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Cited by 666Dementia and Cognitive Impairment ResearchAlzheimer's disease research and treatmentsNeurological Disease Mechanisms and Treatments

Rate of medial temporal lobe atrophy in typical aging and Alzheimer's disease

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Jack, C. R., Petersen, R. C., Xu, Y., O'Brien, P. C., Smith, G. E., Ivnik, R. J., Tangalos, E. G., Kokmen, E.·1998·Neurology
DOI 10.1212/wnl.51.4.993PMC PMC2768817
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Abstract

OBJECTIVES: To determine the annual rates of volumetric change of the hippocampus and temporal horn in cognitively normal elderly control subjects and individually matched patients with AD, and to test the hypothesis that these rates were different. BACKGROUND: Cross-sectional studies consistently reveal cerebral atrophy in elderly nondemented subjects compared with healthy young adults, and greater atrophy in patients with AD relative to elderly control subjects. However, rates of atrophy are estimated most accurately by performing serial measurements in the same individuals. METHODS: MRI-based volumetric measurements of the hippocampi and temporal horns were performed in 24 cognitively normal subjects aged 70 to 89 years who were individually matched with respect to gender and age with 24 patients with AD. Each subject underwent an MRI protocol twice, separated by 12 months or more. RESULTS: The mean annual rate of hippocampal volume loss among control subjects was -1.55+/-1.38% and the temporal horns increased in volume by 6.15+/-7.69% per year. These rates were significantly greater among AD patients: hippocampus, -3.98+/-1.92% per year, p < 0.001; temporal horn, 14.16+/-8.47% per year, p = 0.002. CONCLUSION: A statistically significant yearly decline in hippocampal volume and an increase in temporal horn volume was identified in elderly control subjects who represent typical aging individuals. These rates were approximately 2.5 times greater in patients with AD than in individually age- and gender-matched control subjects.

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Written from the paper’s full text.

TL;DR

In a longitudinal MRI study, cognitively normal elderly controls showed significant annual hippocampal volume loss and temporal horn enlargement, and these rates were approximately twice as great in individually age- and gender-matched patients with Alzheimer’s disease. The authors conclude that serial medial temporal lobe volumetry detects typical aging-related atrophy and accelerated AD-related atrophy, but overlap limits stand-alone diagnostic use.

Key findings

  • Controls had mean annualized hippocampal volume loss of −1.55% ± 1.38%/year (75 ± 60 mm³/year) and temporal horn increase of 6.15% ± 7.69%/year (167 ± 200 mm³/year).
  • AD patients had significantly greater rates: hippocampal loss −3.98% ± 1.92%/year (150 ± 73 mm³/year), P < .001; temporal horn increase 14.16% ± 8.47%/year (660 ± 439 mm³/year), P = .002.
  • Baseline volumes already differed: controls had hippocampi 5078.28 ± 766.17 mm³ and temporal horns 2779.77 ± 1372.01 mm³; AD patients had hippocampi 3945.02 ± 945.19 mm³ and temporal horns 4564.24 ± 1697.37 mm³, all P < .001.
  • No analyzed clinical variable—age, gender, APOE genotype, estrogen replacement, hypertension, cardiac ischemic disease, or diabetes—was significantly associated with rates of hippocampal or temporal horn volume change; APOE ε4 carrier prevalence was higher in AD cases (11/24) than controls (6/24), P = .042.

Methods

  • Longitudinal serial MRI study of 48 subjects: 24 cognitively normal controls aged 70–89 years individually matched by gender and age ±4 years to 24 patients with AD diagnosed by NINCDS/ADRDA criteria; AD severity was CDR 0.5 in 11, CDR 1 in 11, and CDR 2 in 2.
  • Each subject underwent two MRI scans separated by 12 months or more (mean interval 1.96 ± 0.75 years for controls and 1.89 ± 0.68 years for cases); hippocampal and temporal horn volumes were measured from 1.5T 3D spoiled gradient echo images, with manual hippocampal tracing and region-growing temporal horn tracing by the same trained research assistant blinded to clinical information.
  • Annualized percent volume change was compared between groups with rank sum tests; stepwise regression assessed associations with clinical variables; paired t-tests compared sides and hippocampal segments; reproducibility was assessed in 10 young adult volunteers with test-retest median coefficients of variation of 0.28% for hippocampus and 0.95% for temporal horn.

