Using diffusion tensor imaging and mixed-effects models to investigate primary and secondary white matter degeneration in Alzheimer’s disease and mild cognitive impairment
JAD. 2011-10-04; 26(4): 667-682
DOI: 10.3233/JAD-2011-110137
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1. J Alzheimers Dis. 2011;26(4):667-82. doi: 10.3233/JAD-2011-110137.
Using diffusion tensor imaging and mixed-effects models to investigate primary
and secondary white matter degeneration in Alzheimer’s disease and mild cognitive
impairment.
O’Dwyer L(1), Lamberton F, Bokde AL, Ewers M, Faluyi YO, Tanner C, Mazoyer B,
O’Neill D, Bartley M, Collins DR, Coughlan T, Prvulovic D, Hampel H.
Author information:
(1)Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, Goethe
University, Frankfurt, Germany.
White matter (WM) degeneration in Alzheimer’s disease (AD) and mild cognitive
impairment (MCI) may be a key indicator of early damage in AD. Here, we analyzed
WM diffusion tensor data using Tract-Based Spatial Statistics in conjunction with
mixed-effects models. Four indices of diffusion were assessed in 61 healthy
control, 19 non-amnestic MCIs, 14 amnestic MCIs, and 9 AD patients. The aim of
the study was to use advanced mixed-effects models to investigate the
retrogenesis hypothesis of AD, which suggests that tracts that are late to
myelinate in ontogenetic development are the earliest to be affected in AD. Our
results show that a number of late-myelinating pathways, including the
parahippocampal region and the inferior longitudinal fasciculus, were
predominantly affected by changes in WM volume. Conversely, early-myelinating
pathways were found to be affected by a combination of both WM and gray matter
(GM) atrophy. A model of the entire WM structure of the brain returned GM models
for two indices of diffusion, suggesting that more complex regional landscapes of
diffusion lie hidden beneath a global analysis of the entire brain. Our results
warn against an explanation of white matter damage that points simply to one of
two mechanisms: secondary degeneration or direct damage of myelin. We suggest
that tracts may be affected by both mechanisms, with the balance depending on
whether tracts are early or late-myelinating. A greater understanding of the
pattern of WM changes in AD may prove useful for the early detection of AD.
DOI: 10.3233/JAD-2011-110137
PMID: 21694456 [Indexed for MEDLINE]