 · Cited by 118
Can visuospatial measures improve the diagnosis of Alzheimer's disease?
Salimi, S., Irish, M., Foxe, D., Hodges, J. R., Piguet, O., & Burrell, J. R. (2017) · Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring · doi:10.1016/j.dadm.2017.10.004 · Cited by 121
“A proportion of AD patients will not meet the criteria for any single dementia syndrome, including the recognized atypical AD syndromes, but rather present with an undifferentiated mix of cognitive and behavioral symptoms and signs [2].”
BackgroundFunctional brain networks in the evaluation of patients with neurodegenerative disorders
Perovnik, M., Rus, T., Schindlbeck, K. A., & Eidelberg, D. (2022) · Nature Reviews Neurology · doi:10.1038/s41582-022-00753-3 · Cited by 119
Seibyl, J. P., Catafau, A. M., Barthel, H., Ishii, K., Rowe, C. C., Leverenz, J. B., Ghetti, B. F., Ironside, J. W., Takao, M., Akatsu, H., et al. (2016) · Journal of Nuclear Medicine · doi:10.2967/jnumed.115.161927 · Cited by 108
“, individuals diagnosed with AD dementia who do not show b-amyloid plaques on autopsy) in 10%–30% of cases (13).”
BackgroundSabbagh, M. N., Lue, L.-F., Fayard, D., & Shi, J. (2017) · Neurology and Therapy · doi:10.1007/s40120-017-0069-5 · Cited by 107
“Twenty-five percent of patients clinically diagnosed with probable AD during their lifetime did not have evidence of AD at autopsy [8].”
BackgroundAn update on fluid biomarkers for neurodegenerative diseases: recent success and challenges ahead
Simrén, J., Ashton, N. J., Blennow, K., & Zetterberg, H. (2019) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2019.11.019 · Cited by 105
“often coexist, which is seen at a rate of 27-68% among the groups examined, according to several recent studies [1-3].”
ResultMullane, K., & Williams, M. J. (2020) · Biochemical Pharmacology · doi:10.1016/j.bcp.2020.113945 · Cited by 109
Toledo, J. B., Korff, A., Shaw, L. M. J., Trojanowski, J. Q., & Zhang, J. (2013) · Acta Neuropathologica · doi:10.1007/s00401-013-1148-z · Cited by 106
“Pathologically, AD is defined by the presence of amyloid-β (Aβ) plaques and neurofibrillary tangles in the brain [35], but the accuracy of the clinical diagnosis of AD verified at autopsy is ~90 %, even in specialized centers [2, 57].”
Alawode, D. O. T., Heslegrave, A., Ashton, N. J., Karikari, T. K., Simrén, J., Montoliu‐Gaya, L., Pannee, J., O’Connor, A., Weston, P. S. J., Lantero‐Rodriguez, J., et al. (2021) · Journal of Internal Medicine · doi:10.1111/joim.13332 · Cited by 107
Artificial intelligence and neuropsychological measures: the case of Alzheimer's disease
Battista, P., Salvatore, C., Berlingeri, M., Cerasa, A., & Castiglioni, I. (2020) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2020.04.026 · Cited by 98
Blinowska, K. J., Rakowski, F., Kamiński, M., Fallani, F. D. V., Percio, C. D., Lizio, R., & Babiloni, C. (2016) · Clinical Neurophysiology · doi:10.1016/j.clinph.2016.10.002 · Cited by 109
“What about the comparison in the classification accuracy between the markers of EEG connectivity and those based on CSF, MRI, and PET? Results based on CFS study yielded discrimination sensitivity (SEN) in the range: 70–100% and 40–85% for amyloid b and tau respectively, corresponding specificities (SPE) were 40–85% a…”
Validity of the 2014 traumatic encephalopathy syndrome criteria for CTE pathology
Mez, J., Alosco, M. L., Daneshvar, D. H., Saltiel, N. A., Baucom, Z., Abdolmohammadi, B., Uretsky, M., Nicks, R., Martin, B. M., Palmisano, J. N., et al. (2021) · Alzheimer s & Dementia · doi:10.1002/alz.12338 · Cited by 107
Devanand, D. P., Lee, S., Huey, E. D., & Goldberg, T. E. (2022) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2021.4363 · Cited by 105
Alzheimer's disease outlook: controversies and future directions
Frisoni, G. B., Aho, E., Brayne, C., Ciccarelli, O., Dubois, B., Fox, N. C., Frederiksen, K. S., Gabay, C., Garibotto, V., Hofmarcher, T., et al. (2025) · The Lancet · doi:10.1016/s0140-6736(25)01389-3 · Cited by 116
Cascaded multi-modal mixing transformers for Alzheimer’s disease classification with incomplete data
Liu, L., Liu, S., Zhang, L., To, X. V., Nasrallah, F., & Chandra, S. S. (2023) · NeuroImage · doi:10.1016/j.neuroimage.2023.120267 · Cited by 101
PET Imaging of Tau Pathology in Alzheimer’s Disease and Tauopathies
James, O. G., Doraiswamy, P. M., & Borges-Neto, S. (2015) · Frontiers in Neurology · doi:10.3389/fneur.2015.00038 · Cited by 104
“Likewise, nearly 30% of patients, who were thought to have AD, clinically do not meet postmortem pathologic criteria for AD (3).”
