The DOI matches its Crossref record; 36 of the 36 references it cites were found in a registry or an index; 3 of the 8 sources its claims cite were checked for support.
Ecology of the Aging Human Brain
Open accessAbstract
BACKGROUND: Alzheimer disease, cerebral vascular brain injury, and isocortical Lewy body disease (LBD) are the major contributors to dementia in community- and population-based studies. OBJECTIVE: To estimate the prevalence of clinically silent forms of these diseases in cognitively normal (CN) adults. DESIGN: Autopsy study. SETTING: Community- and population based. PARTICIPANTS: A total of 1672 brain autopsies from the Adult Changes in Thought study, Honolulu-Asia Aging Study, Nun Study, and Oregon Brain Aging Study, of which 424 met the criteria for CN. MAIN OUTCOME MEASURES: Of these, 336 cases had a comprehensive neuropathologic examination of neuritic plaque density, Braak stage for neurofibrillary tangles, LB distribution, and number of cerebral microinfarcts. RESULTS: Forty-seven percent of CN cases had moderate or frequent neuritic plaque density; of these, 6% also had Braak stage V or VI for neurofibrillary tangles. Fifteen percent of CN cases had medullary LBD; 8% also had nigral and 4% isocortical LBD. The presence of any cerebral microinfarcts was identified in 33% and of high-level cerebral microinfarcts in 10% of CN individuals. Overall, the burden of lesions in each individual and their comorbidity varied widely within each study but were similar across studies. CONCLUSIONS: These data show an individually varying complex convergence of subclinical diseases in the brain of older CN adults. Appreciating this ecology should help guide future biomarker and neuroimaging studies and clinical trials that focus on community- and population-based cohorts.
Overview
AI snapshot
Written from the paper’s full text.
TL;DR
In harmonized autopsies from four community- or population-based cohorts, clinically silent Alzheimer’s disease, microvascular brain injury, and Lewy body disease were common in cognitively normal older adults, with widely varying individual burden and co-morbidity. The findings suggest that the aging brain often contains multiple subclinical dementia-associated lesions, which should inform biomarker, neuroimaging, and prevention studies.
Key findings
- Among 336 cognitively normal (CN) older adults with complete neuropathologic examination, 47% had moderate or frequent neuritic plaque (NP) density; only 6% of those also had Braak stage V or VI neurofibrillary tangles.
- Lewy body disease (LBD) showed an apparent anatomic progression: 15% had medullary LBD, 8% also had nigral LBD, and 4% also had isocortical LBD.
- Any cerebral microinfarcts (CMIs) were identified in 33% of CN individuals, and high-level CMIs (≥3) in 10%; there was no significant correlation between CERAD NP score and CMI categories.
- Summary neuropathology score differed significantly across CN, lower cognitive function, and dementia groups (Kruskal-Wallis P < 0.0001; Dunn’s paired post tests P < 0.0001 for each comparison), and 10–15% of CN individuals harbored clinically silent AD, μVBI, and/or LBD at levels equal to or exceeding the average burden in dementia cases.
Methods
- The study evaluated 1,672 brain autopsies from the Adult Changes in Thought (ACT) study, Honolulu-Asia Aging Study (HAAS), Nun Study (NS), and Oregon Brain Aging Study (OBAS); 424 met criteria for CN, and 336 had complete neuropathologic examination.
- CN was defined as last clinical evaluation within 2 years of death, diagnosis of “not dementia,” and cognitive screening scores in the upper four quintiles (MMSE ≥24 for NS, MMSE ≥28 for OBAS, CASI ≥83 for HAAS, CASI >90 for ACT).
- Harmonized histopathologic assessment included CERAD NP score, Braak staging for NFTs, α-synuclein immunohistochemistry for LBs, and screening H&E-stained sections for CMIs across the same 12 sections from six bilateral cerebral regions; analyses used descriptive prevalence, a summary neuropathology score, and non-parametric tests in GraphPad Prism.
Limitations
- The paper states that interpretation of these cross-sectional autopsy data is limited, that the interval between last clinical evaluation and autopsy creates potential for misclassification especially given prodromal dementia, and that neuropathologic protocols likely have varying sensitivities.
