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Cited by 290Dementia and Cognitive Impairment ResearchAlzheimer's disease research and treatmentsMemory and Neural Mechanisms

Hippocampal subfield volumetry in mild cognitive impairment, Alzheimer's disease and semantic dementia

Open access
La Joie, Renaud, Perrotin, Audrey, de La Sayette, Vincent, Egret, Stéphanie, Doeuvre, Loïc, Belliard, Serge, Eustache, Francis, Desgranges, Béatrice +1 more·2013·NeuroImage: Clinical
DOI 10.1016/j.nicl.2013.08.007PMC PMC3791274
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Abstract

BACKGROUND: Hippocampal atrophy is a well-known feature of Alzheimer's disease (AD), but sensitivity and specificity of hippocampal volumetry are limited. Neuropathological studies have shown that hippocampal subfields are differentially vulnerable to AD; hippocampal subfield volumetry may thus prove to be more accurate than global hippocampal volumetry to detect AD. METHODS: CA1, subiculum and other subfields were manually delineated from 40 healthy controls, 18 AD, 17 amnestic Mild Cognitive Impairment (aMCI), and 8 semantic dementia (SD) patients using a previously developed high resolution MRI procedure. Non-parametric group comparisons and receiver operating characteristic (ROC) analyses were conducted. Complementary analyses were conducted to evaluate differences of hemispheric asymmetry and anterior-predominance between AD and SD patients and to distinguish aMCI patients with or without β-amyloid deposition as assessed by Florbetapir-TEP. RESULTS: Global hippocampi were atrophied in all three patient groups and volume decreases were maximal in the CA1 subfield (22% loss in aMCI, 27% in both AD and SD; all p < 0.001). In aMCI, CA1 volumetry was more accurate than global hippocampal measurement to distinguish patients from controls (areas under the ROC curve = 0.88 and 0.76, respectively; p = 0.05) and preliminary analyses suggest that it was independent from the presence of β-amyloid deposition. In patients with SD, whereas the degree of CA1 and subiculum atrophy was similar to that found in AD patients, hemispheric and anterior-posterior asymmetry were significantly more marked than in AD with greater involvement of the left and anterior hippocampal subfields. CONCLUSIONS: The findings suggest that CA1 measurement is more sensitive than global hippocampal volumetry to detect structural changes at the pre-dementia stage, although the predominance of CA1 atrophy does not appear to be specific to AD pathophysiological processes.

AI snapshot

Written from the paper’s full text.

TL;DR

Manual hippocampal subfield volumetry in 40 controls, 17 aMCI, 18 AD, and 8 semantic dementia patients showed maximal atrophy in CA1 across patient groups. CA1 volume was more accurate than global hippocampal volume for distinguishing aMCI from controls, but CA1 predominance was not specific to AD pathophysiology.

Key findings

  • Global hippocampal volume was reduced in all patient groups: −12% in aMCI, −22% in AD, and −17% in SD. CA1 showed the largest losses: −22% in aMCI and −27% in both AD and SD (all p < 0.001).
  • In aMCI, CA1 volumetry discriminated patients from controls better than global hippocampal volume (AUC = 0.88 [0.78–0.98] vs. 0.76 [0.60–0.93], p = 0.05). In AD vs. controls, no subfield outperformed the whole hippocampus (whole hippocampus AUC = 0.91 [0.78–1]; CA1 = 0.92 [0.85–0.99]).
  • SD showed greater hemispheric asymmetry than AD for the whole hippocampus (p = 0.001), subiculum (p = 0.02), and other subfields (p = 0.01), with a trend for CA1 (p = 0.06); SD also had a lower anterior–posterior index for whole hippocampus, CA1, and subiculum, indicating anterior-predominant atrophy.
  • Among 15 aMCI patients with Florbetapir PET, Aβ-positive aMCI had lower CA1 (p < 0.001), subiculum (p = 0.01), and hippocampal volumes (p = 0.01) than controls, while Aβ-negative aMCI only showed lower CA1 volume (p = 0.04); direct Aβ-positive vs. Aβ-negative comparisons were not significant (all p > 0.25).