BackgroundStocker, H. R., Beyer, L., Perna, L., Rujescu, D., Holleczek, B., Beyreuther, K. T., Stockmann, J., Schöttker, B., Gerwert, K. B., & Brenner, H. (2022) · Alzheimer s & Dementia · doi:10.1002/alz.12614 · Cited by 103
How early can we predict Alzheimer's disease using computational anatomy?
Adaszewski, S., Dukart, J., Kherif, F., Frackowiak, R. S. J., & Draganski, B. (2013) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2013.06.015 · Cited by 100
“Given very recent pathologic-clinical diagnostic results, this is clearly an important area for further research (Beach et al., 2012).”
Preanalytical sample handling recommendations for Alzheimer's disease plasma biomarkers
Rózga, M., Bittner, T., Batrla, R., & Karl, J. (2019) · Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring · doi:10.1016/j.dadm.2019.02.002 · Cited by 99
Skinner, T., Scott, I., & Martin, J. (2016) · International Journal of General Medicine · doi:10.2147/ijgm.s96741 · Cited by 99
“8%.(23) All four studies assessing overdiagnosis in DLB had significant bias and applicability concerns.”
Post-mortem histopathology underlying β-amyloid PET imaging following flutemetamol F 18 injection
Ikonomović, M. D., Buckley, C. J., Heurling, K., Sherwin, P. F., Jones, P. A., Zanette, M., Mathis, C. A., Klunk, W. E., Chakrabarty, A., Ironside, J. W., et al. (2016) · Acta Neuropathologica Communications · doi:10.1186/s40478-016-0399-z · Cited by 102
“The relatively modest accuracy of a clinical diagnosis of Alzheimer’s disease (AD) when compared to the definitive neuropathological findings at autopsy [4] demonstrates a current unmet need to detect the neuropathological hallmarks of AD (β-amyloid plaques and neurofibrillary tangles) in life.”
BackgroundSelf-citationRuthirakuhan, M. T., Herrmann, N., Vieira, D., Gallagher, D., & Lanctôt, K. L. (2019) · American Journal of Geriatric Psychiatry · doi:10.1016/j.jagp.2019.02.003 · Cited by 112
A brief history of “Alzheimer disease”
Knopman, D. S., Petersen, R. C., & Jack, C. R. (2019) · Neurology · doi:10.1212/wnl.0000000000007583 · Cited by 104
del Campo, M., Peeters, C. F. W., Johnson, E. C. B., Vermunt, L., Hok-A-Hin, Y. S., van Nee, M., Chen-Plotkin, A., Irwin, D. J., Hu, W. T., Lah, J. J., et al. (2022) · Nature Aging · doi:10.1038/s43587-022-00300-1 · Cited by 95
“The results obtained in the discovery cohort were compared to (1) those obtained with the external cohort of validation step 1 (AD versus control) and (2) those from the multidisease CSF cohort previously analyzed by MS approaches(13,25) (AD versus controls (n = 35); AD versus a group of non-AD neurodegenerative disor…”
MethodResultPopuri, K., Ma, D., Wang, L., & Beg, M. F. (2020) · Human Brain Mapping · doi:10.1002/hbm.25115 · Cited by 96
The Longitudinal Early‐onset Alzheimer's Disease Study (LEADS): Framework and methodology
Apostolova, L. G., Aisen, P. S. S., Eloyan, A., Fagan, A. M., Fargo, K. N., Foroud, T., Gatsonis, C. A., Grinberg, L. T., Jack, C. R., Kramer, J. H., et al. (2021) · Alzheimer s & Dementia · doi:10.1002/alz.12350 · Cited by 93
