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Cited by 937Dementia and Cognitive Impairment ResearchAlzheimer's disease research and treatmentsCancer-related cognitive impairment studies

Rates of hippocampal atrophy correlate with change in clinical status in aging and AD

Open access
Jack, C.R., Petersen, R.C., Xu, Y., O’Brien, P.C., Smith, G.E., Ivnik, R.J., Boeve, B.F., Tangalos, E.G. +1 more·2000·Neurology
DOI 10.1212/wnl.55.4.484PMC PMC2724764
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Abstract

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.

AI snapshot

Written from the paper’s full text.

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.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1212/wnl.55.4.484

Cites

34 of 34 references verified0 citation errors · 0 not checkable

Statistics

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Claims the paper makes

0 of 21 cited sources checked · 0 supported · 0 flagged

  • Findingown data
    § Results

    The annualized rates of hippocampal volume loss for each of the three initial clinical groups decreased progressively in the order AD > MCI > control.

    “The annualized rates of hippocampal volume loss for each of the three initial clinical groups decreased progressively in the following order: AD > MC > C.”
    Quote in the paperSubstantial claim
  • Findingown data
    § Results

    Within the control and MCI groups, subjects who declined had a significantly greater rate of hippocampal volume loss than those who remained clinically stable.

    “Within the control and MCI groups, those who declined had a significantly greater rate of volume loss than those who remained clinically stable.”
    Quote in the paperSubstantial claim
  • Findingown data
    § Results

    Over the observation period, 10 (17%) of the initial cohort of 58 controls declined to either the MCI or probable AD categories.

    “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.”
    Quote in the paperNot a substantial claim
  • Findingown data
    § Results

    The difference in annualized rate of hippocampal volume loss between control and MCI groups was significant at p <0.001.

    “The differences between the control and MCI groups, and between control and AD groups were significant at p <0.001.”
    Quote in the paperSubstantial claim
  • Findingown data
    § Results

    The differences among all three baseline groups were significant at p <0.000.

    “The differences among all three baseline groups were significant at p <0.000.”
    Quote in the paperNot a substantial claim
  • May combine two claims. 10
  • Classified as probably not a substantial claim. 24

  • May combine two claims.

    Findingown data
    § Results

    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%, and AD 3.5%.

    “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%.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data
    § Results

    A positive volume change over time of +0.1% was measured in one of the stable AD patients.

    “A positive volume change over time of +0.1% was measured in one of the stable AD patients.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingcitation
    § Discussion

    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.

    “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.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [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 in the free run.

    • cites [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

      Not checked in the free run.

  • May combine two claims.

    Findingown data
    § Discussion

    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.

    “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.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingcitation
    § Discussion

    This prior rate is close to the rate of 3.5%/yr observed in the current study.

    “This is close to the rate of 3.5%/yr observed in the current study.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data
    § Discussion

    A positive change over time, an increase in volume of 0.1%, was measured in one of the patients.

    “A positive change over time, an increase in volume of 0.1%, was measured in one of the patients.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data
    § 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.

    “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.”
    Quote in the paperSubstantial claim
    • 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.

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation
    § Conclusion

    The intermediate state between normal cognition and Alzheimer's disease has been termed mild cognitive impairment (MCI), and clinical criteria for this diagnosis have been suggested.

    “This intermediate state has been termed mild cognitive impairment (MCI) and clinical criteria for this diagnosis have been suggested(1–3).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [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 in the free run.

    • cites [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 in the free run.

    • cites [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

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductreasoning
    § Conclusion

    Restricting the analysis to individuals with 3±1 years of followup duration minimized statistical difficulties that would otherwise arise from comparing patients with different followup intervals.

    “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.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductreasoning
    § Conclusion

    The rate of hippocampal volume change was calculated over the same period of observation covered by the two clinical assessment points, temporally coupling change or absence of change in cognitive status with change in hippocampal volume.

    “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.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given
    § Conclusion

    The date of each MRI scan was masked in the digital image file so that hippocampal measurements were done without knowledge of the chronologic ordering of the scans in each pair.

    “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.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductreasoning
    § Conclusion

    When the W-score method is applied to the normal elderly control database, the resulting W scores precisely follow a standard normal distribution.

    “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.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductnone given
    § Conclusion

    All image processing steps in every patient were performed by the same research associate, who was blinded to all clinical information including age, gender, and clinical status.

    “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).”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Premisecitation
    § Conclusion

    The authors have previously described the rates of hippocampal atrophy in patients with probable AD and in age- and sex-matched elderly controls.

    “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).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [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

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductnone given
    § Conclusion

    The hippocampal volume data derived from MRI and the APOE genotypes were not known to the ADPR/ADRC consensus committee throughout the study.

    “The hippocampal volume data derived from the MRI examination and APOE genotypes were not known to the ADPR/ADRC consensus committee throughout the study.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation
    § Conclusion

    The diagnosis of probable AD was made according to DSM-III-R criteria for dementia and NINCDS/ADRDA criteria for AD.

    “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).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [8] American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. Revised Third Edition. Washington, D C: 1987. [Google Scholar]

      Not checked in the free run.

    • cites [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

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data
    § Conclusion

    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.

    “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.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data
    § Discussion

    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.

    “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.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing).

    Study design and conductreasoning
    § Discussion

    Dichotomization of the control and MCI groups into those who remained stable vs decliners is a crude way to define change in cognition because 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.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Change in cognition over time occurs as a continuous rather than a step-wise function.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data
    § Discussion

    The reported rates of hippocampal atrophy were by default a linear fit to two time points.

    “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.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationnone given
    § Discussion

    Individuals who began the study as controls but declined to MCI or AD were actually in a presymptomatic phase of AD at baseline.

    “Certainly individuals who began the study as controls but declined to MCI or AD were actually in a presymptomatic phase of AD at baseline.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationreasoning
    § Discussion

    AD pathology then progressed between baseline and followup to such an extent that cognitive impairment became clinically apparent.

    “AD pathology then progressed between baseline and followup to such an extent that cognitive impairment became clinically apparent.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation
    § Discussion

    The annualized rate of hippocampal volume loss in probable AD patients in a prior longitudinal study of ours was 3.98% (6).

    “The annualized rate of hippocampal volume loss in probable AD patients in a prior longitudinal study of ours was 3.98% (6).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [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

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data
    § Discussion

    The number of controls who converted was fairly small (n=10).

    “The number of controls who converted was fairly small (n=10).”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Interpretationreasoning
    § Discussion

    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.

    “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.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data
    § Discussion

    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.

    “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.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data
    § Discussion

    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).

    “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).”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation
    § Discussion

    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).

    “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).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [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 in the free run.

    • cites [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]

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S2 (checkable).

    Interpretationown data
    § Discussion

    Serial measurements of hippocampal volume may therefore be a useful adjunctive tool to monitor the efficacy of therapeutic trials in groups of patients.

    “Serial measurements of hippocampal volume may therefore be a useful adjunctive tool to monitor the efficacy of therapeutic trials in groups of patients.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationown data
    § Discussion

    We attribute this positive change to measurement error.

    “We attribute this to measurement error.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: The measured change in hippocampal volume in every elderly individual should be ≤0.
30 of 30

  • 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.”
9 of 9

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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)
ORCID
Venue
Neurology
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2000-08-22
Volume
55
Issue
4
Pages
484-490
ISSN
  • 0028-3878 (ISSN-L)
  • 1526-632X
DOI
10.1212/wnl.55.4.484
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
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
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › 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

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