Methods

  • Cross-sectional study of 83 right-handed participants: 40 healthy controls, 17 aMCI, 18 AD, and 8 SD patients.
  • CA1, subiculum, and “other” subfields (CA2–CA3–CA4 plus dentate gyrus) were manually delineated on high-resolution 3-Tesla MRI slices perpendicular to the hippocampal long axis; volumes were TIV-normalized and converted to age- and gender-adjusted W-scores.
  • Non-parametric group comparisons (Kruskal–Wallis, Mann–Whitney U), ROC/AUC analyses, asymmetry and anterior–posterior indices, and Florbetapir PET analyses in 18 AD and 15 aMCI patients using a neocortical SUVr threshold of 1.1.

Limitations

  • Stated: patient groups were relatively small, especially when aMCI was split by Aβ status; Aβ-related findings were considered preliminary. The paper also states that subfield volumetry provides approximations based on anatomical landmarks, that protocols differ across studies without direct comparison to neuropathological gold standard, and that high-resolution scans are prone to motion artifacts.
  • Stated: the absence of significant AD vs. SD differences could be due to lack of statistical power.
  • Evident: manual delineation was performed by a single rater, and the text does not report inter-rater or test–retest reliability metrics for the present sample; the design is cross-sectional, so diagnostic/prognostic accuracy over time is not established.

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

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Registry

Crossref · 10.1016/j.nicl.2013.08.007

Cites

57 of 57 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 53 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    Hemispheric asymmetry is significantly stronger in SD than in AD for the other subfield (p = 0.01).

    “Asymmetry was significantly stronger in SD than in AD for the whole hippocampus (p = 0.001), subiculum (p = 0.02), other (p = 0.01) and a trend was found for CA1 (p = 0.06).”
    Quote in the paperNot a substantial claim
  • Findingown data

    In SD, subiculum volume is reduced by 24% relative to healthy controls (p < 0.001).

    “In the SD group, both CA1 and subiculum volumes were significantly reduced relative to HC (− 27% and − 24% respectively, both p < 0.001).”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Healthy controls are free of preclinical Alzheimer's disease pathology.
  • Findingown data

    In discriminating AD from healthy controls, none of the subfield AUCs is significantly higher than the whole hippocampus AUC (0.91 [0.78-1]).

    “For the AD versus HC discrimination, the AUC of all subfields was significantly higher than 0.5 (mean [95% CI] = 0.92 [0.85–0.99] for CA1, 0.88 [0.76–1] for subiculum, 0.81 [0.67–0.94] for other) but none of them was significantly higher than that of the whole hippocampus (0.91 [0.78–1]).”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Healthy controls are free of preclinical Alzheimer's disease pathology.
  • Findingown data

    Among healthy controls, Aβ-positive aMCI, and Aβ-negative aMCI, there is a significant effect of group on global hippocampus volume (H = 5.98; p = 0.05).

    “A Kruskal–Wallis ANOVA with three groups (HC, Aβ-positive aMCI, Aβ-negative aMCI) was performed on TIV-normalized hippocampal measurements. A significant effect of group was found for CA1 (H = 13.8; p = 0.001), subiculum (H = 5.99; p = 0.05) and global hippocampus (H = 5.98; p = 0.05).”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Healthy controls are free of preclinical Alzheimer's disease pathology.
  • Findingown data

    There is a trend for stronger hemispheric asymmetry in SD than in AD for CA1 (p = 0.06).

    “Asymmetry was significantly stronger in SD than in AD for the whole hippocampus (p = 0.001), subiculum (p = 0.02), other (p = 0.01) and a trend was found for CA1 (p = 0.06).”
    Quote in the paperNot a substantial claim
  • May combine two claims. 29
  • Classified as probably not a substantial claim. 13

  • May combine two claims.

