scholarly journals Contribution of Inflammation and Hypoperfusion to White Matter Hyperintensities-Related Cognitive Impairment

2022 ◽  
Vol 12 ◽  
Author(s):  
Chao-Juan Huang ◽  
Xia Zhou ◽  
Xin Yuan ◽  
Wei Zhang ◽  
Ming-Xu Li ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
White Matter ◽  
White Matter Hyperintensities ◽  
Small Vessel Disease ◽  
Inferior Frontal Gyrus ◽  
Multivariate Logistic Regression Analysis ◽  
Middle Temporal Gyrus ◽  
Whole Brain ◽  
Triangular Part ◽  
Orbital Part

White matter hyperintensities (WMHs) of presumed vascular origin are one of the most important neuroimaging markers of cerebral small vessel disease (CSVD), which are closely associated with cognitive impairment. The aim of this study was to elucidate the pathogenesis of WMHs from the perspective of inflammation and hypoperfusion mechanisms. A total of 65 patients with WMHs and 65 healthy controls were enrolled in this study. Inflammatory markers measurements [hypersensitive C-reactive protein (hsCRP) and lipoprotein-associated phospholipase A2 (Lp-PLA2)], cognitive evaluation, and pseudocontinuous arterial spin labeling (PCASL) MRI scanning were performed in all the subjects. The multivariate logistic regression analysis showed that Lp-PLA2 was an independent risk factor for WMHs. Cerebral blood flow (CBF) in the whole brain, gray matter (GM), white matter (WM), left orbital medial frontal gyrus [MFG.L (orbital part)], left middle temporal gyrus (MTG.L), and right thalamus (Tha.R) in the patients was lower than those in the controls and CBF in the left triangular inferior frontal gyrus [IFG.L (triangular part)] was higher in the patients than in the controls. There was a significant correlation between Lp-PLA2 levels and CBF in the whole brain (R = −0.417, p < 0.001) and GM (R = −0.278, p = 0.025), but not in the WM in the patients. Moreover, CBF in the MFG.L (orbital part) and the Tha.R was, respectively, negatively associated with the trail making test (TMT) and the Stroop color word test (SCWT), suggesting the higher CBF, the better executive function. The CBF in the IFG.L (triangular part) was negatively correlated with attention scores in the Cambridge Cognitive Examination-Chinese Version (CAMCOG-C) subitems (R = −0.288, p = 0.020). Our results revealed the vascular inflammation roles in WMHs, which may through the regulation of CBF in the whole brain and GM. Additionally, CBF changes in different brain regions may imply a potential role in the modulation of cognitive function in different domains.

scholarly journals Higher white matter hyperintensity lesion load is associated with reduced long-range functional connectivity

2020 ◽  
Vol 2 (2) ◽  
Author(s):  
Fanny Quandt ◽  
Felix Fischer ◽  
Julian Schröder ◽  
Marlene Heinze ◽  
Iris Lettow ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
White Matter ◽  
Functional Connectivity ◽  
White Matter Hyperintensities ◽  
Small Vessel Disease ◽  
White Matter Lesion ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Lesion Load ◽  
Vessel Disease

Abstract Cerebral small vessel disease is a common disease in the older population and is recognized as a major risk factor for cognitive decline and stroke. Small vessel disease is considered a global brain disease impacting the integrity of neuronal networks resulting in disturbances of structural and functional connectivity. A core feature of cerebral small vessel disease commonly present on neuroimaging is white matter hyperintensities. We studied high-resolution resting-state EEG, leveraging source reconstruction methods, in 35 participants with varying degree of white matter hyperintensities without clinically evident cognitive impairment in an observational study. In patients with increasing white matter lesion load, global theta power was increased independently of age. Whole-brain functional connectivity revealed a disrupted network confined to the alpha band in participants with higher white matter hyperintensities lesion load. The decrease of functional connectivity was evident in long-range connections, mostly originating or terminating in the frontal lobe. Cognitive testing revealed no global cognitive impairment; however, some participants revealed deficits of executive functions that were related to larger white matter hyperintensities lesion load. In summary, participants without clinical signs of mild cognitive impairment or dementia showed oscillatory changes that were significantly related to white matter lesion load. Hence, oscillatory neuronal network changes due to white matter lesions might act as biomarker prior to clinically relevant behavioural impairment.