“De-identified data are downloaded from LONI by the LEADSMRI Core Mayo site, which employs the ADNI QC pipeline, including (1) visual inspection for artifacts (eg, subject motion) and evaluation of image quality; (2) verification of adherence to all sequence protocols (protocol consistency check) based on DICOM header…”
Self-citationTherriault, J., Pascoal, T. A., Benedet, A. L., Tissot, C., Savard, M., Chamoun, M., Lussier, F., Kang, M. S., Berzgin, G., Wang, T., et al. (2021) · Neurology · doi:10.1212/wnl.0000000000011416 · Cited by 91
Therriault, J., Brum, W. S., Trudel, L., Macedo, A. C., Bitencourt, F. V., Martins, C. C., Nakouzi, M., Pola, I., Wong, M. W. K., Kac, P. R., et al. (2025) · The Lancet Neurology · doi:10.1016/s1474-4422(25)00227-3 · Cited by 118
Paul, B. D., & Snyder, S. H. (2019) · Frontiers in Neurology · doi:10.3389/fneur.2019.01315 · Cited by 92
Multi-ancestry meta-analysis and fine-mapping in Alzheimer’s disease
Lake, J., Solsberg, C. W., Kim, J. J., Acosta‐Uribe, J., Makarious, M. B., Li, Z., Levine, K. S., Heutink, P., Alvarado, C. X., Vitale, D., et al. (2023) · Molecular Psychiatry · doi:10.1038/s41380-023-02089-w · Cited by 81
Considerations in the clinical use of amyloid PET and CSF biomarkers for Alzheimer's disease
Leuzy, A., Bollack, A., Pellegrino, D., Teunissen, C. E., Joie, R. L., Rabinovici, G. D., Franzmeier, N., Johnson, K. A., Barkhof, F., Shaw, L. M. J., et al. (2025) · Alzheimer s & Dementia · doi:10.1002/alz.14528 · Cited by 109
How early can we diagnose Alzheimer disease (and is it sufficient)?
Petersen, R. C. (2018) · Neurology · doi:10.1212/wnl.0000000000006088 · Cited by 94
Monsell, S. E., Kukull, W. A., Roher, A. E., Maarouf, C. L., Serrano, G., Beach, T. G., Caselli, R. J., Montine, T. J., & Reiman, E. M. (2015) · JAMA Neurology · doi:10.1001/jamaneurol.2015.1721 · Cited by 82
“5), mild (1), moderate (2), or severe (3).”
Self-citationMattsson, N., Groot, C., Jansen, W. J., Landau, S. M., Villemagne, V. L., Engelborghs, S., Mintun, M. M., Lleo, A., Molinuevo, J. L., Jagust, W. J., et al. (2018) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2018.02.009 · Cited by 88
“33 [15] Beach TG, Monsell SE, Phillips LE, Kukull W.”
Molecular imaging in dementia: Past, present, and future
Laforce, R. J., Soucy, J., Sellami, L., Dallaire‐Théroux, C., Brunet, F., Bergeron, D., Miller, B. L., & Ossenkoppele, R. (2018) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2018.06.2855 · Cited by 88
“Face-to-face versus combined studies of amyloid accumulation and metabolic activity in the diagnosis of atypical patients The clinical diagnosis of AD has only moderate sensitivity and specificity when compared with the pathological cause of neurodegenerative diseases as determined at autopsy [233].”
BackgroundResultCurrent understanding of magnetic resonance imaging biomarkers and memory in Alzheimer's disease
Bayram, E., Caldwell, J., & Banks, S. J. (2018) · Alzheimer s & Dementia Translational Research & Clinical Interventions · doi:10.1016/j.trci.2018.04.007 · Cited by 92
“Without the integration of supporting biomarkers, the positive predictive value of clinical diagnostic criteria is rather limited with poor negative predictive value [126].”
