Diffuse Tract Damage in the Hemispheric Deep White Matter May Correlate with Global Cognitive Impairment and Callosal Atrophy in Patients with Extensive Leukoaraiosis

Otsuka, Yoshinobu; Yamauchi, Hiroshi; Sawamoto, Nobukatsu; Iseki, Kazuo; Tomimoto, Hidekazu; Fukuyama, Hidenao

doi:10.3174/ajnr.a2853

Cited by 29 publications

(43 citation statements)

References 33 publications

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“…Only the presented β for Processing speed was lower than a previously reported CI (but only in one of these papers; our β = 0.058 , previous CIs = –0.24 to – 0.06 [12] and –0.33 to 0.06 [38]). Conversely, previously reported β-values from all the eight papers fell within the CIs found in the presented analyses in all instances except for one case of Verbal memory being greater than our CI (previous β = –0.86 [31], our CI = – 0.157 to 0.355 ) and one case of Verbal fluency being lower than our CI (previous β = -–.11 [12], our CI = 0.140 – 0.612 ).…”

Section: Resultssupporting

confidence: 66%

“…An additional five papers were identified from reference lists. Eight of these 42 papers met inclusion criteria [8,12,29–31,38–40]. Supplementary Table S2 details these papers and includes key findings from each study.…”

Section: Resultsmentioning

confidence: 99%

“…In addition to DTI, measures describing WMH, lacunes and brain volume are frequently investigated as potential markers of SVD [8,12,29–31]. In the present study, these were analysed as a comparison with DTI.…”

Section: Methodsmentioning

confidence: 99%

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Using DTI to assess white matter microstructure in cerebral small vessel disease (SVD) in multicentre studies

et al. 2017

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Diffusion tensor imaging (DTI) metrics such as fractional anisotropy (FA) and mean diffusivity (MD) have been proposed as clinical trial markers of cerebral small vessel disease (SVD) due to their associations with outcomes such as cognition. However, studies investigating this have been predominantly single-centre. As clinical trials are likely to be multisite, further studies are required to determine whether associations with cognition of similar strengths can be detected in a multicentre setting. One hundred and nine patients (mean age =68 years) with symptomatic lacunar infarction and confluent white matter hyperintensities (WMH) on MRI was recruited across six sites as part of the PRESERVE DTI substudy. After handling missing data, 3T-MRI scanning was available from five sites on five scanner models (Siemens and Philips), alongside neuropsychological and quality of life (QoL) assessments. FA median and MD peak height were extracted from DTI histogram analysis. Multiple linear regressions were performed, including normalized brain volume, WMH lesion load, and n° lacunes as covariates, to investigate the association of FA and MD with cognition and QoL. DTI metrics from all white matter were significantly associated with global cognition (standardized β =0.268), mental flexibility (β =0.306), verbal fluency (β =0.376), and Montreal Cognitive Assessment (MoCA) (β =0.273). The magnitudes of these associations were comparable with those previously reported from single-centre studies found in a systematic literature review. In this multicentre study, we confirmed associations between DTI parameters and cognition, which were similar in strength to those found in previous single-centre studies. The present study supports the use of DTI metrics as biomarkers of disease progression in multicentre studies.

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Section: Resultssupporting

confidence: 66%

Section: Resultsmentioning

confidence: 99%

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Using DTI to assess white matter microstructure in cerebral small vessel disease (SVD) in multicentre studies

et al. 2017

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“…Intriguingly, the occurrence of MCI in the context of SVD has been hypothesized to be the effect of WM tract damage, which in turn can result in a disconnection syndrome [12], [13], [14] involving mainly transcallosal WM fibers [15]. Diffusion tensor imaging (DTI) is a well-established technique for in-vivo characterization of directional and overall diffusivity of water molecules in WM tracts which has been successfully employed to unveil microstructural changes and their connection to neurophysiological mechanisms underlying various neurodegenerative disorders (for a review, see Goveas et al [16]) as well as in elderly subjects with variable cognitive status [14], [17].…”

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confidence: 99%

Prediction of Impaired Performance in Trail Making Test in MCI Patients With Small Vessel Disease Using DTI Data

Ciulli

Citi

Salvadori

et al. 2016

IEEE J. Biomed. Health Inform.

