scholarly journals Longitudinal change of small-vessel disease-related brain abnormalities

2015 ◽  
Vol 36 (1) ◽  
pp. 26-39 ◽  
Author(s):  
Reinhold Schmidt ◽  
Stephan Seiler ◽  
Marisa Loitfelder
Keyword(s):  
White Matter ◽  
Treatment Effects ◽  
Small Vessel Disease ◽  
Surrogate Marker ◽  
White Matter Lesions ◽  
Surrogate Endpoint ◽  
Longitudinal Change ◽  
Small Vessel ◽  
Brain Abnormalities ◽  
Vessel Disease

Knowledge about the longitudinal change of cerebral small-vessel disease–related magnetic resonance imaging abnormalities increases our pathophysiologic understanding of cerebral microangiopathy. The change of specific lesion types may also serve as secondary surrogate endpoint in clinical trials. A surrogate endpoint needs to progress fast enough to allow monitoring of treatment effects within a reasonable time period, and change of the brain abnormality needs to be correlated with clinical change. Confluent white matter lesions show fast progression and correlations with cognitive decline. Thus, the change of confluent white matter lesions may be used as a surrogate marker in proof-of-concept trials with small patient numbers needed to show treatment effects on lesion progression. Nonetheless if the expected change in cognitive performance resulting from treatment effects on lesion progression is used as outcome, the sample size needed to show small to moderate treatment effects becomes very large. Lacunes may also fulfill the prerequisites of a surrogate marker, but in the general population the incidence of lacunes over short observational periods is small. For other small-vessel disease–related brain abnormalities including microbleeds and microstructural changes in normal-appearing white matter longitudinal change and correlations with clinical decline is not yet fully determined.

Detection of white matter lesions in cerebral small vessel disease

2013 ◽  
Author(s):  
Medhat M. Riad ◽  
Bram Platel ◽  
Frank-Erik de Leeuw ◽  
Nico Karssemeijer
Keyword(s):  
White Matter ◽  
Small Vessel Disease ◽  
White Matter Lesions ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Vessel Disease

scholarly journals Frontal white matter lesions in Alzheimer’s disease are associated with both small vessel disease and AD-associated cortical pathology

2021 ◽  
Author(s):  
Kirsty E. McAleese ◽  
Mohi Miah ◽  
Sophie Graham ◽  
Georgina M. Hadfield ◽  
Lauren Walker ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
White Matter ◽  
Regional Differences ◽  
Small Vessel Disease ◽  
White Matter Lesions ◽  
Small Vessel ◽  
Published Data ◽  
Axonal Loss ◽  
Vessel Disease

AbstractCerebral white matter lesions (WML) encompass axonal loss and demyelination and are assumed to be associated with small vessel disease (SVD)-related ischaemia. However, our previous study in the parietal lobe white matter revealed that WML in Alzheimer’s disease (AD) are linked with degenerative axonal loss secondary to the deposition of cortical AD pathology. Furthermore, neuroimaging data suggest that pathomechanisms for the development of WML differ between anterior and posterior lobes with AD-associated degenerative mechanism driving posterior white matter disruption, and both AD-associated degenerative and vascular mechanisms contributed to anterior matter disruption. In this pilot study, we used human post-mortem brain tissue to investigate the composition and aetiology of frontal WML from AD and non-demented controls to determine if frontal WML are SVD-associated and to reveal any regional differences in the pathogenesis of WML. Frontal WML tissue sections from 40 human post-mortem brains (AD, n = 19; controls, n = 21) were quantitatively assessed for demyelination, axonal loss, cortical hyperphosphorylated tau (HPτ) and amyloid-beta (Aβ) burden, and arteriolosclerosis as a measure of SVD. Biochemical assessment included Wallerian degeneration-associated protease calpain and the myelin-associated glycoprotein to proteolipid protein ratio as a measure of ante-mortem ischaemia. Arteriolosclerosis severity was found to be associated with and a significant predictor of frontal WML severity in both AD and non-demented controls. Interesting, frontal axonal loss was also associated with HPτ and calpain levels were associated with increasing Aβ burden in the AD group, suggestive of an additional degenerative influence. To conclude, this pilot data suggest that frontal WML in AD may result from both increased arteriolosclerosis and AD-associated degenerative changes. These preliminary findings in combination with previously published data tentatively indicate regional differences in the aetiology of WML in AD, which should be considered in the clinical diagnosis of dementia subtypes: posterior WML maybe associated with degenerative mechanisms secondary to AD pathology, while anterior WML could be associated with both SVD-associated and degenerative mechanisms.

