scholarly journals Heterogeneous Disease Progression in a Mouse Model of Vascular Cognitive Impairment

2020 ◽  
Vol 21 (8) ◽  
pp. 2820 ◽  
Author(s):  
Na Kyung Lee ◽  
Hunnyun Kim ◽  
Jehoon Yang ◽  
Jeyun Kim ◽  
Jeong Pyo Son ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Disease Progression ◽  
Treatment Options ◽  
Neuronal Loss ◽  
Vascular Cognitive Impairment ◽  
Wild Type ◽  
Heterogeneous Nature ◽  
Vascular Compromise ◽  
5Xfad Mice ◽  
The Right

Recently, an asymmetric vascular compromise approach that replicates many aspects of human vascular cognitive impairment (VCI) has been reported. The present study aimed to first investigate on the reproducibility in the disease progression of this newly reported VCI model using wild-type C57BL6/J mice. The second aim was to assess how this approach will affect the disease progression of transgenic Alzheimer’s disease (AD) 5XFAD mice subjected to VCI. C57BL6/J and 5XFAD mice were subjected to VCI by placing an ameroid constrictor on the right CCA and a microcoil on the left CCA. Infarcts and hippocampal neuronal loss did not appear predominantly in the right (ameroid side) as expected but randomly in both hemispheres. The mortality rate of C57BL6/J mice was unexpectedly high. Inducing VCI reduced amyloid burden in the hippocampi of 5XFAD mice. Since VCI is known to be complex and complicated, the heterogeneous disease progression observed from this current study shares close resemblance to the clinical manifestation of VCI. This heterogeneity, however, makes it challenging to test novel treatment options using this model. Further study is warranted to tackle the heterogeneous nature of VCI.

scholarly journals Cerebral Microinfarcts: A Systematic Review of Neuropathological Studies

2012 ◽  
Vol 32 (3) ◽  
pp. 425-436 ◽  
Author(s):  
Manon Brundel ◽  
Jeroen de Bresser ◽  
Jeroen J van Dillen ◽  
L Jaap Kappelle ◽  
Geert Jan Biessels
Keyword(s):  
Cognitive Impairment ◽  
High Resolution ◽  
Neuronal Loss ◽  
Weighted Average ◽  
Vascular Cognitive Impairment ◽  
Brain Regions ◽  
Older Individuals ◽  
High Resolution Mri ◽  
Magnetic Resonance Imaging Mri

Vascular cognitive impairment is an umbrella term for cognitive dysfunction associated with and presumed to be caused by vascular brain damage. Autopsy studies have identified microinfarcts as an important neuropathological correlate of vascular cognitive impairment that escapes detection by conventional magnetic resonance imaging (MRI). As a frame of reference for future high-resolution MRI studies, we systematically reviewed the literature on neuropathological studies on cerebral microinfarcts in the context of vascular disease, vascular risk factors, cognitive decline and dementia. We identified 32 original patient studies involving 10,515 people. The overall picture is that microinfarcts are common, particularly in patients with vascular dementia (weighted average 62%), Alzheimer's disease (43%), and demented patients with both Alzheimer-type and cerebrovascular pathology (33%) compared with nondemented older individuals (24%). In many patients, multiple microinfarcts were detected. Microinfarcts are described as minute foci with neuronal loss, gliosis, pallor, or more cystic lesions. They are found in all brain regions, possibly more so in the cerebral cortex, particularly in watershed areas. Reported sizes vary from 50 μm to a few mm, which is within the detection limit of current high-resolution MRI. Detection of these lesions in vivo would have a high potential for future pathophysiological studies in vascular cognitive impairment.

