White matter damage in Alzheimer's disease assessed in vivo using diffusion tensor magnetic resonance imaging

Objective: To investigate the extent and the nature of white matter tissue damage of patients with Alzheimer's disease using diffusion tensor magnetic resonance imaging (DT-MRI). Background: Although Alzheimer's disease pathology mainly affects cortical grey matter, previous pathological and MRI studies showed that also the brain white matter of patients is damaged. However, the nature of Alzheimer's disease associated white matter damage is still unclear. Methods: Conventional and DT-MRI scans were obtained from16 patients with Alzheimer's disease and 10 sex and age matched healthy volunteers. The mean diffusivity (D̅), fractional anisotropy (FA), and inter-voxel coherence (C) of several white matter regions were measured. Results: D̅ was higher and FA lower in the corpus callosum, as well as in the white matter of the frontal, temporal, and parietal lobes from patients with Alzheimer's disease than in the corresponding regions from healthy controls. D̅ and FA of the white matter of the occipital lobe and internal capsule were not different between patients and controls. C values were also not different between patients and controls for any of the regions studied. Strong correlations were found between the mini mental state examination score and the average overall white matter D̅ (r=0.92, p<0.001) and FA (r=0.78; p<0.001). Conclusions: White matter changes in patients with Alzheimer's disease are likely to be secondary to wallerian degeneration of fibre tracts due to neuronal loss in cortical associative areas.

[1]  S. Folstein,et al.  "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. , 1975, Journal of psychiatric research.

[2]  M. Folstein,et al.  Clinical diagnosis of Alzheimer's disease , 1984, Neurology.

[3]  G K Wilcock,et al.  Anatomical correlates of the distribution of the pathological changes in the neocortex in Alzheimer disease. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[4]  J. Morrison,et al.  Quantitative morphology and regional and laminar distributions of senile plaques in Alzheimer's disease , 1985, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[5]  A. Brun,et al.  A white matter disorder in dementia of the Alzheimer type: A pathoanatomical study , 1986, Annals of neurology.

[6]  M J Campbell,et al.  Laminar and regional distributions of neurofibrillary tangles and neuritic plaques in Alzheimer's disease: a quantitative study of visual and auditory cortices , 1987, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[7]  J Aharon-Peretz,et al.  Vascular dementia and dementia of the Alzheimer type. Cognition, ventricular size, and leuko-araiosis. , 1988, Archives of neurology.

[8]  B C Bowen,et al.  MR signal abnormalities in memory disorder and dementia. , 1990, AJNR. American journal of neuroradiology.

[9]  A. Delacourte,et al.  Could Wallerian degeneration contribute to "leuko-araiosis" in subjects free of any vascular disorder? , 1991, Journal of neurology, neurosurgery, and psychiatry.

[10]  J. Mazziotta,et al.  Automated image registration , 1993 .

[11]  Modifications of the rate matrix required for the quantitative analysis of NOESY spectra of proteins. , 1994, Journal of magnetic resonance. Series B.

[12]  P. Basser,et al.  Estimation of the effective self-diffusion tensor from the NMR spin echo. , 1994, Journal of magnetic resonance. Series B.

[13]  P. Basser,et al.  MR diffusion tensor spectroscopy and imaging. , 1994, Biophysical journal.

[14]  Nick C Fox,et al.  Visualisation and quantification of rates of atrophy in Alzheimer's disease , 1996, The Lancet.

[15]  P. Basser,et al.  Toward a quantitative assessment of diffusion anisotropy , 1996, Magnetic resonance in medicine.

[16]  N. Lundbom,et al.  Cortical and subcortical chemical pathology in Alzheimer's disease as assessed by multislice proton magnetic resonance spectroscopic imaging , 1996, Neurology.

[17]  E Magni,et al.  Mini‐Mental State Examination: a normative study in Italian elderly population , 1996, European journal of neurology.

[18]  G. Fein,et al.  Regional gray and white matter metabolite differences in subjects with AD, with subcortical ischemic vascular dementia, and elderly controls with 1H magnetic resonance spectroscopic imaging. , 1996, Archives of neurology.

[19]  J A Yesavage,et al.  Selective cortical and hippocampal volume correlates of Mattis Dementia Rating Scale in Alzheimer disease. , 1997, Archives of neurology.

[20]  K M Heilman,et al.  Atrophy of the hippocampus, parietal cortex, and insula in Alzheimer's disease: a volumetric magnetic resonance imaging study. , 1997, Neuropsychiatry, neuropsychology, and behavioral neurology.

[21]  M Takasaki,et al.  Increased water diffusion in cerebral white matter in Alzheimer's disease. , 1997, Gerontology.

[22]  D L Hill,et al.  Automated three-dimensional registration of magnetic resonance and positron emission tomography brain images by multiresolution optimization of voxel similarity measures. , 1997, Medical physics.

[23]  Scott T. Grafton,et al.  Automated image registration: I. General methods and intrasubject, intramodality validation. , 1998, Journal of computer assisted tomography.

[24]  B Horwitz,et al.  Corpus callosum atrophy is a possible indicator of region- and cell type-specific neuronal degeneration in Alzheimer disease: a magnetic resonance imaging analysis. , 1998, Archives of neurology.

[25]  Hirofumi Sakurai,et al.  Diffusion-weighted and magnetization transfer imaging of the corpus callosum in Alzheimer’s disease , 1999, Journal of the Neurological Sciences.

[26]  M. Horsfield,et al.  Optimal strategies for measuring diffusion in anisotropic systems by magnetic resonance imaging , 1999, Magnetic resonance in medicine.

[27]  R. Edelman,et al.  Diffusion-Weighted Magnetic Resonance Imaging in Alzheimer’s Disease , 1999, Dementia and Geriatric Cognitive Disorders.

[28]  K. Lim,et al.  Age‐related decline in brain white matter anisotropy measured with spatially corrected echo‐planar diffusion tensor imaging , 2000, Magnetic resonance in medicine.

[29]  S. Rose,et al.  Loss of connectivity in Alzheimer's disease: an evaluation of white matter tract integrity with colour coded MR diffusion tensor imaging , 2000, Journal of neurology, neurosurgery, and psychiatry.

[30]  Marco Rovaris,et al.  Sensitivity and reproducibility of volume change measurements of different brain portions on magnetic resonance imaging in patients with multiple sclerosis , 2000, Journal of Neurology.

[31]  C. Jack,et al.  Mild cognitive impairment and Alzheimer disease: regional diffusivity of water. , 2001, Radiology.

[32]  G. Scotti,et al.  Quantification of tissue damage in AD using diffusion tensor and magnetization transfer MRI , 2001, Neurology.

[33]  R. Floris,et al.  Diffusion and perfusion MR imaging in cases of Alzheimer's disease: correlations with cortical atrophy and lesion load. , 2001, AJNR. American journal of neuroradiology.

[34]  G. Comi,et al.  Intra-voxel and inter-voxel coherence in patients with multiple sclerosis assessed using diffusion tensor MRI , 2002, Journal of Neurology.

[35]  Patrick Vermersch,et al.  White matter magnetic resonance imaging hyperintensity in Alzheimer's disease: correlations with corpus callosum atrophy , 1996, Journal of Neurology.