Medial temporal atrophy on MRI in normal aging and very mild Alzheimer's disease
Open accessAbstract
Magnetic resonance imaging (MRI)-based volumetric measurements of medial temporal lobe (MTL) structures can discriminate between normal elderly control subjects and patients with Alzheimer's disease (AD) of moderate to advanced severity. In terms of clinical utility, however, a more important issue concerns the ability of the technique to differentiate between normal elderly control subjects and AD patients with the very mildest form of the disease. We performed MRI-based volumetric measurements of the hippocampus, parahippocampal gyrus, and amygdala in 126 cognitively normal elderly control subjects and 94 patients with probable AD. The diagnosis of AD was made according to NINDS/ADRDA criteria, and disease severity was categorized by Clinical Dementia Rating (CDR) scores. Patients with CDR 0.5 were classified as very mild, CDR 1 as mild, and CDR 2 as moderate disease severity. Volumes of each structure declined with increasing age in control subjects and did so in parallel for men and women. The volume of each measured MTL structure also declined with age in patients with AD. The volume of each MTL structure was significantly smaller in AD patients than control subjects (p < 0.001). Of the several MTL measures, the total hippocampal volumetric measurements were best at discriminating control subjects from AD patients. The mean hippocampal volumes for AD patients relative to control subjects by severity of disease were as follows: very mild AD (CDR 0.5) -1.75 SD below the control mean, mild AD (CDR 1) -1.99 SD, and moderate AD (CDR 2) -2.22 SD. Age- and gender-adjusted, normalized MRI-based hippocampal volumetric measurements provide a sensitive marker of the MTL neuroanatomic degeneration in AD early in the disease process.
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Written from the paper’s full text.
TL;DR
MRI-based volumetric measurements of medial temporal lobe structures, especially the hippocampus, distinguish cognitively normal elderly controls from patients with probable Alzheimer's disease, including those with only very mild disease (CDR 0.5). Age- and gender-adjusted normalized hippocampal volumes are a sensitive marker of MTL degeneration early in AD.
Key findings
- In 126 controls and 94 AD patients, volumes of the hippocampus, parahippocampal gyrus (PHG), and amygdala were significantly smaller in AD than controls (P<.001); total hippocampal volume best discriminated the groups.
- Mean hippocampal volume deficits relative to controls, expressed as W scores (age/gender-adjusted normal deviates), were −1.75 SD for very mild AD (CDR 0.5), −1.99 SD for mild AD (CDR 1), and −2.22 SD for moderate AD (CDR 2); all mean W scores differed significantly from 0 (P<.001).
- At a fixed specificity of 80%, sensitivity of hippocampal volume for discriminating controls from cases was 77.8% (CDR 0.5), 83.7% (CDR 1), and 86.7% (CDR 2); 97.2% of CDR 0.5 patients fell below the 50th percentile of normal.
- MTL volumes declined linearly with age in both controls and AD patients, with parallel slopes; the hippocampal head showed the greatest age-related decline and the largest control–AD difference. Mean non-normalized decline in controls was 45.63 mm³/year for total hippocampus and 46.65 mm³/year for PHG.
Methods
- Cross-sectional study of 220 subjects (126 cognitively normal controls, 94 probable AD patients diagnosed by NINCDS/ADRDA criteria) recruited from the Mayo Clinic Alzheimer's Disease Center/Patient Registry; AD severity staged by Clinical Dementia Rating (CDR 0.5 = very mild, 1 = mild, 2 = moderate).
- MRI at 1.5T using a T1-weighted 3D spoiled gradient echo sequence (124 contiguous 1.6 mm partitions); hippocampus, PHG, and amygdala manually traced by a single blinded research assistant, with blinded three-member panel review; intra-rater test-retest coefficient of variation for hippocampal volume 1.9%.
- Volumes normalized to total intracranial volume; stepwise regression for age/gender associations, age- and gender-specific percentiles converted to W scores, ANOVA/paired t tests for structure comparisons, and stepwise linear discriminant analysis to identify best discriminating measures.
Limitations
- Stated by the paper: PHG measurements were not possible in 16 controls and 14 AD patients because a clearly identifiable collateral sulcus was absent along the entire antero-posterior extent; the sample is cross-sectional, so secular effects of different environmental or socioeconomic conditions across age groups may be unrecognized; controls included subjects with medical conditions such as hypertension, diabetes, and heart disease, which may account for some age-related volume loss; absolute numeric output of any image-based volume measurement is methodology-dependent, so specific values may vary across sites; hippocampal volume will not discriminate among conditions sharing MTL atrophy; and predicting future AD in currently normal or mildly impaired subjects requires longitudinal studies still in progress.
- Evident from the text: the study population is drawn from a single Mayo Clinic primary-care/registry pool, and the amygdala's anterior boundary is described as ill-defined and defined operationally, which may limit generalizability and measurement precision.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
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Cites
Statistics
Claims the paper makes
0 of 20 cited sources checked · 0 supported · 0 flagged
- Findingown data
The mean hippocampal volume for mild Alzheimer's disease patients (CDR 1) was 1.99 SD below the control mean.
“The mean hippocampal volumes for AD patients relative to controls by severity of disease were as follows: very mild AD (CDR 0.5) - 1.75 SD below the control mean, mild AD (CDR 1) - 1.99 SD, and moderate AD (CDR 2) - 2.22 SD.”
Quote in the paperSubstantial claim - Findingown data
Of the several medial temporal lobe measures, total hippocampal volume measurements were best at discriminating controls from Alzheimer's disease cases.
“Of the several MTL measures, the total hippocampal volume measurements were best at discriminating controls from AD cases.”
Quote in the paperSubstantial claim - Findingown data
In cognitively normal elderly controls, the volumes of each measured medial temporal lobe structure declined with increasing age in a linear fashion.
“Volumes of each structure declined with increasing age in control subjects and did so in parallel for men and women.”
- Also stated in: § Control Subjects · plain
“Normalized MTL volumes declined with age in a linear fashion([Table 2](#T2), [Figure 2](#F2)).”