scholarly journals Heterogeneity of White Matter Hyperintensities in Cognitively Impaired Patients With Cerebral Small Vessel Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Tingting Wang ◽  
Aoming Jin ◽  
Ying Fu ◽  
Zaiqiang Zhang ◽  
Shaowu Li ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
White Matter ◽  
White Matter Hyperintensities ◽  
Small Vessel Disease ◽  
Cerebral Small Vessel Disease ◽  
Cognitively Impaired ◽  
Imaging Features ◽  
Vessel Disease

ObjectiveSimilar white matter hyperintensities (WMH) might have different impact on the cognitive outcomes in patients with cerebral small vessel disease (CSVD). This study is to assess the possible factors related to the heterogeneity of WMH in cognitively impaired patients with CVSD.MethodsWe analyzed data from a cohort of patients with CVSD who were recruited consecutively from the Beijing Tiantan Hospital from 2015 to 2020. WMH, lacunes, enlarged perivascular space (ePVS), microbleeds and lacunar infarcts were rated on brain MRI. A score of <26 on the Montreal Cognitive Assessment (MoCA) indicated cognitive impairment. A mismatch was defined as the severity of WMH not matching the severity of cognitive dysfunction. Type-1 mismatch was defined as a mild WMH (Fazekas score = 0-1) associated with cognitive impairment, and type-2 mismatch was defined as a severe WMH (Fazekas score = 5-6) associated with normal cognitive function. Ultrasmall superparamagnetic iron oxide (USPIO)-enhanced SWI on 3-Tesla MRI was used to image the penetrating arteries in basal ganglia to explore the underlying mechanism of this mismatch. Multivariable logistic regression was used to analyze the association between the imaging features and cognitive impairment.ResultsIn 156 patients, 118 (75.6%) had cognitive impairment and 37 (23.7%) showed mismatch. Twenty five (16.0%) had type-1 mismatch and 12 (7.7%) had type-2 mismatch. Regression analysis found that WMH, lacunes, microbleeds and total CSVD scores were associated with cognitive impairment and were independent of vascular risk factors. However, lacunes, microbleeds and total CSVD scores were related to the mismatch between WMH and cognitive impairment (p=0.006, 0.005 and 0.0001, respectively). Specially, age and ePVS in basal ganglia were related to type-1 mismatch (p=0.04 and 0.02, respectively); microbleeds and total CSVD scores were related to type-2 mismatch (p=0.01 and 0.03, respectively). Although the severity of WMH was similar, the injury scores of penetrating arteries were significantly different between those with and without cognitive impairment (p=0.04).ConclusionsHeterogeneity of WMH was present in cognitively impaired patients with CSVD. Conventional imaging features and injury of penetrating arteries may account for such heterogeneity, which can be a hallmark for early identification and prevention of cognitive impairment.

scholarly journals Nonfocal Transient Neurological Attacks Are Associated With Cerebral Small Vessel Disease

Stroke ◽  
2019 ◽  
Vol 50 (12) ◽  
pp. 3540-3544 ◽  
Author(s):  
Eline A. Oudeman ◽  
Jacoba P. Greving ◽  
Renske M. Van den Berg-Vos ◽  
Geert Jan Biessels ◽  
Esther E. Bron ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
White Matter ◽  
Odds Ratio ◽  
Adjusted Odds Ratio ◽  
White Matter Hyperintensities ◽  
Small Vessel Disease ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Vessel Disease ◽  
Increased Risk

