scholarly journals Increase of blood-brain barrier leakage is related to cognitive decline in vascular mild cognitive impairment

BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Man Li ◽  
Yue Li ◽  
Long Zuo ◽  
Wenli Hu ◽  
Tao Jiang
Keyword(s):  
Cognitive Impairment ◽  
Cognitive Function ◽  
White Matter ◽  
Grey Matter ◽  
Leakage Rate ◽  
White Matter Hyperintensity ◽  
Normal Appearing White Matter ◽  
Cortical Grey Matter ◽  
Deep Grey Matter ◽  
The Relationship

Abstract Background Blood-brain barrier (BBB) breakdown, as an early biomarker for vascular mild cognitive impairment (vMCI), has only been validated by a few studies. The aim of this study was to investigate whether compromised BBB integrity is involved in vMCI patients, and detect the relationship between BBB breakdown and cognitive function. BBB leakage in vMCI was explored, and the relationship between BBB leakage and cognitive function was discussed in this study. Methods This is a cross-sectional study involving 26 vMCI patients and 21 sex- and age-matched healthy controls. Dynamic contrast-enhanced-magnetic resonance imaging was performed for all participants, to determine BBB leakage. Leakage volume, leakage rate, and fractional blood plasma volume (Vp) in the grey and white matter were evaluated. Neuropsychological tests were used to determine cognitive function. Leakage rate, leakage volume, and Vp in different brain locations, including deep grey matter, cortical grey matter, white matter hyperintensity, and normal-appearing white matter were compared between the two groups. Results Multivariable linear regression analyses revealed that in all regions of interest, the leakage rate was significantly higher in vMCI patients relative to controls. Leakage volume in normal-appearing white matter and white matter hyperintensity were significantly higher, while Vp in normal-appearing white matter, deep grey matter, and cortical grey matter were significantly lower in vMCI patients. Moreover, Montreal Cognitive Assessment scores decreased with the increase of leakage rate in white matter hyperintensity. Conclusion Increased BBB permeability was detected in vMCI patients and was related to cognitive decline, which suggested that BBB breakdown might be involved in cognitive dysfunction pathogenesis.

Abstract 44: Associations of Atrial Fibrillation, Neuroimaging Measures of Cerebrovascular Disease and Alzheimer’S Disease-related Pathology, and Cognitive Impairment

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Jonathan Graff-Radford ◽  
Rosebud Roberts ◽  
Malini Madhavan ◽  
Alejandro Rabinstein ◽  
Ruth Cha ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
White Matter ◽  
Cerebrovascular Disease ◽  
Regression Models ◽  
Grey Matter ◽  
White Matter Hyperintensity ◽  
Carrier Status

The objective of this study was to investigate the cross-sectional associations of atrial fibrillation with neuroimaging measures of cerebrovascular disease and Alzheimer’s disease-related pathology, and their interaction with cognitive impairment. MRI scans of non-demented individuals (n=1044) from the population-based Mayo Clinic Study of Aging were analyzed for infarctions, total grey matter, hippocampal and white matter hyperintensity volumes. A subset of 496 individuals underwent FDG and C-11 Pittsburgh compound B (PiB) PET scans. We assessed the associations of atrial fibrillation with i) categorical MRI measures (cortical and subcortical infarctions) using multivariable logistic regression models, and with ii) continuous MRI measures ( hippocampal, total grey matter, and white matter hyperintensity volumes) and FDG-PET and PiB-PET measures using multivariable linear regression models, and adjusting for confounders. Among participants who underwent MRI (median age, 77.8, 51.6% male), 13.5% had atrial fibrillation. Presence of atrial fibrillation was associated with subcortical infarctions (odds ratio [OR], 1.83; p=0.002), cortical infarctions (OR, 1.91; p=0.03), total grey matter volume (Beta [β], -.025, p<.0001) after controlling for age, education, gender, APOE e4 carrier status, coronary artery disease, diabetes, history of clinical stroke, and hypertension. However, atrial fibrillation was not associated with white matter hyperintensity volume, hippocampal volume, Alzheimer’s pattern of FDG hypometabolism or PiB uptake. There was a significant interaction of cortical infarction (p for interaction=0.004) and subcortical infarction (p for interaction =0.015) with atrial fibrillation with regards to odds of mild cognitive impairment (MCI). Using subjects with no atrial fibrillation and no infarction as the reference, the OR (95% confidence intervals [CI]) for MCI was 2.98 (1.66, 5.35;p = 0.0002) among participants with atrial fibrillation and any infarction, 0.69 (0.36, 1.33;p= 0.27) for atrial fibrillation and no infarction, and 1.50 (0.96, 2.32;p = 0.07) for no atrial fibrillation and any infarction. These data highlight that atrial fibrillation is associated with MCI in the presence of infarctions.