    Findingown data

    In AD, the 'other' subfield (CA2-CA4 and dentate gyrus) volume is reduced by 17% relative to healthy controls, significantly less than CA1 and subiculum (p < 0.005).

    “In AD, volume decreases were highly significant (p < 0.001) for all three subfields, but atrophy in the other region (− 17%) was significantly lower (p < 0.005 using Wilcoxon rank-sum test) than in both CA1 and subiculum (both − 27%).”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Healthy controls are free of preclinical Alzheimer's disease pathology.

  • May combine two claims.

    Findingown data

    In AD, CA1 volume is reduced by 27% relative to healthy controls, with a highly significant decrease (p < 0.001).

    “In AD, volume decreases were highly significant (p < 0.001) for all three subfields, but atrophy in the other region (− 17%) was significantly lower (p < 0.005 using Wilcoxon rank-sum test) than in both CA1 and subiculum (both − 27%).”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Healthy controls are free of preclinical Alzheimer's disease pathology.

  • May combine two claims.

    Findingown data

    In AD, subiculum volume is reduced by 27% relative to healthy controls, with a highly significant decrease (p < 0.001).

    “In AD, volume decreases were highly significant (p < 0.001) for all three subfields, but atrophy in the other region (− 17%) was significantly lower (p < 0.005 using Wilcoxon rank-sum test) than in both CA1 and subiculum (both − 27%).”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Healthy controls are free of preclinical Alzheimer's disease pathology.

  • May combine two claims.

    Findingown data

    None of the volume measurements separated AD from SD; none of the AUCs was significantly different from 0.5 (CA1 0.51 [0.27-0.74], subiculum 0.64 [0.43-0.85], other 0.69 [0.45-0.94], whole hippocampus 0.69 [0.47-0.90]).

    “Finally, none of the volume measurements were allowed to separate AD from SD as none of the AUCs was significantly different from 0.5: 0.51 [0.27–0.74] for CA1, 0.64 [0.43–0.85] for subiculum, 0.69 [0.45–0.94] for other, and 0.69 [0.47–0.90] for the whole hippocampus.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In aMCI, subiculum volume loss is 17% and significant (p = 0.01) relative to healthy controls.

    “In aMCI, atrophy was highly significant in CA1 (− 22%, p < 0.001) and to a lesser extent in the subiculum (− 17%, p = 0.01).”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Healthy controls are free of preclinical Alzheimer's disease pathology.

  • May combine two claims.

    Findingown data

    In discriminating AD from healthy controls, the AUC of subiculum is 0.88 [0.76-1], significantly higher than 0.5.

    “For the AD versus HC discrimination, the AUC of all subfields was significantly higher than 0.5 (mean [95% CI] = 0.92 [0.85–0.99] for CA1, 0.88 [0.76–1] for subiculum, 0.81 [0.67–0.94] for other) but none of them was significantly higher than that of the whole hippocampus (0.91 [0.78–1]).”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Healthy controls are free of preclinical Alzheimer's disease pathology.

  • May combine two claims.

    Findingown data

    In discriminating AD from healthy controls, the AUC of the other subfields is 0.81 [0.67-0.94], significantly higher than 0.5.

    “For the AD versus HC discrimination, the AUC of all subfields was significantly higher than 0.5 (mean [95% CI] = 0.92 [0.85–0.99] for CA1, 0.88 [0.76–1] for subiculum, 0.81 [0.67–0.94] for other) but none of them was significantly higher than that of the whole hippocampus (0.91 [0.78–1]).”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Healthy controls are free of preclinical Alzheimer's disease pathology.

  • May combine two claims.

    Findingown data

    In discriminating AD from healthy controls, the AUC of CA1 is 0.92 [0.85-0.99], significantly higher than 0.5.

