Damage to the cingulum contributes to alzheimer's disease pathophysiology by deafferentation mechanism

Marco Bozzali, Giovanni Giulietti, Barbara Basile, Laura Serra, Barbara Spanò, Roberta Perri, Franco Giubilei, Camillo Marra, Carlo Caltagirone, Mara Cercignani

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This study investigates the differential contribution of gray matter (GM) atrophy and deafferentation through white matter (WM) damage in the clinical progression of Alzheimer's disease (AD). Thirty-one patients with probable AD, 23 with amnestic mild cognitive impairment (a-MCI), and 14 healthy subjects underwent MRI scanning at 3T. Voxel-based morphometry was used to assess regional GM atrophy in AD and a-MCI patients. Diffusion tensor-MRI tractography was used to reconstruct the cingulum bilaterally, and to quantify, voxel-by-voxel, its fractional anisotropy (FA) and mean diffusivity (MD) (measures of microscopic WM integrity). Atrophy of the cinguli was also assessed by means of jacobian determinants (JD) of local transformations. In AD patients, four clusters of reduced GM were found nearby the cinguli, in the posterior (PCC) and anterior cingulate cortex, and in the hippocampal/parahippocampal areas. Widespread areas of reduced FA and increased MD were found in the cinguli of both, AD and a-MCI patients. A region of macroscopic atrophy was detectable in AD patients only. Strong associations were found between local GM densities in the four identified clusters, and measures of micro- and (to a lesser extent) macroscopic damage of patients' cinguli. Linear regression analyses revealed that MD in the cinguli predicts patients' measures of episodic memory in combination with GM density of hippocampal/parahippocampal areas, and measures of global cognition in combination with GM density of the PCC. This study indicates that brain deafferentation though the cingulum is likely to play a remarkable role in progressive development of cognitive impairment in AD.

Original languageEnglish
Pages (from-to)1295-1308
Number of pages14
JournalHuman Brain Mapping
Issue number6
Publication statusPublished - Jun 2012


  • AD
  • Cingulum
  • Deafferentation
  • DT-MRI
  • MCI
  • Tractography
  • VBM

ASJC Scopus subject areas

  • Clinical Neurology
  • Anatomy
  • Neurology
  • Radiology Nuclear Medicine and imaging
  • Radiological and Ultrasound Technology


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