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Rates of hippocampal atrophy correlate with change in clinical status in aging and AD
Open accessAbstract
BACKGROUND: The cognitive continuum in the elderly population can be conceptually divided into those who are functioning normally (control subjects), those with a mild cognitive impairment (MCI), and those with probable AD. OBJECTIVES: To test the hypothesis that the annualized rates of hippocampal atrophy differ as a function of both baseline and change in clinical group membership (control, MCI, or AD). METHODS: The authors identified 129 subjects from the Mayo Clinic AD Research Center/AD Patient Registry who met established criteria for normal control subjects, MCI, or probable AD, both at entry and at the time of a subsequent clinical follow-up evaluation 3 +/- 1 years later. Each subject underwent an MRI examination of the head at the time of the initial assessment and at follow-up clinical assessment; the annualized percentage change in hippocampal volume was computed. Subjects who were classified as controls or patients with MCI at baseline could either remain cognitively stable or could decline to a lower functioning group over the period of observation. RESULTS: The annualized rates of hippocampal volume loss for each of the three initial clinical groups decreased progressively in the following order: AD > MC > control. Within the control and MCI groups, those who declined had a significantly greater rate of volume loss than those who remained clinically stable. The mean annualized rates of hippocampal atrophy by follow-up clinical group were: control-stable 1.73%, control-decliner 2.81%, MCI-stable 2.55%, MCI-decliner 3.69%, AD 3. 5%. CONCLUSION: Rates of hippocampal atrophy match both baseline cognitive status and the change in cognitive status over time in elderly persons who lie along the cognitive continuum from normal to MCI to AD.
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TL;DR
In 129 Mayo ADPR/ADRC subjects with baseline and 3 ± 1 year follow-up, annualized hippocampal atrophy rates increased across control, MCI, and AD groups and were greater in clinical decliners than in stable subjects within the control and MCI groups. The results support the hypothesis that rates of hippocampal atrophy match both baseline cognitive status and change in cognitive status over time.
Key findings
- Annualized hippocampal volume loss by initial clinical group was control −1.9 ± 1.1%, MCI −3.0 ± 1.6%, and AD −3.5 ± 1.8%; control vs MCI and control vs AD differences were significant at p < 0.001.
- By follow-up clinical group, mean annualized rates were control-stable −1.7 ± 0.9%, control-decliner −2.8 ± 1.7%, MCI-stable −2.5 ± 1.5%, MCI-decliner −3.7 ± 1.5%, and AD −3.5 ± 1.8%; control-stable vs control-decliner p = 0.03 and MCI-stable vs MCI-decliner p = 0.03.
- Baseline hippocampal volume decreased progressively from control to MCI to AD, with all three baseline group differences significant at p < 0.000; median normal percentiles were 41 for control, 11 for MCI, and 2 for AD.
- Over follow-up, 10 of 58 controls (17%) declined to MCI or probable AD, and 18 of 43 MCI subjects (42%) declined to AD.
Methods
- The study identified 129 subjects from the Mayo Clinic AD Research Center/AD Patient Registry who met criteria for normal control, MCI, or probable AD at entry and at a follow-up clinical evaluation 3 ± 1 years later; subjects with symptoms felt unrelated to AD, such as stroke or depression, were excluded.
- Each subject underwent MRI at baseline and follow-up; hippocampal volumes were manually traced, and annualized percentage change was computed as scan 2 volume minus scan 1 volume, divided by scan 1 volume, divided by years between scans, × 100.
- Baseline hippocampal volumes were normalized for head size, age, and sex using W scores from a normal elderly control database; comparisons used two-way ANOVA on ranked data by baseline clinical group and stable/decliner status, followed by rank sum tests.
Limitations
- The paper states that dichotomizing control and MCI subjects into stable vs decliner is crude because cognitive change is continuous, that the rates are a linear fit to only two time points and may not be linear, and that requiring two artifact-free MRI studies 2–4 years apart may exclude rapidly progressive dementia patients and therefore underestimate atrophy in decliner groups.
