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Diffusion imaging is a promising marker of microstructural damage in neurodegenerative disorders, but interpretation of its relationship with underlying neuropathology can be complex. Here, we examined both volumetric and brain microstructure abnormalities in 13 amnestic patients with mild cognitive impairment (MCI), who progressed to probable Alzheimer's disease (AD) no earlier than 2 years after baseline scanning, in order to focus on early, and hence more sensitive, imaging markers. We compared them to 22 stable amnestic MCI patients with similar cognitive performance and episodic memory impairment but who did not show progression of symptoms for at least 3 years. Significant group differences were mainly found in the volume and microstructure of the left hippocampus, while white matter group differences were also found in the body of the fornix, left fimbria, and superior longitudinal fasciculus (SLF). Diffusion index abnormalities in the SLF were the sign of a subtle microstructural injury not detected by standard atrophy measures in the corresponding gray matter regions. The microstructural measure obtained in the left hippocampus using diffusion imaging showed the most substantial differences between the two groups and was the best single predictor of future progression to AD. An optimal prediction model (91% accuracy, 85% sensitivity, 96% specificity) was obtained by combining MRI measures and CSF protein biomarkers. These results highlight the benefit of using the information of brain microstructural damage, in addition to traditional gray matter volume, to detect early, subtle abnormalities in MCI prior to clinical progression to probable AD and, in combination with CSF markers, to accurately predict such progression.

Original publication

DOI

10.1523/JNEUROSCI.4437-12.2013

Type

Journal article

Journal

The Journal of neuroscience : the official journal of the Society for Neuroscience

Publication Date

01/2013

Volume

33

Pages

2147 - 2155

Addresses

Functional MRI of the Brain (FMRIB) Centre, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford OX3 9DU, United Kingdom. douaud@fmrib.ox.ac.uk

Keywords

Brain, Humans, Alzheimer Disease, Amnesia, Atrophy, Disease Progression, Peptide Fragments, tau Proteins, Magnetic Resonance Imaging, Sensitivity and Specificity, Predictive Value of Tests, Neuropsychological Tests, Phosphorylation, Image Processing, Computer-Assisted, Aged, Middle Aged, Female, Male, Amyloid beta-Peptides, Cognitive Dysfunction