- The paper notes that LBD data were not collected identically across all studies (medulla in two studies, substantia nigra in three, isocortex in all four), that missing CMI data were the most frequent cause of incomplete evaluation, and that caution is needed in extrapolating findings to other ethnic or racial groups or societies.
- Evident from the text: only 336 of 424 CN cases had complete neuropathologic evaluation, and the four cohorts differed in size, age, and sex composition, which the authors note may affect age-related correlation results.
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Claims the paper makes
27 Own result · 14 Own interpretation · 7 Own method · 4 No full text of the sources · 1 Supported · 1 Partly supported · accuracy not yet measured
Every source the paper cites for this claim was checked and supports it.
In the paper
“The proportion of CN older adults with moderate or frequent CERAD NP score, a metric significantly correlated with Aβ peptide-immunoreactive plaque area and detergent-insoluble Aβ42 accumulation, matches well with reports using fibrillar Aβ PET imaging in cognitively normal individuals.”
§ Ecology of aging human brain > DISCUSSION
What the sources say
- Supportedcites [34] Aizenstein HJ Nebes RD Saxton JA Frequent amyloid deposition without significant cognitive impairment among the elderly Arch Neurol 2008 65 11 1509 1517 19001171 PMC2636844 source
The Comment section reports that 21% of cognitively unimpaired older participants were amyloid-positive on PiB PET. It explicitly says this estimate closely matches a postmortem finding of 18% meeting CERAD criteria for possible Alzheimer’s disease, supporting the claimed agreement in proportions. This paper does not itself measure CERAD neuritic-plaque scores. (LLM, conf=0.90)
- Supportedcites [35] Gomperts SN Rentz DM Moran E Imaging amyloid deposition in Lewy body diseases Neurology 2008 71 12 903 910 18794492 PMC2637553 source
The Discussion reports cortical PiB PET retention in more than 20% of apparently normal people and PiB positivity in 51% of the paper’s normal-control sample. This supports the cited paper’s role as a PET-imaging report in cognitively normal individuals; it does not need to supply the citing authors’ CERAD measurement. (LLM, conf=0.91)
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- 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
“There were no instances of other less common diseases that can cause dementia in this cohort of CN individuals, e.g., fronto-temporal lobar degeneration or prion disease.”
§ Ecology of aging human brain > RESULTS
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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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
“it is uncommon for CN older individuals to have no neuropathologic evidence of disease(s) that can cause dementia”
§ Ecology of aging human brain > RESULTS
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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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
“4% isocortical LBD”
- Also stated in: § RESULTS · plain
“a further subset (4%) also had isocortical LBD”
§ Ecology of aging human brain > Abstract > RESULTS
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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- Also stated in: § RESULTS · 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
“15% of CN cases had medullary LBD”
- Also stated in: § RESULTS · plain
“15% showing medullary LBD”
§ Ecology of aging human brain > Abstract > RESULTS
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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- Also stated in: § RESULTS · 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
“8% also had nigral”
- Also stated in: § RESULTS · plain
“a subset of these (8%) also had LBD in substantia nigra”
§ Ecology of aging human brain > Abstract > RESULTS
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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- Also stated in: § RESULTS · 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
“Two of 116 CN cases from the ACT cohort had amygdala-only LBD; this was not evaluated in the other cohorts.”
§ Ecology of aging human brain > RESULTS
plainn = 116- Asserted: passes — The authors put it forward as true.
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- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“When all four cohorts were combined, there was a weak correlation between summary neuropathology score and age (Spearman ranked correlation P < 0.05)”
§ Ecology of aging human brain > RESULTS
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“of these 6% also had Braak stage V or VI for NFTs.”
- Also stated in: § RESULTS · plain
“However only 6% of these individuals also had Braak stage V or VI for NFTs.”
§ Ecology of aging human brain > Abstract > RESULTS
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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- Also stated in: § RESULTS · 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
“These data support the conclusion that individuals with LCF or dementia carry progressively greater average burden of lesions from AD, μVBI, and/or LBD.”
