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Dynamics of Gray Matter Loss in Alzheimer's Disease
Open accessAbstract
We detected and mapped a dynamically spreading wave of gray matter loss in the brains of patients with Alzheimer's disease (AD). The loss pattern was visualized in four dimensions as it spread over time from temporal and limbic cortices into frontal and occipital brain regions, sparing sensorimotor cortices. The shifting deficits were asymmetric (left hemisphere > right hemisphere) and correlated with progressively declining cognitive status ( p < 0.0006). Novel brain mapping methods allowed us to visualize dynamic patterns of atrophy in 52 high-resolution magnetic resonance image scans of 12 patients with AD (age 68.4 ± 1.9 years) and 14 elderly matched controls (age 71.4 ± 0.9 years) scanned longitudinally (two scans; interscan interval 2.1 ± 0.4 years). A cortical pattern matching technique encoded changes in brain shape and tissue distribution across subjects and time. Cortical atrophy occurred in a well defined sequence as the disease progressed, mirroring the sequence of neurofibrillary tangle accumulation observed in cross sections at autopsy. Advancing deficits were visualized as dynamic maps that change over time. Frontal regions, spared early in the disease, showed pervasive deficits later (>15% loss). The maps distinguished different phases of AD and differentiated AD from normal aging. Local gray matter loss rates (5.3 ± 2.3% per year in AD v 0.9 ± 0.9% per year in controls) were faster in the left hemisphere ( p < 0.029) than the right. Transient barriers to disease progression appeared at limbic/frontal boundaries. This degenerative sequence, observed in vivo as it developed, provides the first quantitative, dynamic visualization of cortical atrophic rates in normal elderly populations and in those with dementia.
Overview
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Written from the paper’s full text.
TL;DR
This longitudinal MRI study mapped a dynamically spreading wave of cortical gray matter loss in Alzheimer’s disease, from temporal/limbic regions into frontal and occipital cortex while sparing sensorimotor areas. Loss was asymmetric (left faster than right) and correlated with declining MMSE scores.
Key findings
- In 12 patients with AD versus 14 controls, AD showed significant gray matter deficits in bilateral temporal and parietal cortices (baseline permutation p < 0.00495 left, p < 0.0154 right; follow-up p < 0.00027 left, p < 0.00056 right), with deficits exceeding 15% in most affected regions and relative sparing of sensorimotor cortex (0–5% loss).
- Frontal cortex was initially only mildly affected (6–10% loss) but became severely affected later (>15% everywhere) as MMSE declined from 17.7 ± 1.9 to 12.9 ± 2.5 (mean change 5.5 ± 1.9; p < 0.00054); controls remained stable at MMSE 29.5 ± 0.3.
- Local gray matter loss rates were 5.03 ± 2.28% per year in AD versus 0.91 ± 0.92% per year in controls; left hemisphere loss was faster in AD by 0.79% per year (p < 0.04). Whole-brain atrophy was 5.22 ± 2.04% per year in AD versus 0.88 ± 0.15% per year in controls (p < 0.003 group difference).
- Lower MMSE scores were linked to greater gray matter deficits in temporal-parietal and limbic cortices, but not in sensorimotor cortex; correlation maps were significant by permutation (e.g., p < 0.0013 left, p < 0.0028 right when mean MMSE was 18).
Methods
- Longitudinal MRI study: 12 AD patients (six men, six women; mean age 68.4 ± 1.9 years at first scan) and 14 elderly controls (seven men, seven women; mean age 71.4 ± 0.9 years), each scanned twice. Methods report mean interscan intervals of 1.5 ± 0.3 years for AD and 2.6 ± 0.3 years for controls; the abstract reports an overall interscan interval of 2.1 ± 0.4 years.
- Image processing included bias correction, stereotaxic registration, tissue classification, 3D cortical surface extraction, and cortical pattern matching using 72 sulcal landmarks per brain (30 sulci traced per hemisphere). Gray matter density was measured as the proportion of gray matter within 15 mm of each cortical point.
- Statistical maps used pointwise multiple regression across the cortex and permutation testing (1 million permutations) with a primary threshold of p = 0.01 and corrected map-wise p values; left and right hemispheres were assessed separately.
Limitations
- Stated in the paper: only two time points per subject were used, forcing the assumption of linear loss during the interscan interval; future studies with multiple time points are needed to test whether AD accelerates or progresses nonlinearly.
- Evident from the text: the sample is small (12 AD patients and 14 controls), limiting generalizability and power for subgroup analyses.
- Evident from the text: reported interscan intervals differ between the abstract (2.1 ± 0.4 years overall) and the Methods (AD 1.5 ± 0.3 years; controls 2.6 ± 0.3 years), which may affect rate estimates.
