Difference of the hippocampal and white matter microalterations in MCI patients according to the severity of subcortical vascular changes: Neuropsychological correlates of diffusion tensor imaging
Introduction
Most imaging studies that are concerned with mild cognitive impairment (MCI) have focused on gray matter alterations such as hippocampal atrophy and diffuse cortical atrophy [1], [2], [3], [4], [5], [6], [7], [8]. However, many MCI patients show white matter changes on magnetic resonance imaging (MRI) [9]. MCI may be a transitional state between normal aging and dementia, and it is a clinically and etiologically heterogenous syndrome that can even evolve into vascular dementia (VaD) other than degenerative dementia such as primarily Alzheimer's disease (AD) [10], [11]. Among a variety of conditions, individuals with MCI can be divided into two identifiable separate subgroups: vascular MCI and non-vascular, degenerative MCI. On routine MRI, vascular MCI reveals many vascular lesions and these lesions are thought to lead to VaD. However, vascular lesions revealed by routine MRI are very common in elderly people. The lesions themselves are not enough to diagnose vascular MCI and VaD [12], [13]. The other group, which is thought to include largely amnestic MCI, is considered to be prodromal for Alzheimer's disease, and this group shows medial temporal atrophy. Besides being seen in VaD, these white matter changes have also been observed in AD [14], [15], which is generally considered to affect the gray matter. Pathologically, several white matter abnormalities have been observed: rarefaction, loss of axons and oligodendrocytes and reactive astrocytosis, although the pathogenetic mechanisms of these white matter damages are still unclear. First, the white matter changes in AD may be indicative of anterograde Wallerian degeneration especially in regions close to the cortical areas with the greatest pathological burden [16], [17]. Second, there may be white matter rarefaction with axonal damage and gliosis [17]. This type of change, which may be vascular or ischemic in origin, is diffuse and it does not follow the regional extension of the pathologically involved gray matter. Third, it has recently been suggested that myelin breakdown is an important component of the disease process in AD [18], [19], [20].
Diffusion tensor imaging (DTI) is a recently developed MRI technique, and this allows determining the orientation and integrity of white matter tracts by virtue of its ability to image water diffusion characteristics [21], [22], [23]. DTI detects brain white matter changes with greater sensitivity than the prior techniques. In the normal white matter, water molecules move relatively freely in the direction parallel to the nerve fiber tracts, but their movements are restricted across the tracts, which causes diffusion anisotropy of the white matter. The mean diffusivity (MD) and fractional anisotropy (FA) are the most widely used among the DTI parameters. MD is the average value of the diffusion coefficients over that voxel and it represents the magnitude of diffusion in a voxel. FA is the measure of directionally restricted diffusion. In line with above the observations of white matter damage, DTI studies have also shown microscopic white matter changes in patients with AD and MCI that are undetected when using conventional MRI. The DTI changes in AD patients have been described in the frontal, temporal and parietal white matter regions [24], [25], [26], and diffusively distributed changes including the temporal area have also been reported in MCI patients [27], [28], [29], [30], [31], [32]. However, the precise topography and extent of these white matter changes currently remain debated, and it has been difficult to correlate the clinical impact of these white matter changes with using only conventional MRI.
The aim of this study was to compare the microstructural changes of the hippocampal area and the various white matter areas in patients with MCI according to the severity of subcortical vascular changes that are seen on conventional MRI, and we wanted to correlate the neuropsychological findings with these regional, microstructural changes. This technique allows us to assess the clinical impact of the white matter changes found on conventional MRI in patients with MCI, and to identify the distribution of the microstructural white matter changes in patients with MCI so as to improve our understanding of this disease process.
Section snippets
Subjects
The diagnosis of general MCI was based on the consensus criteria of the International Working Group on MCI [33]. The patients did not fulfill the diagnostic criteria for dementia by the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) [34]. Their basic functional activities of daily living were mainly preserved. However, they had evidence of cognitive decline, as measured either by self- and/or informant reports in conjunction with deficits on objective cognitive
Results
The age and K-MMSE score were not different between the nvMCI and vMCI patients. However, for the vMCI patients, the scores for the PVHI (6.16 ± 2.65) and DWHI (3.42 ± 1.57) were higher than those (PVHI: 3.95 ± 2.11 and DWHI: 0.76 ± 1.26) for the nvMCI patients (all p < 0.001). The HIS and the number of lacunes were also higher for the vMCI subgroup (6.16 ± 2.65 and 3.79 ± 1.99, respectively) compared to the nvMCI subgroup (2.19 ± 1.94 and 0.95 ± 1.50, respectively) (all p < 0.001) (Table 1). The patients with
Discussion
As a result of neurodegeneration, cell loss leads to increased diffusion of water molecules that can be quantified by the elevated MD values. In contrast, those processes that lead to disturbances of white matter homogeneity can be detected by the decreased FA values, which indicate violation of the white matter integrity in the brain. In early AD, neuronal degeneration is common in the hippocampal and entorhinal areas, and this then expands into the temporal and parietal association cortices.
Acknowledgements
This study was supported by a grant of the Korea Health 21 R&D Project, Ministry of Health & Welfare, Republic of Korea (A050079).
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