Vascular aspects of cognitive impairment and dementia.
Ontology highlight
ABSTRACT:
SUBMITTER: Wiesmann M
PROVIDER: S-EPMC3824191 | biostudies-other | 2013 Nov
REPOSITORIES: biostudies-other
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Project description:Homocysteine is produced physiologically in all cells, and is present in plasma of healthy individuals (plasma [HCy]: 3-10?M). While rare genetic mutations (CBS, MTHFR) cause severe hyperhomocysteinemia ([HCy]: 100-200?M), mild-moderate hyperhomocysteinemia ([HCy]: 10-100?M) is common in older people, and is an independent risk factor for stroke and cognitive impairment. As B-vitamin supplementation (B6, B12 and folate) has well-validated homocysteine-lowering efficacy, this may be a readily-modifiable risk factor in vascular contributions to cognitive impairment and dementia (VCID). Here we review the biochemical and cellular actions of HCy related to VCID. Neuronal actions of HCy were at concentrations above the clinically-relevant range. Effects of HCy <100?M were primarily vascular, including myocyte proliferation, vessel wall fibrosis, impaired nitric oxide signalling, superoxide generation and pro-coagulant actions. HCy-lowering clinical trials relevant to VCID are discussed. Extensive clinical and preclinical data support HCy as a mediator for VCID. In our view further trials of combined B-vitamin supplementation are called for, incorporating lessons from previous trials and from recent experimental work. To maximise likelihood of treatment effect, a future trial should: supply a high-dose, combination supplement (B6, B12 and folate); target the at-risk age range; and target cohorts with low baseline B-vitamin status. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia edited by M. Paul Murphy, Roderick A. Corriveau and Donna M. Wilcock.
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Project description:The alteration of the functional topological organization in subcortical ischemic vascular cognitive impairment with no dementia (SIVCIND) patients has been illuminated by previous neuroimaging studies. However, in regard to the changes in the structural connectivity of brain networks, little has been reported. In this study, a total of 27 subjects, consisting of 13 SIVCIND patients, and 14 normal controls, were recruited. Each of the structural connectivity networks was constructed by diffusion tensor tractography. Subsequently, graph theory, and network-based statistics (NBS) were employed to analyze the whole-brain mean factional anisotropy matrix. After removing the factor of age, gender, and duration of formal education, the clustering coefficients (C p ) and global efficiency (E glob ) were significantly decreased and the mean path length (L p ) was significantly increased in SIVCIND patients compared with normal controls. Using the combination of four network topological parameters as the classification feature, a classification accuracy of 78% was obtained by leave-one-out cross-validation for all subjects with a sensitivity of 69% and a specificity of 86%. Moreover, we also found decreased structural connections in the SIVCIND patients, which mainly concerned fronto-occipital, fronto-subcortical, and tempo-occipital connections (NBS corrected, p < 0.01). Additionally, significantly altered nodal centralities were found in several brain regions of the SIVCIND patients, mainly located in the prefrontal, subcortical, and temporal cortices. These results suggest that cognitive impairment in SIVCIND patients is associated with disrupted topological organization and provide structural evidence for developing reliable biomarkers related to cognitive decline in SIVCIND.
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