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

Abstract

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.

Microstructural integrity of the cingulum is related to verbal memory performance in elderly with cerebral small vessel disease

“…Our finding is in line with the results of previous studies in patients with MCI or AD showing that loss of structural integrity of the cingulum is associated to impaired verbal memory performance (Bozzali et al, 2012;Fellgiebel et al, 2005;Kantarci et al, 2011;Mielke et al, 2009;Sexton et al, 2010).…”

White Matter Damage Along the Uncinate Fasciculus Contributes to Cognitive Decline in AD and DLB

“…In AD, changes in WM FA are traditionally interpreted as reflecting demyelination (i.e., reduction in axonal diameter) and Wallerian degeneration (i.e., reduction in axonal density) as secondary to damage to cortical neurons [40,41]. The typical pattern of pathophysiological events in AD includes a prominent degeneration of neurons located within the medial temporal lobes structures, followed by a spread of pathology to the whole association cortex [42,43]. This results in the progressive damage of all association tracts, with a relative preservation of projective systems (i.e., sensory and motor pathways) until advanced disease stages [44].…”

BootGraph: Probabilistic fiber tractography using bootstrap algorithms and graph theory

“…Nevertheless, it is important to provide enhanced tractography algorithms to neuroscientists still using DTI. For example, ongoing studies in the field of aging and neurodegenerative diseases, such as mild cognitive impairment or dementia including Alzheimer's disease, are based on DTI (Bozzali et al, 2012;Douaud et al, 2011;Lo et al, 2010). Thereby, the BootGraph would be very well suited to reconstruct virtual fibers and connectivity maps due to its high repeatability.…”