Quote in the paperSubstantial claim- Rests on an assumption: The cross-sectional decline in medial temporal lobe volumes with age observed in controls reflects the effect of normal aging rather than cohort or other differences.
- Also stated in: § Control Subjects · plain
- Findingown data
The volume of each measured medial temporal lobe structure declined with age in patients with Alzheimer's disease.
“The volume of each measured MTL structure also declined with age in patients with AD.”
Quote in the paperNot a substantial claim - Findingown data
The mean hippocampal volume for moderate Alzheimer's disease patients (CDR 2) was 2.22 SD below the control mean.
“The mean hippocampal volumes for AD patients relative to controls by severity of disease were as follows: very mild AD (CDR 0.5) - 1.75 SD below the control mean, mild AD (CDR 1) - 1.99 SD, and moderate AD (CDR 2) - 2.22 SD.”
Quote in the paperNot a substantial claim
- Findingown data
The volume of each measured medial temporal lobe structure was significantly smaller in Alzheimer's disease patients than in control subjects (P<.001).
“The volume of each MTL structure was significantly smaller in AD patients than control subjects (P<.001).”
Quote in the paperSubstantial claim- Rests on an assumption: The clinically characterized control subjects are free of Alzheimer's disease-related medial temporal lobe pathology.
- Findingown data
The mean hippocampal volume for very mild Alzheimer's disease patients (CDR 0.5) was 1.75 SD below the control mean.
“The mean hippocampal volumes for AD patients relative to controls by severity of disease were as follows: very mild AD (CDR 0.5) - 1.75 SD below the control mean, mild AD (CDR 1) - 1.99 SD, and moderate AD (CDR 2) - 2.22 SD.”
Quote in the paperSubstantial claim - Findingown data
The age-related decline in medial temporal lobe volumes did not differ significantly between men and women.
“The decline in volume associated with age did not differ significantly between men and women.”
Quote in the paperNot a substantial claim - Findingown data
Among AD patients, larger normalized MTL volumes were observed among women than men.
“larger normalized volumes were observed among female AD patients”
Quote in the paperNot a substantial claim - Findingown data
The association between MTL volume and age did not differ between men and women among AD patients.
“Associations between MTL volume and age were linear, and did not differ between men and women.”
Quote in the paperNot a substantial claim - Findingown data
In AD patients, mean W scores for each MTL structure were significantly less than 0 (p<.001).
“All mean W scores were significantly different from 0 (the expected value for normal subjects), p<.001.”
- Also stated in: § Alzheimer's Disease Patients · plain
“for each anatomic structure W scores were significantly less than 0 among AD patients, (P<.001)”
Quote in the paperSubstantial claim - Also stated in: § Alzheimer's Disease Patients · plain
- Findingown data
At the 1st percentile of normal, discrimination improved as patient's disease severity (CDR score) increased.
“and, at the 1st percentile of normal, discrimination improved as patient's disease severity (CDR score) increased.”
Quote in the paperNot a substantial claim - Findingown data
W scores for the total hippocampus (p<0.05) and hippocampal head (p<0.001) were significantly different among AD patients of different CDR severity grades.
“W scores for the total hippocampus (P <0.05) and hippocampal head (P<0.001) were significantly different among AD patients of different CDR severity grades (Spearman Rank Correlation).”
Quote in the paperSubstantial claim - Findingown data
Among hippocampal segments, the head demonstrated the greatest decline in volume with age.
“The segment of the hippocampus that demonstrated the greatest decline with age was the head.”
Quote in the paperNot a substantial claim - Findingown data
The slopes of the age-volume regression lines were not significantly different between AD patients and controls over the age range studied.
“The slopes of the age-volume regression lines were not significantly different between patients and controls over the age range studied ([Table 2](#T2), [Figure 2](#F2)).”
Quote in the paperSubstantial claim - Findingown data
In stepwise linear discriminant analysis predicting AD, the only variables in the final model were hippocampal volume, hippocampal volume squared, and age.
“Using stepwise linear discriminant analysis (including age, gender, and TIV-normalized volumes as independent variables) to predict AD, the only variables which appeared in the final model were hippocampal volume, hippocampal volume squared, and age.”
Quote in the paperNot a substantial claim - Findingown data
The analysis of segmental hippocampal volumes in controls demonstrated that age-associated volume loss in the head of the hippocampus exceeds that of either the body or the tail.
“The analysis of segmental hippocampal volumes in controls demonstrated that age associated volume loss in the head of the hippocampus exceeds that of either the body or the tail.”
Quote in the paperSubstantial claim - Findingown data
Discrimination between controls and AD patients was roughly equivalent among the three AD severity groups at the 50th and 20th percentile of normal.
“Discrimination between controls and AD patients was roughly equivalent among the three AD severity groups at the 50th and 20th percentile of normal;”
Quote in the paperSubstantial claim - Findingown data
Of the hippocampal segments, the largest volumetric difference between controls and AD patients was found in the hippocampal head.
“In addition, of the hippocampal segments, the largest volumetric difference between controls and AD patients was found in the hippocampal head.”
Quote in the paperSubstantial claim - Findingown data
Discrimination was greater for CDR 1 and 2 than CDR 0.5 patients at the 10th and 5th percentile of normal.
“discrimination was greater for CDR 1 and 2 than CDR 0.5 patients at the 10th and 5th percentile of norma;”
Quote in the paperNot a substantial claim - Findingown data
When AD patients were categorized by disease severity (very mild, mild, moderate), W scores within each group remained significantly less than 0 (p<.001).
“When AD patients were categorized by disease severity into those with very mild, mild, or moderate disease, W scores within each group remained significantly less than 0, (P <.001)([Table 4](#T4)).”
Quote in the paperSubstantial claim - Findingown data
The accuracy of the prediction using the discriminant model was identical to that obtained using hippocampal W scores alone.