Vascular Cognitive Impairment

2017 ◽  
Author(s):  
Rahul Karamchandani ◽  
Nancy R. Barbas
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Treatment Options ◽  
Large Body ◽  
Vascular Cognitive Impairment ◽  
Common Cause ◽  
Small Vessels ◽  
Cognitive Disturbances ◽  
Large Vessels

Vascular cognitive impairment (VCI) refers to the spectrum of cognitive disturbances that result from cerebrovascular brain injury. Cerebrovascular disease is associated with multiple underlying pathologies. Risk factors, clinical features, and treatment options overlap with those associated with Alzheimer’s disease, another common cause of cognitive decline. The complexity of vascular cognitive impairment and, notably, the interplay between clinical, pathologic, genetic, and biomarker characteristics of VCI and Alzheimer’s disease are discussed. The chapter places an emphasis on vascular cognitive impairment resulting from disease affecting small vessels, in contrast to that due to disease involving large vessels, in an effort to focus on a large body of evolving work and ongoing attempts at improving understanding of this complex entity.

scholarly journals The Associations Between White Matter Disruptions and Cognitive Decline at the Early Stage of Subcortical Vascular Cognitive Impairment: A Case–Control Study

2021 ◽  
Vol 13 ◽  
Author(s):  
Yanan Qiao ◽  
Xuwen He ◽  
Junying Zhang ◽  
Ying Liang ◽  
Wen Shao ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Cognitive Assessment ◽  
Case Control Study ◽  
Early Stage ◽  
Vascular Cognitive Impairment ◽  
Case Control ◽  
Bonferroni Correction ◽  
The Right ◽  
Control Study ◽  
Subcortical Vascular Cognitive Impairment

ObjectiveEmerging evidence suggests that white matter (WM) disruption is associated with the incidence of subcortical vascular cognitive impairment (SVCI). However, our knowledge regarding this relationship in the early stage of SVCI is limited. We aimed to investigate the associations between WM disruptions and cognitive declines at the early stage of SVCI.MethodWe performed a case–control study, involving 22 cases and 19 controls. The cases were patients at the early stage of SVCI, which was defined as subcortical ischemic vascular disease with normal global cognitive measures (pre-SVCI). The controls were healthy people matched by age, sex, and education years. We assessed the differences in a battery of neuropsychological tests between the two groups, investigated the diffusion changes in 40 WM tracts among the participants via an atlas-based segmentation strategy, and compared the differences between the cases and controls by multiple linear regression analysis. We then evaluated the relationships between diffusion indices and cognitive assessment scores by Pearson’s correlation.ResultsThe pre-SVCI group exhibited significant differences in the Montreal cognitive assessment (MoCA), Rey–Osterrieth Complex Figure (R-O)-copy, and Trail Making Test (TMT)-B test compared with the controls. Compared with the controls, some long associative and projective bundles, such as the right anterior corona radiata (ACR), the right inferior fronto-occipital fasciculus (IFOF), and the left external capsule (EC), were extensively damaged in cases after Bonferroni correction (p < 0.05/40). Damages to specific fibers, such as the right ACR, IFOF, and posterior thalamic radiation (PTR), exhibited significant correlations with declines in MoCA, R-O delay, and the Mini-Mental State Examination (MMSE), respectively, after Bonferroni correction (p < 0.05/14).ConclusionLong WM tracts, especially those in the right hemisphere, were extensively damaged in the pre-SVCI patients and correlated with declines in executive functions and spatial processing. Patients of pre-SVCI are likely at an ultra-early stage of SVCI, and there is a very high risk of this condition becoming SVCI.

scholarly journals Microbial pathogens induce neurodegeneration in Alzheimer’s disease mice: protection by microglial regulation

2022 ◽  
Vol 19 (1) ◽  
Author(s):  
Tal Ganz ◽  
Nina Fainstein ◽  
Amit Elad ◽  
Marva Lachish ◽  
Smadar Goldfarb ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cortical Neuron ◽  
Neuronal Death ◽  
Neuronal Loss ◽  
Microbial Pathogens ◽  
Wild Type ◽  
Tlr Agonists ◽  
Neurodegenerative Process ◽  
5Xfad Mice

