Hippocampal atrophy patterns in mild cognitive impairment and Alzheimer's disease

May combine two claims.

Compared to controls, AD patients had smaller volumes of entorhinal cortex, subiculum, CA1, CA1-2 transition, and total hippocampus.

“Compared to controls, AD had smaller volumes of ERC, subiculum, CA1, CA1-2, and total hippocampal volumes.”

• Also stated in: § Pattern of Subfield Volume Loss · plain

  “Post-hoc analyses (cf Tables II and III) showed that compared to controls AD had significantly reduced ERC, subiculum, CA1, CA1-2 transition, and hippocampal volumes, whereas CA3&DG volumes were not different.”

May combine two claims.

CA1 had the smallest z-score, indicating it was the subfield with the most pronounced volume loss in AD.

“CA1 had the smallest z-score indicating that this was the subfield with the most pronounced volume loss.”

May combine two claims.

CA1-2 transition volume loss incorrectly classified 23% of controls as MCI, and CA1 and CA1-2 transition classified 25% of controls as AD.

“However, CA1-2 transition volume loss also incorrectly classified 23% of the controls as MCI and CA1 and CA1-2 transition classified 25% of the controls as AD.”

May combine two claims.

Most AD subjects in this study had mild AD (mean MMSE 21.6), whereas subjects in autopsy studies tend to have more advanced AD with more pronounced atrophy.

“Furthermore, although fulfilling the criteria for AD, most of the AD subjects in this study suffered from mild AD (mean MMSE 21.6) while subjects in autopsy studies tend to suffer from more advanced AD with more pronounced atrophy,”

May combine two claims.

Total hippocampal volume has a larger standard deviation in AD than in the other groups, reducing its ability to correctly classify AD subjects.

“Finally, the total hippocampal volume has a larger standard deviation in AD than in the two other groups which reduces its ability to correctly classify AD subjects.”

May combine two claims.

AD subjects misclassified by CA1 and CA1-2 transition volumes were younger but similarly impaired compared with correctly identified AD subjects.

“AD who where misclassified by CA1 and CA1-2 transition volumes were also younger but similarly impaired compared to the correctly identified AD (misclassified AD vs. correctly classified AD: mean age: 66.7 vs. 69.6 years, mean MMSE 21.5 vs. 22.0).”

May combine two claims.

The power to detect a difference between MCI and controls was 0.35 for total hippocampus, 0.28 for ERC, and 0.97 for CA1-2 transition.

“The power to detect a difference between those two groups was 0.35 for total hippocampus and 0.28 for ERC but 0.97 for CA1-2 transition.”

May combine two claims.

The three groups differed in MMSE score, with AD lower than MCI and controls, and MCI lower than controls.

“The three groups differed regarding MMSE score (Kruskal–Wallis, P < 0.001), with the AD group having lower scores than the MCI group and controls (Mann–Whitney, P < 0.05) and the MCI group having lower scores than controls (Mann–Whithey, P < 0.05).”

May combine two claims.

Multiple regression analysis showed significant disease-group effects for ERC, subiculum, CA1, CA1-2 transition, and hippocampal volume, but not for CA3&DG.

“Multiple regression analysis showed significant effects for disease group for ERC (P = 0.004), subiculum (P = 0.003), CA1 (P = 0.0001), CA1-2 transition (P < 0.0001), and hippocampal volume (P = 0.0005) but not for CA3&DG.”

May combine two claims.

There were no significant differences between AD and MCI; MCI volumes tended to be between controls and AD, except CA1-2 transition volume, which was close to the AD volume.

“There were no significant differences between AD and MCI and the volumes of the MCI group tended to be in-between the volumes of controls and AD with the exception of the CA1-2 transition volume which was close to the volume measured in AD.”

May combine two claims.

The patterns of subfield atrophy in AD and MCI were consistent with histopathological patterns of neuronal cell loss or reduced synaptic density, suggesting that the volumetric measurements reflect those histopathological changes.

“The patterns of subfield atrophy in AD and MCI were consistent with patterns of neuronal cell loss/reduced synaptic density described by histopathology.”