Limitations

  • The paper states that the sample size was modest and the age range was fairly narrow (70–89 years), and that the absence of associations with clinical variables could be due to the modest number of subjects.
  • The paper states that annualized rates overlapped between controls and AD patients, making these measures unlikely to serve as a useful stand-alone diagnostic test for AD in individual patients.
  • The text makes evident that manual hippocampal tracing took approximately 2 hours per patient and that measurement imprecision was present, including small paradoxical volume increases in one control and one AD case and temporal horn decreases in four controls.

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

Integrity signals

Registry

Crossref · 10.1212/wnl.51.4.993

Cites

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Statistics

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Claims the paper makes

0 of 35 cited sources checked · 0 supported · 0 flagged

  • Findingown data
    § Results

    Among controls, none of the clinical variables analyzed-age, gender, APOE genotype, estrogen replacement, hypertension, cardiac ischemic disease or diabetes-were significantly associated with the rate of hippocampal or temporal horn volume change.

    “None of the clinical variables analyzed-age, gender, APOE genotype, estrogen replacement, hypertension, cardiac ischemic disease or diabetes were significantly associated with the rate of hippocampal or temporal horn volume change.”
    Quote in the paperSubstantial claim
  • Findingown data
    § Results

    Among controls, the average annualized rate of hippocampal volume loss was 75 mm3 ± 60 mm3/year or −1.55% ± 1.38%/year.

    “The average annualized rate of hippocampal volume loss among controls was 75 mm3 ± 60 mm3/year or −1.55% ± 1.38%/year.”
    Quote in the paperSubstantial claim
  • Findingown data
    § Results

    Among AD cases, the mean annualized rate of hippocampal volume loss was 150 mm3 ± 73 mm3/year or −3.98% ± 1.92%/year.

    “The mean annualized rate of hippocampal volume loss among AD cases was 150 mm3 ± 73 mm3/year or −3.98% ± 1.92%/year (Table 2).”
    Quote in the paperSubstantial claim
  • Findingown data
    § Results

    The initial (at scan 1) hippocampal and temporal horn volumes were significantly different between controls and cases (P<.001).

    “All volumes were significantly different between controls and cases, P<.001.”
    Quote in the paperNot a substantial claim
  • Findingown data
    § Results

    Among AD cases, none of the clinical variables analyzed-age, gender, APOE genotype, estrogen replacement, hypertension, cardiac ischemic disease, or diabetes-were significantly associated with the annualized rate of hippocampal or temporal horn volume change.

    “None of the clinical variables analyzed—age, gender, APOE genotype, estrogen replacement, hypertension, cardiac ischemic disease, or diabetes were significantly associated with the annualized rate of hippocampal or temporal horn volume change.”
    Quote in the paperSubstantial claim
  • May combine two claims. 29
  • The quote only partly states this claim. 5
  • Classified as probably not a substantial claim. 24

  • May combine two claims.

    Findingown data
    § Results

    No differences in the prevalence of hypertension, cardiac ischemic disease, or diabetes, nor in the prevalence or duration of estrogen replacement, were identified between the case and control groups.

    “No differences in the prevalence of any of the three vascular risk factors—hypertension, cardiac ischemic disease, or diabetes— nor in the prevalence or duration of estrogen replacement was identified between the case and control groups(Table 1).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data
    § Results

    Six controls and 11 cases had APOE genotypes (∈3/4 or 4/4) which are known to increase the risk of AD; the difference was significant (p = 0.042).

    “Six controls and 11 cases had APOE genotypes (∈3/4 or 4/4) which are known to increase the risk of AD. The difference was significant (p = 0.042).”
    Quote in the paperNot a substantial claim

  • The quote only partly states this claim.

    Findingown data
    § Conclusion

    These rates were approximately 2.5 times greater in patients with AD than in individually age and gender matched controls.

    “These rates were approximately 2◻ times greater in patients with AD than in individually age and gender matched controls.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data
    § Results

    Among AD cases, measured hippocampal volumes decreased over time in all but 1 case, and temporal horn volumes increased in all cases.

    “Measured hippocampal volumes decreased over time in all but 1 AD case and temporal horn volumes increased in all AD cases(Figure 2).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data
    § Discussion

    In the group of 48 cases and controls, hippocampal volume increased between the two MRI studies in one control (by 1.41%) and one AD case (by 0.19%).