- The paper notes that the number of control decliners was small (n = 10), that diagnostic utility in predicting future AD will likely be limited by inter-group overlap, and that whether atrophy rate adds predictive power beyond baseline hippocampal volume was not formally addressed.
- Evident from the text: this is an observational, single-center clinical cohort study using clinical diagnostic classifications without pathologic confirmation, and the authors acknowledge that control-decliner is a “misnomer” because such individuals were likely presymptomatic AD at baseline.
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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
“The annualized rates of hippocampal volume loss for each of the three initial clinical groups decreased progressively in the following order: AD > MC > C.”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Within the control and MCI groups, those who declined had a significantly greater rate of volume loss than those who remained clinically stable.”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Over the course of the observation period 10 (17%) of the initial cohort of 58 controls declined to either the MCI or probable AD categories.”
Strength:plain· not yet calibratedn = 58Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The differences between the control and MCI groups, and between control and AD groups were significant at p <0.001.”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The differences among all three baseline groups were significant at p <0.000.”
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In the paper
“The annualized rates of hippocampal volume loss for each of the three initial clinical groups decreased progressively in the following order: AD > MCI > C (Table 2).”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The p-values obtained by pair-wise between group comparisons in Table 3 which were significant or nearly so (p<0.10) were: control-stable vs control-decliner, p=0.03; control-stable vs MCI-stable, p=0.02; control-stable vs MCI-decliner, p<0.000; control-stable vs AD, p<0.000; MCI-stable vs MCI-decliner, p=0.03; MCI-stable vs AD, p=0.06.”
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“The MMSE and DRS scores at baseline declined in the following order: control-stable > control-decliner > MCI-stable > MCI-decliner > AD(18).”
What the sources say
- Not checked yetcites [18] Folstein MF, Folstein SE, McHugh PR. "Mini Mental State": A practical method for grading the cognitive state of patients for the clinician. Journal of Psychiatric Research. 1975;12:189–198. doi: 10.1016/0022-3956(75)90026-6. [DOI] [PubMed] [Google Scholar] source
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In the paper
“The baseline hippocampal volume in each of the three initial clinical groups decreased progressively in the following order: control > MCI > AD (Table 4).”
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The p-values obtained by pair-wise between group comparisons in Table 3 which were significant or nearly so (p<0.10) were: control-stable vs control-decliner, p=0.03; control-stable vs MCI-stable, p=0.02; control-stable vs MCI-decliner, p<0.000; control-stable vs AD, p<0.000; MCI-stable vs MCI-decliner, p=0.03; MCI-stable vs AD, p=0.06.”
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- It may state two separate claims as one. 10
- Probably not a substantial claim. 24
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The mean annualized rates of hippocampal atrophy by followup clinical group were: control-stable 1.73%, control-decliner 2.81%, MCI-stable 2.55%, MCI-decliner 3.69 %, AD 3.5%.”
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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
“A positive volume change over time of +0.1% was measured in one of the stable AD patients.”
Strength:plain· not yet calibratedSingle caseTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably 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
“This rate was also within the range described in another study (27) using MRI volumetrics, but less than described by a different group (28) who measured the change in thickness of the medial temporal lobe on CT.”
What the sources say
- Not checked yetcites [27] Fox NC, Warrington EK, Freeborough PA, et al. Presymptomatic hippocampal atrophy in Alzheimer's disease. A longitudinal MRI study. Brain. 1996;119:2001–2007. doi: 10.1093/brain/119.6.2001. [DOI] [PubMed] [Google Scholar] source
- Not checked yetcites [28] Jobst KA, Smith AD, Szatmari M, et al. Rapidly progressing atrophy of medial temporal lobe in Alzheimer's disease. Lancet. 1994;343:829–830. doi: 10.1016/s0140-6736(94)92028-1. [DOI] [PubMed] [Google Scholar] source
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A 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
“Over the course of longitudinal clinical observation 17 members of the AD group declined to a lower functioning level as defined by an increase in CDR score, and the remaining 11 retained their baseline CDR score.”