Abstract Background Neurodegeneration is considered the consequence of misfolded proteins’ deposition. Little is known about external environmental effects on the neurodegenerative process. Infectious agent-derived pathogen-associated molecular patterns (PAMPs) activate microglia, key players in neurodegenerative diseases. We hypothesized that systemic microbial pathogens may accelerate neurodegeneration in Alzheimer’s disease (AD) and that microglia play a central role in this process. Methods We examined the effect of an infectious environment and of microbial Toll-like receptor (TLR) agonists on cortical neuronal loss and on microglial phenotype in wild type versus 5xFAD transgenic mice, carrying mutated genes associated with familial AD. Results We examined the effect of a naturally bred environment on the neurodegenerative process. Earlier and accelerated cortical neuron loss occurred in 5xFAD mice housed in a natural (“dirty”) environment than in a specific-pathogen-free (SPF) environment, without increasing the burden of Amyloid deposits and microgliosis. Neuronal loss occurred in a microglia-rich cortical region but not in microglia-poor CA regions of the hippocampus. Environmental exposure had no effect on cortical neuron density in wild-type mice. To model the neurodegenerative process caused by the natural infectious environment, we injected systemically the bacterial endotoxin lipopolysaccharide (LPS), a TLR4 agonist PAMP. LPS caused cortical neuronal death in 5xFAD, but not wt mice. We used the selective retinoic acid receptor α agonist Am580 to regulate microglial activation. In primary microglia isolated from 5xFAD mice, Am580 markedly attenuated TLR agonists-induced iNOS expression, without canceling their basic immune response. Intracerebroventricular delivery of Am580 in 5xFAD mice reduced significantly the fraction of (neurotoxic) iNOS + microglia and increased the fraction of (neuroprotective) TREM2 + microglia. Furthermore, intracerebroventricular delivery of Am580 prevented neurodegeneration induced by microbial TLR agonists. Conclusions Exposure to systemic infections causes neurodegeneration in brain regions displaying amyloid pathology and high local microglia density. AD brains exhibit increased susceptibility to microbial PAMPs’ neurotoxicity, which accelerates neuronal death. Microglial modulation protects the brain from microbial TLR agonist PAMP-induced neurodegeneration.

scholarly journals Impaired Glymphatic Function and Pulsation Alterations in a Mouse Model of Vascular Cognitive Impairment

2022 ◽  
Vol 13 ◽  
Author(s):  
Mosi Li ◽  
Akihiro Kitamura ◽  
Joshua Beverley ◽  
Juraj Koudelka ◽  
Jessica Duncombe ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Carotid Stenosis ◽  
Molecular Layer ◽  
Amyloid Β ◽  
Vascular Cognitive Impairment ◽  
Wild Type ◽  
Fluorescent Tracer ◽  
Pial Arteries ◽  
Dorsolateral Cortex ◽  
Large Vessel Disease

Large vessel disease and carotid stenosis are key mechanisms contributing to vascular cognitive impairment (VCI) and dementia. Our previous work, and that of others, using rodent models, demonstrated that bilateral common carotid stenosis (BCAS) leads to cognitive impairment via gradual deterioration of the neuro-glial-vascular unit and accumulation of amyloid-β (Aβ) protein. Since brain-wide drainage pathways (glymphatic) for waste clearance, including Aβ removal, have been implicated in the pathophysiology of VCI via glial mechanisms, we hypothesized that glymphatic function would be impaired in a BCAS model and exacerbated in the presence of Aβ. Male wild-type and Tg-SwDI (model of microvascular amyloid) mice were subjected to BCAS or sham surgery which led to a reduction in cerebral perfusion and impaired spatial learning acquisition and cognitive flexibility. After 3 months survival, glymphatic function was evaluated by cerebrospinal fluid (CSF) fluorescent tracer influx. We demonstrated that BCAS caused a marked regional reduction of CSF tracer influx in the dorsolateral cortex and CA1-DG molecular layer. In parallel to these changes increased reactive astrogliosis was observed post-BCAS. To further investigate the mechanisms that may lead to these changes, we measured the pulsation of cortical vessels. BCAS impaired vascular pulsation in pial arteries in WT and Tg-SwDI mice. Our findings show that BCAS influences VCI and that this is paralleled by impaired glymphatic drainage and reduced vascular pulsation. We propose that these additional targets need to be considered when treating VCI.

Prevalence of Vascular Cognitive Impairment Among a Veteran Population

2008 ◽  
Author(s):  
Ruth E. Yoash-Gantz ◽  
Kristin L. Humphrey ◽  
Jacqueline W. Friedman
Keyword(s):  
Cognitive Impairment ◽  
Vascular Cognitive Impairment
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