Research Article: Effectiveness of diffusion tensor imaging in differentiating early-stage subcortical ischemic vascular disease, Alzheimer’s disease and normal ageing

Date Published: April 7, 2017

Publisher: Public Library of Science

Author(s): Min-Chien Tu, Chung-Ping Lo, Ching-Feng Huang, Yen-Hsuan Hsu, Wen-Hui Huang, Jie Fu Deng, Yung-Chuan Lee, Linda Chao.


To describe and compare diffusion tensor imaging (DTI) parameters between patients with subcortical ischemic vascular disease (SIVD) and Alzheimer’s disease (AD) diagnosed using structuralized neuropsychiatric assessments, and investigate potential neuronal substrates related to cognitive performance.

Thirty-five patients with SIVD, 40 patients with AD, and 33 cognitively normal control (NC) subjects matched by age and education level were consecutively recruited and underwent cognitive function assessments and DTI examinations. Comparisons among these three subgroups with regards to cognitive performance and DTI parameters including fractional anisotropy (FA) and mean diffusivity (MD) values were performed. Partial correlation analysis after controlling for age and education was used to evaluate associations between cognitive performance and DTI parameters.

With regards to cognitive performance, the patients with SIVD had lower total scores in frontal assessment battery (FAB) compared to those with AD (p < 0.05) in the context of comparable Mini-Mental Status Examination and Cognitive Abilities Screening Instrument scores. With regards to DTI parameters, there were more regions of significant differences in FA among these three subgroups compared with MD. Compared with NC group, the patients with SIVD had significant global reductions in FA (p < 0.001 ~ 0.05), while significant reductions in FA among the patients with AD were regionally confined within the left superior longitudinal fasciculus, genu and splenium of the corpus callosum, and bilateral forceps major, and the anterior thalamic radiation, uncinate fasciculus, and cingulum of the left side (p < 0.01 ~ 0.05). Analysis of FA values within the left forceps major, left anterior thalamic radiation, and genu of the corpus callosum revealed a 71.8% overall correct classification (p < 0.001) with sensitivity of 69.4%, specificity of 73.8%, positive predictive value of 69.4%, and negative predictive value of 73.8% in discriminating patients with SIVD from those with AD. In combined analysis of the patients with SIVD and AD (n = 75), the total FAB score was positively correlated with FA within the bilateral forceps minor, genu of the corpus callosum, left forceps major, left uncinate fasciculus, and right inferior longitudinal fasciculus (p = 0.001 ~ 0.038), and inversely correlated with MD within the right superior longitudinal fasciculus, genu and body of the corpus callosum, bilateral forceps minor, right uncinate fasciculus, and right inferior longitudinal fasciculus (p = 0.003 ~ 0.040) Our findings suggest the effectiveness of DTI measurements in distinguishing patients with early-stage AD from those with SIVD, with discernible changes in spatial distribution and magnitude of significance of the DTI parameters. Strategic FA assessments provided the most robust discriminative power to differentiate SIVD from AD, and FAB may serve as an additional cognitive marker. We also identified the neuronal substrates responsible for FAB performance.

Partial Text

Dementia is a syndrome in which there is deterioration in memory, thinking, behavior and the ability to perform everyday activities [1]. Diagnosing the subtype of dementia generally requires a clinical profile, neuropsychological assessments, and neuroimaging studies. Although Alzheimer’s disease (AD) and vascular cognitive impairment (VCI) constitute the majority of patients with dementia [2], diagnosing and differentiating the subtypes of dementia, particularly during the early stage, remains a challenge. For example, both AD and VCI may present with an insidious onset and progressive course. When a history of prior clinical stroke is unavailable, the differential diagnosis appears to be somewhat difficult. In addition to the slow rate of disease progression, there is also considerable overlap between AD and VCI with regards to their underlying pathology, neuropsychological profile, and neuroimaging features. In pathological reports, ischemic changes and arteriosclerosis have been reported in patients with AD [3,4], and about one third of patients diagnosed with VCI may have AD-type pathology at autopsy [5]. In neuropsychological tests, although some researchers have concluded that patients with AD and VCI have their own specific characteristic cognitive profiles [6–8], others have reported a poor diagnostic accuracy in differentiating dementia subtypes [9,10]. This inconsistency may partly be because VCI encompasses a group of heterogeneous pathological properties (e.g., ischemia, micro/macro-hemorrhage) and involves different regions (e.g., cortex, subcortical regions, and strategic infarcts) with variable severity (e.g., local, multifocal, and diffuse lesions) [11]. The diagnosis of subcortical ischemic vascular dementia (SIVD) appears to be associated with a pathology more confined within subcortical regions, and with lacunes and white matter changes involving cognitive impairment. Therefore the pathogenesis of SIVD appears to be more homogeneous. Typical neuroimaging features of patients with SIVD include hyperintensities extending into periventricular and deep white matter on T2-weighted magnetic resonance imaging (MRI), and lacunes within the deep gray matter [12]. However, both periventricular and deep white matter hyperintensities have also been documented in patients with AD [13,14] and in normal elderly subjects [15,16], making it a challenge to differentiate between SIVD and AD in the early stage, and even more for normal ageing process.

Thirty-five patients with SIVD and 40 patients with AD who visited the Department of Neurology of our hospital from July 2014 to June 2016 were consecutively recruited. Data on demographics, serology tests, general cognitive function assessments, and brain MRI (including DTI) studies were recorded for each patient.

In this study, we compared cognitive assessment test results and DTI parameters between patients with SIVD and AD during the early stage of disease. Our results support the effectiveness of DTI in differentiating patients with SIVD from those with AD as well as correlating executive function. We observed a clearly different DTI profile between the SIVD and AD groups on the basis of comparable disease severity and general cognition. Compared to the cognitive assessments, it was easier to use changes in FA and MD to differentiate SIVD from AD, highlighting the different microstructural changes as the fundamental pathogenesis in these two diseases.

Our findings suggest the effectiveness of DTI parameters in distinguishing patients with the early stage of AD and SIVD, as reflected by the discernible changes in spatial distribution and magnitude of significant modification in DTI parameters. Critical relation between white matter hyperintensities and DTI parameters was identified. The disconnection of white matter in the patients with SIVD appeared to be more profound than that in the patients with AD. The FA values within three ROIs (the left forceps major, left anterior thalamic radiation, and the genu of the corpus callosum) provided a satisfactory discriminative power (71.8% overall correct classification; sensitivity 69.4%; specificity 73.8%). The FAB may serve as an additional cognitive marker to differentiate patients with SIVD from those with AD. That the white matter integrity within the bilateral forceps minor, genu and body of the corpus callosum, bilateral uncinate fasciculus, left forceps major, and right superior/inferior longitudinal fasciculus was associated with FAB performance highlights the fundamental implication of executive function and relevant circuit connectivity.




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