“Although all these terms were significant at the .02 level, the prediction equation was dominated by the linear hippocampal volume term, and the accuracy of the prediction was identical to that obtained using hippocampal W scores alone.”
Quote in the paperNot a substantial claim - Findingown data
The unnormalized medial temporal lobe structure volumes of men were generally larger than those of women.
“The unnormalized MTL structure volumes of men were generally larger than those of women, while the normalized MTL volumes of women were generally larger than those of men ([Table 2](#T2), [Figure 2](#F2)).”
Quote in the paperNot a substantial claim - Findingown data
Associations between MTL volume and age were linear in AD patients.
“Associations between MTL volume and age were linear, and did not differ between men and women.”
Quote in the paperNot a substantial claim - Findingown data
The normalized medial temporal lobe volumes of women were generally larger than those of men.
“The unnormalized MTL structure volumes of men were generally larger than those of women, while the normalized MTL volumes of women were generally larger than those of men ([Table 2](#T2), [Figure 2](#F2)).”
Quote in the paperNot a substantial claim - Findingown data
A decline in normalized MTL volumes with age was observed among AD patients.
“A decline in normalized MTL volumes with age was observed among AD patients.”
- Also stated in: § Alzheimer's Disease Patients · plain
“In AD patients, MTL volumes declined with advancing age in parallel with those of controls.”
Quote in the paperSubstantial claim - Also stated in: § Alzheimer's Disease Patients · plain
- Findingown data
Within the hippocampus, W values were most negative for the head.
“Within the hippocampus, W values were most negative for the head([Table 4](#T4)).”
Quote in the paperNot a substantial claim - Findingown data
The prediction equation was dominated by the linear hippocampal volume term.
“Although all these terms were significant at the .02 level, the prediction equation was dominated by the linear hippocampal volume term, and the accuracy of the prediction was identical to that obtained using hippocampal W scores alone.”
Quote in the paperNot a substantial claim - Findingown data
The mean TIV of AD patients (1369 cm3, SD 138 cm3) was not significantly different from that of controls.
“The mean TIV of AD patients, 1369 cm3 (SD 138cm3), was not significantly different from that of controls.”
Quote in the paperNot a substantial claim - Findingown data
All MTL limbic structures measured declined in volume with advancing age.
“All MTL limbic structures measured declined in volume with advancing age.”
Quote in the paperSubstantial claim - Findingown data
The deficit in MTL volumes relative to controls was not associated with age or gender among AD patients.
“As would be expected from [Table 2](#T2), the deficit in volumes relative to controls was not associated with age or gender.”
Quote in the paperNot a substantial claim - Findingown data
The MTL structure with the lowest W scores was the hippocampus for all 3 AD groups.
“The MTL structure with the lowest W scores was the hippocampus for all 3 AD groups.”
Quote in the paperNot a substantial claim - Findingown data
The duration of disease in younger AD patients in this study was not different from that in older AD patients.
“The duration of disease in younger AD patients in this study was not different from that in older AD patients.”
Quote in the paperSubstantial claim - Findingown data
Hippocampal W values progressively decline (increasing atrophy) with increasing CDR score.
“Hippocampal W values progressively decline (increasing atrophy) with increasing CDR score in [Table 4](#T4).”
Quote in the paperSubstantial claim - Premisecitation
MRI-based volumetric measurements of medial temporal lobe (MTL) structures can discriminate between normal elderly controls and patients with Alzheimer's disease of moderate to advanced severity.
“Magnetic resonance imaging(MRI) based volumetric measurements of medial temporal lobe (MTL) structures can discriminate between normal elderly controls and patients with Alzheimer's disease (AD) of moderate to advanced severity.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [13]-[21]
Not checked in the free run.
- Interpretationown data
Age and gender adjusted normalized MRI-based hippocampal volume measurements provide a sensitive marker of medial temporal lobe neuroanatomic degeneration in Alzheimer's disease early in the disease process.
“Age and gender adjusted normalized MRI-based hippocampal volume measurements provide a sensitive marker of the MTL neuroanatomic degeneration in AD early in the disease process.”
Quote in the paperSubstantial claim - Premisecitation
Several principal medial temporal lobe limbic structures (the hippocampal formation, amygdala, and parahippocampal gyrus) are amenable to accurate volumetric quantitation by MRI.
“several principal MTL limbic structures are amenable to accurate volumetric quantitation by MRI— the hippocampal formation, amygdala, and parahippocampal gyrus (PHG) ([8](#R8)-[12](#R12)).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [8]-[12]
Not checked in the free run.
- Premisecitation
Medial temporal lobe limbic structures are central to the integrity of declarative memory function.
“Medial temporal lobe (MTL) limbic structures are central to the integrity of declarative memory function ([5](#R5));”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [5] Squire LR. memory and the hippocampus: a synthesis from findings with rats, monkeys, and humans. Psychological Review. 1992;99:195–231. doi: 10.1037/0033-295x.99.2.195. [[DOI](https://doi.org/10.1037/0033-295x.99.2.195)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/1594723/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Psychological%20Review&title=memory%20and%20the%20hippocampus:%20a%20synthesis%20from%20findings%20with%20rats,%20monkeys,%20and%20humans.&author=LR%20Squire&volume=99&publication_year=1992&pages=195-231&pmid=1594723&doi=10.1037/0033-295x.99.2.195&)]
Not checked in the free run.
- Premisenone given
A memory impairment is usually the earliest and most severe clinical manifestation of Alzheimer's disease.
“A memory impairment is usually the earliest and most severe clinical manifestation of AD;”
Quote in the paperNot a substantial claim - Study design and conductcitation
The intra-rater test-retest coefficient of variation of hippocampal volume measurements with this method is 1.9%.