    “For the AD versus HC discrimination, the AUC of all subfields was significantly higher than 0.5 (mean [95% CI] = 0.92 [0.85–0.99] for CA1, 0.88 [0.76–1] for subiculum, 0.81 [0.67–0.94] for other) but none of them was significantly higher than that of the whole hippocampus (0.91 [0.78–1]).”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Healthy controls are free of preclinical Alzheimer's disease pathology.

  • May combine two claims.

    Findingown data

    In discriminating aMCI from healthy controls, the AUC of CA1 (0.88 [0.78-0.98]) is significantly higher than 0.5 and higher than the AUC of the whole hippocampus (0.76 [0.60-0.93], p = 0.05).

    “For the discrimination between HC and aMCI, the AUC of CA1 (0.88 [0.78–0.98]) was significantly higher than 0.5 and higher than the AUC of the whole hippocampus (0.76 [0.60–0.93], p = 0.05; see Fig. 3)”
    • Also stated in: § Results · plain
      “In aMCI, CA1 volumetry was more accurate than global hippocampal measurement to distinguish patients from controls (areas under the ROC curve = 0.88 and 0.76, respectively; p = 0.05)”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Healthy controls are free of preclinical Alzheimer's disease pathology.

  • May combine two claims.

    Findingown data

    In discriminating aMCI from healthy controls, the subiculum AUC (0.74 [0.59-0.90]) is significantly higher than 0.5 but does not perform better than the whole hippocampus.

    “whereas the subiculum AUC (0.74 [0.59–0.90]) was significantly higher than 0.5 but did not perform better than the whole hippocampus”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Healthy controls are free of preclinical Alzheimer's disease pathology.

  • May combine two claims.

    Findingown data

    Global hippocampal volume is decreased in patients with aMCI, AD and SD compared with healthy controls (mean volume loss 12% in aMCI, 22% in AD, 17% in SD).

    “Briefly, the volume of the whole hippocampus was significantly decreased in all three patient groups as compared to HC (mean volume loss = − 12% for aMCI, − 22% for AD and − 17% for SD).”
    • Also stated in: § Results · plain
      “Global hippocampi were atrophied in all three patient groups and volume decreases were maximal in the CA1 subfield (22% loss in aMCI, 27% in both AD and SD; all p < 0.001).”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Healthy controls are free of preclinical Alzheimer's disease pathology.

  • May combine two claims.

    Findingown data

    In aMCI, CA1 volume loss is 22% and highly significant (p < 0.001) relative to healthy controls.

    “In aMCI, atrophy was highly significant in CA1 (− 22%, p < 0.001) and to a lesser extent in the subiculum (− 17%, p = 0.01).”
    • Also stated in: § Results · plain
      “volume decreases were maximal in the CA1 subfield (22% loss in aMCI, 27% in both AD and SD; all p < 0.001).”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Healthy controls are free of preclinical Alzheimer's disease pathology.

  • May combine two claims.

    Findingown data

    All AD patients were classified as Aβ-positive and 9 aMCI patients (60% of aMCI patients who underwent Florbetapir-PET) were classified as Aβ-positive.

    “All AD patients were classified as Aβ-positive and 9 aMCI patients (60% of aMCI patients who underwent Florbetapir-PET) were classified as Aβ-positive.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Hippocampal atrophy is a major feature of Alzheimer's disease and strongly correlates with AD neuropathology.

    “Hippocampal atrophy is a major feature of Alzheimer's disease (AD) (Frisoni et al., 2010) that strongly correlates with AD neuropathology (Bobinski et al., 1996; Jack et al., 2002).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Frisoni et al., 2010 source

      Not checked in the free run.

    • cites Bobinski et al., 1996

      Not checked in the free run.

    • cites Jack et al., 2002 source

      Not checked in the free run.

  • May combine two claims.

    Study design and conductcitation

    Patients were selected according to internationally agreed criteria: Petersen's criteria for aMCI, NINCDS-ADRDA criteria for probable Alzheimer's disease, and Neary et al. criteria for semantic dementia.