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Claims the paper makes
82 Own result · 34 Not checked yet · 23 Own interpretation · 13 Own method · 2 No basis given
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 shifting deficits were asymmetric (left hemisphere Ͼ right hemisphere) and correlated with progressively declining cognitive status ( p Ͻ 0.0006).”
§ Dynamics of Gray Matter Loss in Alzheimer's Disease > Abstract
plaincorrelationaln = 12 ·- 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.
- Rests on an assumption: MRI-visible gross atrophy reflects the neuronal loss caused by AD pathology.
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 shifting deficits were asymmetric (left hemisphere Ͼ right hemisphere) and correlated with progressively declining cognitive status ( p Ͻ 0.0006).”
§ Dynamics of Gray Matter Loss in Alzheimer's Disease > Abstract
plaincorrelationaln = 12 ·- 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.
- Rests on an assumption: MRI-visible gross atrophy reflects the neuronal loss caused by AD pathology.
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
“We detected and mapped a dynamically spreading wave of gray matter loss in the brains of patients with Alzheimer's disease (AD).”
§ Dynamics of Gray Matter Loss in Alzheimer's Disease > Abstract
plainn = 12- 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.
- Rests on an assumption: MRI-visible gross atrophy reflects the neuronal loss caused by AD pathology.
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 disease stages were effectively mapped in this new, longitudinal sample.”
- Also stated in: § Subjects · hedged
“These broadly correspond to healthy aging and the transition from moderate to severe AD (with MMSE scores of 29, 18, and 13, respectively).”
§ Dynamics of Gray Matter Loss in Alzheimer's Disease > Subjects
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.
- Also stated in: § Subjects · hedged
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
“Transient barriers to disease progression appeared at limbic/frontal boundaries.”
§ Dynamics of Gray Matter Loss in Alzheimer's Disease > Abstract
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: MRI-visible gross atrophy reflects the neuronal loss caused by AD pathology.
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
“Patients with AD show minimal primary visual, sensorimotor, and frontal atrophy until late in the disease.”
§ Dynamics of Gray Matter Loss in Alzheimer's Disease > Introduction
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.
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
“Local gray matter loss rates (5.3 Ϯ 2.3% per year in AD v 0.9 Ϯ 0.9% per year in controls) were faster in the left hemisphere ( p Ͻ 0.029) than the right.”
§ Dynamics of Gray Matter Loss in Alzheimer's Disease > Abstract
plainn = 12 ·- 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.
- Rests on an assumption: MRI-visible gross atrophy reflects the neuronal loss caused by AD pathology.
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
“During the study, subjects' cognitive status declined rapidly from an initial MMSE score of 17.7 Ϯ 1.9 to 12.9 Ϯ 2.5 (mean change 5.5 Ϯ 1.9 points; p Ͻ 0.00054, one-tailed t test; maximum score 30).”
§ Dynamics of Gray Matter Loss in Alzheimer's Disease > Subjects
plainn = 12- 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.
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 sharp division occurred in the loss maps (Fig. 6b, blue), with central and post-central gyri displaying minimal loss compared with the parietal association cortices immediately posterior to them.”
§ Dynamics of Gray Matter Loss in Alzheimer's Disease > Mapping average gray matter deficits in AD
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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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
“although both groups lost significant white matter over time ( p Ͻ 0.035).”
§ Dynamics of Gray Matter Loss in Alzheimer's Disease > Whole-brain atrophic rates
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. 50
- Probably not a substantial claim. 24
- The quote only partly states this claim. 1
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 loss pattern was visualized in four dimensions as it spread over time from temporal and limbic cortices into frontal and occipital brain regions, sparing sensorimotor cortices.”
§ Dynamics of Gray Matter Loss in Alzheimer's Disease > Abstract
plaindirectn = 12- 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.
- Rests on an assumption: MRI-visible gross atrophy reflects the neuronal loss caused by AD pathology.
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
“Frontal regions, spared early in the disease, showed pervasive deficits later (Ͼ15% loss).”
§ Dynamics of Gray Matter Loss in Alzheimer's Disease > Abstract
plainn = 12- 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.
- Rests on an assumption: MRI-visible gross atrophy reflects the neuronal loss caused by AD pathology.
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
“Local gray matter loss rates (5.3 Ϯ 2.3% per year in AD v 0.9 Ϯ 0.9% per year in controls) were faster in the left hemisphere ( p Ͻ 0.029) than the right.”
§ Dynamics of Gray Matter Loss in Alzheimer's Disease > Abstract
plainn = 12- 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.
- Rests on an assumption: MRI-visible gross atrophy reflects the neuronal loss caused by AD pathology.