“Validation studies show the intra-rater test-retest coefficient of variation of hippocampal volume measurements to be 1.9% with this method([12](#R12)).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [12] Jack CR, Jr., Bentley M, Twomey CK, Zinsmeister AR. MR-based volume measurements of the hippocampal formation and anterior temporal lobe: validation studies. Radiology. 1990;176:205–209. doi: 10.1148/radiology.176.1.2353093. [[DOI](https://doi.org/10.1148/radiology.176.1.2353093)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/2353093/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Radiology&title=MR-based%20volume%20measurements%20of%20the%20hippocampal%20formation%20and%20anterior%20temporal%20lobe:%20validation%20studies.&author=CR%20Jack&author=M%20Bentley&author=CK%20Two
Not checked in the free run.
- Study design and conductreasoning
All image processing steps, including boundary tracing, in every subject were performed by the same trained research assistant blinded to all clinical information.
“All image processing steps (including boundary tracing) in every subject were performed by the same trained research assistant who was blinded to all clinical information in order to ensure that the volumetric data were generated in an unbiased fashion.”
Quote in the paperSubstantial claim - Study design and conductreasoning
The large number of subjects and careful attention to details of technical and neuroanatomic boundary criteria employed in this study should convincingly demonstrate the absence of additional discriminatory power provided by measurements of the PHG or amygdala.
“However, the large number of subjects and careful attention to details of technical and neuroanatomic boundary criteria employed in this study should convincingly demonstrate the absence of additional discriminatory power provided by measurements of the PHG or amygdala.”
Quote in the paperSubstantial claim - Interpretationown data
MR volumetric measurements of the hippocampal formation are useful in discriminating between very mild AD and elderly controls.
“In this study involving a large group of well characterized AD patients and elderly control subjects we have demonstrated that MR volumetric measurements of the hippocampal formation are useful in discriminating between very mild AD and elderly controls.”
Quote in the paperSubstantial claim - Premisecitation
These results are at odds with those published by several other investigators who found that combinations of different volumetric measurements more effectively separated controls from AD patients than measurement of any single structure.
“These results are at odds with those published by several other investigators who found that combinations of different volumetric measurements more effectively separated controls from AD patients than measurement of any single structure ([15](#R15), [16](#R16), [19](#R19), [55](#R55), [56](#R56)).”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [15] Lehericy S, Baulac M, Chiras J, et al. Amygdalohippocampal MR volume measurements in the early stages of Alzheimer disease. AJNR. 1994;15:927–937. [[PMC free article](/articles/PMC8332162/)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/8059663/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=AJNR&title=Amygdalohippocampal%20MR%20volume%20measurements%20in%20the%20early%20stages%20of%20Alzheimer%20disease.&author=S%20Lehericy&author=M%20Baulac&author=J%20Chiras&volume=15&publication_year=1994&pages=927-937&pmid=8059663&)]
Not checked in the free run.
- cites [16] Laakso MP, Soininen H, Partanen K, Helkala E-L, Hartikainen P, et al. Volumes of hippocampus, amygdala and frontal lobes in the MRI-based diagnosis of early Alzheimer's disease: correlation with memory functions. J of Neural Transmission. 1995;9:73–86. doi: 10.1007/BF02252964. [[DOI](https://doi.org/10.1007/BF02252964)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/7605591/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=J%20of%20Neural%20Transmission&title=Volumes%20of%20hippocampus,%20amygdala%20and%20frontal%20lobes%20in%20the%20MRI-based%20diagnosis%20of%20early%20Alzheim
Not checked in the free run.
- cites [19] Killiany RJ, Moss MB, Albert MS, et al. Temporal lobe regions on magnetic resonance imaging identify patients with early Alzheimer's disease. Arch Neurol. 1993;50:949–954. doi: 10.1001/archneur.1993.00540090052010. [[DOI](https://doi.org/10.1001/archneur.1993.00540090052010)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/8363449/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Arch%20Neurol&title=Temporal%20lobe%20regions%20on%20magnetic%20resonance%20imaging%20identify%20patients%20with%20early%20Alzheimer's%20disease.&author=RJ%20Killiany&author=MB%20Moss&author=MS%20Albert
Not checked in the free run.
- Interpretationown data
The most encouraging finding in this study was the ability of hippocampal volume measurements to discriminate between controls and AD patients with very mild disease.
“In summary, the most encouraging finding in this study was the ability of hippocampal volume measurements to discriminate between controls and AD patients with very mild disease.”
Quote in the paperSubstantial claim - Interpretationown data
Hippocampal volume measurements are a sensitive marker of the degenerative neuroanatomic substrate of the progressively more severe memory impairment seen with advancing CDR scores in AD.
“This suggests that hippocampal volume measurements are a sensitive marker of the degenerative neuroanatomic substrate of the progressively more severe memory impairment seen with advancing CDR scores in AD.”
Quote in the paperSubstantial claim - Interpretationown data
MRI volume measurements of hippocampal atrophy are a sensitive marker of the pathology of AD in its most mild form.
“These data derived from a large number of subjects demonstrate that MRI volume measurements of hippocampal atrophy are a sensitive marker of the pathology of AD in its most mild form.”
Quote in the paperSubstantial claim - Interpretationcitation
Hippocampal volume measurements will not discriminate among different conditions that share MTL atrophy as a common pathologic feature.
“Hippocampal volume measurements will not, however, discriminate among different conditions that share MTL atrophy as a common pathologic feature([58](#R58)).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [58] Laakso MP, Partanen K, Riekkinen P, et al. Hippocampal volumes in Alzheimer's disease, Parkinson's disease with and without dementia, and in vascular dementia: An MRI study. Neurology. 1996;46:678–681. doi: 10.1212/wnl.46.3.678. [[DOI](https://doi.org/10.1212/wnl.46.3.678)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/8618666/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Neurology&title=Hippocampal%20volumes%20in%20Alzheimer's%20disease,%20Parkinson's%20disease%20with%20and%20without%20dementia,%20and%20in%20vascular%20dementia:%20An%20MRI%20study.&author=MP%20Laakso&auth
Not checked in the free run.
- May combine two claims. 17
- Classified as probably not a substantial claim. 18
- The quote only partly states this claim. 1
May combine two claims.