    “In our group of 48 cases and controls, hippocampal volume measurements increased by a small amount between the 2 MRI studies in one control (by 1.41%) and one AD case (by 0.19%)(Figure 2).”
    Quote in the paperNot a substantial claim

  • May combine two claims. The quote only partly states this claim.

    Findingown data
    § Results

    Among controls, the rates of hippocampal and temporal volume change were not different between the right and left side, nor were they associated with the interval between the 2 MRI studies.

    “The rates of hippocampal and temporal volume change were not different between the right and left side, nor were they associated with the interval between the 2 MRI studies.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data
    § Results

    Among AD cases, the annualized rates of volume change for the hippocampus and temporal horn were not associated with the interval between MRI scans, position within the hippocampus (head, body, tail), or side (right, left).

    “The annualized rates of volume change for the hippocampus and temporal horn were not associated with the interval between MRI scans, position within the hippocampus (head, body, tail), or side (right, left).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data
    § Results

    The rates of hippocampal volume loss (P < .001) and temporal horn enlargement (P = .002) were significantly greater in AD cases than in controls.

    “The rates of hippocampal volume loss,P < .001, and temporal horn enlargement, P = .002, were significantly greater in AD cases than in controls (Table 2).”
    Quote in the paperSubstantial claim

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

    Findingown data
    § Results

    Among controls, hippocampal volume measurements increased between the first and second MRI studies in 1 subject, and temporal horn volumes decreased in 4 subjects.

    “Hippocampal volume measurements increased between the first and second MRI studies in 1 control subject, and temporal horn volumes decreased in 4 control subjects(Figure 2).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data
    § Conclusion

    A statistically significant yearly decline in hippocampal volume and increase in temporal horn volume was identified in elderly controls who represent typical aging individuals.

    “A statistically significant yearly decline in hippocampal volume and increase in temporal horn volume was identified in elderly controls who represent typical aging individuals.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The 24 cognitively normal elderly control subjects are representative of typical aging individuals.

  • The quote only partly states this claim.

    Findingown data
    § Results

    Among controls, the annual percent volume loss was significantly greater for the hippocampal head than for either the hippocampal body (P=.001) or tail (P=.014).

    “The annual percent volume loss was significantly greater for the hippocampal head than for either the hippocampal body (P=.001) or tail (P=.014).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingnone given
    § Discussion

    The prevalence of vascular risk factors was not significantly different between AD cases and controls, nor was the number of women treated with estrogen replacement or the treatment duration.

    “The prevalence of vascular risk factors was not significantly different between AD cases and controls, nor was the number of women treated with estrogen replacement or the treatment duration.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data
    § Discussion

    In control subjects, the annual rate of hippocampal volume change was −1.55%/year and the annual rate of temporal horn volume change was 6.15%/year.

    “The rates of volumetric change in the hippocampus (−1.55%/year), and the temporal horn (6.15%/year) that we found, seem large in comparison to those reported in prior cross-sectional studies.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data
    § Discussion

    In controls, there was no association between age and the rates of volumetric change or the interval between scans.

    “The absence of an association between age and the rates of volumetric change or the interval between scans suggests a linear decline in volume with age.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data
    § Discussion

    The temporal horns increased in volume in all AD cases and the hippocampi declined in volume in all but one AD case.

    “The temporal horns increased in volume in all AD cases and the hippocampi declined in volume in all but one case(Fig. 2).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data
    § Discussion

    The rate of hippocampal atrophy in AD cases was not different between the right and left sides or among the hippocampal segments (head, body, tail).

    “The rate of hippocampal atrophy was not different between the right and left sides or among the hippocampal segments (head, body, tail).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data
    § Discussion

    At the initial baseline scan, the hippocampi of AD patients were smaller (P<.001) and the temporal horns larger (P<.001) than those of matched controls.

    “In addition, the hippocampi of AD patients were smaller (P<.001) and the temporal horns larger (P< .001) than those of matched controls at the initial baseline scan (Table 3).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data
    § Discussion

    We found no evidence that the rates of hippocampal and temporal horn volumetric change in controls were related to estrogen replacement, APOE genotype, presence of hypertension, ischemic cardiac disease, or diabetes.