Background and Purpose— Nonfocal transient neurological attacks (TNAs), such as unsteadiness, bilateral weakness, or confusion, are associated with an increased risk of stroke and dementia. Cerebral ischemia plays a role in their pathogenesis, but the precise mechanisms are unknown. We hypothesized that cerebral small vessel disease is involved in the pathogenesis of TNAs and assessed the relation between TNAs and manifestations of cerebral small vessel disease on magnetic resonance imaging. Methods— We included participants from the HBC (Heart-Brain Connection) study. In this study, hemodynamic and cardiovascular contributions to cognitive impairment have been studied in patients with heart failure, carotid artery occlusion, or possible vascular cognitive impairment, as well as in a reference group. We excluded participants with a history of stroke or transient ischemic attacks. The occurrence of the following 8 TNAs was assessed with a standardized interview: unconsciousness, confusion, amnesia, unsteadiness, bilateral leg weakness, blurred vision, nonrotatory dizziness, and paresthesias. The occurrence of TNAs was related to the presence of lacunes or white matter hyperintensities (Fazekas score, ≥2; early confluent or confluent lesions) in logistic regression analysis, adjusted for age, sex, and hypertension. Results— Of 304 participants (60% men; mean age, 67±9 years), 63 participants (21%) experienced ≥1 TNAs. Lacunes and early confluent or confluent white matter hyperintensities were more common in participants with TNAs than in participants without TNAs (35% versus 20%; adjusted odds ratio, 2.32 [95% CI, 1.22–4.40] and 48% versus 27%; adjusted odds ratio, 2.65 [95% CI, 1.44–4.90], respectively). Conclusions— In our study, TNAs are associated with the presence of lacunes and early confluent or confluent white matter hyperintensities of presumed vascular origin, which indicates that cerebral small vessel disease might play a role in the pathogenesis of TNAs.

Hippocampus-Based Static Functional Connectivity Mapping within White Matter in Mild Cognitive Impairment

2021 ◽  
Author(s):  
Yuan Jiang ◽  
Pan Wang ◽  
Jiaping Wen ◽  
Jianlin Wang ◽  
Hongyi Li ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
White Matter ◽  
Functional Connectivity ◽  
Inferior Frontal Gyrus ◽  
Structural Connectivity ◽  
Memory Loss ◽  
Middle Temporal Gyrus ◽  
Pathophysiological Mechanism ◽  
Temporal Pole

Abstract Mild cognitive impairment (MCI), as the early important stage of Alzheimer’s disease (AD), is clinically characterized by memory loss and cognitive impairment closely associated with the hippocampus. Accumulating studies have confirmed the presence of neural signal changes within white matter (WM) in resting-state fMRI. However, how the abnormal hippocampus affects the WM regions remained unclear in MCI. The current study employed 43 MCI, 71 very MCI (VMCI) and 87 matched healthy controls (HC) participants from the public OASIS 3 dataset. Adopting left and right hippocampus (HIP.R) as seed points respectively, whole-brain functional connectivity (FC) maps were obtained for each subject. Subsequently, one-way ANOVA was performed to explore the abnormal FC regions with hippocampus within gray matter (GM)/WM. Further probabilistic tracking was performed to explore whether the abnormal FC corresponded to structural connectivity. Compared to HC, MCI and VMCI groups exhibited common reduced static FC (SFC) in the middle temporal gyrus within GM, and temporal pole and inferior frontal gyrus within WM. Specific dysconnectivity was shown in the cerebellum_crus2 and inferior temporal gyrus within GM, and frontal gyrus within WM. In addition, the fiber bundle connecting the HIP.R and temporal pole within WM showed abnormally increased mean diffusion in MCI. The current study extended a new functional imaging direction for exploring the mechanism of memory decline, and promoted the understanding for pathophysiological mechanism in different early stages of AD.

scholarly journals The Cerebellum Is Related to Cognitive Dysfunction in White Matter Hyperintensities