Findingown dataAlthough all MTL limbic structures measured were significantly smaller in AD patients than controls, the structure which best discriminated between AD patients and controls was the total hippocampal volume.
“Although all the MTL limbic structures measured were significantly smaller in AD patients than controls, the structure which best discriminated between AD patients and controls was the total hippocampal volume.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataWithin the hippocampus, volumes differed significantly among the head, body, and tail, and pairwise differences between head and body, and body and tail were significant.
“Within the hippocampus, volumes differed significantly among the head, body, and tail (P = <.001, ANOVA), and pairwise differences between the head and body, and body and tail were also significant (P<.001, paired t-tests).”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Findingown dataTwo hundred twenty subjects were included in the study: 126 controls and 94 Alzheimer's disease patients.
“Two-hundred-twenty subjects are included in this report—126 controls and 94 AD patients ([Table 1](#T1)).”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataNo significant hemispheric differences in age-related volume loss were observed in any medial temporal lobe structure except the parahippocampal gyrus, where the age-related volume loss was greater on the left than the right side (P = .024).
“No significant hemispheric differences in volume loss with age were observed in any MTL structure, except the PHG where the age related volume loss was greater on the left than the right side (P = .024).”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Findingown dataMean total intracranial volume in controls was 1393 cm3 (SD 133 cm3).
“Mean total intracranial volume in controls was 1393cm3 (SD 133cm3).”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataThe mean non-normalized volumetric decline with age was 45.63 mm3/year for the total hippocampus, 27.43 for the hippocampal head, 8.84 for the hippocampal body, 9.68 for the hippocampal tail, 46.65 for the parahippocampal gyrus, and 20.75 for the amygdala.
“The mean non-normalized volumetric decline with age was 45.63 mm3/year for the total hippocampus; 27.43 for the hippocampal head; 8.84 for the hippocampal body; 9.68 for the hippocampal tail; 46.65 for the PHG; and 20.75 for the amygdala.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataThe magnitude of the volumetric deficit in AD patients relative to controls differed significantly among hippocampus, PHG, and amygdala, with all pairwise comparisons significant.
“The differences among hippocampus, PHG, and amygdala were significant (P = <.001, ANOVA), and all pairwise comparisons (paired t-tests) were also significant (hippocampus vs. amygdala, P<.001; hippocampus vs. PHG, P<.001, amygdala vs. PHG, P=.006)([Table 4](#T4)).”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Findingown dataAmong AD patients, unnormalized MTL volumes were generally larger among men than women.
“unnormalized volumes were generally larger among men than women”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataAt a fixed specificity of 80%, the sensitivity of hippocampal volume measurements in discriminating controls from cases was 77.8% for CDR=0.5, 83.7% for CDR=1, and 86.7% for CDR=2.
“For example, at a fixed specificity of 80% the sensitivity of hippocampal volume measurements in discriminating controls from cases was 77.8% for CDR=0.5; 83.7% CDR=1; and 86.7% for CDR=2.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataIn AD patients, age and gender adjusted normalized MTL volumes were significantly smaller than those of controls, for each MTL structure, at all ages, and for both men and women.
“However, the age and gender adjusted normalized MTL volumes of AD patients were significantly smaller than those of controls. This was true for each MTL structure, at all ages, and for both men and women.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataPairwise comparison of W scores were significant for the total hippocampus between CDR 0.5 vs 1.0 (p<0.01) and CDR 1.0 vs 2.0 (p<0.01).
“Pairwise comparison of the W scores were also significant for the total hippocampus—CDR 0.5 vs 1.0 (P < 0.01), CDR 1.0 vs 2.0 (P < 0.01) (Rank Sum Test).”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Findingown dataDementia Rating Scale and Mini-Mental State Exam scores declined with increasing CDR grade in Alzheimer's disease patients.
“As expected, Dementia Rating Scale([39](#R39)) and Mini-Mental State Exam ([40](#R40)) scores declined with increasing CDR grade in AD patients.”
Quote in the paperNot a substantial claimThe quote only partly states this claim.
Findingown dataThe segment of the hippocampus showing the greatest decline with age was the head.
“The segment of the hippocampus showing the greatest decline with age was the head.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataThe mean hippocampal volume in very mild (CDR 0.5) AD patients was 1.75 SD below the control mean, and 97.2% of all CDR 0.5 AD patients had hippocampal volumes below the 50th percentile of normal.
“The mean hippocampal volume in very mild (CDR 0.5) AD patients was 1.75 SD below the control mean and 97.2% of all CDR 0.5 AD patients had hippocampal volumes below the 50th percentile of normal.”
Quote in the paperSubstantial claimClassified as probably not a substantial claim.
PremisecitationCerebral atrophy is a well accepted biological concomitant of Alzheimer's disease.
“A well accepted biological concomitant of AD is cerebral atrophy([4](#R4)).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [4] DeCarli C, Kaye JA, Horwitz B, Rapoport SI. Critical analysis of the use of computer-assisted transverse axial tomography to study human brain in aging and dementia of the Alzheimer type. Neurology. 1990;40:872–883. doi: 10.1212/wnl.40.6.872. [[DOI](https://doi.org/10.1212/wnl.40.6.872)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/2189080/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Neurology&title=Critical%20analysis%20of%20the%20use%20of%20computer-assisted%20transverse%20axial%20tomography%20to%20study%20human%20brain%20in%20aging%20and%20dementia%20of%20the%20Alzhei source
Not checked in the free run.
Classified as probably not a substantial claim.
Premisenone givenMost previous studies of MRI-based medial temporal lobe volumetry have included primarily subjects with Alzheimer's disease of moderate severity.
“Most previous studies have included primarily subjects with AD of moderate severity.”
Quote in the paperSubstantial claimClassified as probably not a substantial claim.
PremisecitationMRI-based volume measurements of the medial temporal lobe have been proposed as a clinically useful test for the diagnosis of Alzheimer's disease.