    “All patients were recruited from local memory clinics and selected according to corresponding internationally agreed criteria: Petersen's criteria for aMCI (Petersen & Morris, 2005), NINCDS-ADRDA criteria for probable Alzheimer's disease (McKhann et al., 1984) and Neary et al. criteria for SD (Neary et al., 1998).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Petersen & Morris, 2005 source

      Not checked in the free run.

    • cites McKhann et al., 1984 source

      Not checked in the free run.

    • cites Neary et al., 1998 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    At the aMCI stage, CA1 volume loss predominated and better discriminated aMCI patients from healthy controls than global hippocampal volume.

    “By contrast, at the aMCI stage, CA1 volume loss predominated and was found to better discriminate aMCI patients from HC than global hippocampal volume.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    Hippocampal volume has been proposed as a neuroimaging biomarker for early Alzheimer's disease diagnosis.

    “Hippocampal volume has thus been proposed as a neuroimaging biomarker for early AD diagnosis (Albert et al., 2011; Dubois et al., 2010).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Albert et al., 2011 source

      Not checked in the free run.

    • cites Dubois et al., 2010 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    The differential subfield atrophy pattern was not discriminant at the dementia stage because no differences were found between AD and SD and hippocampal subfields did not perform better than the whole hippocampus in discriminating AD from healthy controls.

    “This pattern was not discriminant at the dementia stage as i) no differences were found between AD and SD and ii) hippocampal subfields did not perform better than the whole hippocampus in discriminating AD from HC.”
    Quote in the paperSubstantial claim

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

    Study design and conductown data

    The main results were unchanged when performing comparisons on raw volumes or TIV-normalized volumes instead of age- and gender-adjusted W-scores.

    “Note that the main results were unchanged when performing comparisons on raw volumes or TIV-normalized volumes instead of age- and gender-adjusted W-scores as presented here (see Supplementary Fig. 2).”
    Quote in the paperNot a substantial claim

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

    Study design and conductown data

    All results remained unchanged when using W-scores instead of TIV-normalized volumes.

    “All the results remained unchanged when using W-scores instead of TIV-normalized volumes (data not shown).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductreasoning

    A visual quality check and repeat scans ensured that the 83 participants included in the present study had high quality data.

    “The 83 participants included in the present study had high quality data.”
    Quote in the paperSubstantial claim

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

    Study design and conductreasoning

    Subfield volumetry as performed in the present study only provides approximations of the exact volumes of the hippocampal subfields, based on anatomical landmarks derived from histological atlases.

    “It should also be noted that subfield volumetry as performed in the present study only provides approximations of the exact volumes of the hippocampal subfields, based on anatomical landmarks derived from histological atlases”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    A severe neuronal loss in the CA1 subfield together with a preservation of neurons in the dentate gyrus, consistent with our imaging findings, was reported independently of the histopathological subtypes.

    “Despite this variability, a severe neuronal loss in the CA1 subfield together with a preservation of neurons in the dentate gyrus, consistent with our imaging findings, was reported independently of the histopathological subtypes (Davies et al., 2005).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Davies et al., 2005 source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductown data

    Healthy controls performed in the normal range on a neuropsychological examination assessing multiple cognitive domains.

    “HC were recruited from the community and performed in the normal range on a neuropsychological examination assessing multiple domains of cognition including episodic and semantic memory, executive and visuo-spatial functions, language and praxis.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    The pathological substrate of hippocampal atrophy in SD is not clear, notably because patients with SD can present with heterogeneous pathological features.

    “Yet, the pathological substrate of hippocampal atrophy in SD is not clear, notably because patients with SD can present with heterogeneous pathological features (Davies et al., 2005).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Davies et al., 2005 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

    The IMAP Study was approved by a regional ethics committee and registered with ClinicalTrials.gov (number NCT01638949).