§ Ecology of aging human brain > RESULTS
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- It may state two separate claims as one. 13
- The quote only partly states this claim. 1
- Probably not a substantial claim. 10
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Any interval between last clinical evaluation and autopsy creates a potential for misclassification, especially since progression to dementia typically seems to be preceded by a prodrome.33”
§ Ecology of aging human brain > DISCUSSION
What the sources say
- Partly supportedcites [33] Petersen RC Roberts RO Knopman DS Mild cognitive impairment: ten years later Arch Neurol 2009 66 12 1447 1455 20008648 PMC3081688 sourceExperimental — accuracy not yet measured
The History section describes mild cognitive impairment as a prodromal condition distinct from dementia, supporting the point that dementia can be preceded by a prodrome. The Neuropathological Analysis section discusses clinical classifications and findings after death, but does not say that any interval between the last clinical evaluation and autopsy creates a risk of misclassification. No page numbers are available in our copy. (LLM, conf=0.84)
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- 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
“Overall burden of lesions in each individual and their co-morbidity varied widely within each study”
- Also stated in: § RESULTS · plain
“the burden of diseases ranged widely within each study and showed substantial individually varying co-morbidity.”
§ Ecology of aging human brain > Abstract > RESULTS
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
- Also stated in: § RESULTS · 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
“high level CMIs in 10% of CN individuals”
- Also stated in: § RESULTS · plain
“of these 10% had ≥ 3 CMI”
§ Ecology of aging human brain > Abstract > RESULTS
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The quote only partly states this claim.
- Also stated in: § RESULTS · 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 overall result of Kruskal-Wallis test was significant (P < 0.0001) for the three groups, as was Dunn’s corrected paired post tests (P < 0.0001) for each of the three paired comparisons.”
§ Ecology of aging human brain > RESULTS
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“but were similar among studies.”
- Also stated in: § RESULTS · plain
“Results from ACT (Figure 1A), HAAS (Figure 1B), NS (Figure 1C), and OBAS (Figure 1D) are similar”
- Also stated in: § DISCUSSION · boosted
“the extent of co-morbidity was remarkably similar in CN older adults among the four studies.”
§ Ecology of aging human brain > Abstract > RESULTS
boosted- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Also stated in: § RESULTS · 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
“Three instances of hippocampal sclerosis were observed (one each in ACT, HAAS and NS); each was co-morbid with AD and/or μVBI.”
§ Ecology of aging human brain > RESULTS
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
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
“however, this was driven by the relatively younger ACT cohort of men and women (Spearman ranked correlation P < 0.01) but none of the other three cohorts (Spearman ranked correlation P > 0.05)”
§ Ecology of aging human brain > RESULTS
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Amygdala-only LBD appears to be uncommon in CN individuals as was hippocampal sclerosis.”
§ Ecology of aging human brain > DISCUSSION
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
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 similarly sized subset of individuals with dementia have a burden of lesions in cerebrum that is less than the average burden in CN individuals.”
§ Ecology of aging human brain > DISCUSSION
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
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
“Braak staging for NFTs was determined by the same method in all four studies.”
§ Ecology of aging human brain > METHODS > Histopathologic Scoring
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
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
“Interpretation of these necessarily cross-sectional data is limited but does suggest that, while accumulation of cerebral cortical Aβ is common, the full spectrum of pathologic changes of AD is relatively uncommon in CN older adults.”
§ Ecology of aging human brain > RESULTS
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
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
“Our results from four independent community- or population-based studies of brain aging and dementia demonstrate that clinically silent AD, μVBI, and LBD are prevalent and commonly co-morbid but with extensive individual variation.”
§ Ecology of aging human brain > DISCUSSION
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Our data suggest that future imaging modalities for LBD should expect to detect medullary LBD in approximately one in six CN individuals; about one-half of these also will have nigral LBD, and about one-half of those with midbrain LBD will have isocortical LBD.”
§ Ecology of aging human brain > DISCUSSION
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“CMIs were determined in all four studies by the same method of screening hematoxylin & eosin (H&E)-stained sections of cerebrum for infarcts that were not observed grossly.”
§ Ecology of aging human brain > METHODS > Histopathologic Scoring
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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Probably not a substantial claim.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Our results show an intricate complexity among clinically silent diseases.”
§ Ecology of aging human brain > DISCUSSION
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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Probably not a substantial claim.
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
“our neuropathologic protocols likely have varying sensitivities and this should be remembered when considering our estimates of disease burden.”