    “We found no evidence to indicate that the rates of hippocampal and temporal horn volumetric change in controls were related to several other clinical variables—estrogen replacement, APOE genotype, presence of hypertension, ischemic cardiac disease, or diabetes.”
    Quote in the paperSubstantial claim

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

    Premisenone given
    § Background

    Cross-sectional studies consistently reveal cerebral atrophy in elderly non-demented subjects compared to healthy young adults.

    “Cross-sectional studies consistently reveal cerebral atrophy in elderly non-demented subjects compared to healthy young adults”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S2 (checkable), S4 (based).

    Premisereasoning
    § Conclusion

    In order to directly assess the effects of aging on the medial temporal lobe, serial measurements in the same individuals are required.

    “In order to directly assess the effects of aging on the medial temporal lobe, serial measurements in the same individuals are required.”
    Quote in the paperNot a substantial claim

  • The quote only partly states this claim.

    Study design and conductown data
    § Results

    Test-retest measurement reproducibility for the temporal horn in 10 young adult volunteers had a median coefficient of variation of 0.95% (range 0.08% to 3.36%).

    “For the temporal horn the median coefficient of variation was 0.95% (range 0.08% to 3.36%).”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Premisenone given
    § Conclusion

    With a few exceptions, these studies have been cross-sectional in design.

    “with a few exceptions these studies have been cross-sectional in design”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductown data
    § 16 patients in each group (case, control) were women

    Each AD patient was matched with a control subject by gender and age ±4 years.

    “A control subject was identified for each AD patient and matched by gender, and age ±4 years.”
    Quote in the paperSubstantial claim

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

    Premisenone given
    § Conclusion

    A number of pathologic and imaging studies have documented a decline in brain volume in typical aging.

    “a number of pathologic and imaging studies have documented a decline in brain volume in typical aging”
    Quote in the paperNot a substantial claim

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

    Premisenone given
    § Background

    Cross-sectional studies consistently reveal greater atrophy in patients with AD relative to elderly controls.

    “greater atrophy in patients with AD relative to elderly controls”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Premisecitation
    § Conclusion

    The medial temporal lobe limbic structures play a central role in memory function.

    “the central role they play in memory function”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [13] Hyman BT, Van Hoesen GW, Damasio AR, Barnes CL. Alzheimer's disease: cell-specific pathology isolates the hippocampal formation. Science. 1984;225:1168–1170. doi: 10.1126/science.6474172. [DOI] [PubMed] [Google Scholar]

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § Discussion

    Imaging studies (MRI and CT) have generally found a loss of global hemispheric parenchymal volume and an increase in CSF volume with advancing age in cognitively normal subjects.

    “Imaging studies, both MRI and CT, have generally found a loss of global hemispheric parenchymal volume, and an increase in CSF volume with advancing age in cognitively normal subjects[10, 26–29].”
    Quote in the paperNot a substantial claim0 of 5 sources checked
    • cites [10] Murphy DGM, DeCarli C, Schapiro MB, et al. Age-related differences in volumes of subcortical muclei, brain matter, and cerebrospinal fluid in healthy men as measured with magnetic resonance imaging. Arch Neurol. 1992;49:839–845. doi: 10.1001/archneur.1992.00530320063013. [DOI] [PubMed] [Google Scholar]

      Not checked in the free run.

    • cites [26] Pfefferbaum A, Mathalon DH, Sullivan EV, et al. A quantitative magnetic resonance imaging study of changes in brain morphology from infancy to late adulthood. Arch Neurol. 1994;51:874–887. doi: 10.1001/archneur.1994.00540210046012. [DOI] [PubMed] [Google Scholar] source

      Not checked in the free run.

    • cites [27] George AE, deLeon MJ, Rosenbloom S, et al. Ventricular volume and cognitive deficit: a computed tomographic study. Radiology. 1983;149:493–498. doi: 10.1148/radiology.149.2.6622694. [DOI] [PubMed] [Google Scholar]

      Not checked in the free run.

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      Not checked in the free run.

  • May combine two claims.

    Interpretationown data
    § Discussion

    The small increases in hippocampal volume in one control and one AD case are examples of measurement imprecision and are reasonably close to the expected test-retest variability.

    “These are clearly examples of measurement imprecision, but are reasonably close to the expected test-retest variability found in the reproducibility study.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: The test-retest variability measured in healthy young volunteers is applicable to the older control and AD subjects.