“Based on initial studies, MRI-based volume measurements of the MTL have been proposed as a clinically useful test for the diagnosis of AD([13](#R13)-[21](#R21)).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [13]-[21]
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationAlzheimer's disease is the most common cause of dementia in individuals over 60 years of age.
“Alzheimer's disease(AD) is the most common cause of dementia in individuals over 60 years of age([1](#R1)-[3](#R3)).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [1]-[3]
Not checked in the free run.
May combine two claims.
PremisecitationMedial temporal lobe limbic structures are involved earliest and most extensively in the pathology of Alzheimer's disease.
“MTL limbic structures are involved earliest and most extensively in the pathology of AD([6](#R6), [7](#R7));”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [6], [7]
Not checked in the free run.
Probably not a substantial claim: may not pass S2 (checkable).
InterpretationreasoningThe most important test of the utility of MRI-based medial temporal lobe volumetry is in patients with very mild Alzheimer's disease, in whom diagnostic decision making is difficult.
“The most important test of the utility of the technique would be in patients with very mild AD in whom the diagnostic decision making process is difficult.”
Quote in the paperNot a substantial claimMay combine two claims.
InterpretationcitationHippocampal measurements have less measurement error and less noise introduced as a function of normal anatomic variation than those of the PHG or amygdala.
“Hippocampal measurements therefore have less measurement error and also less “noise” introduced as a function of normal anatomic variation than those of the PHG or amygdala ([57](#R57)).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [57] Laakso MP, Partanen K, Lehtovirta M, et al. MRI of amygdala fails to diagnose early Alzheimer's disease. NeuroReport. 1995;6:2414–2418. doi: 10.1097/00001756-199511270-00032. [[DOI](https://doi.org/10.1097/00001756-199511270-00032)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/8747165/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=NeuroReport&title=MRI%20of%20amygdala%20fails%20to%20diagnose%20early%20Alzheimer's%20disease.&author=MP%20Laakso&author=K%20Partanen&author=M%20Lehtovirta&volume=6&publication_year=1995&pages=2414-2418&pmid=8747165&doi=10.1097/00001756-199511270
Not checked in the free run.
Classified as probably not a substantial claim.
Study design and conductcitationDisease severity in Alzheimer's disease patients was assessed by the Clinical Dementia Rating scale (very mild CDR 0.5; mild CDR 1; moderate CDR 2).
“Disease severity in AD patients was assessed by the Clinical Dementia Rating (CDR) scale; very mild - CDR 0.5; mild - CDR 1; moderate - CDR 2([28](#R28)).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [28] Morris JC. The clinical dementia rating (CDR): current version and scoring rules. Neurology. 1993;43:2412–2414. doi: 10.1212/wnl.43.11.2412-a. [[DOI](https://doi.org/10.1212/wnl.43.11.2412-a)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/8232972/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Neurology&title=The%20clinical%20dementia%20rating%20(CDR):%20current%20version%20and%20scoring%20rules.&author=JC%20Morris&volume=43&publication_year=1993&pages=2412-2414&pmid=8232972&doi=10.1212/wnl.43.11.2412-a&)]
Not checked in the free run.
May combine two claims.
Interpretationown dataThe head of the hippocampus is more susceptible both to age-related atrophy and to the degenerative change associated with AD.
“These data would suggest that the head of the hippocampus is more susceptible both to age related atrophy and also more susceptible to the degenerative change associated with AD.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductreasoningParahippocampal gyrus measurements were not possible in 16 controls and 14 Alzheimer's disease patients.
“For this reason, PHG measurements were not possible in 16 controls and 14 AD patients.”
Quote in the paperNot a substantial claimClassified as probably not a substantial claim.
Study design and conductnone givenThe reformatting, realignment and anatomic tracing of the MRI images in every subject were reviewed by a three-member panel blinded to all clinical information.
“The reformatting and realignment of the MRI images and all anatomic tracing in every subject was reviewed by a three member panel who were likewise blinded to all clinical information, and corrections were made at that time if necessary.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Study design and conductcitationThe analysis of the association between MTL volume and age is based on a cross-sectional sample, and secular effects of different environmental or socioeconomic conditions experienced by successive age groups may be unrecognized.
“In analyzing the association between MTL volume and age we recognize that this is a cross-sectional sample and that secular effects of different environmental or socioeconomic conditions experienced by successive age groups may be unrecognized ([4](#R4)).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [4] DeCarli C, Kaye JA, Horwitz B, Rapoport SI. Critical analysis of the use of computer-assisted transverse axial tomography to study human brain in aging and dementia of the Alzheimer type. Neurology. 1990;40:872–883. doi: 10.1212/wnl.40.6.872. [[DOI](https://doi.org/10.1212/wnl.40.6.872)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/2189080/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Neurology&title=Critical%20analysis%20of%20the%20use%20of%20computer-assisted%20transverse%20axial%20tomography%20to%20study%20human%20brain%20in%20aging%20and%20dementia%20of%20the%20Alzhei source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
InterpretationreasoningThese data do not address the issue of optimal aging or the aging process without any co-morbid illnesses.
“These data do not address the issue of optimal aging or the aging process without any co-morbid illnesses.”
Quote in the paperNot a substantial claimMay combine two claims.
PremisecitationOf the three MTL structures measured, the anatomic boundaries presented by MRI are more precise, and less normal anatomic variability exists, for the hippocampus than for the amygdala or PHG.
“Of the three MTL structures measured, the anatomic boundaries presented by MRI are more precise, and less normal anatomic variability exits, for the hippocampus than for the amygdala or PHG ([29](#R29)).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [29] Jack CR., Jr MRI-based hippocampal volume measurements in epilepsy. Epilepsia. 1994;35(Suppl 6):S21–S29. doi: 10.1111/j.1528-1157.1994.tb05986.x. [[DOI](https://doi.org/10.1111/j.1528-1157.1994.tb05986.x)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/8206012/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Epilepsia&title=MRI-based%20hippocampal%20volume%20measurements%20in%20epilepsy.&author=CR%20Jack&volume=35&issue=Suppl%206&publication_year=1994&pages=S21-S29&pmid=8206012&doi=10.1111/j.1528-1157.1994.tb05986.x&)] source
Not checked in the free run.