BackgroundSoluble TREM2 changes during the clinical course of Alzheimer’s disease: A meta-analysis
Liu, D., Cao, B., Zhao, Y., Huang, H., McIntyre, R. S., Rosenblat, J. D., & Zhou, H. (2018) · Neuroscience Letters · doi:10.1016/j.neulet.2018.08.038 · Cited by 88
Freeze, W. M., Jacobs, H. I. L., de Jong, J. J. A., Verheggen, I. C. M., Gronenschild, E. H. B. M., Palm, W. M., Hoff, E. I., Wardlaw, J. M., Jansen, J. F. A., Verhey, F. R. J., et al. (2019) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2019.09.017 · Cited by 87
Self-reported head injury and risk of late-life impairment and AD pathology in an AD center cohort
Abner, E. L., Nelson, P. T., Schmitt, F. A., Browning, S. R., Fardo, D. W., Wan, L., Jicha, G. A., Cooper, G. E., Smith, C. D., Caban-Holt, A. M., et al. (2014) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000355478 · Cited by 84
“This is significant because an estimated 20–30% of cases clinically diagnosed with AD have dementia due to another cause.[1] The current study re-examines the association between self-reported head injury, risk of clinical dementia, and AD pathology using data from participants with detailed longitudinal cognitive ass…”
MethodAlzheimer’s disease and its treatment–yesterday, today, and tomorrow
Kim, A. Y., Jerdi, S. A., MacDonald, R., & Triggle, C. R. (2024) · Frontiers in Pharmacology · doi:10.3389/fphar.2024.1399121 · Cited by 99
Factors Influencing Clinical Correlates of Chronic Traumatic Encephalopathy (CTE): a Review
Asken, B. M., Sullan, M. J., Snyder, A., Houck, Z. M., Bryant, V. E., Hizel, L. P., McLaren, M. E., Dede, D. E., Jaffee, M. S., DeKosky, S. T., et al. (2016) · Neuropsychology Review · doi:10.1007/s11065-016-9327-z · Cited by 90
“Additionally, 39 % of subjects without a clinical diagnosis of either probable or possible AD met minimum histopathological criteria for AD (Beach et al. 2012).”
BackgroundNeuropathological assessment of the Alzheimer spectrum
Jellinger, K. A. (2020) · Journal of Neural Transmission · doi:10.1007/s00702-020-02232-9 · Cited by 85
Olfactory Dysfunction as a Global Biomarker for Sniffing out Alzheimer’s Disease: A Meta-Analysis
Kotecha, A., Corrêa, A., Fisher, K., & Rushworth, J. V. (2018) · Biosensors · doi:10.3390/bios8020041 · Cited by 82
“However, AD shares many neuropathological features with other diseases, meaning that a definitive diagnosis is only achievable through clinical assessment and post-mortem verification of the hallmarks of disease in the brain [11].”
BackgroundGenome-wide analysis of genetic predisposition to Alzheimer’s disease and related sex disparities
Nazarian, A., Yashin, A. I., & Kulminski, A. M. (2019) · Alzheimer s Research & Therapy · doi:10.1186/s13195-018-0458-8 · Cited by 82
“8%, respectively, indicating a relatively high possibility of clinically false-negative and false-positive classification of subjects as controls and cases, respectively [122].”
BackgroundResultAssociation of APOE e2 genotype with Alzheimer’s and non-Alzheimer’s neurodegenerative pathologies
Goldberg, T. E., Huey, E. D., & Devanand, D. P. (2020) · Nature Communications · doi:10.1038/s41467-020-18198-x · Cited by 82
Macdonald, I. R., Maxwell, S. P., Reid, G. A., Cash, M. K., DeBay, D. R., & Darvesh, S. (2017) · Journal of Alzheimer s Disease · doi:10.3233/jad-170164 · Cited by 85
“5), because of potential clinical overlap with AD [50].”
BackgroundDynamic Regulation of Cerebral Blood Flow in Patients With Alzheimer Disease
de Heus, R. A. A., de Jong, D. L. K., Sanders, M. L., van Spijker, G. J., Oudegeest‐Sander, M. H., Hopman, M. T. E., LAWLOR, B. A., Rikkert, M. G. M. O., & Claassen, J. A. H. R. (2018) · Hypertension · doi:10.1161/hypertensionaha.118.10900 · Cited by 82
LaClair, K. D., Donde, A., Ling, J. P., Jeong, Y. H., Chhabra, R., Martin, L. J., & Wong, P. C. (2016) · Acta Neuropathologica · doi:10.1007/s00401-016-1637-y · Cited by 76
“Second, 20–40% of cognitively normal individuals have levels of Aβ and tau pathology that are indistinguishable from cases with severe clinical symptoms of AD [5, 11].”