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
“During the study, the control subjects' cognitive status remained stable.”
- Also stated in: § Subjects · plain
“Their MMSE score was 29.5 Ϯ 0.3 at both baseline and follow-up, with no change.”
§ Dynamics of Gray Matter Loss in Alzheimer's Disease > Subjects
plainn = 14- 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: § Subjects · 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 maps distinguished different phases of AD and differentiated AD from normal aging.”
§ Dynamics of Gray Matter Loss in Alzheimer's Disease > Abstract
plaincorrelationaln = 12- 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.
- Rests on an assumption: MRI-visible gross atrophy reflects the neuronal loss caused by AD pathology.
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
“Statistical maps were generated indicating locally the degree to which gray matter loss rates were statistically linked with diagnosis and cognitive performance (MMSE scores) (Fig. 5).”
§ Dynamics of Gray Matter Loss in Alzheimer's Disease > Mapping gray matter loss
hedgedcorrelational- 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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Probably not a substantial 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
“The white matter loss rate in AD (3.30Ϯ 2.06% per year; left hemisphere 3.20 Ϯ 2.91% per year, right hemisphere 3.40 Ϯ 3.03% per year) was comparable with that in controls (2.72 Ϯ 1.44% per year; left hemisphere 2.91 Ϯ 2.09% per year, right hemisphere 2.52 Ϯ 2.07%/year), and no asymmetries were detected ( p Ͼ 0.1).”
§ Dynamics of Gray Matter Loss in Alzheimer's Disease > Whole-brain atrophic rates
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.
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
“In AD, the left hemisphere had 2.4% (Ϯ2.0%) less gray matter overall than the right at baseline, and 3.5% (Ϯ2.0%) less gray matter at follow-up.”
§ Dynamics of Gray Matter Loss in Alzheimer's Disease > Loss rate asymmetries
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In patients with AD, the left hemisphere lost volume at 5.86 Ϯ 8.60% per year, compared with 0.99 Ϯ 0.59% in controls ( p Ͻ 0.019 for significant loss in controls, p Ͻ 0.023 for group difference)”
§ Dynamics of Gray Matter Loss in Alzheimer's Disease > Whole-brain atrophic rates
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.
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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
“Here, gray matter maps, at a single time point, better discriminated AD ( p Ͻ 0.00027 at follow-up) than longitudinal loss rates for total cerebral volume ( p Ͻ 0.003) and rates of overall gray matter loss ( p Ͻ 0.04).”
§ Dynamics of Gray Matter Loss in Alzheimer's Disease > Detection power
plaincorrelational- Asserted: passes — The authors put it forward as true.
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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
“whereas with AD the right hemisphere lost volume at 4.57 Ϯ 5.61% per year, compared with 0.88 Ϯ 0.46% in controls ( p Ͻ 0.0083 for significant loss in controls, p Ͻ 0.0095 for group difference; all tests one-tailed).”
§ Dynamics of Gray Matter Loss in Alzheimer's Disease > Whole-brain atrophic rates
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.
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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
“Here, control subjects show an average 15-20% less gray matter in sensorimotor regions ( a), which is highly significant ( c).”
§ Dynamics of Gray Matter Loss in Alzheimer's Disease > Dynamic, four-dimensional maps
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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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“When rates of change were considered, MMSE decline over time was highly significant in AD ( p Ͻ 0.00054), whereas no changes were detected in the controls (mean change, 0.0; p Ͼ 0.05).”
§ Dynamics of Gray Matter Loss in Alzheimer's Disease > Cognitive correlates
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
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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
“These disease effects were found in multiple regressions that controlled for age and gender (although effects of these covariates were not significant; overall multiple r ϭ 0.48; p Ͻ 0.006).”
§ Dynamics of Gray Matter Loss in Alzheimer's Disease > Whole-brain atrophic rates
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
“Again, the cortex exhibits substantial gray matter loss, with deficits intensifying still further in the most severely affected regions (Fig. 6e,f ) (using permutation tests for an effect of diagnosis; p Ͻ 0.00027 left hemisphere, p Ͻ 0.00056 right hemisphere).”
§ Dynamics of Gray Matter Loss in Alzheimer's Disease > Mapping average gray matter deficits in AD
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
“Both controls ( p Ͻ 0.0069) (Fig. 7c,d) and patients ( p Ͻ 0.0091) had significantly less cortical gray matter in the left hemisphere.”
§ Dynamics of Gray Matter Loss in Alzheimer's Disease > Loss rate asymmetries
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.
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 transit of deficits from temporoparietal into frontal cortices is dramatic and so is the sparing of sensorimotor areas.”
§ Dynamics of Gray Matter Loss in Alzheimer's Disease > Dynamic, four-dimensional maps
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.
