Review: Differences in Hippocampal Metabolism Between Amnestic and Non-Amnestic MCI Subjects

The reviewed article is  ‘Differences in hippocampal metabolism between amnestic and non-amnestic MCI subjects: automated FDG-PET image analysis’ by Mariani and colleagues and freely available here at the time of writing. In the abstract, the researchers conclude that

Comparison between the two MCI subtypes showed MTL hypometabolism in aMCI subjects possibly reflecting the fact that most had prodromal AD

In the introduction, the researchers outline some of the previous evidence showing a deficit in glucose metabolism in the Medial Temporal Lobe and providing a context for the current study. The aim of the study is clearly described  in the abstract

The aim of this study was to assess whether 18F-fluorodeoxyglucose positron emission tomogrpaphy differentiates amnestic (aMCI) from single-non-amnestic mild cognitive impairment (snaMCI) with executive dysfunction

Methodology

  • The study included 30 right-handed MCI subjects who had been referred to the University of Milan neurology department.
  • 85% were referred by the GP
  • 15% were self-referred. The self-referrals are interesting as this might be different from the usual referral routes in other healthcare systems.
  • The diagnostic criteria are clearly stipulated – 6/12 of subjective/objective evidence of cognitive impairment, normal ADL, MMSE >= 24, CDR of 0.5, performance of 1.5 SD below norms on >= 1 cognitive dimension on neuropsychological testing.
  • There was an extensive list of exclusion criteria and here I thought that the subjects might differ significantly from a routine clinical population with MCI e.g Hachinski ischemic score > 4, thyroid disorders, kidney or liver disorders, history of alcohol dependence as well as a number of other criteria.
  • Subjects underwent a battery of neuropsychological investigations.
  • Petersen’s criteria for amnestic MCI were used and those for single non-amnestic MCI are stipulated in the paper.
  • The protocol for PET imaging and analysis of the images was clearly described.
  • PET images were compared to a control group of previously acquired images on 7 subjects

Results

  • The average age in both MCI groups was roughly 73 years (see paper for exact figures)
  • There were significant differences between the two MCI groups on a number of neuropsychological tests which might be expected. I wasn’t clear on whether there was an adjustment for multiple comparisons
  • 13 aMCI subjects went on to develop dementia
  • Compared to the controls both MCI groups showed hypometabolism in the posterior Cingulate gyrus
  • Compared to the single non-amnestic executive dysfunction MCI group the Amnestic MCI group had hypometabolism in the Medial Temporal Lobe
  • I couldn’t see the data on the control group (I might have just missed this)

Discussion

The researchers draw some interesting conclusions. They caution on the small sample size while noting that the posterior cingulate gyrus hypometabolism might be a result of a disconnection from limbic areas since it is not usually affected by Alzheimer’s pathology in the early stages of the disease while also adding that a number of the subjects with aMCI went on to develop AD. They suggest that the executive dysfunction group exhibiting hypometabolism in the PCG might mean that this area is also disconnected with this pathology.

It will be interesting to see if these findings with the posterior cingulate gyrus are replicated with larger sample sizes as this might suggest a potentially important location for pathology in both executive and amnestic MCI as well as associated pathologies such as Alzheimer’s Disease.

Acknowledgements

Public Domain PET image by Jans Langner (see here).

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