Regional White Matter Hyperintensity Influences Grey Matter Atrophy in Mild Cognitive Impairment

2018 ◽  
Vol 66 (2) ◽  
pp. 533-549 ◽  
Author(s):  
Ashwati Vipin ◽  
Heidi Jing Ling Foo ◽  
Joseph Kai Wei Lim ◽  
Russell Jude Chander ◽  
Ting Ting Yong ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
White Matter ◽  
Grey Matter ◽  
White Matter Hyperintensity ◽  
Grey Matter Atrophy

scholarly journals The Association between Cerebral White Matter Lesions and Plasma Omega-3 to Omega-6 Polyunsaturated Fatty Acids Ratio to Cognitive Impairment Development

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Michihiro Suwa ◽  
Shigeru Yamaguchi ◽  
Tsuyoshi Komori ◽  
Sachiko Kajimoto ◽  
Masaya Kino
Keyword(s):  
Risk Factors ◽  
Cognitive Impairment ◽  
Cognitive Function ◽  
White Matter ◽  
White Matter Lesions ◽  
White Matter Hyperintensity ◽  
Cerebral White Matter ◽  
Omega 3 ◽  
Arachidonic Acids ◽  
Low Serum

Objective. Cerebral white matter hyperintensity (WMH) with magnetic resonance imaging (MRI) has a potential for predicting cognitive impairment. Serum polyunsaturated fatty acid (PUFA) levels are important for evaluating the extent of atherosclerosis. We investigated whether abnormal PUFA levels affected WMH grading and cognitive function in patients without significant cognitive impairment.Methods. Atherosclerotic risk factors, the internal carotid artery (ICA) plaque, and serum ratios of eicosapentaenoic to arachidonic acids (EPA/AA) and docosahexaenoic to arachidonic acids (DHA/AA) were assessed in 286 patients. The relationship among these risk factors, WMH, and cognitive function was evaluated using WMH grading and the Mini-Mental State Examination (MMSE).Results. The development of WMH was associated with aging, hypertension, ICA plaques, and a low serum EPA/AA ratio (<0.38, obtained as the median value) but was not related to dyslipidemia, diabetes, smoking, and a low serum DHA/AA ratio (<0.84, obtained as the median value). In addition, the MMSE score deteriorated slightly with the progression of WMH (29.7 ± 1.0 compared to 28.4 ± 2.1,P<0.0001).Conclusions. The progression of WMH was associated with a low serum EPA/AA ratio and accompanied minimal deterioration in cognitive function. Sufficient omega-3 PUFA intake may be effective in preventing the development of cognitive impairment.

scholarly journals Loss of Integrity of Corpus Callosum White Matter Hyperintensity Penumbra Predicts Cognitive Decline in Patients With Subcortical Vascular Mild Cognitive Impairment

2021 ◽  
Vol 13 ◽  
Author(s):  
Yage Qiu ◽  
Ling Yu ◽  
Xin Ge ◽  
Yawen Sun ◽  
Yao Wang ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Cognitive Function ◽  
White Matter ◽  
Linear Regression ◽  
Corpus Callosum ◽  
Linear Regression Analysis ◽  
Multiple Linear Regression Analysis ◽  
The Relationship