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In the paper
“This is close to the rate of 3.5%/yr observed in the current study.”
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
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 positive change over time, an increase in volume of 0.1%, was measured in one of the patients.”
Strength:plain· not yet calibratedSingle caseTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Rates of hippocampal atrophy match both baseline cognitive status and the change in cognitive status over time in elderly persons who lie along the cognitive continuum from normal to MCI to AD.”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: The transition from normal cognition to Alzheimer's disease is gradual.
- Rests on an assumption: Patients who develop clinically evident Alzheimer's disease pass through a transitional period during which they experience declining cognitive abilities relative to age mates.
None of the sources cited for this claim have been checked yet.
In the paper
“This intermediate state has been termed mild cognitive impairment (MCI) and clinical criteria for this diagnosis have been suggested(1–3).”
What the sources say
- Not checked yetcites [1] Petersen RC, Smith GE, Waring SC, Ivnik RJ, Tangalos EG, Kokmen E. Mild cognitive impairment clinical characterization and outcome. Arch Neurol. 1999;56:303–308. doi: 10.1001/archneur.56.3.303. [DOI] [PubMed] [Google Scholar] source
- Not checked yetcites [2] Smith GE, Petersen RC, Parisi JE, et al. Definition, Course, and Outcome of Mild Cognitive Impairment. Aging, Neuropsychology, and Cognition. 1996;3:141–147. [Google Scholar] source
- Not checked yetcites [3] Flicker C, Ferris SH, Reisberg B. Mild cognitive impairment in the elderly: predictors of dementia. Neurology. 1991;41:1006–1009. doi: 10.1212/wnl.41.7.1006. [DOI] [PubMed] [Google Scholar] source
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In the paper
“By restricting the analysis in this study to those individuals with 3± 1 years of followup duration, we were able to minimize the statistical difficulties that otherwise would have been associated with comparing patients with different followup intervals.”
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What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“In addition, the rate of hippocampal volume change was calculated over the same period of observation covered by the two clinical assessment points, which temporally coupled change or absence of change in cognitive status with change in hippocampal volume.”
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What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The date of each MRI scan was also masked in the digital image file so that the hippocampal measurements were done without knowledge of the chronologic ordering of the scans in each pair.”
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What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“When this method of assigning W scores is applied to the normal elderly control database, the resulting W scores precisely follow a standard normal distribution.”
Strength:plain· not yet calibratedn = 126Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
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In the paper
“All image processing steps in every patient were performed by the same research associate who was blinded to all clinical information (age, gender, and clinical status).”
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In the paper
“We have previously described the rates of hippocampal atrophy in patients with a diagnosis of probable AD and a group of age and sex matched elderly controls (14 controls and 10 AD patients from that prior study are included in the current work)(6).”
What the sources say
- Not checked yetcites [6] Jack CR, Jr, Petersen RC, Xu Y, et al. The rate of medial temporal lobe atrophy in typical aging and Alzheimer's disease. Neurology. 1998;51:993–999. doi: 10.1212/wnl.51.4.993. [DOI] [PMC free article] [PubMed] [Google Scholar] source
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In the paper
“The hippocampal volume data derived from the MRI examination and APOE genotypes were not known to the ADPR/ADRC consensus committee throughout the study.”
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None of the sources cited for this claim have been checked yet.
In the paper
“The diagnosis of probable AD was made according to the Diagnostic and Statistical Manual for Mental Disorders, III Edition–Revised (DSM-III-R) Criteria for dementia, and National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association Criteria (NINCDS/ADRDA) for AD(8, 9).”