Apostolova, L. G., Zarow, C., Biado, K., Hurtz, S., Boccardi, M., Somme, J. H., Honarpisheh, H., Blanken, A. E., Brook, J. K., Tung, S., et al. (2015) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2015.01.001 · Cited by 77
“It is well known that the clinical AD diagnosis has suboptimal accuracy [1,2].”
Chételat, G., Ossenkoppele, R., Villemagne, V. L., Perrotin, A., Landeau, B., Mézenge, F., Jagust, W. J., Dore, V., Miller, B. L., Egret, S., et al. (2016) · Brain · doi:10.1093/brain/aww159 · Cited by 80
“Even in post-mortem studies a significant proportion ( 20%) of the cases not meeting the neuropathological threshold for Alzheimer’s disease were diagnosed with Alzheimer’s disease anyway as no other neuropathological diagnosis could be found (Beach et al., 2012).”
BackgroundSingulani, M. P., Pereira, C. P. M., Ferreira, A. F. F., Garcia, P. C., Ferrari, G. D., Alberici, L. C., & Britto, L. R. (2020) · Experimental Gerontology · doi:10.1016/j.exger.2020.110882 · Cited by 81
Diagnostic Accuracy of Amyloid versus FDG PET in Patients with Cognitive Impairment and Autopsy
Lesman‐Segev, O. H., Joie, R. L., Iaccarino, L., Lobach, I. V., Rosen, H. J., Seo, S. W., Janabi, M., Baker, S. L., Edwards, L., Pham, J. Q., et al. (2019) · Annals of Neurology · doi:10.1002/ana.25968 · Cited by 82
“8% compared with neuropathological diagnosis.(4) The accuracy of a non-AD clinical diagnosis is similarly imperfect.”
BackgroundThe A/T/N biomarker scheme and patterns of brain atrophy assessed in mild cognitive impairment
Ekman, U., Ferreira, D., & Westman, E. (2018) · Scientific Reports · doi:10.1038/s41598-018-26151-8 · Cited by 79
“MMSE* 27,58 (1,52) 26,71 (1,45) 25,90 (1,66) 27,78 (1,70) 26,67 (2,01) 26,36 (1,58) 26,68 (2,11) 26,00 (1,23)”
InfluentialSadikki, H., Fayossé, A., Cognat, E., Sabia, S., Engelborghs, S., Wallon, D., Alexopoulos, P., Blennow, K., Zetterberg, H., Parnetti, L., et al. (2019) · PLoS Medicine · doi:10.1371/journal.pmed.1003289 · Cited by 87
“Diagnosis of AD based on clinical criteria is marked by poor overall specificity, ranging from 40% to 70% compared with neuropathologic examination [12], which can lead to misclassification bias in studies [13].”
BackgroundA systematic review and meta‐analysis of 18F‐labeled amyloid imaging in Alzheimer's disease
Yeo, J. M., Waddell, B., Khan, Z. H., & Pal, S. (2015) · Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring · doi:10.1016/j.dadm.2014.11.004 · Cited by 83
“AD and non-AD pathology with up to 40% of patients diagnosed with non-AD dementias identified as having pathology consistent with AD at postmortem in some series [1].”
BackgroundSeven challenges for neuroscience.
Markram, H. (2013) · Europe PMC (PubMed Central) · doi:10.11138/fneur/2013.28.3.145 · Cited by 78
Schindler, S. E., Jasielec, M. S., Weng, H., Hassenstab, J. J., Grober, E. H., McCue, L. M., Morris, J. C., Holtzman, D. M., Xiong, C., & Fagan, A. M. (2017) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2017.04.004 · Cited by 77
LTP-like cortical plasticity predicts conversion to dementia in patients with memory impairment
Lorenzo, F. D., Motta, C., Casula, E. P., Bonnì, S., Assogna, M., Caltagirone, C., Martorana, A., & Koch, G. (2020) · Brain stimulation · doi:10.1016/j.brs.2020.05.013 · Cited by 82
“For instance, current definition of neurodegeneration entails different pathological situations, endowed under the Suspected Non Alzheimer Pathology (SNAP) definition [49].”