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Abstract-Mild cognitive impairment (MCI) is a common condition in patients with diffuse hyperintensities of cerebral white matter (WM) in T2-weighted magnetic resonance images and cerebral small vessel disease (SVD). In MCI due to SVD, the most prominent feature of cognitive impairment lies in degradation of executive functions, i.e. of processes which supervise the organization and execution of complex behavior. The Trail Making Test (TMT) is a widely employed test sensitive to cognitive processing speed and executive functioning. MCI due to SVD has been hypothesized to be the effect of WM damage and diffusion tensor imaging (DTI) is a well-established technique for in-vivo characterization of WM. We propose a machine learning scheme tailored to 1) predicting the impairment in executive functions in patients with MCI and SVD, and 2) examining the brain substrates of this impairment. We employed data from 40 MCI patients with SVD and created feature vectors by averaging mean diffusivity (MD) and fractional anisotropy maps within 50 WM regions of interest. We trained support vector machines (SVMs) with polynomial as well as radial basis function kernels using different DTI-derived features while simultaneously optimizing parameters in leave-one-out nested crossvalidation. The best performance was obtained using MD features only and linear kernel SVMs, which were able to distinguish an impaired performance with high sensitivity (72.7%-89.5%), specificity (71.4%-83.3%) and accuracy (77.5%-80.0%). While brain substrates of executive functions are still debated, feature ranking confirm that MD in several WM regions, not limited to the frontal lobes, are truly predictive of executive functions.

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“…The tract skeleton is the basis for voxel-wise cross-subject statistics and reduces potential misregistrations as the source for false-positive or false-negative analysis results. Applying voxel-wise DTI analyses, a significant decrease of fractional anisotropy values was detected in hemispheric deep white matter and corpus callosum in patients with VCI compared to healthy controls [42]. Although still in its infancy, the automatic processing of DTI data at an individual level using support vector machine analysis may allow identification of the very first signs of biological compromise of white matter in VCI.…”

Section: Neuroimaging Of Vascular Changesmentioning

confidence: 99%

Is the time ripe for new diagnostic criteria of cognitive impairment due to cerebrovascular disease? Consensus report of the International Congress on Vascular Dementia working group

Perneczky

Tene

Attems

et al. 2016

BMC Med

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BackgroundLong before Alzheimer’s disease was established as the leading cause of dementia in old age, cerebrovascular lesions were known to cause cognitive deterioration and associated disability. Since the middle of the last century, different diagnostic concepts for vascular dementia and related syndromes were put forward, yet no widely accepted diagnostic consensus exists to date.DiscussionSeveral international efforts, reviewed herein, are ongoing to define cognitive impairment due to cerebrovascular disease in its different stages and subtypes. The role of biomarkers is also being discussed, including cerebrospinal fluid proteins, structural and functional brain imaging, and genetic markers. The influence of risk factors, such as diet, exercise and different comorbidities, is emphasised by population-based research, and lifestyle changes are considered for the treatment and prevention of dementia.ConclusionTo improve the diagnosis and management of vascular cognitive impairment, further progress has to be made in understanding the relevant pathomechanisms, including shared mechanisms with Alzheimer’s disease; bringing together fragmented research initiatives in coordinated international programs; testing if known risk factors are modifiable in prospective interventional studies; and defining the pre-dementia and pre-clinical stages in line with the concept of mild cognitive impairment due to Alzheimer’s disease.

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Diffuse Tract Damage in the Hemispheric Deep White Matter May Correlate with Global Cognitive Impairment and Callosal Atrophy in Patients with Extensive Leukoaraiosis

Cited by 29 publications

References 33 publications

Using DTI to assess white matter microstructure in cerebral small vessel disease (SVD) in multicentre studies

Using DTI to assess white matter microstructure in cerebral small vessel disease (SVD) in multicentre studies

Prediction of Impaired Performance in Trail Making Test in MCI Patients With Small Vessel Disease Using DTI Data

Is the time ripe for new diagnostic criteria of cognitive impairment due to cerebrovascular disease? Consensus report of the International Congress on Vascular Dementia working group

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