The Uncinate Fasciculus as a Predictor of Conversion from aMCI to Alzheimer Disease

BACKGROUND AND PURPOSE Amnestic mild cognitive impairment (aMCI) is associated with the risk of Alzheimer’s disease (AD). Although diffusion tensor imaging (DTI)-based fractional anisotropy (FA) analyses have been used to evaluate white matter changes in patients with AD, it remains unknown how FA values change during the conversion of aMCI to AD. This study aimed to elucidate the prediction of conversion to AD and cognitive decline by FA values in uncinate fasciculus (UF) in aMCI patients. METHODS Twenty-two aMCI patients were evaluated for their UF FA values by a tractography-based method with DTI and cognitive performance by neuropsychological testing at baseline and after a 3-year follow-up. Patients were divided into 2 groups after 3 years: 14 aMCI-stable (aMCI-aMCI) and 8 AD-conversion (aMCI-AD). RESULTS At baseline, FA values in the right UF were significantly lower in the aMCI-AD group than in the aMCI-aMCI group. These values also showed significant correlations with the neuropsychological scores after a 3-year follow-up. The area under the curve of the receiver operation characteristic curves for predicting conversion to AD was .813. CONCLUSION These results suggested that FA values in the right UF might be an effective predictor of conversion of aMCI to AD. Introduction Mild cognitive impairment (MCI) has been described as an intermediate clinical condition that is thought to be a transitional stage between normal aging and Alzheimer’s disease (AD).1 MCI is classified into 2 subtypes: amnestic MCI (aMCI) and nonamnestic MCI.1 Because patients with aMCI have a high risk of developing AD with a conversion rate of 10-15% per year,2 aMCI is considered a clinical state that may be critical for the detection of early-stage AD and the prediction of conversion to AD. Biological markers, which are used as predictors of the conversion of aMCI to AD, contribute to diagnostic accuracy and add prognostic value. Several recent studies have elucidated the detection of AD with structural and functional neuroimaging techniques. A voxel-based morphometry (VBM) magnetic resonance imaging (MRI) study has shown that the gray matter (GM) density in the posterior association cortex is significantly decreased in patients with AD compared with healthy controls.3 Longitudinal MRI studies have shown that the volumes of other brain areas, such as the hippocampus, entorhinal cortex, and temporal lobe, are decreased more in patients with AD than in those with MCI.4 VBM is a promising technique for evaluating brain atrophy/damage related to conversion to AD, but it remains difficult to predict conversion only by GM atrophy. Therefore, some recent studies have focused on white matter (WM) atrophy as an alternative detector of early-stage AD. WM changes can be evaluated noninvasively by diffusion tensor imaging (DTI).5 DTI is a technique used to investigate WM microstructure based on water diffusion. DTI-derived parameters, such as fractional anisotropy (FA), can be used to evaluate the integrity of fiber tracts. Several investigations conducted with DTI have reported decreased FA values of the temporal and frontal WM in patients with MCI.6 In the conversion of healthy subjects to AD, changes in FA values have been observed in the frontal, parietal, and subcortical WM regions.7 Apart from the frontal and temporal WM, another WM region that may be potentially affected in MCI and AD is the uncinate fasciculus (UF).8 UF is a WM tract connecting Copyright ◦C 2014 by the American Society of Neuroimaging 1 the anterior part of the temporal lobe with the frontal lobe and is associated with episodic memory.9 Although region of interest (ROI)or voxel-based analyses are common methods because they are relatively easy to perform, ROIand voxelbased analyses can include various unnecessary fibers.10 Therefore, Taoka et al. have used a tractography-based method with DTI to avoid the contamination of fibers other than UF; they have indicated that FA values in UF are significantly lower in patients with AD than in healthy controls.11 Our previous study used a tractography-based method and reported that FA values in the left UF were significantly lower in patients with aMCI than in healthy controls.12 However, it is still unclear how FA values in UF change in patients with aMCI during conversion to AD. The aim of this study was to evaluate the temporal changes in FA values in UF in aMCI patients with or without conversion to AD by a tractography-based method using DTI.

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