2021 ◽  
Vol 13 ◽  
Author(s):  
Shanshan Cao ◽  
Jiajia Nie ◽  
Jun Zhang ◽  
Chen Chen ◽  
Xiaojing Wang ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
White Matter ◽  
White Matter Hyperintensities ◽  
Small Vessel Disease ◽  
Gray Matter Volume ◽  
Brain Regions ◽  
Anterior Cingulate ◽  
Magnetic Resonance Imaging Mri ◽  
Fazekas Scale ◽  
And Function

ObjectiveWhite matter hyperintensities (WMHs) on magnetic resonance imaging (MRI) is frequently presumed to be secondary to cerebral small vessel disease (CSVD) and associated with cognitive decline. The cerebellum plays a key role in cognition and has dense connections with other brain regions. Thus, the aim of this study was to investigate if cerebellar abnormalities could occur in CSVD patients with WMHs and the possible association with cognitive performances.MethodsA total of 104 right-handed patients with WMHs were divided into the mild WMHs group (n = 39), moderate WMHs group (n = 37), and severe WMHs group (n = 28) according to the Fazekas scale, and 36 healthy controls were matched for sex ratio, age, education years, and acquired resting-state functional MRI. Analysis of voxel-based morphometry of gray matter volume (GMV) and seed-to-whole-brain functional connectivity (FC) was performed from the perspective of the cerebellum, and their correlations with neuropsychological variables were explored.ResultsThe analysis revealed a lower GMV in the bilateral cerebellum lobule VI and decreased FC between the left- and right-sided cerebellar lobule VI with the left anterior cingulate gyri in CSVD patients with WMHs. Both changes in structure and function were correlated with cognitive impairment in patients with WMHs.ConclusionOur study revealed damaged GMV and FC in the cerebellum associated with cognitive impairment. This indicates that the cerebellum may play a key role in the modulation of cognitive function in CSVD patients with WMHs.

scholarly journals Suffering from cerebral small vessel disease with and without metabolic syndrome

Open Medicine ◽  
2019 ◽  
Vol 14 (1) ◽  
pp. 479-484
Author(s):  
Tatjana Bošković Matić ◽  
Gordana Toncev ◽  
Aleksandar Gavrilović ◽  
Dejan Aleksić
Keyword(s):  
Metabolic Syndrome ◽  
Cognitive Impairment ◽  
White Matter ◽  
White Matter Hyperintensities ◽  
Small Vessel Disease ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Cognitively Impaired ◽  
Vessel Disease ◽  
Neurology Clinic

AbstractBackgroundCerebral small vessel disease (CSVD) and metabolic syndrome were separately associated with cognitive impairment and depression. However, whether metabolic syndrome adds to cognitive impairment and depression in patients who already have CSVD remained unanswered.ObjectiveThe aim of our study was to investigate the association of metabolic syndrome with cognitive impairment and depression in patients with CSVD who have lacunar lesions or white matter hyperintensities.MethodsThis prospective cohort study was conducted at Neurology Clinic, Clinical Center, Kragujevac, Serbia. Main outcomes of the study were cognitive assessment, and assessment of depression among hospitalized patients with or without CSVD.ResultsThe study included 74 inpatients, 25 of them having lacunary infarctions, 24 with the white matter hyperintensities, and 25 control patients without CSVD. The CSVD was accompanied by impairment of cognition and depression, the patients with lacunary lesions being more cognitively impaired and more depressive than the patients with the white matter hyperintensities. The patients with CSVD who also had metabolic syndrome were more cognitively impaired and depressed than the patients with CSVD alone.ConclusionsIn conclusion, our study showed that metabolic syndrome is associated with further worsening of already impaired cognition and existing depression in patients with CSVD.

scholarly journals Enlarged perivascular spaces and cognitive impairment after stroke and transient ischemic attack