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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 trend for faster left hemisphere loss also was observed for cerebral volume ( p Ͻ 0.055), in line with the significantly faster gray matter loss rate mapped in the left hemisphere.”
§ Dynamics of Gray Matter Loss in Alzheimer's Disease > Whole-brain atrophic rates
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.
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
“Patients with AD lost significant gray matter ( p Ͻ 0.05 for overall annual loss of gray matter) (Fig. 4e-h) and at a significantly more rapid rate than controls ( p Ͻ 0.042), with a total gray matter loss rate of 5.03 Ϯ 2.28% per year (left hemisphere 5.43 Ϯ 3.29% per year; right hemisphere 4.64 Ϯ 3.31% per year).”
§ Dynamics of Gray Matter Loss in Alzheimer's Disease > Mapping rates of loss
plaincorrelational- Asserted: passes — The authors put it forward as true.
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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
“(2) the cingulate/paralimbic belts (10 to 15% loss) were significantly but less severely affected (Fig. 8a, yellow);”
§ Dynamics of Gray Matter Loss in Alzheimer's Disease > Medial wall effects
plain- Asserted: passes — The authors put it forward as true.
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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
“Overall cerebral volume loss rates were significantly faster in AD than in controls, with a loss rate of 5.22 Ϯ 2.04% per year in AD ( p Ͻ 2.3 ϫ 10 Ϫ5 ), compared with 0.88 Ϯ 0.15% per year in controls ( p Ͻ 0.013 for significant loss in controls, p Ͻ 0.003 for group difference; both hemispheres pooled).”
§ Dynamics of Gray Matter Loss in Alzheimer's Disease > Whole-brain atrophic rates
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
“MMSE scores were lower in the AD group than in controls both initially ( p Ͻ 2.85 ϫ 10 Ϫ7 ) and after 1.5 years ( p Ͻ 2.6 ϫ 10 Ϫ8 ).”
§ Dynamics of Gray Matter Loss in Alzheimer's Disease > Cognitive correlates
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
“The most significant impairments occurred in temporal and parietal regions (Fig. 6a, red), where deficits exceeded 15% (Fig. 6c).”
§ Dynamics of Gray Matter Loss in Alzheimer's Disease > Mapping average gray matter deficits in AD
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.
In the paper
“Most left hemisphere regions showed a Ͼ15% deficit relative to healthy controls (Fig. 8b), consistent with our earlier cross-sectional studies in an independent sample (Thompson et al., 2001b).”
§ Dynamics of Gray Matter Loss in Alzheimer's Disease > Medial wall effects
What the sources say
- Not checked yetcites Thompson et al., 2001b
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.
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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
“Primary sensory and motor cortices were comparatively spared in the disease (with a 0 -5% deficit on average in the central and postcentral gyri (Fig. 6b, S/M).”
§ Dynamics of Gray Matter Loss in Alzheimer's Disease > Mapping average gray matter deficits in AD
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Occipital regions are also atrophic in this study; changes are not always detected in metabolic or perfusion studies of AD, in which visual cortices often serve as a control region in PET or single photon emission computed tomography imaging studies (Jagust et al., 1996).”
§ Dynamics of Gray Matter Loss in Alzheimer's Disease > Metabolism
What the sources say
- Not checked yetcites Jagust et al., 1996 source
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.
- 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
“Here, control subjects show an average 15-20% less gray matter in sensorimotor regions ( a), which is highly significant ( c).”
§ Dynamics of Gray Matter Loss in Alzheimer's Disease > Relation to previous work
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 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
“Although severe temporal lobe loss ( T ) and parietal loss have already occurred at baseline (top) and subsequently continue (Fig.4), the frontal deficits characteristic of late AD are not found until significant cognitive decline has occurred (bottom).”
§ Dynamics of Gray Matter Loss in Alzheimer's Disease > Relation to previous work
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- The authors state this as an assumption: Gray matter loss is linear during the interval between scans.
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
“As expected, no linkages are found with sensorimotor gray matter variation ( b), which was not in significant deficit in late AD.”
§ Dynamics of Gray Matter Loss in Alzheimer's Disease > Relation to previous work
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.
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
“Note the prominent division between limbic and frontal zones, with different degrees of impairment ( c).”
§ Dynamics of Gray Matter Loss in Alzheimer's Disease > Relation to previous work
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.
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
“One advantage of cortical matching is that it localizes deficits relative to gyral landmarks; it also averages data from corresponding gyri, which would be impossible if data were mapped only linearly into stereotaxic space.”