A Luminex Assay Detects Amyloid β Oligomers in Alzheimer’s Disease Cerebrospinal Fluid
Herskovits, A. Z., Locascio, J. J., Peskind, E. R., Li, G., & Hyman, B. T. (2013) · PLoS ONE · doi:10.1371/journal.pone.0067898 · Cited by 77
“8% specific for AD, based on a large multicenter comparison of clinical assessments and neuropathologic autopsy data from the National Institute on Aging Alzheimer Disease Centers [37].”
MethodInfluentialIaccarino, L., Burnham, S. C., Dell’Agnello, G., Dowsett, S. A., & Epelbaum, S. (2023) · The Journal of Prevention of Alzheimer s Disease · doi:10.14283/jpad.2023.43 · Cited by 87
“This is, in part, a reflection of the shortcoming of clinical diagnosis; it is well recognized that a considerable proportion of individuals with a diagnosis of AD based solely on clinical criteria do not have substantial amyloid and/or tau pathology at autopsy (4).”
BackgroundSugarman, M. A., McKee, A. C., Stein, T. D., Tripodis, Y., Besser, L. M., Martin, B. M., Palmisano, J. N., Steinberg, E. G., O’Connor, M. K., Au, R., et al. (2019) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2018.12.015 · Cited by 77
“Consequently, the etiology of dementia in those samples is unclear and diagnostic misclassification is possible [7].”
BackgroundGaugler, J. E., Ascher-Svanum, H., Roth, D. L., Fafowora, T., Siderowf, A., & Beach, T. G. (2013) · BMC Geriatrics · doi:10.1186/1471-2318-13-137 · Cited by 97
“[4] which identified individuals whose clinical diagnosis matched or mismatched their diagnosis per neuropathologic examination post-mortem.”
BackgroundInfluentialSelf-citationCell-free DNA-based liquid biopsies in neurology
Gaitsch, H., Franklin, R. J. M., & Reich, D. S. (2022) · Brain · doi:10.1093/brain/awac438 · Cited by 84
Alterations of the Neuroinflammatory Markers IL-6 and TRAIL in Alzheimer's Disease
Wu, Y.-Y., Hsu, J., Wang, H.-C., Wu, S.-J., Hong, C., & Cheng, I. H.-J. (2015) · Dementia and Geriatric Cognitive Disorders Extra · doi:10.1159/000439214 · Cited by 76
Association of APOE Genotype With Heterogeneity of Cognitive Decline Rate in Alzheimer Disease
Qian, J., Betensky, R. A., Hyman, B. T., & Serrano-Pozo, A. (2021) · Neurology · doi:10.1212/wnl.0000000000011883 · Cited by 71
Concordance of Lumipulse cerebrospinal fluid t‐tau/Aβ42 ratio with amyloid PET status
Kaplow, J., Vandijck, M., Gray, J., Kanekiyo, M., Huyck, E., Traynham, C. J., Esquivel, R., Fagan, A. M., & Luthman, J. (2020) · Alzheimer's & Dementia · doi:10.1002/alz.12000 · Cited by 81
Rabinovici, G. D., Knopman, D. S., Arbizu, J., Benzinger, T. L. S., Donohoe, K. J., Hansson, O., Herscovitch, P., Kuo, P. H., Lingler, J. H., Minoshima, S., et al. (2025) · Journal of Nuclear Medicine · doi:10.2967/jnumed.124.268756 · Cited by 87
“Neuropathologic investigations ( 23 ) have shown that clinical diagnostic criteria alone have suboptimal accuracy for AD as de fi ned pathologically.”
Nead, K. T., Sinha, S., & Nguyen, P. L. (2017) · Prostate Cancer and Prostatic Diseases · doi:10.1038/pcan.2017.10 · Cited by 73
Psychosis and Clinical Outcomes in Alzheimer Disease: A Longitudinal Study
Connors, M. H., Ames, D. J., Woodward, M., & Brodaty, H. (2017) · American Journal of Geriatric Psychiatry · doi:10.1016/j.jagp.2017.10.011 · Cited by 72
Kivisäkk, P., Sweeney, T., Carlyle, B. C., Trombetta, B. A., LaCasse, K., El‐Mufti, L. H., Tuncali, I., Chibnik, L. B., Das, S., Scherzer, C. R., et al. (2023) · Frontiers in Neurology · doi:10.3389/fneur.2023.1069411 · Cited by 76
Marinescu, R. V., Oxtoby, N. P., Young, A. L., Bron, E. E., Toga, A. W., Weiner, M. W., Barkhof, F., Fox, N. C., Golland, P., Klein, S., et al. (2019) · Lecture notes in computer science · doi:10.1007/978-3-030-32281-6_1 · Cited by 72
“8% specificity, according to [15]).”