• Also stated in: § DISCUSSION · hedged

  “The fact that the patterns of regional volume loss found in this neuroimaging study closely resemble the patterns of neuron loss and reduction of synaptic density described in those neuropathological studies, suggests that these volumetric measurements reflect those histopathological changes.”

• cites West et al., 1994Not checked yet

  Not checked in the free run.

• cites Rössler et al., 2002Not checked yet

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• cites Fukutani et al., 1995Not checked yet

  Not checked in the free run.

• AssumptionThe authors state this as an assumption: Volume loss in the CA1-2 transition region is driven by volume loss in the dorsal aspect of CA1 rather than in CA2 itself.
• AssumptionThe authors state this as an assumption: Volume changes in the CA1-2 transition sector can result from changes in both CA1 and CA2 subfields.

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

The finding that misclassified MCI subjects were younger and less impaired could suggest they were in an earlier stage of AD than correctly identified MCI subjects.

“This could suggest that they were in an earlier stage of AD than the correctly identified MCI.”

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

The finding that misclassified AD subjects were younger but similarly impaired could suggest an earlier onset and atypical presentation of AD or even a different form of dementia.

“This could suggest an earlier onset and thus eventually an atypical presentation of AD or even a different form of dementia and further supports the observation that the AD group was more heterogeneous.”

May combine two claims.

Because the dentate gyrus had to be marked together with CA3, and CA3 is relatively well preserved in AD, it is possible that CA3 overshadowed subtle dentate gyrus effects.

“Since CA3 is relatively well preserved in AD, it is possible that it overshadowed subtle effects in DG.”

May combine two claims.

Normal aging and AD even in its earliest stages are associated with distinct patterns of hippocampal atrophy: aging with volume loss in CA1 and MCI with volume loss in CA1-2 transition.

“In conclusion, these initial findings suggest that normal aging and AD even in its earliest stages are associated with a distinct pattern of atrophy in the hippocampus, i.e. aging with volume loss in CA1 and MCI with volume loss in CA1-2 transition.”

• cites Mueller et al., 2007Not checked yet

  Not checked in the free run.

• AssumptionThe authors state this as an assumption: Volume loss in the CA1-2 transition region is driven by volume loss in the dorsal aspect of CA1 rather than in CA2 itself.

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

ERC and hippocampus have been shown by other studies to be good measures for discriminating between MCI and controls.

“The same was true for the ERC in MCI and controls although ERC and hippocampus have been shown to be a good measure to discriminate between these groups by other studies [Devanand et al., 2007; Pennanen et al., 2004; Xu et al., 2000].”

• cites Devanand et al., 2007Not checked yet

  Not checked in the free run.

• cites Pennanen et al., 2004Not checked yet

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• cites Xu et al., 2000Not checked yet

  Not checked in the free run.

May combine two claims.

The distribution of hippocampal volume loss in AD is different from that in normal aging, which was restricted to CA1 and did not affect CA1-2 transition or subiculum.

“This distribution of hippocampal volume loss in the AD disease process is different from the distribution found in normal aging which was restricted to CA1 and did not affect CA1-2 transition and subiculum [Mueller et al., 2007].”

• cites Mueller et al., 2007Not checked yet

  Not checked in the free run.

Classified as probably not a substantial claim.

All subfield markings were done by a single rater blinded to diagnosis.

“All subfield markings were done by a single rater blinded to the diagnosis using rview”

May combine two claims.

CA1 and CA1-2 transition volumes are less affected by disease-severity heterogeneity because both are atrophied in early and late stages, whereas total hippocampal volume includes subfields that are not or only mildly affected early but develop marked atrophy later.

“CA1 and CA1-2 transition volumes are less affected by this heterogeneity because both are atrophied in the early and late stages of the disease while the total hippocampal volume contains additional subfields which are not (CA3&DG) or only mildly (Sub) affected in the early stages but develop marked atrophy in the later stages [Rössler et al., 2002].”

• cites Rössler et al., 2002Not checked yet

  Not checked in the free run.

May combine two claims.