§ Ecology of aging human brain > DISCUSSION
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence. The paper’s conclusions may not depend on it. 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
“Nevertheless, we should be cautious in extrapolating these validated findings in non-demented or CN individuals to other ethnic or racial groups or other societies.”
§ Ecology of aging human brain > DISCUSSION
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
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Probably not a substantial claim. It may be too vague to check against evidence. The paper’s conclusions may not depend on it.
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
“Only those individuals whose last clinical evaluation was within 2 years of death were included in this study.”
§ Ecology of aging human brain > METHODS > Clinical Assessments
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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Probably not a substantial claim.
In the paper
“These results are consistent with neuroimaging estimates of white matter hyperintensities, imaging abnormalities that appear to derive at least in part from pathogenic mechanisms overlapping with those that produce CMIs (reviewed in 36).”
§ Ecology of aging human brain > DISCUSSION
What the sources say
- Not checked — no full text of the sourcecites [36] Gouw AA Seewann A van der Flier WM Heterogeneity of small vessel disease: a systematic review of MRI and histopathology correlations J Neurol Neurosurg Psychiatry 2010 20935330 source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
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
“To minimize misclassification we further restricted analysis to subjects whose scores on their respective cognitive screening test at last evaluation was in the upper four quintiles for the entire cohort”
§ Ecology of aging human brain > METHODS > Clinical Assessments
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
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 regions evaluated for LBs overlapped among all studies only for frontal and temporal cortex.”
§ Ecology of aging human brain > METHODS > Histopathologic Scoring
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
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
“These results indicate that CERAD NP score, a measure that was applied across all four studies, is highly significantly correlated with cerebral cortical burden of plaque-associated Aβ peptides as determined by immunohistochemistry with antibody 6E10 and with cerebral cortical detergent-insoluble Aβ42.”
§ Ecology of aging human brain > RESULTS
hedgedcorrelationaln = 86 ·- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“HAAS screened more regions of cerebrum for microinfarcts than the other studies; however, all data presented here are limited to the same twelve sections from the same six bilateral cerebral regions as previously described.19”
§ Ecology of aging human brain > METHODS > Histopathologic Scoring
What the sources say
- Not checked — no full text of the sourcecites [19] Sonnen JA Larson EB Crane PK Pathological correlates of dementia in a longitudinal, population-based sample of aging Ann Neurol 2007 62 4 406 413 17879383 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
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
“Our major conclusions are (i) AD, μVBI, and LBD were prevalent among CN older adults”
- Also stated in: § DISCUSSION · plain
“clinically silent AD, μVBI, and LBD are prevalent and commonly co-morbid but with extensive individual variation.”
§ Ecology of aging human brain > DISCUSSION
plainn = 336- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Also stated in: § DISCUSSION · plain
The paper relies on this without support.
There are as yet no validated neuroimaging or biomarker protocols for μVBI or LBD, so current information on clinically silent forms of these diseases is available only from autopsy-based studies.
“Since there are as yet no validated neuroimaging or biomarker protocols for μVBI or LBD, current information on clinically silent forms of these diseases is available only from autopsy-based studies.”
The paper relies on this without support.
The screening protocol for CMIs has been shown independently in HAAS and ACT to be correlated with other forms of VBI, such as lacunes and territorial infarcts.
“This screening protocol for CMIs has been shown independently in HAAS and ACT to be correlated with others forms of VBI, such as lacunes and territorial infarcts.”
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?
In the citing paper
“Significantly, the severity and distribution of AD neuropathologic changes are much different (lower) in preclinical cases than in cases with clinically severe ADD (48, 108, 148-150).”
From Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature (2012) · cites this paper as [150]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated major: it would touch a result — a value a result rests on, reported and recomputed p-values on opposite sides of the significance level, two passages that conflict with no sign which is right, or a cited work retracted before this paper was published.
