J Neurol Neurosurg Psychiatry 82:58-66 doi:10.1136/jnnp.2009.199935
  • Research paper

Regional brain atrophy and functional disconnection across Alzheimer's disease evolution

  1. M Bozzali2
  1. 1Marbilab, Enrico Fermi Centre, Rome, Italy
  2. 2Neuroimaging Laboratory, Santa Lucia Foundation, IRCCS, Rome, Italy
  3. 3Department of Clinical and Behavioral Neurology, Santa Lucia Foundation, IRCCS, Rome, Italy
  4. 4Department of Neuroscience, University of Rome ‘Tor Vergata', Rome, Italy
  1. Correspondence to Dr M Bozzali, Neuroimaging Laboratory, Santa Lucia Foundation, IRCCS, Via Ardeatina 306, Rome 00179, Italy; m.bozzali{at}
  • Received 17 November 2009
  • Revised 13 April 2010
  • Accepted 15 April 2010
  • Published Online First 16 July 2010


Objective To assess the contribution of regional grey matter (GM) atrophy and functional disconnection in determining the level of cognitive decline in patients with Alzheimer's disease (AD) at different clinical stages.

Methods Ten patients with amnesic mild cognitive impairment (a-MCI), 11 patients with probable AD and 10 healthy controls were recruited. T1 volumes were obtained from each subject and postprocessed according to an optimised voxel based morphometry protocol. Resting state functional MRI data were also collected from the same individuals and analysed to produce connectivity maps after identification of the default mode network (DMN) by independent component analysis.

Results Compared with healthy controls, both AD and a-MCI patients showed a similar regional pattern of brain disconnection between the posterior cingulate cortex (PCC) and the medial prefrontal cortex and the rest of the brain. Conversely, the distribution of GM atrophy was significantly more restricted in a-MCI than in AD patients. Interestingly, the PCC showed reduced connectivity in a-MCI patients in the absence of GM atrophy, which was, in contrast, detectable at the stage of fully developed AD.

Conclusions This study indicates that disconnection precedes GM atrophy in the PCC, which is a critical area of the DMN, and supports the hypothesis that GM atrophy in specific regions of AD brains likely reflects a long term effect of brain disconnection. In this context, our study indicates that GM atrophy in PCC accompanies the conversion from MCI to AD.


  • Funding This project was supported by grants from the Italian Ministry of Health and the Italian Ministry of University and Research.

  • Competing interests None.

  • Ethics approval The study was conducted with the approval of the ethics committee of Santa Lucia Foundation, IRCCS.

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

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