What the sources say
- Not checked yetcites [8] American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. Revised Third Edition. Washington, D C: 1987. [Google Scholar]
- Not checked yetcites [9] McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA work group under the auspices of Department of Health and Human Services Task Force on Alzheimer's disease. Neurology. 1984;34:939–944. doi: 10.1212/wnl.34.7.939. [DOI] [PubMed] [Google Scholar] source
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In the paper
“The maximum interval between MRI and clinical assessments was ± 2 months in 125 subjects, ± 4 months in 3 subjects, and ± 6 months in a single subject.”
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This observation supports the idea that some proportion of MCIs who on clinical grounds appear cognitively stable over a 3± 1 year period are actually undergoing anatomic changes that differ significantly from stable controls, and therefore are progressing toward AD.”
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In the paper
“We also acknowledge that dichotomization of the control and MCI groups into those who remained stable vs decliners is a crude way to define change in cognition because the change in cognition over time occurs as a continuous rather than a step-wise function.”
Strength:plain· not yet calibratedTests✓ Asserted: passes✗ Checkable: fails✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. It may be too vague to check against evidence. The paper’s conclusions may not depend on it.
- Rests on an assumption: Change in cognition over time occurs as a continuous rather than a step-wise function.
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
“While the rates of hippocampal atrophy we report were by default a linear fit to two time points, we do not mean to imply that the rates of change in vivo are necessarily linear.”
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
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
“Certainly individuals who began the study as controls but declined to MCI or AD were actually in a presymptomatic phase of AD at baseline.”
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“AD pathology then progressed between baseline and followup to such an extent that cognitive impairment became clinically apparent.”
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In the paper
“The annualized rate of hippocampal volume loss in probable AD patients in a prior longitudinal study of ours was 3.98% (6).”
What the sources say
- Not checked yetcites [6] Jack CR, Jr, Petersen RC, Xu Y, et al. The rate of medial temporal lobe atrophy in typical aging and Alzheimer's disease. Neurology. 1998;51:993–999. doi: 10.1212/wnl.51.4.993. [DOI] [PMC free article] [PubMed] [Google Scholar] source
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What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The number of controls who converted was fairly small (n=10).”
Strength:plain· not yet calibratedn = 10Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“If a therapeutic agent slows or arrests the anatomic progression of AD pathology, this should be detectable as a decrease in the rate of atrophy in a treated vs a placebo group.”
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, the fact that the rates of hippocampal atrophy were significantly different between stable controls vs control decliners and between stable MCI vs MCI decliners, shows promise that the rate of hippocampal atrophy may add additional predictive power to baseline hippocampal volume in assessing the risk of converting to AD for individual patients.”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Our data also indicate that the distinction between stable vs a declining members of a group should be detectable both in early symptomatic patient groups (i.e., MCI) and in presymptomatic subjects (i.e., controls).”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Other groups have also shown that assessments of hippocampal atrophy can provide predictive information in patients who are at elevated risk for AD(27, 30).”
What the sources say
- Not checked yetcites [27] Fox NC, Warrington EK, Freeborough PA, et al. Presymptomatic hippocampal atrophy in Alzheimer's disease. A longitudinal MRI study. Brain. 1996;119:2001–2007. doi: 10.1093/brain/119.6.2001. [DOI] [PubMed] [Google Scholar] source
- Not checked yetcites [30] de Leon MJ, Golomb J, George AE, et al. The radiologic prediction of Alzheimer disease: the atrophic hippocampal formation. AJNR. 1993;14:897–906. [PMC free article] [PubMed] [Google Scholar]
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A 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
“Serial measurements of hippocampal volume may therefore be a useful adjunctive tool to monitor the efficacy of therapeutic trials in groups of patients.”
Tests✓ Asserted: passes✗ Checkable: fails✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. It may be too vague to check against evidence.
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
“We attribute this to measurement error.”
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
- Rests on an assumption: The measured change in hippocampal volume in every elderly individual should be ≤0.
The paper relies on this without support.