    “The IMAP Study was approved by regional ethics committee (Comité de Protection des Personnes Nord-Ouest III) and is registered with ClinicalTrials.gov (number NCT01638949).”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    Hippocampal subfield delineations were performed by a single rater blind to the identity (age, gender, clinical status) of the participants.

    “Delineations were performed on slices perpendicular to the long axis of the hippocampus by a single rater, blind to the identity (age, gender, clinical status) of the participants.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    Discrepancies exist as regards to the area of largest difference between HC and aMCI patients, probably reflecting variations in the anatomical landmarks used for subfield delineation.

    “However, discrepancies exist as regards to the area of largest difference between HC and aMCI patients (CA1 (Pluta et al., 2012), CA1–CA2 transition area (Mueller et al., 2010) or subiculum (Hanseeuw, 2011), probably reflecting variations in the anatomical landmarks used for subfield delineation”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Pluta et al., 2012 source

      Not checked in the free run.

    • cites Mueller et al., 2010 source

      Not checked in the free run.

    • cites Hanseeuw, 2011 source

      Not checked in the free run.

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

    Study design and conductcitation

    Raw volumes of each hippocampal subfield and of the whole hippocampus were normalized by total intracranial volume and transformed into age- and gender-adjusted W-scores.

    “Raw volumes of each hippocampal subfield and of the whole hippocampus (corresponding to the sum of the three subfields) were first normalized by the TIV to account for inter-individual variability in head size (normalized volume = 1000 × raw volume / TIV) and then transformed into W-scores, i.e. age and gender-adjusted Z-scores (Jack et al., 2002).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Jack et al., 2002 source

      Not checked in the free run.

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

    Premisecitation

    Hippocampal atrophy has been shown to induce PCC hypometabolism through a disconnection process in AD.

    “hippocampal atrophy has been shown to induce PCC hypometabolism through a disconnection process in AD (Villain et al., 2008).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Villain et al., 2008 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The connectivity of the hippocampus varies along its anterior-posterior axis, with the posterior part being more strongly connected to the PCC.

    “Besides, the connectivity of the hippocampus varies along its anterior–posterior axis, with the posterior part being more strongly connected to the PCC (Poppenk et al., 2013).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Poppenk et al., 2013 source

      Not checked in the free run.

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

    Study design and conductnone given

    All participants gave written informed consent to the study prior to the investigation.

    “All participants gave written informed consent to the study prior to the investigation.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationcitation

    The higher vulnerability of CA1 neurons is likely to be at least partly due to the neurofibrillary pathology as the CA1 subfield is the first hippocampal area to be affected by NFT.

    “The higher vulnerability of CA1 neurons is likely to be at least partly due to the neurofibrillary pathology as the CA1 subfield is the first hippocampal area to be affected by NFT (Braak & Braak, 1991; Schönheit et al., 2004).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Braak & Braak, 1991 source

      Not checked in the free run.

    • cites Schönheit et al., 2004 source

      Not checked in the free run.

  • May combine two claims.

    Study design and conductown data

    Aβ-positive and Aβ-negative aMCI did not differ in age, gender or education (all p-values > 0.8).

    “Aβ-positive and Aβ-negative aMCI did not differ in age, gender or education (all p-values > 0.8).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    The possibility that neuronal injury biomarkers occur independently of Aβ would rather support hypotheses suggesting that tau pathology could occur independently from Aβ accumulation than the amyloid hypothesis.

    “This would rather support hypotheses suggesting that tau pathology could occur independently from Aβ accumulation (Small, 2008), than the amyloid hypothesis where tau-related neurodegeneration is supposed to appear downstream to Aβ.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Small, 2008 source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    The presence of Aβ deposition significantly increases the likelihood of having AD pathology in patients with aMCI according to current diagnosis recommendations.