Loss of white matter (WM) integrity contributes to subcortical vascular mild cognitive impairment (svMCI). Diffusion tensor imaging (DTI) has revealed damage beyond the area of WM hyperintensity (WMH) including in normal-appearing WM (NAWM); however, the functional significance of this observation is unclear. To answer this question, in this study we investigated the relationship between microstructural changes in the WMH penumbra (WMH-P) and cognitive function in patients with svMCI by regional tract-based analysis. A total of 111 patients with svMCI and 72 patients with subcortical ischemic vascular disease (SIVD) without cognitive impairment (controls) underwent DTI and neuropsychological assessment. WMH burden was determined before computing mean values of fractional anisotropy (FA) and mean diffusivity (MD) within WMHs and WMH-Ps. Pearson’s partial correlations were used to assess the relationship between measurements showing significant intergroup differences and composite Z-scores representing global cognitive function. Multiple linear regression analysis was carried out to determine the best model for predicting composite Z-scores. We found that WMH burden in the genu, body, and splenium of the corpus callosum (GCC, BCC, and SCC respectively); bilateral anterior, superior, and posterior corona radiata; left sagittal stratum was significantly higher in the svMCI group than in the control group (p &lt; 0.05). The WMH burden of the GCC, BCC, SCC, and bilateral anterior corona radiata was negatively correlated with composite Z-scores. Among diffusion parameters showing significant differences across the 10 WM regions, mean FA values of WMH and WMH-P of the BCC were correlated with composite Z-scores in svMCI patients. The results of the multiple linear regression analysis showed that the FA of WMH-P of the BCC and WMH burden of the SCC and GCC were independent predictors of composite Z-score, with the FA of WMH-P of the BCC making the largest contribution. These findings indicate that disruption of the CC microstructure—especially the WMH-P of the BCC—may contribute to the cognitive deficits associated with SIVD.

scholarly journals The Relationship Between Glycaemia, Cognitive Function, Structural Brain Outcomes and Dementia: A Mendelian Randomization Study in the UK Biobank

2021 ◽  
Author(s):  
Victoria Garfield ◽  
Aliki-Eleni Farmaki ◽  
Ghazaleh Fatemifar ◽  
Sophie V. Eastwood ◽  
Rohini Mathur ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Reaction Time ◽  
Cognitive Function ◽  
White Matter ◽  
Visual Memory ◽  
White Matter Hyperintensity ◽  
Uk Biobank ◽  
The Relationship ◽  
Genetic Instruments

We investigated the relationship between glycaemia and cognitive function, brain structure and incident dementia using bidirectional Mendelian randomisation (MR). Data were from UK Biobank (n~500,000). Our exposures were genetic instruments for type-2 diabetes (157 variants) and HbA<sub>1c </sub>(51 variants) and our outcomes were reaction time (RT), visual memory, hippocampal and white matter hyperintensity volumes, Alzheimer’s dementia (AD). We also investigated associations between genetic variants for RT (43 variants) and, diabetes and HbA<sub>1c</sub>. We used conventional inverse-variance weighted (IVW) MR, alongside MR sensitivity analyses. Using IVW, genetic liability to type-2 diabetes was not associated with reaction time (exponentiated ß=1.00, 95%CI=1.00; 1.00), visual memory (expß=1.00, 95%CI=0.99; 1.00), white matter hyperintensity volume (WMHV) (expß=0.99, 95%CI=0.97; 1.01), hippocampal volume (HV) (ß coefficient mm<sup>3</sup>=4.56, 95%CI=-3.98; 13.09) or AD (OR 0.89, 95%CI=0.78; 1.01). HbA<sub>1c </sub>was not associated with RT (expß=1.01, 95%CI=1.00; 1.01), WMHV (expß=0.94, 95%CI=0.81; 1.08), HV (ß=7.21, 95%CI=-54.06; 68.48), or risk of AD (OR 0.94, 95%CI=0.47; 1.86), but HbA<sub>1c</sub> was associated with visual memory (expß=1.06, 95%CI=1.05; 1.07) using a weighted median. IVW showed that reaction time was not associated with diabetes risk (OR 0.96, 95%CI=0.63; 1.46) or with HbA<sub>1c </sub>(ß coefficient mmol/mol=-0.08, 95%CI=-0.57; 0.42). Overall, we observed little evidence of causal association between genetic instruments for T2D or peripheral glycaemia and some measures of cognition and brain structure in midlife.