In the paper
§ Ecology of aging human brain > RESULTS
“Overall, approximately one-third of CN older adults had CMI captured by our screening protocol; of these 10% had ≥ 3 CMI, a level of disease that is associated with increased risk of clinically evident dementia.19”
§ Ecology of aging human brain > DISCUSSION
“High burden of CMIs, meaning lesions at the magnitide significantly associated with dementia,19 was present in approximately one in ten CN older adults.”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Ecology of aging human brain > RESULTS
“we compared tissue burden of detergent-insoluble Aβ42 with CERAD NP score”
§ Ecology of aging human brain > RESULTS
“9.6 ± 4.6 ng/g detergent-soluble Aβ42”
Citations
Cites
Staging of brain pathology related to sporadic Parkinson’s disease
Braak, H., Tredici, K. D., Rüb, U., de Vos, R. A. I., Jansen Steur, E. N. H., & Braak, E. (2003) · Neurobiology of Aging · doi:10.1016/s0197-4580(02)00065-9 · Cited by 10,777
Mirra, 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 1×
“52/64 59/0 0/106 23/32 134/202 Last MMSE score, median (range) 28 (25-30) 27 (23-29) 28 (24-30) 29 (28-30) NA Last CASI score, mean (SD) 95 (3) 89 (4) NA NA NA Brain weight, mean (SD), g 1178 (143) 1292 (101) 1143 (122) 1222 (125) 1209 (64)”
Cerebrospinal fluid biomarker signature in Alzheimer's disease neuroimaging initiative subjects
Shaw, L. M., Vanderstichele, H., Knapik‐Czajka, M., Clark, C. M., Aisen, P. S., Petersen, R. C., Blennow, K., Soares, H., Simon, A., Lewczuk, P., et al. (2009) · Annals of Neurology · doi:10.1002/ana.21610 · Cited by 2,065
Mild Cognitive Impairment: Ten Years Later
Petersen, R. C., Roberts, R. O., Knopman, D. S., Boeve, B. F., Geda, Y. E., Ivnik, R. J., Smith, G. E., & Jack, C. R. (2009) · Archives of Neurology · doi:10.1001/archneurol.2009.266 · Cited by 1,447
Frequent amyloid deposition without significant cognitive impairment among the elderly
Aizenstein, H. J., Nebes, R. D., Saxton, J. A., Price, J. C., Mathis, C. A., Tsopelas, N. D., Ziolko, S. K., James, J. A., Snitz, B. E., Houck, P. R., et al. (2008) · Archives of Neurology · doi:10.1001/archneur.65.11.1509 · Cited by 1,059
[ 11 C]PIB in a nondemented population: Potential antecedent marker of Alzheimer disease
Mintun, M. A., LaRossa, G. N., Sheline, Y. I., Dence, C. S., Lee, S. Y., Mach, R. H., Klunk, W. E., Mathis, C. A., DeKosky, S. T., & Morris, J. C. (2006) · Neurology · doi:10.1212/01.wnl.0000228230.26044.a4 · Cited by 1,036
Price, J. L., Davis, P. B., Morris, J. C., & White, D. L. (1991) · Neurobiology of Aging · doi:10.1016/0197-4580(91)90006-6 · Cited by 818 · cited 2×
“None 23 (6)/5 (1) 6 (4) 0 (1) 29 (8) Sparse 15 (5)/3 (2) 7 (4) 1 (1) 23 (8) Moderate 13 (4)/1 (1) 8 (3) 3 (2) 24 (6) Frequent 12 (4)/0 (1) 9 (3) 3 (1) 24 (7) Total 63 (6)/9 (3) 30 (5) 7 (8) 100”
Dementia and Alzheimer Disease Incidence: A Prospective Cohort Study
Kukull, W. A., Higdon, R., Bowen, J. D., McCormick, W. C., Teri, L., Schellenberg, G. D., van Belle, G., Jolley, L., & Larson, E. B. (2002) · Archives of Neurology · doi:10.1001/archneur.59.11.1737 · Cited by 806 · cited 1×
“52/64 59/0 0/106 23/32 134/202 Last MMSE score, median (range) 28 (25-30) 27 (23-29) 28 (24-30) 29 (28-30) NA Last CASI score, mean (SD) 95 (3) 89 (4) NA NA NA Brain weight, mean (SD), g 1178 (143) 1292 (101) 1143 (122) 1222 (125) 1209 (64)”
Heterogeneity of small vessel disease: a systematic review of MRI and histopathology correlations
Gouw, A. A., Seewann, A., van der Flier, W. M., Barkhof, F., Rozemuller, A. M., Scheltens, P., & Geurts, J. J. G. (2011) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp.2009.204685 · Cited by 766