    “Because the presence of Aβ deposition significantly increases the likelihood of having AD pathology in patients with aMCI according to current diagnosis recommendations (Albert et al., 2011; Dubois et al., 2010)”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Albert et al., 2011 source

      Not checked in the free run.

    • cites Dubois et al., 2010 source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductown data

    These findings regarding Aβ and subfield atrophy should be considered as preliminary given the small size of the aMCI samples when dichotomized in Aβ-positive and Aβ-negative.

    “However, these findings should be considered as preliminary given the small size of the aMCI samples when dichotomized in Aβ-positive and Aβ-negative.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    Our findings in AD and SD are consistent with the topography of neuronal loss described in post-mortem studies as well as with previous imaging studies that used different methods.

    “Overall, our findings in AD and SD are consistent with the topography of neuronal loss described in post-mortem studies as well as with previous imaging studies that used different methods.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Several studies have reported a strong negative correlation between neuronal counts and NFT number in the CA1 subfield, suggesting that the progression of brain atrophy and the progression of NFT are strongly associated.

    “Moreover, several studies have reported a strong negative correlation between neuronal counts and NFT number in the CA1 subfield (Fukutani et al., 2000; Von Gunten et al., 2006) suggesting that the progression of brain atrophy and the progression of NFT are strongly associated (Whitwell et al., 2008).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Fukutani et al., 2000 source

      Not checked in the free run.

    • cites Von Gunten et al., 2006 source

      Not checked in the free run.

    • cites Whitwell et al., 2008 source

      Not checked in the free run.

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

    Study design and conductnone given

    The absence of significant difference between AD and SD in subfield volumetry could be due to a lack of statistical power.

    “Although the absence of significant difference could be due to a lack of statistical power”
    Quote in the paperNot a substantial claim
40 of 40

  • The paper relies on this without support.

    Healthy controls are free of preclinical Alzheimer's disease pathology.

    “HC were recruited from the community and performed in the normal range on a neuropsychological examination assessing multiple domains of cognition including episodic and semantic memory, executive and visuo-spatial functions, language and praxis.”
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Authors
La Joie, R., Perrotin, A., de La Sayette, V., Egret, S., Doeuvre, L., Belliard, S., Eustache, F., Desgranges, B., & Chételat, G.
Affiliations
Inserm (FR)
Corresponding author
Chételat, Gaël
ORCID
Venue
NeuroImage: Clinical
Publisher
Elsevier BV
Published
2013
Volume
3
Pages
155-162
ISSN
2213-1582 (ISSN-L)
DOI
10.1016/j.nicl.2013.08.007
PMC
PMC3791274
OpenAlex
W2060796157
Cited by
290
References
57
Citations by year
2026: 16 · 2025: 20 · 2024: 24 · 2023: 18 · 2022: 26 · 2021: 28 · 2020: 31 · 2019: 24 · 2018: 24 · 2017: 19 · 2016: 25 · 2015: 22 · 2014: 13
FWCI
14.22
Type
journal article
Language
en
Open access
Licence
Locations
  • NeuroImage Clinical (publishedVersion, cc-by-nc-sa)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
  • HAL (submittedVersion, other-oa)
Funders
  • Fondation Plan Alzheimer (Alzheimer Plan 2008–2012)
  • Programme Hospitalier de Recherche Clinique (PHRC National 2011)
  • Agence Nationale de la Recherche (ANR LONGVIE 2007)
  • Région Basse Normandie, and Institut National de la Santé et de la Recherche Médicale (INSERM)
  • Inserm-Liliane Bettencourt School (MD–PhD Program)
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 › Cognitive Neuroscience › Memory and Neural Mechanisms
Keywords
hippocampal subfields, hippocampal volumetry, CA1, subiculum, mild cognitive impairment, Alzheimer's disease, semantic dementia, hippocampal atrophy, amyloid-beta deposition, hemispheric lateralization

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.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-10.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-10.

Statistics and arithmetic are recomputed, not judged.

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