The transition from normal cognition to Alzheimer's disease is gradual.
“The transition from normal cognition to Alzheimer's disease (AD) is gradual.”
The paper relies on this without support.
Patients who develop clinically evident Alzheimer's disease pass through a transitional period during which they experience declining cognitive abilities relative to age mates.
“Patients who develop clinically evident AD pass through a transitional period during which they experience declining cognitive abilities relative to age mates.”
The paper relies on this without support.
No single test is accepted for defining discrete ranges within the cognitive continuum.
“As no single test is accepted for defining discrete ranges within the cognitive continuum, we chose to use the designations of control, MCI, and AD which are ultimately clinical judgments that are derived from a number of different factors.”
The paper relies on this without support.
Change in cognition over time occurs as a continuous rather than a step-wise function.
“We also acknowledge that dichotomization of the control and MCI groups into those who remained stable vs decliners is a crude way to define change in cognition because the change in cognition over time occurs as a continuous rather than a step-wise function.”
The paper relies on this without support.
The largest volume loss over time should occur in patients who were the most rapid clinical decliners.
“The reported rates of atrophy in the decliner groups may therefore be underestimated, because the largest volume loss over time should occur in patients who were the most rapid clinical decliners.”
The paper relies on this without support.
The pathologic progression leading to AD may extend over decades.
“In any individual patient the pathologic progression leading to AD may extend over decades.”
The paper relies on this without support.
The measured change in hippocampal volume in every elderly individual should be ≤0.
“Theoretically the measured change in hippocampal volume in every elderly individual should be ≤ 0, indicating either no change or volume loss over time.”
The paper relies on this without support.
To our knowledge this is the first study which describes the rates of hippocampal atrophy in MCI patients.
“To our knowledge this is the first study which describes the rates of hippocampal atrophy in MCI patients.”
The paper relies on this without support.
Prior studies on rates of hippocampal atrophy have not distinguished stable controls from control decliners.
“Prior studies on rates of hippocampal atrophy have not distinguished stable controls from control decliners.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“MCI reflects a preclinical stage of AD and other types of dementia in 50 to 60% of the MCI subjects”
From Early dementia diagnosis, MCI-to-dementia risk prediction, and the role of machine learning methods for feature extraction from integrated biomarkers, in particular for EEG signal analysis (2022) · cites this paper as [7]
Experimental — accuracy not yet measuredIn the citing paper
“Among structural imaging studies examining the conversion of MCI to AD, there are one longitudinal (40) and several prediction studies (one scan predicting clinical outcome).”
From Prediction of cognitive decline in normal elderly subjects with 2-[ 18 F]fluoro-2-deoxy- d -glucose/positron-emission tomography (FDG/PET) (2001) · cites this paper as [40]
Citations
Cites
Folstein, M. F., Folstein, S. E., & McHugh, P. R. (1975) · Journal of Psychiatric Research · doi:10.1016/0022-3956(75)90026-6 · Cited by 88,282
McKhann, G., Drachman, D., Folstein, M., Katzman, R., Price, D., & Stadlan, E. M. (1984) · Neurology · doi:10.1212/wnl.34.7.939 · Cited by 27,915
Hirono, N., Mori, E., Ikejiri, Y., Imamura, T., Shimomura, T., Hashimoto, M., Yamashita, H., & Ikeda, M. (1997) · PubMed · Cited by 21,012