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

    Premisecitation
    § Discussion

    Other autopsy studies found a linear decline in brain weight with advancing age beginning about at age 20.

    “Other autopsy studies [24, 25] found a linear decline with advancing age beginning about at age 20.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [24] Pakkenberg H, Voight F. Brain weight of the Danes. Acat Anatomaica. 1964;56:297–307. [Google Scholar]

      Not checked in the free run.

    • cites [25] Peress NS, Kane WC, M AS. Central nervous system findings in a tenth decade autopsy population. In: Ford DH, editor. Progress in Brain Research. Elsevier; Amsterdam: 1973. [DOI] [PubMed] [Google Scholar] source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § Discussion

    Results from recent studies assessing the impact of aging on hippocampal and other temporal lobe structures have been variable: some found age-related declines in volume in normal elderly individuals, while others did not.

    “Results from recent studies assessing the impact of aging on hippocampal and other temporal lobe structures have been variable. Some have found age-related declines in volume in normal elderly individuals [4, 30, 31] while others have not [3, 32].”
    Quote in the paperNot a substantial claim0 of 5 sources checked
    • cites [4] 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] [PubMed] [Google Scholar] source

      Not checked in the free run.

    • cites [30] Coffey CE, Wilkinson WE, Parashos IA, et al. Quantitative cerebral anatomy of the aging human brain: A cross-sectional study using magnetic resonance imaging. Neurology. 1992;42:527–536. doi: 10.1212/wnl.42.3.527. [DOI] [PubMed] [Google Scholar] source

      Not checked in the free run.

    • cites [31] Blatter DD, Bigler ED, Gale SD, et al. Quantitative volumetric analysis of brain MR: normative database spanning 5 decades of life. AJNR. 1995;16:241–251. [PMC free article] [PubMed] [Google Scholar]

      Not checked in the free run.

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      Not checked in the free run.

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      Not checked in the free run.

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

    Premisenone given
    § Conclusion

    A number of pathologic and imaging studies have documented an accelerated rate of volume loss in AD.

    “an accelerated rate of volume loss in AD”
    Quote in the paperNot a substantial claim

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

    Study design and conductcitation
    § 16 patients in each group (case, control) were women

    The severity of AD was classified on the basis of the clinical dementia rating (CDR) score.

    “The severity of AD was classified on the basis of the clinical dementia rating (CDR) score [16].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [16] 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] [PubMed] [Google Scholar]

      Not checked in the free run.

  • May combine two claims.

    Study design and conductreasoning
    § 16 patients in each group (case, control) were women

    Cases and controls were well matched on education, and by virtue of the study design on age and gender as well.

    “Cases and controls were well matched on education, and by virtue of the study design on age and gender as well(Table 1).”
    Quote in the paperNot a substantial claim

  • The quote only partly states this claim.

    Study design and conductown data
    § Results

    Test-retest measurement reproducibility for the sum of the right and left hippocampus in 10 young adult volunteers had a median coefficient of variation of 0.28% (range 0.02% to 0.70%).

    “For the sum of the right and left hippocampus the median coefficient of variation was 0.28% (range 0.02% to 0.70%).”
    Quote in the paperSubstantial claim

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

    Premisecitation
    § Discussion

    Hypertension increases in prevalence with advancing age and is associated with impaired cognition in elderly individuals.

    “Of particular interest are several vascular risk factors, most notably hypertension, which increase in prevalence with advancing age and also are associated with impaired cognition in elderly individuals[20, 21].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [20] Elias MF, Wolf PA, D'Agostini RB, et al. Untreated blood pressure level is inversely related to cognitive functioning: the Framingham study. Amerian Journal of Epidemiology. 1993;138:353–364. doi: 10.1093/oxfordjournals.aje.a116868. [DOI] [PubMed] [Google Scholar]

      Not checked in the free run.

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      Not checked in the free run.

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

    Study design and conductown data
    § 16 patients in each group (case, control) were women

    All image processing steps were performed by the same trained research assistant who was blinded to all clinical information, and the date of each MRI scan was masked.

    “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 (age, gender and clinical status). The date of each MRI scan was also masked in the image file so that the image processing was done without knowledge of the chronologic ordering of the scans in each pair.”
    Quote in the paperSubstantial claim

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

    Premisenone given
    § Background

    Rates of atrophy are most accurately estimated by performing serial measurements in the same individuals.