2016 ◽  
Vol 13 (1) ◽  
pp. 47-56 ◽  
Author(s):  
Francesco Arba ◽  
Terence J Quinn ◽  
Graeme J Hankey ◽  
Kennedy R Lees ◽  
Joanna M Wardlaw ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Regression Analysis ◽  
Cognitive Impairment ◽  
White Matter ◽  
White Matter Hyperintensities ◽  
Small Vessel Disease ◽  
Small Vessel ◽  
Perivascular Spaces ◽  
Vessel Disease ◽  
One Year

Background Previous studies suggested that enlarged perivascular spaces are neuroimaging markers of cerebral small vessel disease. However, it is not clear whether enlarged perivascular spaces are associated with cognitive impairment. We aimed to determine the cross-sectional relationship between enlarged perivascular spaces and small vessel disease, and to investigate the relationship between enlarged perivascular spaces and subsequent cognitive impairment in patients with recent cerebral ischemic event. Methods Anonymized data were accessed from the virtual international stroke trial archive. We rated number of lacunes, white matter hyperintensities, brain atrophy, and enlarged perivascular spaces with validated scales on magnetic resonance brain images after the index stroke. We defined cognitive impairment as a mini mental state examination score of ≤26, recorded at one year post stroke. We examined the associations between enlarged perivascular spaces and clinical and imaging markers of small vessel disease at presentation and clinical evidence of cognitive impairment at one year using linear and logistic regression models. Results We analyzed data on 430 patients with mean (±SD) age 64.7 (±12.7) years, 276 (64%) males. In linear regression analysis, age (β = 0.24; p < 0.001), hypertension (β = 0.09; p = 0.025), and deep white matter hyperintensities (β = 0.31; p < 0.001) were associated with enlarged perivascular spaces. In logistic regression analysis, basal ganglia enlarged perivascular spaces were independently associated with cognitive impairment at one year after adjusting for clinical confounders (OR = 1.72, 95% CI = 1.22–2.42) and for clinical and imaging confounders (OR = 1.54; 95% CI = 1.03–2.31). Conclusions Our data show that in patients with ischemic cerebral events, enlarged perivascular spaces are cross-sectionally associated with age, hypertension, and white matter hyperintensities and suggest that enlarged perivascular spaces in the basal ganglia are associated with cognitive impairment after one year.

scholarly journals Role of White Matter Hyperintensities and Related Risk Factors in Vascular Cognitive Impairment: A Review

Biomolecules ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1102
Author(s):  
Yiyi Chen ◽  
Xing Wang ◽  
Ling Guan ◽  
Yilong Wang
Keyword(s):  
Cognitive Impairment ◽  
White Matter ◽  
White Matter Hyperintensities ◽  
Small Vessel Disease ◽  
Treatment Strategies ◽  
Vascular Cognitive Impairment ◽  
Older Individuals ◽  
The Status ◽  
Vascular Origin ◽  
Detection And Diagnosis

White matter hyperintensities (WMHs) of presumed vascular origin are one of the imaging markers of cerebral small-vessel disease, which is prevalent in older individuals and closely associated with the occurrence and development of cognitive impairment. The heterogeneous nature of the imaging manifestations of WMHs creates difficulties for early detection and diagnosis of vascular cognitive impairment (VCI) associated with WMHs. Because the underlying pathological processes and biomarkers of WMHs and their development in cognitive impairment remain uncertain, progress in prevention and treatment is lagging. For this reason, this paper reviews the status of research on the features of WMHs related to VCI, as well as mediators associated with both WMHs and VCI, and summarizes potential treatment strategies for the prevention and intervention in WMHs associated with VCI.