scholarly journals Diffusion tensor tractography in cerebral small vessel disease: correlation with cognitive function

2017 ◽  
Vol 31 (1) ◽  
pp. 83-89 ◽  
Author(s):  
Maria M D’Souza ◽  
SP Gorthi ◽  
Kunal Vadwala ◽  
Richa Trivedi ◽  
C Vijayakumar ◽  
...  
Keyword(s):  
Cognitive Function ◽  
White Matter ◽  
Diffusion Tensor ◽  
Small Vessel Disease ◽  
Surrogate Marker ◽  
Mean Diffusivity ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
White Matter Damage ◽  
Vessel Disease

Background Patients with cerebral small vessel disease may suffer from varying levels of cognitive deficit and may progress on to vascular dementia. The extent of involvement, as seen on conventional magnetic resonance (MR) measures, correlates poorly with the level of cognitive decline. The purpose of this study was to investigate the utility of diffusion tensor imaging (DTI) as a marker for white matter damage in small vessel disease and to assess its correlation with cognitive function. Methods Thirty consecutive patients with cerebral small vessel disease underwent conventional MR imaging, DTI, and neuropsychological assessment. Results On tractographic analysis, fractional anisotropy was significantly reduced while mean diffusivity significantly increased in several white matter tracts. The alteration in DTI indices correlated well with cognitive function. No significant correlation was identified between T2 lesion load and cognitive performance. Conclusions Tractographic analysis of white matter integrity is a useful measure of disease severity and correlates well with cognitive function. It may have a significant potential in monitoring disease progression and may serve as a surrogate marker for treatment trials.

White matter lesion progression: A surrogate endpoint for trials in cerebral small-vessel disease

Neurology ◽  
2004 ◽  
Vol 63 (1) ◽  
pp. 139-144 ◽  
Author(s):  
R. Schmidt ◽  
Ph. Scheltens ◽  
T. Erkinjuntti ◽  
L. Pantoni ◽  
H. S. Markus ◽  
...  
Keyword(s):  
White Matter ◽  
Small Vessel Disease ◽  
White Matter Lesion ◽  
Surrogate Endpoint ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Vessel Disease

scholarly journals Do polygenic scores of cerebral small vessel disease MRI markers predict white matter lesions?

2021 ◽  
Vol 17 (S1) ◽  
Author(s):  
Eric de Silva ◽  
Carole H Sudre ◽  
Jo Barnes ◽  
Marzia Antonella Scelsi ◽  
Andre Altmann
Keyword(s):  
White Matter ◽  
Small Vessel Disease ◽  
White Matter Lesions ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Vessel Disease ◽  
Polygenic Scores

scholarly journals Early Small Vessel Disease Affects Frontoparietal and Cerebellar Hubs in Close Correlation with Clinical Symptoms—A Resting-State fMRI Study

2014 ◽  
Vol 34 (7) ◽  
pp. 1091-1095 ◽  
Author(s):  
Alexander Schaefer ◽  
Eva M Quinque ◽  
Judy A Kipping ◽  
Katrin Arélin ◽  
Elisabeth Roggenhofer ◽  
...  
Keyword(s):  
White Matter ◽  
Resting State ◽  
Clinical Symptoms ◽  
Small Vessel Disease ◽  
White Matter Lesions ◽  
Close Correlation ◽  
Small Vessel ◽  
Eigenvector Centrality ◽  
Functional Changes ◽  
Vessel Disease

Cerebral small vessel disease, mainly characterized by white matter lesions and lacunes, has a high clinical impact as it leads to vascular dementia. Recent studies have shown that this disease impairs frontoparietal networks. Here, we apply resting-state magnetic resonance imaging and data-driven whole-brain imaging analysis methods (eigenvector centrality) to investigate changes of the functional connectome in early small vessel disease. We show reduced connectivity in frontoparietal networks, whereas connectivity increases in the cerebellum. These functional changes are closely related to white matter lesions and typical neuropsychological deficits associated with small vessel disease.

Sign in / Sign up

Export Citation Format

Share Document