§ Dynamics of Gray Matter Loss in Alzheimer's Disease > Cortical pattern matching
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
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
“An image analyst (K.M.H.) who was blind to subject diagnosis, gender, and age traced each of 30 sulci in each hemisphere on the surface rendering of each subject's brain (13 on the medial surface, 17 on the lateral surface).”
§ Dynamics of Gray Matter Loss in Alzheimer's Disease > Cortical pattern matching
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.
In the paper
“All patients were reassessed at intervals of 3-6 months with a full clinical evaluation, and their cognitive status was evaluated using the Mini-Mental State Exam (MMSE) (Folstein et al., 1975).”
§ Dynamics of Gray Matter Loss in Alzheimer's Disease > Subjects
What the sources say
- Not checked yetcites Folstein et al., 1975
plainn = 12- 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.
None of the sources cited for this claim have been checked yet.
In the paper
“Recently, we used dynamic brain mapping to uncover the trajectory of cortical change as schizophrenia develops in the teenage brain (Thompson et al., 2001d) and as normal adolescents lose gray matter (Sowell et al., 2001).”
§ Dynamics of Gray Matter Loss in Alzheimer's Disease > Introduction
What the sources say
- Not checked yetcites Thompson et al., 2001d
- Not checked yetcites Sowell et al., 2001
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“These patients were diagnosed with AD using criteria listed in the Diagnostic and Statistical Manual of Mental Disorders (American Psychiatric Association, 2000), and they had a typical clinical presentation.”
- Also stated in: § Subjects · plain
“They also fulfilled the standards for probable AD according to criteria established by the National Institute of Neurological Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (McKhann et al., 1984).”
§ Dynamics of Gray Matter Loss in Alzheimer's Disease > Subjects
What the sources say
- Not checked yetcites American Psychiatric Association, 2000
- Not checked yetcites McKhann et al., 1984
plainn = 12- 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: § Subjects · plain
None of the sources cited for this claim have been checked yet.
In the paper
“This protocol is available on the internet (Hayashi et al., 2002) and has known inter-rater and intrarater reliability, as reported previously (Sowell et al., 2001).”
§ Dynamics of Gray Matter Loss in Alzheimer's Disease > Cortical pattern matching
What the sources say
- Not checked yetcites Hayashi et al., 2002
- Not checked yetcites Sowell et al., 2001
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“These deposits are composed of hyperphosphorylated tau-protein (Hulstaert et al., 1999).”
§ Dynamics of Gray Matter Loss in Alzheimer's Disease > Introduction
What the sources say
- Not checked yetcites Hulstaert et al., 1999 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“we established a primary threshold of p ϭ 0.01 for all significance maps and measured the total area of the cortex with statistics more significant, at a voxel level, than this threshold”
§ Dynamics of Gray Matter Loss in Alzheimer's Disease > Mapping gray matter loss
What the sources say
- Not checked yetcites Sowell et al., 2001
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
In the paper
“Exclusion criteria for the two groups included the presence of white matter lesions on T2-weighted MRI scans, preexisting psychiatric illness or head injury, and history of substance abuse or depression as measured by the Geriatric Depression Scale (Yesavage, 1988).”
§ Dynamics of Gray Matter Loss in Alzheimer's Disease > Subjects
What the sources say
- Not checked yetcites Yesavage, 1988
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
In the paper
“The inter-rater and intra-rater reliability of this protocol, and its robustness to changes in image acquisition parameters, have been described previously (Sowell et al., 1999).”
§ Dynamics of Gray Matter Loss in Alzheimer's Disease > Tissue maps
What the sources say
- Not checked yetcites Sowell et al., 1999
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Landmarks were defined according to a detailed anatomical protocol (Steinmetz et al., 1990;Leonard, 1996;Sowell et al., 2001;Hayashi et al., 2002) based on the Atlas of the Cerebral Sulci (Ono et al., 1990).”
§ Dynamics of Gray Matter Loss in Alzheimer's Disease > Cortical pattern matching
What the sources say
- Not checked yetcites Steinmetz et al., 1990
- Not checked yetcites Leonard, 1996
- Not checked yetcites Sowell et al., 2001
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.
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 approach models and controls for gyral pattern variations across subjects, and it visualizes average maps of cortical change in a population and encodes its variance and any group differences.”
§ Dynamics of Gray Matter Loss in Alzheimer's Disease > Cortical pattern matching
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
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
“Despite the selection of a low significance threshold at the voxel level to define clusters, the overall p value for the map still controls for type I error, because the threshold to define significant clusters is the same in the real and in the null simulations from which the permutation distribution is drawn.”
§ Dynamics of Gray Matter Loss in Alzheimer's Disease > Mapping gray matter loss
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The previous study suggested that large areas of cortex would be diffusely affected at a voxel-wise significance level stronger than 0.01.”