Increasing the reproducibility of fluid biomarker studies in neurodegenerative studies
Mattsson, N., Palmqvist, S., Blennow, K., & Hansson, O. (2020) · Nature Communications · doi:10.1038/s41467-020-19957-6 · Cited by 70
Chapleau, M., Joie, R. L., Yong, K. X. X., Agosta, F., Allen, I. E., Apostolova, L. G., Best, J., Boon, B. D. C., Crutch, S. J., Filippi, M., et al. (2024) · The Lancet Neurology · doi:10.1016/s1474-4422(23)00414-3 · Cited by 73
“12,21 In these previous studies, 12,21 Alzheimer’s disease pathological features were noted in about 70% of individuals with an amnestic presentation and 76% of those presenting with logopenic-variant primary progressive aphasia.”
BackgroundMorris, J. C., Weiner, M., Xiong, C., Beckett, L., Coble, D., Saito, N., Aisen, P. S., Allegri, R., Benzinger, T. L. S., Berman, S. B., et al. (2022) · Brain · doi:10.1093/brain/awac181 · Cited by 68
“34 At the earliest stages of cognitive impairment, it can be dif fi cult to distinguish Alzheimer ’ s disease as the underlying aeti- ologyfromotherpotentialnon-progressivecausesofcognitivedysfunc-tion such as depression and polypharmacy.”
Biomarkers of Alzheimer's disease and mild cognitive impairment: A current perspective
Lewczuk, P., Mroczko, B., Fagan, A. M., & Kornhuber, J. (2014) · Advances in Medical Sciences · doi:10.1016/j.advms.2014.11.002 · Cited by 73
“biomarker information; reasonable sensitivities of approximately 71–88% have been observed, but the specificities are much lower (44–71% depending on the specific histopathological diagnostic criteria employed [15]).”
BackgroundAtri, A., Dickerson, B. C., Clevenger, C. K., Karlawish, J. H., Knopman, D. S., Lin, P., Norman, M., Onyike, C. U., Sano, M., Scanland, S., et al. (2024) · Alzheimer s & Dementia · doi:10.1002/alz.14333 · Cited by 84
“77,107,108 74–77 In addition, many older adults with cognitive impairment have other potentially contributing conditions (e.g., obstructive sleep apnea, use of cognitively impairing medications, excessive alcohol consumption) that can exacerbate cognitive or behavioral symptoms.”
The pros and cons of early diagnosis in dementia
Fox, C., Lafortune, L., Boustani, M. A., & Brayne, C. (2013) · British Journal of General Practice · doi:10.3399/bjgp13x669374 · Cited by 70
Visual system manifestations of Alzheimer's disease
Kusne, Y. N., Wolf, A. B., Townley, K., Conway, M. D., & Peyman, G. A. (2016) · Acta Ophthalmologica · doi:10.1111/aos.13319 · Cited by 74
“While the mechanism of RNFL reduction has yet to be elucidated, proposed hypotheses include Ab plaques and NFTs disrupting normal retinal cell function, reduced vascularization, retrograde degeneration from loss of cortical neurons or inflammation.”
BackgroundInfluentialImaging and Molecular Mechanisms of Alzheimer’s Disease: A Review
Femminella, G. D., Thayanandan, T., Calsolaro, V., Komici, K., Rengo, G., Corbi, G., & Ferrara, N. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19123702 · Cited by 74
“At the moment, no tau tracers have been validated for clinical use [97], and some researchers highlight the inconsistencies between the in vitro and in vivo binding profiles of the tracers [98].”
BackgroundLeuzy, A., Ashton, N. J., Mattsson, N., Dodich, A., Boccardi, M., Corre, J., Drzezga, A. E., Nordberg, A. K., Ossenkoppele, R., Zetterberg, H., et al. (2021) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-021-05258-7 · Cited by 73
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.)
About these checks
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