May combine two claims.
Study design and conductown dataThe control and Alzheimer's disease groups were well matched on education and gender distribution, with approximately a 2:1 female to male ratio in both groups.
“The control and AD patients were well matched on education and gender distribution with approximately a 2:1 female to male ratio in both groups.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationThis observation is in agreement with a similar analysis performed on autopsy specimens.
“This observation is in agreement with a similar analysis that was performed on autopsy specimens ([51](#R51)).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [51] Chang F-LF, Parisi JE, Jack CRJ, Petersen RC. Morphometric analysis of the hippocampus in Alzheimer's Disease: Post-mortem MRI and histological correlates. Annals of Neurology. 1992;32:268. [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Annals%20of%20Neurology&title=Morphometric%20analysis%20of%20the%20hippocampus%20in%20Alzheimer's%20Disease:%20Post-mortem%20MRI%20and%20histological%20correlates.&author=F-LF%20Chang&author=JE%20Parisi&author=CRJ%20Jack&author=RC%20Petersen&volume=32&publication_year=1992&pages=268&)] source
Not checked in the free run.
Classified as probably not a substantial claim.
Study design and conductnone givenThe volumetric MRI data were not used to aid in the clinical diagnosis of Alzheimer's disease.
“The volumetric data were not used to aid in the clinical diagnosis of AD.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationThe observation of age-related brain atrophy is consistent with other imaging and autopsy studies.
“This is consistent with observations of age related brain atrophy in other imaging and autopsy studies ([14](#R14), [41](#R41)-[46](#R46)).”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [14] Jack CR, Jr., Petersen RC, O'Brien PC, et al. MR-based hippocampal volumetry in the diagnosis of Alzheimer's disease. Neurology. 1992;42:183–188. doi: 10.1212/wnl.42.1.183. [[DOI](https://doi.org/10.1212/wnl.42.1.183)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/1734300/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Neurology&title=MR-based%20hippocampal%20volumetry%20in%20the%20diagnosis%20of%20Alzheimer's%20disease.&author=CR%20Jack&author=RC%20Petersen&author=PC%20O'Brien&volume=42&publication_year=1992&pages=183-188&pmid=1734300&doi=10.1212/wnl.42.1.183&)] source
Not checked in the free run.
- cites [41]-[46]
Not checked in the free run.
May combine two claims.
InterpretationreasoningWhile the associations reported should be generalizable, the specific numeric values may vary among different sites.
“Therefore while the associations reported should be generalizable, the specific numeric values may vary among different sites.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationThe absolute numeric output of any image-based volume measurement technique is methodology-dependent.
“One caveat however is that the absolute numeric output of any image based volume measurement technique is methodology-dependent([29](#R29)).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [29] Jack CR., Jr MRI-based hippocampal volume measurements in epilepsy. Epilepsia. 1994;35(Suppl 6):S21–S29. doi: 10.1111/j.1528-1157.1994.tb05986.x. [[DOI](https://doi.org/10.1111/j.1528-1157.1994.tb05986.x)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/8206012/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Epilepsia&title=MRI-based%20hippocampal%20volume%20measurements%20in%20epilepsy.&author=CR%20Jack&volume=35&issue=Suppl%206&publication_year=1994&pages=S21-S29&pmid=8206012&doi=10.1111/j.1528-1157.1994.tb05986.x&)] source
Not checked in the free run.
The paper relies on this without support.
The cross-sectional decline in medial temporal lobe volumes with age observed in controls reflects the effect of normal aging rather than cohort or other differences.
“Normalized MTL volumes declined with age in a linear fashion([Table 2](#T2), [Figure 2](#F2)).”
The paper relies on this without support.
The clinically characterized control subjects are free of Alzheimer's disease-related medial temporal lobe pathology.
“The criteria for cognitively normal controls were 1) no active neurological or psychiatric disorders, and 2) like the cases, some had ongoing medical problems, however the illnesses or their treatments did not interfere with cognitive function.”
The paper relies on this without support.
Very mild AD patients present significant diagnostic difficulties for clinicians.
“These patients present significant diagnostic difficulties for the clinician and constitute an area where a structural imaging test may be particularly useful.”
The paper relies on this without support.
The control population in this study is typical of that which a clinician faces in daily practice.
“Yet, this control population is typical of that which a clinician faces in daily practice.”
The paper relies on this without support.
The very mild AD subjects (CDR=0.5) qualify for the diagnosis of probable AD by clinical research criteria yet exhibit only the minimal symptoms necessary for this diagnostic classification.
“The very mild AD subjects (CDR=0.5) qualify for the diagnosis of probable AD by clinical research criteria yet exhibit only the minimal symptoms necessary for this diagnostic classification.”
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?
Reduced volume of the hippocampus was frequently positioned immediately following entorhinal cortex volume reductions, which is consistent with it being recognised as one of the preliminary sites of grey matter volumetric decline in Alzheimer's disease.
“Furthermore, reduced volume of the hippocampus was frequently positioned immediately following entorhinal cortex volume reductions, which is consistent with it being recognised as one of the preliminary sites of grey matter volumetric decline in AD (Jack Jr. et al 1997).”
From White matter microstructural abnormality precedes cortical volumetric decline in Alzheimer’s disease: evidence from data-driven disease progression modelling (2022) · cites this paper as Jack Jr. et al 1997
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredNeurodegeneration is the major driver of cognitive decline in Alzheimer's disease.
“Neurodegeneration, which encompasses brain structural damage at the micro-and macroscopic scale, occurs in both white and grey matter, and is the major driver of cognitive decline in AD (Englund 1998, Jack Jr. et al 1997, Frisoni et al 2002, McDonald et al 2012).”