§ Dynamics of Gray Matter Loss in Alzheimer's Disease > Mapping gray matter loss
What the sources say
- Not checked yetcites Thompson et al., 2001b
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.
Probably not a substantial claim.
In the paper
“This fraction provides an overall significance value for the map (corrected for multiple comparisons) (Nichols and Holmes, 2002).”
§ Dynamics of Gray Matter Loss in Alzheimer's Disease > Mapping gray matter loss
What the sources say
- Not checked yetcites Nichols and Holmes, 2002
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
“We preferred this process over using an analytical null distribution to avoid assuming that the smoothness tensor of the residuals of the statistical model were stationary across the cortical surface.”
§ Dynamics of Gray Matter Loss in Alzheimer's Disease > Mapping gray matter loss
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.
None of the sources cited for this claim have been checked yet.
In the paper
“Temporoparietal association cortices and the medial temporal lobe are severely atrophied in AD (De-Carli, 2000), with the entorhinal cortex and hippocampus the earliest and most severely affected (Janke et al., 2001;Thompson et al., 2001b).”
§ Dynamics of Gray Matter Loss in Alzheimer's Disease > Introduction
What the sources say
- Not checked yetcites De-Carli, 2000
- Not checked yetcites Janke et al., 2001
- Not checked yetcites Thompson et al., 2001b
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.
None of the sources cited for this claim have been checked yet.
In the paper
“To quantify local gray matter, we used a measure termed gray matter density, which has been used in many previous studies to compare the spatial distribution of gray matter across subjects (Wright et al., 1995;Bullmore et al., 1999;Sowell et al., 1999;Ashburner and Friston, 2000;Mummery et al., 2000;Rombouts et al., 2000;Baron et al., 2001;Good et al., 2001;Thompson et al., 2001a,b).”
§ Dynamics of Gray Matter Loss in Alzheimer's Disease > Cortical pattern matching
What the sources say
- Not checked yetcites Wright et al., 1995
- Not checked yetcites Bullmore et al., 1999
- Not checked yetcites Sowell et al., 1999
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.
None of the sources cited for this claim have been checked yet.
In the paper
“We used permutation here to avoid making assumptions about the spatial covariance of the residuals (Nichols and Holmes, 2002) and to avoid complex corrections for data localized on surfaces [for a discussion of this issue, see Thompson et al. (2000a,b)].”
§ Dynamics of Gray Matter Loss in Alzheimer's Disease > Mapping gray matter loss
What the sources say
- Not checked yetcites Nichols and Holmes, 2002
- Not checked yetcites Thompson et al., 2000a,b
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Braak and Braak (1997) noted at autopsy that NFT distribution was initially restricted to entorhinal cortices, spreading to higher-order temporoparietal association cortices, then to frontal, and ultimately, to primary sensory and visual areas (Delacourte et al., 1999;Price and Morris, 1999).”
§ Dynamics of Gray Matter Loss in Alzheimer's Disease > Introduction
What the sources say
- Not checked yetcites Braak and Braak (1997)
- Not checked yetcites Delacourte et al., 1999 source
- Not checked yetcites Price and Morris, 1999
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.
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
“Maps identifying these linkages were computed pointwise across the cortex and assessed statistically by permutation.”
§ Dynamics of Gray Matter Loss in Alzheimer's Disease > Mapping gray matter loss
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.
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
“An image analysis technique known as cortical pattern matching was used to better localize disease effects on cortical anatomy over time and to increase the power to detect systematic changes.”
§ Dynamics of Gray Matter Loss in Alzheimer's Disease > Cortical pattern matching
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. 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
“Patients and controls were scanned identically with the same scanning protocol over time.”
§ Dynamics of Gray Matter Loss in Alzheimer's Disease > MRI scanning
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
“Microvascular changes may therefore contribute to changing cortical metabolism and neocortical atrophy in AD, because these changes progress in a similar sequence.”
§ Dynamics of Gray Matter Loss in Alzheimer's Disease > Metabolism
hedgedconditional- 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
“(2) the left hemisphere degenerates faster than the right, and this asymmetric loss rate increases the existing asymmetry in cortical gray matter (LϽR) found in healthy elderly subjects;”
§ Dynamics of Gray Matter Loss in Alzheimer's Disease > Discussion
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
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
“The left hemisphere was engulfed fastest, with the right after a similar sequence after a time lag.”
§ Dynamics of Gray Matter Loss in Alzheimer's Disease > Discussion
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 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
“The resulting in vivo maps differentiate AD from normal aging and visualize atrophic patterns associated with specific disease stages.”
§ Dynamics of Gray Matter Loss in Alzheimer's Disease > Discussion
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.