The CA2 label volume is relatively small and therefore sensitive to small marking inaccuracies.

“However, the volume of this label is relatively small thus rendering it sensitive to small marking inaccuracies (cf. Table I).”

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

The subfield marking strategy shows good correspondence with hippocampal subfields in histopathological samples, but validation in a direct histopathology-imaging correlation study is necessary.

“(5) Although the subfields marking strategy used in this article shows a good correspondence with hippocampal subfields in histopathological samples, it will be necessary to validate the subfield marking strategy in a direct histopathology, imaging correlation study.”

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

Five MCI, five AD, and ten control subjects were randomly selected and marked twice to establish test-retest reliability in subjects with diseased hippocampi.

“Five MCI and five AD and 10 control subjects were randomly selected from the study population and marked twice to establish test–retest reliability in subjects with diseased hippocampi.”

May combine two claims.

The imaging sequence did not allow distinguishing details at histological resolution, so arbitrarily defined hippocampal landmarks were used to assign regions to subfields.

“Although the sequence used in this study provides superior resolution, it does not allow distinguishing details on the resolution of a histological preparation. Therefore, a set of arbitrarily defined hippocampal landmarks was used to assign different regions to different subfields.”

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

Total hippocampal volume maps were visually checked and manually corrected by specially trained raters blinded to diagnosis.

“All maps were visually checked for accuracy by different, specially trained raters who were blinded to the diagnosis and manually corrected by overlaying the label generated in FreeSurfer onto the T1 image in rview.”

Classified as probably not a substantial claim.

The study was cross-sectional.

“(2) The study was cross-sectional and we cannot exclude that some of the misclassified controls were in the early stages of AD or some MCI might remain stable or not progress to AD but other dementia types.”

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

The CA1-2 transition volume is influenced by the width of dorsal CA1 and likely overlaps with the dorsomedial part of CA1.

“Furthermore, the volume of this subfield is influenced by the width of the dorsal CA1 and it is likely to have some overlap with the dorsomedial part of CA1.”

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

Hippocampal subfields were marked only in a relatively small region of the anterior hippocampus, so effects with a regional preference cannot be excluded.

“(4) Hippocampal subfields were only marked in a relatively small region of the anterior hippocampus. Therefore, we cannot exclude that we missed effects with a regional preference.”

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

The position of CA2 relative to the fimbriae varies slightly depending on the shape of the hippocampus.

“Although the position of CA2 showed good correspondence with the localization of CA2 in histological preparations, its position relatively to the fimbriae, which can be used as a macroscopic landmark of CA3 in this section of the hippocampus (cf Fig. 1b), varies slightly depending on the shape of the hippocampus.”

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

Five subjects were excluded because the internal hippocampal structure could not be sufficiently visualized.

“Five subjects (3 AD, 1 MCI, and 1 control) fulfilling the inclusion criteria and thus selected for the project could not be marked because the internal structure could not be sufficiently visualized and had to be excluded.”

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

The technique for subfield volumetry requires a high-resolution image that reliably depicts internal hippocampal structure, which may limit its applicability to severely cognitively impaired or noncompliant subjects or those with diseases destroying the internal structure.

“(6) This technique for subfield volumetry requires a high resolution image which reliably depicts details of the internal structure of the hippocampus, i.e. an image of good quality. This might limit the applicability of this method to severely cognitively impaired and hence noncompliant subjects or subjects suffering from diseases which destroy the internal structure of the hippocampus.”

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

Patients were referred from different memory clinics that used slightly different evaluation procedures, which might have added to the diversity of the MCI and AD groups.

“(3) The patients were referred from different memory clinics which although adhering to the same general concept for the diagnosis of MCI and AD (clinical and neuropsychologic evaluation, consensus conference within clinic) use slightly different evaluation procedures. This might have added to the diversity of the MCI and AD groups.”

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

The subfield assignment is not claimed to correspond to histological subfields but is claimed to provide a good and reproducible approximation.

“We do not claim that this subfield assignment actually corresponds to the histological subfields but merely that it provides a good and reproducible approximation.”