Disruption of limbic white matter pathways in mild cognitive impairment and Alzheimer's disease: a DTI/FDG-PET study

Hum Brain Mapp. 2012 Aug;33(8):1792-802. doi: 10.1002/hbm.21320. Epub 2011 Jun 14.


Background: Alzheimer's disease (AD) and mild cognitive impairment (MCI) affect the limbic system, causing medial temporal lobe (MTL) atrophy and posterior cingulate cortex (PCC) hypometabolism. Additionally, diffusion tensor imaging (DTI) studies have demonstrated that MCI and AD involve alterations in cerebral white matter (WM) integrity.

Objectives: To test if (1) patients with MCI and AD exhibit decreases in the integrity of limbic WM pathways; (2) disconnection between PCC and MTL, manifested as disruption of the cingulum bundle, contributes to PCC hypometabolism during incipient AD.

Methods: We measured fractional anisotropy (FA) and volume of the fornix and cingulum using DTI in 23 individuals with MCI, 21 with mild-to-moderate AD, and 16 normal control (NC) subjects. We also measured PCC metabolism using (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) in AD and MCI patients.

Results: Fornix FA and volume were reduced in MCI and AD to a similar extent. Descending cingulum FA was reduced in AD while volume was reduced in MCI and even more so in AD. Both FA and volume of the fornix and descending cingulum reliably discriminated between NC and AD. Fornix FA and descending cingulum volume also reliably discriminated between NC and MCI. Only descending cingulum volume reliably discriminated between MCI and AD. In the combined MCI-AD cohort, PCC metabolism directly correlated with both FA and volume of the descending cingulum.

Conclusions: Disruption of limbic WM pathways is evident during both MCI and AD. Disconnection of the PCC from MTL at the cingulum bundle contributes to PCC hypometabolism during incipient AD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease / pathology*
  • Brain Mapping*
  • Cognitive Dysfunction / pathology*
  • Diffusion Tensor Imaging
  • Female
  • Humans
  • Image Interpretation, Computer-Assisted
  • Male
  • Nerve Fibers, Myelinated / pathology*
  • Neural Pathways / pathology*
  • Positron-Emission Tomography