Influence of White Matter Hyperintensities on Baseline and Longitudinal Amyloid-β in Cognitively Normal Individuals

2021 ◽  
pp. 1-11
Author(s):  
Fennie Choy Chin Wong ◽  
Seyed Ehsan Saffari ◽  
Chathuri Yatawara ◽  
Kok Pin Ng ◽  
Nagaendran Kandiah ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Executive Function ◽  
White Matter ◽  
White Matter Hyperintensities ◽  
Small Vessel Disease ◽  
Amyloid Β ◽  
Intracranial Volume ◽  
Linear Regression Models ◽  
Cognitively Normal

Background: The associations between small vessel disease (SVD) and cerebrospinal amyloid-β1-42 (Aβ1-42) pathology have not been well-elucidated. Objective: Baseline (BL) white matter hyperintensities (WMH) were examined for associations with month-24 (M24) and longitudinal Aβ1-42 change in cognitively normal (CN) subjects. The interaction of WMH and Aβ1-42 on memory and executive function were also examined. Methods: This study included 72 subjects from the Alzheimer’s Disease Neuroimaging Initiative. Multivariable linear regression models evaluated associations between baseline WMH/intracranial volume ratio, M24 and change in Aβ1-42 over two years. Linear mixed effects models evaluated interactions between BL WMH/ICV and Aβ1-42 on memory and executive function. Results: Mean age of the subjects (Nmales = 36) = 73.80 years, SD = 6.73; mean education years = 17.1, SD = 2.4. BL WMH was significantly associated with M24 Aβ1-42 (p = 0.008) and two-year change in Aβ1-42 (p = 0.006). Interaction between higher WMH and lower Aβ1-42 at baseline was significantly associated with worse memory at baseline and M24 (p = 0.003). Conclusion: BL WMH was associated with M24 and longitudinal Aβ1-42 change in CN. The interaction between higher WMH and lower Aβ1-42 was associated with poorer memory. Since SVD is associated with longitudinal Aβ1-42 pathology, and the interaction of both factors is linked to poorer cognitive outcomes, the mitigation of SVD may be correlated with reduced amyloid pathology and milder cognitive deterioration in Alzheimer’s disease.

Altered Functional Connectivity Patterns of Parietal Subregions Contribute to Cognitive Dysfunction in Patients with White Matter Hyperintensities

2021 ◽  
pp. 1-11
Author(s):  
Qiang Wei ◽  
Shanshan Cao ◽  
Yang Ji ◽  
Jun Zhang ◽  
Chen Chen ◽  
...  
Keyword(s):  
White Matter ◽  
Functional Connectivity ◽  
White Matter Hyperintensities ◽  
Parietal Lobe ◽  
Small Vessel Disease ◽  
Anterior Cingulate ◽  
Healthy Controls ◽  
Cingulate Gyrus ◽  
Anterior Cingulate Gyrus ◽  
Resting State Functional Connectivity

Background: The white matter hyperintensities (WMHs) are considered as one of the core neuroimaging findings of cerebral small vessel disease and independently associated with cognitive deficit. The parietal lobe is a heterogeneous area containing many subregions and play an important role in the processes of neurocognition. Objective: To explore the relationship between parietal subregions alterations and cognitive impairments in WHMs. Methods: Resting-state functional connectivity (rs-FC) analyses of parietal subregions were performed in 104 right-handed WMHs patients divided into mild (n = 39), moderate (n = 37), and severe WMHs (n = 28) groups according to the Fazekas scale and 36 healthy controls. Parietal subregions were defined using tractographic Human Brainnetome Atlas and included five subregions for superior parietal lobe, six subregions for inferior parietal lobe (IPL), and three subregions for precuneus. All participants underwent a neuropsychological test battery to evaluate emotional and general cognitive functions. Results: Differences existed between the rs-FC strength of IPL_R_6_2 with the left anterior cingulate gyrus, IPL_R_6_3 with the right dorsolateral superior frontal gyrus, and the IPL_R_6_5 with the left anterior cingulate gyrus. The connectivity strength between IPL_R_6_3 and the left anterior cingulate gyrus were correlated with AVLT-immediate and AVLT-recognition test in WMHs. Conclusion: We explored the roles of parietal subregions in WMHs using rs-FC. The functional connectivity of parietal subregions with the cortex regions showed significant differences between the patients with WMHs and healthy controls which may be associated with cognitive deficits in WMHs.

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