Hope for Vascular Cognitive Impairment: Ac-YVAD-cmk as a Novel Treatment Against White Matter Rarefaction
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ABSTRACT:
ORGANISM(S): Rattus norvegicus (brown rat)
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PROVIDER: S-BSST1354 | biostudies-other |
REPOSITORIES: biostudies-other
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Project description:Changes in white matter (WM) microstructure may relate to the pathophysiology of cognitive impairment. Whether WM microstructure differs in two common pre-dementia subtypes, vascular mild cognitive impairment (VaMCI) and amnestic mild cognitive impairment (aMCI), is largely unknown. This study included 28 VaMCI (12 men, age: 46 ~ 77 years) and 34 aMCI patients (14 men, age: 51 ~ 79 years). All patients underwent a battery of neuropsychological tests and structural and diffusion magnetic resonance imaging (MRI) scanning. WM microstructure was quantified using diffusion MRI parameters: fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AxD) and radial diffusivity (RD). These parameters were compared between the two patient groups using tract-based spatial statistics (TBSS) after controlling for age, gender, and education. No significant differences in FA/MD/AxD/RD were observed between the VaMCI and aMCI groups, which suggests a similar pattern of WM microstructure in the early stage of cognitive impairment for different dementia types. However, the two groups exhibited significant differences in the relationship between FA and the Auditory Verbal Learning Test (AVLT), which were primarily located around the corona radiate and corpus callosum. Specifically, there were significant positive correlations (R = 0.64, P < 0.001) between the FA and AVLT in the VaMCI group, but the opposite trend was observed in the aMCI group (R = -0.34, P = 0.047). The differential relationship between WM and memory between VaMCI and aMCI indicates an independent neuropathology for specific memory deficits in different types of dementia.
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Project description:Cerebral white matter rarefaction (CWMR) was considered by Binswanger and Alzheimer to be due to cerebral arteriolosclerosis. Renewed attention came with CT and MR brain imaging, and neuropathological studies finding a high rate of CWMR in Alzheimer disease (AD). The relative contributions of cerebrovascular disease and AD to CWMR are still uncertain. In 1181 autopsies by the Arizona Study of Aging and Neurodegenerative Disorders (AZSAND), large-format brain sections were used to grade CWMR and determine its vascular and neurodegenerative correlates. Almost all neurodegenerative diseases had more severe CWMR than the normal control group. Multivariable logistic regression models indicated that Braak neurofibrillary stage was the strongest predictor of CWMR, with additional independently significant predictors including age, cortical and diencephalic lacunar and microinfarcts, body mass index, and female sex. It appears that while AD and cerebrovascular pathology may be additive in causing CWMR, both may be solely capable of this. The typical periventricular pattern suggests that CWMR is primarily a distal axonopathy caused by dysfunction of the cell bodies of long-association corticocortical projection neurons. A consequence of these findings is that CWMR should not be viewed simply as "small vessel disease" or as a pathognomonic indicator of vascular cognitive impairment or vascular dementia.
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Project description:Background and Purpose: Hemoglobin is one of the main proteins in erythrocytes. There are significant correlations between low hemoglobin and white matter hyperintensities (WMH) and cognitive impairment. This study explored whether erythrocytopenia has predictive value for vascular cognitive impairment (VCI) in patients with WMH. Method: We conducted a cross-sectional study of 302 patients, including 62 with cerebral small vessel disease and 240 with stroke. Basic demographic data and fasting blood were collected. First, all patients were divided into normal cognition (NC), mild VCI (mVCI), and severe VCI (sVCI) groups (subgroups later) based on cognitive behavior scores. Second, all patients were divided into mild WMH (mWMH) and severe WMH (sWMH) groups based on Fazekas scores. The differences in blood markers between different groups or subgroups with different cognitive levels were analyzed by univariate analysis. Then, binary logistic regression was used to analyze the diagnostic value of erythrocyte counts for VCI in the sWMH group, and ordinal logistic regression was used to analyze the predictive value of multiple variables for different cognitive levels. Results: Univariate analysis showed that erythrocytes, hemoglobin, high-sensitivity C-reactive protein, retinol binding protein and prealbumin were potential blood markers for different cognitive levels in sWMH patients. Among them, erythrocytopenia has good predictive value for the diagnosis of mVCI (AUC = 0.685, P = 0.008) or sVCI (AUC = 0.699, P = 0.003) in patients with sWMH. Multivariate joint analysis showed that erythrocytes were an independent protective factor reducing the occurrence of VCI in patients with sWMH (OR = 0.633, P = 0.045). Even after adjusting for age, there was still a significant difference (P = 0.047). Conclusion: Erythrocytes are an independent protective factor for VCI in patients with sWMH. Promoting hematopoietic function may have potential value for prevention of cognitive decline in patients with cerebrovascular disease.
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Project description:Normal-appearing white matter (NAWM) surrounding white matter hyperintensities (WMHs), frequently known as the WMH penumbra, is associated with subtle white matter injury and has a high risk for future conversion to WMHs. The goal of this study was to define WMH penumbras and to further explore whether the diffusion and perfusion parameters of these penumbras could better reflect cognitive function alterations than WMHs in subjects with subcortical vascular mild cognitive impairment (svMCI). Seventy-three svMCI subjects underwent neuropsychological assessments and 3T MRI scans, including diffusion tensor imaging (DTI) and arterial spin labeling (ASL). To determine the extent of cerebral blood flow (CBF) and DTI penumbras. A NAWM layer mask was generated for periventricular WMHs (PVWMHs) and deep WMHs (DWMHs) separately. Mean values of CBF, fractional anisotropy (FA), mean diffusivity (MD) within the WMHs and their corresponding NAWM layer masks were computed and compared using paired t-tests. Pearson's partial correlations were used to assess the relations of the mean CBF, FA, and MD values within the corresponding penumbras with composite z-scores of global cognition and four cognitive domains controlling for age, sex, and education. For both PVWMHs and DWMHs, the CBF penumbras were wider than the DTI penumbras. Only the mean FA value of the PVWMH-FA penumbra was correlated with the composite z-scores of global cognition before correction (r = 0.268, p = 0.024), but that correlation did not survive after correcting the p-value for multiple comparisons. Our findings showed extensive white matter perfusion disturbances including white matter tissue, both with and without microstructural alterations. The imaging parameters investigated, however, did not correlate to cognition.
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