Diffusion tensor changes in patients with amnesic mild cognitive impairment and various dementias
Introduction
Pathological characteristics of Alzheimer's disease (AD) are conventionally noted as cortical involvement with neurofibrillary tangles and senile plaques (Arnold et al., 1991). However, white matter damage and its contribution to clinical manifestations in patients with dementia have been increasingly recognized. Decline in intelligence is associated with changes in white matter volume (Garde et al., 2005). White matter lesions may be predictors of neuropsychological deficits in post-stroke patients (Jokinen et al., 2005). AD patients with white matter changes at baseline show a rapid decline of cognitive function (de Leeuw et al., 2005).
Frontotemporal dementia (FTD) is characterized by early language dysfunction or personality change. Two types of pathological features can be found. In some patients, there is microvacuolation of upper cortical layers, and in others, there is gliosis of cortical and subcortical white matter (Neary et al., 2005). The topography of the pathological changes corresponds to the cognitive domains involved, being restricted to frontal and temporal regions (Rosen et al., 2002). A recent diffusion tensor imaging study showed significant white matter damage in the early phase of FTD (Borroni et al., 2007).
Vascular dementia includes a heterogeneous group of patients presenting cognitive impairment from various cerebrovascular lesions. Impairments in cognitive function are related to the location and extent of the vascular insult (Gold et al., 2005). Subcortical ischemic vascular dementia (SIVD) is a subtype of vascular dementia with small lacunes in the basal ganglia, thalamus, or subcortical white matter regions. White matter disruption measured by diffusion tensor imaging was correlated with executive dysfunction in patients with SIVD (O’Sullivan et al., 2004).
Both AD and FTD have pathological features of cortical neuron loss and have been considered to be primary degenerative processes in the neocortex (Pearson et al., 1985, Rogers and Morrison, 1985). However, white matter involvement was invariably found in either group of patients. It could be secondary to the degeneration of cortical neurons or due to primary pathology occurring in the white matter regions. On the other hand, SIVD has primary white matter lesions from ischemic injury.
Current magnetic resonance imaging (MRI) technology has made possible the in vivo assessment of white matter integrity by using diffusion tensor imaging (DTI). In normal white matter tissue, axons are regularly aligned and well myelinated. Thus, the random diffusion of water molecules is restricted to a predominant diffusion orientation. Fractional anisotropy (FA) estimates this preference and is used to assess fiber tract integrity and alignment so that normal white matter tissue shows high FA (Pierpaoli et al., 1996). Mean diffusivity (MD) is a measure of the average motion of water molecules, which is independent of tissue directionality. Normal white matter tissue has low MD (Basser and Pierpaoli, 1996). Diseases that disrupt the directionality of fiber tracts and the tissue integrity of brain white matter reduce FA and increase MD (Englund et al., 2004).
A number of DTI studies have examined AD (Bozzali et al., 2002, Choi et al., 2005, Naggara et al., 2006), mild cognitive impairment (Fellgiebel et al., 2006, Medina et al., 2006) and cognitive declines associated with chronic vascular disease or leukoaraosis (O'Sullivan et al., 2004). There are few studies, however, on non-AD forms of dementia (Yoshiura et al., 2006). Furthermore, it is not feasible to carry out cross-study comparisons across different types of dementia because published studies have been performed with variable platforms using different methods of analysis such as region of interest (ROI), histogram, or voxel-by-voxel approaches (Bozzali and Cherubini, 2007). Thus, we investigated white matter integrity with DTI in patients with amnesic mild cognitive impairment (MCI), AD, vascular dementia (VaD), and frontotemporal dementia (FTD). The aim was to explore patterns specific or common to different types of dementia, and to understand more about the white matter pathology of dementia on an image platform with a uniform analysis method.
Section snippets
Patients
We examined 10 patients with MCI, 30 with AD, 18 with SIVD, 7 with FTD and 20 control subjects (Table 1). All subjects received a comprehensive clinical examination including medical history, physical and neurological examination, laboratory investigation and brain MRI study. Patients with MCI and various dementias were evaluated with the Mini-Mental State Examination, the Clinical Dementia Rating scale (CDR), the Behavioral Pathology in Alzheimer's Disease Rating Scale, Lawton's Instrumental
Results
There was a significant group effect of age (F = 5.4, P < 0.01). A post hoc test showed that patients with FTD were younger than patients with AD and SIVD (both P < 0.05). However, the pairwise post hoc test showed no significant age effect between control subjects and patients with MCI or other dementias (all P > 0.05). There was no gender effect between groups (Pearson Chi-square = 4.82, P > 0.1). The severity of dementia was about equivalent (χ2 = 0.171, P > 0.5) as assessed by the Clinical Dementia Rating
Discussion
Previous DTI studies demonstrated associations of pathology in brain white matter with progression of cognitive deficits (de Leeuw et al., 2005, Fellgiebel et al., 2006, Yoshiura et al., 2002). Our study using DTI showed patterns of white matter abnormalities in patients with different types of dementia.
AD patients had diffusion tensor changes in both the anterior and posterior cerebral white matter, including the genu and the splenium of the corpus callosum. The splenium of the corpus callosum
Acknowledgement
The study was supported in part by a grant from National Taiwan University Hospital (NTUH 93A16-3) and in part by a grant from the Taiwan National Science Council (NSC 95-2314-B-144).
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Reduced fractional anisotropy of the genu of the corpus callosum as a cerebrovascular disease marker and predictor of longitudinal cognition in MCI
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Dr. C.C. Lin is an equal first author.