From White matter microstructural abnormality precedes cortical volumetric decline in Alzheimer’s disease: evidence from data-driven disease progression modelling (2022) · cites this paper as Jack Jr. et al 1997
The Discussion (page unavailable) links greater hippocampal atrophy with more severe memory impairment in AD, describing hippocampal volume as a marker of its degenerative neuroanatomic substrate. It does not establish that neurodegeneration is the major driver of cognitive decline across AD, or assess that causal claim against other contributors. (LLM, conf=0.86)
Experimental — accuracy not yet measuredStructural MRI has established itself as a reliable biomarker in the clinical diagnosis of Alzheimer's disease.
“Structural MRI has already established itself as a reliable biomarker in the clinical diagnosis of Alzheimer's disease (Dubois et al., 2007, Frisoni et al., 2010, Jack et al., 1997); characteristic grey matter reduction and ventricular enlargement can be visualised using standard T1-weighted sequences.”
From In vivo imaging of tau pathology using multi-parametric quantitative MRI (2015) · cites this paper as Jack et al., 1997
The Results report that hippocampal volume measurements distinguished patients with Alzheimer’s disease from controls, and the Discussion calls them a sensitive marker in very mild disease (pages not provided). But the Discussion describes the measurement as a potentially helpful adjunct to clinical diagnosis, not structural MRI generally as an already established, reliable clinical biomarker. (LLM, conf=0.86)
Experimental — accuracy not yet measuredMedial temporal lobe atrophy on MRI is considered an early and sensitive marker for AD, and is assumed to reflect underlying neuronal loss in hippocampus and temporal lobe.
“Medial temporal lobe (MTA) atrophy as observed on MRI is considered to be an early and sensitive marker for AD, and is assumed that it reflects underlying neuronal loss in hippocampus and temporal lobe (Clerx et al., 2013; Jack et al., 1997; Duara et al., 2008).”
From T1rho MRI and CSF biomarkers in diagnosis of Alzheimer's disease (2015) · cites this paper as Jack et al., 1997
The Abstract describes MRI-based hippocampal volume as a sensitive marker of medial temporal neuroanatomic degeneration early in AD, and the Discussion reports that it distinguishes very mild AD from elderly controls. The paper does not establish the more specific assumption that the MRI atrophy reflects neuronal loss in the hippocampus and temporal lobe. (LLM, conf=0.85)
Experimental — accuracy not yet measuredIn noncarriers, hippocampal volumes decreased with age.
“As expected, there was an age-dependent decrease in hippocampal volumes in noncarriers (Fig. 1D).22”
From Clinical and biomarker changes in dominantly inherited Alzheimer's disease (2012) · cites this paper as [22]
The authors have previously determined age- and gender-specific normal percentiles for normalized hippocampal volume in a group of 126 cognitively normal elderly controls.
“We have previously determined age and gender specific normal percentiles for normalized hippocampal volume in a group of 126 cognitively normal elderly controls (17).”
From Rates of hippocampal atrophy correlate with change in clinical status in aging and AD (2000) · cites this paper as [17]
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.
Moderate-AD PHG score does not support the stated significance
MajorThe moderate-AD PHG mean is −0.512 with SD 1.344 and at most 15 patients. Even using all 15, a test against zero gives t≈1.48 and p≈0.16, not P<.001. Fewer PHG measurements would not resolve the discrepancy.
“When AD patients were categorized by disease severity into those with very mild, mild, or moderate disease, W scores within each group remained significantly less than 0, (P <.001)([Table 4](#T4)).”
“| CDR = 0.5 (N = 36) | CDR = 1 (N = 43) | CDR = 2 (N = 15) | | --- | --- | --- | | Variable | | Mean W Value | SD | Mean W Value | SD | Mean W Value | SD | | Total Hippocampus | −1.752 | 0.939 | −1.989 | 1.193 | −2.225 | 1.183 | | PHG | −0.874 | 1.035 | −0.996 | 1.101 | −0.512 | 1.344 |”
The citation lists haven’t been fetched yet
References 79 · Cited by 1,128
Research works printed but not linked: 1
- 10.1212/WNL.42.1.1 · DOI · Paper page
- Authors
- Jack, C. R., Petersen, R. C., Xu, Y. C., Waring, S. C., O'Brien, P. C., Tangalos, E. G., Smith, G. E., Ivnik, R. J., & Kokmen, E.
- Affiliations
- Mayo Clinic (US)
- From the Departments of Diagnostic Radiology (Drs. Jack and Xu), Neurology(Drs. Petersen and Kokmen), Health Sciences Research (Drs. Waring, O'Brien, and Petersen), Internal Medicine (Dr. Tangalos), Department of Psychiatry and Psychology (Drs. Smith and Ivnik), Mayo Clinic and Foundation, Rochester, MN.
- Venue
- Neurology
- Published
- 1997-09
- Volume
- 49
- Issue
- 3
- Pages
- 786-794
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- PMC
- PMC2730601
- OpenAlex
- W2063136428
- Semantic Scholar
- 7ab5bfe2900f12600d42b0ee4884600419a7dccf
- Cited by
- 1,128
- References
- 79
- Citations by year
- 2026: 32 · 2025: 42 · 2024: 30 · 2023: 43 · 2022: 26 · 2021: 37 · 2020: 30 · 2019: 38 · 2018: 30 · 2017: 48 · 2016: 33 · 2015: 40 · 2014: 40 · 2013: 38 · 2012: 53
- FWCI
- 18.22
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neurology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (AG-08031, P30AG008031, AG-06786, U01AG006786, R01AG011378, AG-11378, R37AG011378)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cancer-related cognitive impairment studies
- Keywords
- Alzheimer's disease, medial temporal lobe atrophy, hippocampal volume, parahippocampal gyrus, amygdala, normal aging, volumetric MRI, Clinical Dementia Rating, early diagnosis
- MeSH terms
- Aging, Alzheimer Disease, Amygdala, Atrophy, Female, Hippocampus, Humans, Magnetic Resonance Imaging, Male, Severity of Illness Index, Temporal Lobe
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