    “However, rates of atrophy are most accurately estimated by performing serial measurements in the same individuals.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductcitation
    § 16 patients in each group (case, control) were women

    The diagnosis of AD was made according to the NINCDS/ADRDA criteria.

    “The diagnosis of AD was made according to the NINCDS/ADRDA criteria [14, 15].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [14] 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]

      Not checked in the free run.

    • cites [15] Association AP. Diagnostic and Statistical Manual of Mental Disorders. Revised Third Edition Washington, D C.: 1987. [Google Scholar]

      Not checked in the free run.

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

    Study design and conductown data
    § 16 patients in each group (case, control) were women

    Controls were defined as having no active neurologic or psychiatric disorders, and any ongoing medical problems did not interfere with cognitive function.

    “The criteria for cognitively normal controls were 1) no active neurologic or psychiatric disorders and 2) some had ongoing medical problems, however the illnesses or their treatments did not interfere with cognitive function.”
    Quote in the paperSubstantial claim

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

    Premisecitation
    § Discussion

    Some studies indicate that brain weight is stable from roughly age 20-60, after which an age-related decline is seen.

    “Some studies [22, 23], indicate that brain weight is stable from roughly age 20–60, after which an age related decline is seen.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [22] Davis PJM, Wright EA. A new method for measuring cranial cavity volume and its application to the assessment of cerebral atrophy at autopsy. Neuropathology and Applied Neurobiology. 1977;3:341–358. [Google Scholar]

      Not checked in the free run.

    • cites [23] Miller AKH, Alston RL, Corsellis JAN. Variation with age in the volumes of grey and white matter in the cerebral hemispheres of man: measurements with an image analyser. Neuropathol Appl Neurobiol. 1980;6:119–132. doi: 10.1111/j.1365-2990.1980.tb00283.x. [DOI] [PubMed] [Google Scholar] source

      Not checked in the free run.

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

    Premisecitation
    § Discussion

    Some authors have found an association between hemispheric atrophy/ventricular enlargement and hypertension.

    “In contrast some authors have found an association between hemispheric atrophy/ventricular enlargement and hypertension[35, 36].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [35] DeCarli C, Murphy DGM, Tranh M, et al. The effect of white matter hyperintensity volume on brain structure, cognitive performance, and cerebral metabolism of glucose in 51 healthy adults. Neurology. 1995;45:2077–2084. doi: 10.1212/wnl.45.11.2077. [DOI] [PubMed] [Google Scholar]

      Not checked in the free run.

    • cites [36] Salerno JA, Murphy DGM, Horwitz B, et al. Brain atrophy in hypertension. A volumetric magnetic resonance imaging study. Hypertension. 1992;20:340–348. doi: 10.1161/01.hyp.20.3.340. [DOI] [PubMed] [Google Scholar]

      Not checked in the free run.

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

    Premisecitation
    § Discussion

    Coffey et al. estimated a rate of volume loss of the amygdala/hippocampus of 0.3%/year.

    “Coffey et al [30] estimated a rate of volume loss of the amygdala/hippocampus of 0.3%/year.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [30] Coffey CE, Wilkinson WE, Parashos IA, et al. Quantitative cerebral anatomy of the aging human brain: A cross-sectional study using magnetic resonance imaging. Neurology. 1992;42:527–536. doi: 10.1212/wnl.42.3.527. [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 conductnone given
    § Discussion

    The age range evaluated in this study was fairly narrow-70 to 89 years-and the sample size was modest.

    “However, the age range evaluated in this study was fairly narrow—70 to 89 years—and the sample size was modest.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation
    § Discussion

    Jobst et al. used CT, oriented images in a tilted axial plane, and made a single linear measurement of the minimum thickness of each medial temporal lobe.

    “Jobst et al [37] used CT, the images were oriented in a tilted axial plane, and a single linear measurement of the minimum thickness of each medial temporal lobe was made.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [37] Jobst KA, Smith AD, Szatmari M, et al. Rapidly progressing atrophy of medial temporal lobe in Alzheimer's disease. Lancet. 1994;343:829–30. doi: 10.1016/s0140-6736(94)92028-1. [DOI] [PubMed] [Google Scholar] source

      Not checked in the free run.