None of the sources cited for this claim have been checked yet.
In the paper
“Consistent with the deficit maps observed here, NFT accumulation is minimal in sensory and motor cortices, but it occurs preferentially in entorhinal pyramidal cells, the limbic periallocortex (layers II/IV), the hippocampus/amygdala and subiculum, the basal forebrain cholinergic systems, and subsequently, in temporoparietal and frontal association cortices (layers III/V) (Pearson et al., 1985;Arn”
§ Dynamics of Gray Matter Loss in Alzheimer's Disease > Pathology
What the sources say
- Not checked yetcites Pearson et al., 1985
- Not checked yetcites Arnold et al., 1991
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A 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
“When the components of this gray matter asymmetry are factored apart, the loss process in AD therefore occurs first at an asymmetric rate (left faster than right), and second, on top of a prevailing gray matter asymmetry (left less than right) observed in AD and even in healthy elderly subjects.”
§ Dynamics of Gray Matter Loss in Alzheimer's Disease > Loss rate asymmetries
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
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
“(1) the overall deficit pattern spreads through the brain in a temporal-frontalsensorimotor sequence, with a time lag in the right hemisphere;”
§ Dynamics of Gray Matter Loss in Alzheimer's Disease > Discussion
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 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
“Regionally selective atrophy was found in distinct disease phases, with initial sparing of frontal and then only sensorimotor cortices.”
§ Dynamics of Gray Matter Loss in Alzheimer's Disease > Discussion
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
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
“A limitation of our current study is our use of only two time points per subject, which forces us to”
§ Dynamics of Gray Matter Loss in Alzheimer's Disease > Relation to previous work
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.
None of the sources cited for this claim have been checked yet.
In the paper
“The overall strategy described here also provides quantitative and visual criteria to assess genetic effects on brain structure (Thompson et al., 2001a;Thompson and Toga, 2002) and to map drug effects in clinical trials.”
§ Dynamics of Gray Matter Loss in Alzheimer's Disease > Relation to previous work
What the sources say
- Not checked yetcites Thompson et al., 2001a
- Not checked yetcites Thompson and Toga, 2002
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
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
“Regionally significant effects are coded red and assessed by permutation, which corrects for multiple comparisons.”
§ Dynamics of Gray Matter Loss in Alzheimer's Disease > Relation to previous work
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
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
“Comparisons are made after adjusting for both cortical pattern differences across subjects and gyral pattern asymmetries, using cortical pattern matching (Fig.2).”
§ Dynamics of Gray Matter Loss in Alzheimer's Disease > Relation to previous work
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
The paper relies on this without support.
MRI-visible gross atrophy reflects the neuronal loss caused by AD pathology.
“The result-ing neuronal loss is observable as gross atrophy with magnetic resonance imaging (MRI).”
The paper relies on this without support.
In early AD, neurofibrillary tangles accumulate inside neurons.
“In early AD, intraneuronal filamentous deposits, or neurofibrillary tangles (NFTs), accumulate within neurons.”
The authors state this as an assumption.
Gray matter loss is linear during the interval between scans.
“which forces us to assume linear loss during the interscan interval.”
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 cited source says what the claim attributes to it.
In the citing paper
“Landmarks were defined according to a detailed anatomical protocol. This protocol is available on the Internet (www.loni.ucla.edu/∼khayashi/Public/medial_surface) and has known inter- and intrarater reliability as reported (25).”
From Dynamic mapping of human cortical development during childhood through early adulthood (2004) · cites this paper as [25]
The cited source says what the claim attributes to it.
In the citing paper
“An image-analysis technique known as cortical pattern matching (25–27) was used to better localize cortical differences over time and increase the power to detect systematic changes (25).”
From Dynamic mapping of human cortical development during childhood through early adulthood (2004) · cites this paper as [25]
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
“During the study, subjects' cognitive status declined rapidly from an initial MMSE score of 17.7 Ϯ 1.9 to 12.9 Ϯ 2.5 (mean change 5.5 Ϯ 1.9 points; p Ͻ 0.00054, one-tailed t test; maximum score 30).”
§ Dynamics of Gray Matter Loss in Alzheimer's Disease > Subjects
Reported 5.5 · recomputed 4.8
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
§ Dynamics of Gray Matter Loss in Alzheimer's Disease > Abstract
“Local gray matter loss rates (5.3 Ϯ 2.3% per year in AD v 0.9 Ϯ 0.9% per year in controls)”
§ Dynamics of Gray Matter Loss in Alzheimer's Disease > Mapping rates of loss
“with a total gray matter loss rate of 5.03 Ϯ 2.28% per year”
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
§ Dynamics of Gray Matter Loss in Alzheimer's Disease > Loss rate asymmetries
“These maps were created by subtracting the gray matter map in the left hemisphere from that on the right, in each individual, before averaging data from corresponding cortical regions across subjects.”