scholarly journals Cognitive impairment in early MS: contribution of white matter lesions, deep grey matter atrophy, and cortical atrophy

2020 ◽  
Vol 267 (8) ◽  
pp. 2307-2318 ◽  
Author(s):  
Christina Engl ◽  
Laura Tiemann ◽  
Sophia Grahl ◽  
Matthias Bussas ◽  
Paul Schmidt ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
White Matter ◽  
Grey Matter ◽  
White Matter Lesions ◽  
Cortical Atrophy ◽  
Deep Grey Matter ◽  
Grey Matter Atrophy

Exploring the Contribution of Myelin Content in Normal Appearing White Matter to Cognitive Outcomes in Cerebral Small Vessel Disease

2021 ◽  
pp. 1-11
Author(s):  
Elizabeth Dao ◽  
Roger Tam ◽  
Ging-Yuek R. Hsiung ◽  
Lisanne ten Brinke ◽  
Rachel Crockett ◽  
...  
Keyword(s):  
Working Memory ◽  
Cognitive Function ◽  
White Matter ◽  
Processing Speed ◽  
Small Vessel Disease ◽  
Cognitive Outcomes ◽  
White Matter Hyperintensity ◽  
Normal Appearing White Matter ◽  
Trail Making

Background: Myelin damage is a salient feature in cerebral small vessel disease (cSVD). Of note, myelin damage extends into the normal appearing white matter (NAWM). Currently, the specific role of myelin content in cognition is poorly understood. Objective: The objective of this exploratory study was to investigate the association between NAWM myelin and cognitive function in older adults with cSVD. Methods: This exploratory study included 55 participants with cSVD. NAWM myelin was measured using myelin water imaging and was quantified as myelin water fraction (MWF). Assessment of cognitive function included processing speed (Trail Making Test Part A), set shifting (Trail Making Test Part B minus A), working memory (Verbal Digit Span Backwards Test), and inhibition (Stroop Test). Multiple linear regression analyses assessed the contribution of NAWM MWF on cognitive outcomes controlling for age, education, and total white matter hyperintensity volume. The overall alpha was set at ≤0.05. Results: After accounting for age, education, and total white matter hyperintensity volume, lower NAWM MWF was significantly associated with slower processing speed (β  = –0.29, p = 0.037) and poorer working memory (β= 0.30, p = 0.048). NAWM MWF was not significantly associated with set shifting or inhibitory control (p >  0.132). Conclusion: Myelin loss in NAWM may play a role in the evolution of impaired processing speed and working memory in people with cSVD. Future studies, with a longitudinal design and larger sample sizes, are needed to fully elucidate the role of myelin as a potential biomarker for cognitive function.

scholarly journals Cortical and Subcortical Grey Matter Abnormalities in White Matter Hyperintensities and Subsequent Cognitive Impairment

2021 ◽  
Author(s):  
Wenhao Zhu ◽  
◽  
Hao Huang ◽  
Shiqi Yang ◽  
Xiang Luo ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
White Matter ◽  
Cognitive Decline ◽  
Grey Matter ◽  
White Matter Hyperintensities ◽  
Grey Matter Volume ◽  
Independent Dataset ◽  
The Relationship ◽  
Robust Evidence ◽  
Bilateral Thalamus

AbstractGrey matter (GM) alterations may contribute to cognitive decline in individuals with white matter hyperintensities (WMH) but no consensus has yet emerged. Here, we investigated cortical thickness and grey matter volume in 23 WMH patients with mild cognitive impairment (WMH-MCI), 43 WMH patients without cognitive impairment, and 55 healthy controls. Both WMH groups showed GM atrophy in the bilateral thalamus, fronto-insular cortices, and several parietal-temporal regions, and the WMH-MCI group showed more extensive and severe GM atrophy. The GM atrophy in the thalamus and fronto-insular cortices was associated with cognitive decline in the WMH-MCI patients and may mediate the relationship between WMH and cognition in WMH patients. Furthermore, the main results were well replicated in an independent dataset from the Alzheimer's Disease Neuroimaging Initiative database and in other control analyses. These comprehensive results provide robust evidence of specific GM alterations underlying WMH and subsequent cognitive impairment.

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