Snowdon, D. A. (1996) · JAMA · doi:10.1001/jama.1996.03530310034029 · Cited by 696
Research works printed but not linked: 1
- [17]Montine TJ Sonnen JA Mini-Forum on Clinical-Pathologic Correlations in Population- and Community-Based Studies of Brain Aging Journal of Alzheimer’s disease 2009 18 643 725
Cited by
Sorted by citations
NIA‐AA Research Framework: Toward a biological definition of Alzheimer's disease
Jack, C. R., Bennett, D. A., Blennow, K., Carrillo, M. C., Dunn, B., Haeberlein, S. B., Holtzman, D. M., Jagust, W., Jessen, F., Karlawish, J., et al. (2018) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2018.02.018 · Cited by 10,537
Jack, C. R., Knopman, D. S., Jagust, W. J., Petersen, R. C., Weiner, M. W., Aisen, P. S., Shaw, L. M., Vemuri, P., Wiste, H. J., Weigand, S. D., et al. (2013) · The Lancet Neurology · doi:10.1016/s1474-4422(12)70291-0 · Cited by 4,396
Nelson, P. T., Alafuzoff, I., Bigio, E. H., Bouras, C., Braak, H., Cairns, N. J., Castellani, R. J., Crain, B. J., Davies, P., Tredici, K. D., et al. (2012) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e31825018f7 · Cited by 2,050
“Significantly, the severity and distribution of AD neuropathologic changes are much different (lower) in preclinical cases than in cases with clinically severe ADD (48, 108, 148 Y 150).”
BackgroundSelf-citationPrimary age-related tauopathy (PART): a common pathology associated with human aging
Crary, J. F., Trojanowski, J. Q., Schneider, J. A., Abisambra, J. F., Abner, E. L., Alafuzoff, I., Arnold, S. E., Attems, J., Beach, T. G., Bigio, E. H., et al. (2014) · Acta Neuropathologica · doi:10.1007/s00401-014-1349-0 · Cited by 1,467
“NFTs are practically universal in older persons’ brains [22, 30, 108, 132], and are also observed in a more limited distribution in many younger individuals [30, 32, 42].”
BackgroundBiomarker Modeling of Alzheimer’s Disease
Jack, C. R., & Holtzman, D. M. (2013) · Neuron · doi:10.1016/j.neuron.2013.12.003 · Cited by 1,002
Metadata
- Authors
- Sonnen, J. A.
- Affiliations
- University of Washington (US)
- Corresponding author
- Sonnen, Joshua A.
- ORCID
- Sonnen, Joshua A.
- Venue
- Archives of Neurology
- Publisher
- American Medical Association (AMA)
- Published
- 2011-08-01
- Volume
- 68
- Issue
- 8
- Pages
- 1049
- ISSN
- 0003-9942 (ISSN-L)
- PMC
- PMC3218566
- OpenAlex
- W2131428961
- Semantic Scholar
- 83fa5578cb861ec34b69f3898d76445f8adbbafc
- Cited by
- 174
- References
- 36
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 6 · 2023: 8 · 2022: 13 · 2021: 16 · 2020: 10 · 2019: 10 · 2018: 8 · 2017: 15 · 2016: 18 · 2015: 15 · 2014: 14 · 2013: 17 · 2012: 13
- FWCI
- 9.05
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Archives of Neurology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (submittedVersion)
- Funders
- National Institutes of Health (5p30ag008017-30, 5r01ag011378-25)
- National Institute on Aging (AG 05136, P50 AG 005136, AG008017, R01 AG023801, R01-AG011378, U01 AG006781, R37AG011378, P30-AG008017, AG-11378, R01AG017155, AG-06781)
- National Institute of Neurological Disorders and Stroke (P50NS062684, NS62684)
- 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
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Keywords
- Alzheimer's disease, cognitively normal older adults, neuritic plaques, neurofibrillary tangles, cerebral microinfarcts, Lewy bodies, neuropathology, comorbidities, brain aging
- MeSH terms
- Aged, Aged, 80 and over, Aging, Alzheimer Disease, Brain, Female, Hawaii, Humans, Male, Oregon, Dementia, Vascular, Cohort Studies, Prevalence, Lewy Body Disease
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