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

    Premisecitation
    § Discussion

    These results are in accord with several CT and MRI studies which demonstrated both cross-sectional and longitudinal differences in global hemispheric brain/CSF measurements between controls and AD patients.

    “These results are in accord with several CT and MRI studies which demonstrated both cross-sectional and longitudinal differences in global hemispheric brain/CSF measurements between controls and AD patients [39, 40].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [39] DeCarli C, Haxby JV, Gillette JA, et al. Longitudinal changes in lateral ventricular volume in patients with dementia of the Alzheimer type. Neurology. 1993;42:2029–2036. doi: 10.1212/wnl.42.10.2029. [DOI] [PubMed] [Google Scholar]

      Not checked in the free run.

    • cites [40] Wippold FJ, Gado MH, Morris JC, et al. Senile dementia and healthy aging: a longitudinal CT study. Radiology. 1992;179:215–219. doi: 10.1148/radiology.179.1.2006279. [DOI] [PubMed] [Google Scholar]

      Not checked in the free run.

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

    Premisecitation
    § Discussion

    Growdon et al. found that while the prevalence of APOE ε4 was greater in AD patients than controls, the rate of clinical progression in patients with established AD was not different for ε4 carriers vs ε4 non-carriers.

    “With regard to APOE genotype, our results are in agreement with those of Growdon et al [41, 42] who found that while the prevalence of APOE ∈4 was greater in AD patients than controls, the rate of clinical progression in patients with established AD was not different for ∈4 carriers vs ∈4 non-carriers.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [41] Growdon J, Locasio J, Corkin S, et al. Apolipoprotein E genotype does not influence rates of cognitive decline in Alzheimer's disease. Neurology. 1996;47:444–448. doi: 10.1212/wnl.47.2.444. [DOI] [PubMed] [Google Scholar]

      Not checked in the free run.

    • cites [42] Gomez-Isla T, West HL, Rebeck GW, et al. Clinical and pathological correlates of apolipoprotein E epsilon 4 in Alzheimer's disease. Ann Neurol. 1996;39:62–70. doi: 10.1002/ana.410390110. [DOI] [PubMed] [Google Scholar] source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning
    § Discussion

    Variability in results across centers is likely due to differences in the age range of the study population, the definition of 'normal' aging, and the MRI methods and neuroanatomic boundaries employed.

    “Variability in the results from different centers are likely due to differences in i) the age range of the study population, ii) the definition of “normal” aging, and iii) the MRI methods and neuroanatomic boundaries employed for measuring structure volume.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductown data
    § Discussion

    Our data represents a true longitudinal sample; the initial scan served as the reference point and each subject acted as his/her own control.

    “In contrast, our data represents a true longitudinal sample; the initial scan served as the reference point and each subject acted as his/her own control.”
    Quote in the paperSubstantial claim

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

    Premisecitation
    § Discussion

    Miller et al. calculated a loss of brain weight of 2%/decade in autopsied individuals over 55 years of age.

    “For example, Miller et al [23] calculated a loss of brain weight of 2%/decade in autopsied individuals over 55 years of age.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [23] Miller AKH, Alston RL, Corsellis JAN. Variation with age in the volumes of grey and white matter in the cerebral hemispheres of man: measurements with an image analyser. Neuropathol Appl Neurobiol. 1980;6:119–132. doi: 10.1111/j.1365-2990.1980.tb00283.x. [DOI] [PubMed] [Google Scholar] source

      Not checked in the free run.

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

    Premisecitation
    § Discussion

    Gur et al. found an effect of gender on the rates of regional hemispheric atrophy in a cross-sectional study.

    “In contrast, Gur et al [29] in a cross-sectional study, found an effect of gender on the rates of regional hemispheric atrophy.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [29] Gur RC, Mozley PD, Resnick SM, et al. Gender differences in age effect on brain atrophy measured by magnetic resonance imaging. Proc Natl. Acad. Sci. 1991;88:2845–2849. doi: 10.1073/pnas.88.7.2845. [DOI] [PMC free article] [PubMed] [Google Scholar]

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning
    § Discussion

    As the time interval between serial MRI scans increases, the absolute volumetric difference between them will increase and the magnitude of measurement error in proportion to measured difference will decrease.

    “As the time interval between serial MRI scans increases, the absolute volumetric difference between them will also increase and the magnitude of measurement error in proportion to measured difference will decrease.”
    Quote in the paperSubstantial claim
51 of 51

  • The paper relies on this without support.