§ Dynamics of Gray Matter Loss in Alzheimer's Disease > Dynamic, four-dimensional maps
“These maps are computed by comparing the average gray matter maps on the left and the right and taking their ratio (L/R).”
Citations
Cites
Diagnostic and Statistical Manual of Mental Disorders
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Self-citationGenetic influences on brain asymmetry: A DTI study of 374 twins and siblings
Jahanshad, N., Lee, A. D., Marina Barysheva, A., McMahon, K. L., de Zubicaray, G. I., Martin, N. G., Wright, M. J., Toga, A. W., & Thompson, P. M. (2010) · NeuroImage · doi:10.1016/j.neuroimage.2010.04.236 · Cited by 133
Self-citationSachs‐Ericsson, N., Corsentino, E. A., Moxley, J. H., Hames, J. L., Rushing, N. C., Sawyer, K., Joiner, T. E., Selby, E. A., Zarit, S. H., Gotlib, I. H., et al. (2012) · Aging & Mental Health · doi:10.1080/13607863.2012.717253 · Cited by 140
APOE4 is associated with greater atrophy of the hippocampal formation in Alzheimer's disease
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Self-citationIn vivo mapping of incremental cortical atrophy from incipient to overt Alzheimer’s disease
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In vivo neuropathology of the hippocampal formation in AD: a radial mapping MR-based study
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Self-citationFunctional connectivity changes differ in early and late-onset alzheimer's disease
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Progression of Atrophy in Alzheimer’s Disease and Related Disorders
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3D mapping of ventricular and corpus callosum abnormalities in HIV/AIDS
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Cortical asymmetry in Parkinson's disease: early susceptibility of the left hemisphere
Claassen, D. O., McDonell, K. E., Donahue, M. J., Rawal, S., Wylie, S. A., Neimat, J. S., Kang, H., Hedera, P., Zald, D. H., Landman, B. A., et al. (2016) · Brain and Behavior · doi:10.1002/brb3.573 · Cited by 126
White Matter Integrity Disruptions Associated With Cognitive Impairments in Type 2 Diabetic Patients
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Byun, 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
Normal rates of cognitive change in successful aging: The Freedom House Study
ROYALL, D. R., PALMER, R., CHIODO, L. K., & POLK, M. J. (2005) · Journal of the International Neuropsychological Society · doi:10.1017/s135561770505109x · Cited by 118
Metadata
- Authors
- Thompson, P. M., Hayashi, K. M., de Zubicaray, G., Janke, A. L., Rose, S. E., Semple, J., Herman, D., Hong, M. S., Dittmer, S. S., Doddrell, D. M., & Toga, A. W.
- Affiliations
- University of California, Los Angeles (US)
- The University of Queensland (AU)
- GlaxoSmithKline (United Kingdom) (GB)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2003-02-01
- Volume
- 23
- Issue
- 3
- Pages
- 994-1005
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6741905
- OpenAlex
- W2153996202
- Semantic Scholar
- 94eefd2472c56940cfc76a607cbc8eb4edc4e793
- Cited by
- 1,132
- References
- 105
- Citations by year
- 2026: 17 · 2025: 50 · 2024: 32 · 2023: 42 · 2022: 33 · 2021: 49 · 2020: 56 · 2019: 34 · 2018: 43 · 2017: 38 · 2016: 43 · 2015: 53 · 2014: 51 · 2013: 62 · 2012: 63
- FWCI
- 27.01
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- QUT ePrints (Queensland University of Technology) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- GlaxoSmithKline
- National Institute of Mental Health (P01MH052176, P01 MH52176)
- National Institute on Drug Abuse
- U.S. National Library of Medicine (LM 05639, R01LM005639, R01 LM05639)
- National Center for Research Resources (LM05639, P41RR013642, (M01 RR00865), RR 13642, RR00865, M01RR000865, P41 RR13642)
- 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 › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Keywords
- Alzheimer's disease, cortical atrophy, gray matter loss, atrophy progression, hemispheric lateralization, temporal lobe, limbic cortex, frontal cortex, occipital cortex, neurofibrillary tangles, cognitive decline, normal aging, dementia
- MeSH terms
- Aged, Aging, Alzheimer Disease, Atrophy, Brain, Brain Mapping, Cognition Disorders, Humans, Image Processing, Computer-Assisted, Longitudinal Studies, Magnetic Resonance Imaging, Neuropsychological Tests, Reference Values, Time, Disease Progression, Internet
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-07, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-07 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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