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Older Adults' Reasons for Using Technology while Aging in Place
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Increased CSF-BACE1 activity associated with decreased hippocampus volume in Alzheimer’s disease
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Hampstead, B. M., Khoshnoodi, M., Yan, W., Deshpande, G., & Sathian, K. (2015) · NeuroImage · doi:10.1016/j.neuroimage.2015.10.002 · Cited by 60
Boeve, B., Tremont-Lukats, I., Waclawik, A., Murrell, J., Hermann, B., Jack, C., Shiung, M., Smith, G. E., Nair, A. R., Lindor, N., et al. (2005) · Brain : a journal of neurology · doi:10.1093/brain/awh356 · Cited by 55
Self-citationA multiple hold-out framework for Sparse Partial Least Squares
Monteiro, J. M., Rao, A. W., Shawe-Taylor, J. S., & Mourão-Miranda, J. (2016) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2016.06.011 · Cited by 58
Yohannes, A. M., Baldwin, R. C., & Connolly, M. J. (2000) · International Journal of Geriatric Psychiatry · doi:10.1002/1099-1166(200012)15:12 · Cited by 58
Planche, V., Koubiyr, I., Romero, J. E., Manjón, J. V., Pierrick Coupé, A., Deloire, M., Dousset, V., Brochet, B., Ruet, A., & Tourdias, T. (2018) · Human Brain Mapping · doi:10.1002/hbm.23970 · Cited by 57
Bai, F., Xie, C., Watson, D. R., Shi, Y., Yuan, Y., Wang, Y., Yue, C., Teng, Y., Wu, D., & Zhang, Z. (2011) · PLoS ONE · doi:10.1371/journal.pone.0029288 · Cited by 56
Apostolova, L. G., Hwang, K., Omid Kohannim, A., Avila, D., Elashoff, D. A., Jack, C. R., Shaw, L. M. J., Trojanowski, J. Q., Weiner, M. W., & Thompson, P. M. (2014) · NeuroImage Clinical · doi:10.1016/j.nicl.2013.12.012 · Cited by 59
Self-citationFarias, S. T., Mungas, D., Reed, B., Carmichael, O. T., Beckett, L. A., Harvey, D. J., Olichney, J., Simmons, A. L., & DeCarli, C. S. (2011) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2011.03.017 · Cited by 62
Detection of Alzheimer's Disease with Shape Analysis of MRI Images
Fuse, H., Oishi, K., Maikusa, N., Fukami, T., & Initiative, J. A. D. N. (2018) · Joint International Conference on Soft Computing and Intelligent Systems and International Symposium on Advanced Intelligent Systems (SCIS&ISIS) · doi:10.1109/scis-isis.2018.00171 · Cited by 56
Metadata
- Authors
- Jack, C. R., Petersen, R. C., Xu, Y., O’Brien, P. C., Smith, G. E., Ivnik, R. J., Boeve, B. F., Tangalos, E. G., & Kokmen, E.
- Affiliations
- Mayo Clinic (US)
- Venue
- Neurology
- Published
- 2000-08-22
- Volume
- 55
- Issue
- 4
- Pages
- 484-490
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- PMC
- PMC2724764
- OpenAlex
- W2044367669
- Semantic Scholar
- 412175cf3fadbd098463cf78426d180e44d83935
- Cited by
- 937
- References
- 34
- Citations by year
- 2026: 26 · 2025: 34 · 2024: 33 · 2023: 23 · 2022: 40 · 2021: 47 · 2020: 38 · 2019: 22 · 2018: 31 · 2017: 32 · 2016: 32 · 2015: 21 · 2014: 31 · 2013: 41 · 2012: 42
- FWCI
- 20.00
- 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, P50AG016574)
- 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
- Health Sciences › Medicine › Oncology › Cancer-related cognitive impairment studies
- Keywords
- hippocampal atrophy, Alzheimer's disease, mild cognitive impairment, cognitive decline, cognitive continuum, aging, brain MRI
- MeSH terms
- Aged, Aged, 80 and over, Aging, Alzheimer Disease, Apolipoproteins E, Atrophy, Cognition Disorders, Female, Follow-Up Studies, Hippocampus, Humans, Longitudinal Studies, Magnetic Resonance Imaging, Male, Middle Aged, Predictive Value of Tests, Disease Progression
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 2026-10-09, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-09 (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.
What counts as a claim ›How we measure confidence ›How we check this ›
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