    The 24 cognitively normal elderly control subjects are representative of typical aging individuals.

    “cognitively normal elderly control subjects who represent typical aging individuals”
    “elderly controls who represent typical aging individuals”

  • The paper relies on this without support.

    APOE genotypes ∈3/4 or 4/4 are known to increase the risk of AD.

    “APOE genotypes (∈3/4 or 4/4) which are known to increase the risk of AD”

  • The paper relies on this without support.

    In healthy young volunteers, no substantial biologic change in hippocampal or temporal horn volumes occurs over a 2–4 week period.

    “For that reason we assessed the stability of MRI measures in a serial fashion in healthy young volunteers in whom no substantial biologic change in hippocampal or temporal horn volumes would be expected over the course of a 2–4 week period.”

  • The paper relies on this without support.

    The test-retest variability measured in healthy young volunteers is applicable to the older control and AD subjects.

    “These are clearly examples of measurement imprecision, but are reasonably close to the expected test-retest variability found in the reproducibility study.”
4 of 4

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 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).”

    From Rates of hippocampal atrophy correlate with change in clinical status in aging and AD (2000) · cites this paper as [6]

  • 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).”

    From Rates of hippocampal atrophy correlate with change in clinical status in aging and AD (2000) · cites this paper as [6]

  • The stable control rate is very close to the −1.55%/year calculated in a previous study (6).

    “The rate which we calculated in this study for stable controls (−1.73%/year) is very close to the −1.55%/year which we calculated in a previous study (6), and is comparable to that described for older controls (−2.09%) by another group (25).”

    From Rates of hippocampal atrophy correlate with change in clinical status in aging and AD (2000) · cites this paper as [6]

  • In a prior study of serial hippocampal volume measurements in normal young adults we demonstrated a median coefficient of variation of 0.28% (0.02% - 0.70%) (6).

    “In a prior study of serial hippocampal volume measurements in normal young adults we demonstrated a median coefficient of variation of 0.28% (0.02% – 0.70%) (6).”

    From Rates of hippocampal atrophy correlate with change in clinical status in aging and AD (2000) · cites this paper as [6]

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Related

Authors
Jack, C. R., Petersen, R. C., Xu, Y., O'Brien, P. C., Smith, G. E., Ivnik, R. J., Tangalos, E. G., & Kokmen, E.
Affiliations
  • Mayo Clinic (US)
  • From the Departments of Diagnostic Radiology (Drs. Jack and Xu), Neurology (Drs. Petersen and Kokmen), Health Sciences Research (Dr. O'Brien), Psychiatry and Psychology (Drs. Smith and Ivnik), and Internal Medicine (Dr. Tangalos), Mayo Clinic and Foundation, Rochester, MN.
ORCID
Venue
Neurology
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
1998-10
Volume
51
Issue
4
Pages
993-999
ISSN
  • 0028-3878 (ISSN-L)
  • 1526-632X
DOI
10.1212/wnl.51.4.993
PMC
PMC2768817
OpenAlex
W2012133068
Semantic Scholar
44e6a88d3e6f1718c6ae3ccd7e17aafc155ef2f5
Cited by
666
References
55
Citations by year
2026: 18 · 2025: 21 · 2024: 27 · 2023: 15 · 2022: 21 · 2021: 28 · 2020: 23 · 2019: 20 · 2018: 17 · 2017: 12 · 2016: 20 · 2015: 21 · 2014: 29 · 2013: 16 · 2012: 23
FWCI
12.00
Type
journal article
Language
en
Open access
Locations
  • Neurology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institute on Aging (AG-08031, P30AG008031, NIH-NIA-AG 11378, AG-06786, U01AG006786, R01AG011378, R37AG011378)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
Keywords
Alzheimer's disease, medial temporal lobe atrophy, hippocampal atrophy, temporal horn, brain atrophy rate
MeSH terms
Aged, Aged, 80 and over, Aging, Alzheimer Disease, Apolipoproteins E, Atrophy, Diabetes Mellitus, Type 1, Female, Genotype, Hippocampus, Humans, Hypertension, Male, Risk Factors, Temporal Lobe, Reproducibility of Results, Comorbidity, Prevalence, Myocardial Ischemia, Hormone Replacement Therapy

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