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Grey matter atrophy of basal forebrain and hippocampus in mild cognitive impairment
  1. Haobo Zhang1,
  2. Julian N Trollor1,2,
  3. Wei Wen1,3,
  4. Wanlin Zhu1,
  5. John D Crawford1,
  6. Nicole A Kochan1,3,
  7. Melissa J Slavin1,
  8. Henry Brodaty4,5,
  9. Simone Reppermund1,
  10. Kristan Kang1,
  11. Karen A Mather1,
  12. Perminder S Sachdev1,3
  1. 1Brain and Ageing Research Program, School of Psychiatry, University of New South Wales, Sydney, Australia
  2. 2Department of Developmental Disability Neuropsychiatry, School of Psychiatry, University of New South Wales, Sydney, Australia
  3. 3Neuropsychiatric Institute, Prince of Wales Hospital, Randwick, New South Wales, Australia
  4. 4Academic Department for Old Age Psychiatry, Prince of Wales Hospital, Randwick, New South Wales, Australia
  5. 5Dementia Collaborative Research Centre, School of Psychiatry, University of New South Wales, Sydney, Australia
  1. Correspondence to Professor J Trollor, Department of Developmental Disability Neuropsychiatry, Botany St Houses, University of New South Wales, NSW 2052, Australia; j.trollor{at}


The basal forebrain area (BFA) is closely connected to the hippocampus by virtue of cholinergic neuronal projections. Structural neuroimaging studies have shown reduced volumes of both structures in Alzheimer's disease and its prodromal stage mild cognitive impairment (MCI), but generally not in the same investigation. By combining voxel based morphometry and region of interest methods, we measured the grey matter (GM) volumes of the two brain regions with the goal of elucidating their contributions to MCI and its two subtypes (amnestic MCI and non-amnestic MCI) in an elderly epidemiological sample. The results replicated previous findings that the atrophies of both brain regions were associated with an increased likelihood of MCI and its two subtypes. However, in a regression model for the prediction of MCI with GM volumes for both regions used as predictors, only hippocampal atrophy remained significant. Two possible interpretations for this pattern of results were discussed. One is that the observed correlation between BFA atrophy and MCI is spurious and due to the hippocampal atrophy correlated with both. Alternatively, our observation is consistent with the possibility that BFA atrophy has a causal effect on MCI, which is mediated via its influence on hippocampal atrophy. Furthermore, we found that the left hippocampal atrophy had a stronger effect than the right hippocampus and bilateral BFA in the prediction of amnestic MCI occurrence when the four unilateral areas were entered into one regression model. In addition, a slight but statistically significant difference was found in the left hippocampal volume between APOE ε4 allele carriers and non-carriers, consistent with prior studies.

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  • See Editorial commentary, p 475

  • Linked article 230284.

  • Funding The current study was supported by the National Health and Medical Research Council of Australia Program Grant (ID 350833) and Project Grant (ID 510175), as well as an Australian Research Council Discovery Grant (ID DP0774213). Genetic Repositories Australia is supported by an Enabling facility supported by the NHMRC Grant 401184.

  • Competing interests None.

  • Ethics approval The study was approved by the ethics committee of the University of New South Wales.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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