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.

scholarly journals Automatic Segmentation of the Dorsal Claustrum in Humans Using in vivo High-Resolution MRI

2020 ◽  
Vol 1 (1) ◽  
Author(s):  
Shai Berman ◽  
Roey Schurr ◽  
Gal Atlan ◽  
Ami Citri ◽  
Aviv A Mezer
Keyword(s):  
High Resolution ◽  
Automatic Segmentation ◽  
Thin Sheet ◽  
Brain Regions ◽  
Reproducible Research ◽  
Human Connectome Project ◽  
High Resolution Mri ◽  
Magnetic Resonance Imaging Mri ◽  
And Function

Abstract The claustrum is a thin sheet of neurons enclosed by white matter and situated between the insula and the putamen. It is highly interconnected with sensory, frontal, and subcortical regions. The deep location of the claustrum, with its fine structure, has limited the degree to which it could be studied in vivo. Particularly in humans, identifying the claustrum using magnetic resonance imaging (MRI) is extremely challenging, even manually. Therefore, automatic segmentation of the claustrum is an invaluable step toward enabling extensive and reproducible research of the anatomy and function of the human claustrum. In this study, we developed an automatic algorithm for segmenting the human dorsal claustrum in vivo using high-resolution MRI. Using this algorithm, we segmented the dorsal claustrum bilaterally in 1068 subjects of the Human Connectome Project Young Adult dataset, a publicly available high-resolution MRI dataset. We found good agreement between the automatic and manual segmentations performed by 2 observers in 10 subjects. We demonstrate the use of the segmentation in analyzing the covariation of the dorsal claustrum with other brain regions, in terms of macro- and microstructure. We identified several covariance networks associated with the dorsal claustrum. We provide an online repository of 1068 bilateral dorsal claustrum segmentations.

scholarly journals In vivo staging of regional amyloid deposition

Neurology ◽  
2017 ◽  
Vol 89 (20) ◽  
pp. 2031-2038 ◽  
Author(s):  
Michel J. Grothe ◽  
Henryk Barthel ◽  
Jorge Sepulcre ◽  
Martin Dyrba ◽  
Osama Sabri ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Medial Temporal Lobe ◽  
Brain Regions ◽  
Amyloid Deposition ◽  
Stage Model ◽  
Older Individuals ◽  
Full Cohort ◽  
Cross Sectional ◽  
Amyloid Pathology

Objectives:To estimate a regional progression pattern of amyloid deposition from cross-sectional amyloid-sensitive PET data and evaluate its potential for in vivo staging of an individual's amyloid pathology.Methods:Multiregional analysis of florbetapir (18F-AV45)–PET data was used to determine individual amyloid distribution profiles in a sample of 667 participants from the Alzheimer's Disease Neuroimaging Initiative cohort, including cognitively normal older individuals (CN) as well as patients with mild cognitive impairment and Alzheimer disease (AD) dementia. The frequency of regional amyloid positivity across CN individuals was used to construct a 4-stage model of progressing amyloid pathology, and individual distribution profiles were used to evaluate the consistency of this hierarchical stage model across the full cohort.Results:According to a 4-stage model, amyloid deposition begins in temporobasal and frontomedial areas, and successively affects the remaining associative neocortex, primary sensory-motor areas and the medial temporal lobe, and finally the striatum. Amyloid deposition in these brain regions showed a highly consistent hierarchical nesting across participants, where only 2% exhibited distribution profiles that deviated from the staging scheme. The earliest in vivo amyloid stages were mostly missed by conventional dichotomous classification approaches based on global florbetapir-PET signal, but were associated with significantly reduced CSF Aβ42 levels. Advanced in vivo amyloid stages were most frequent in patients with AD and correlated with cognitive impairment in individuals without dementia.Conclusions:The highly consistent regional hierarchy of PET-evidenced amyloid deposition across participants resembles neuropathologic observations and suggests a predictable regional sequence that may be used to stage an individual's progress of amyloid pathology in vivo.

scholarly journals Diffusion MRI studies in vascular cognitive impairment and dementia

2003 ◽  
Vol 25 (3) ◽  
pp. 188-191 ◽  
Author(s):  
Fabio L Urresta ◽  
David A Medina ◽  
Moises Gaviria
Keyword(s):  
Cognitive Impairment ◽  
Diffusion Tensor ◽  
Brain Connectivity ◽  
Vascular Cognitive Impairment ◽  
In Vivo Studies ◽  
Cerebral White Matter ◽  
Potential Efficacy ◽  
Magnetic Resonance Imaging Mri ◽  
Microstructural Integrity

Since its introduction more than two decades ago, Magnetic Resonance Imaging (MRI) has not only allowed for visualization of the macrostructure of the CNS, but also has been able to study dynamic processes which constitute the substrate of currently available MRI variants. While conventional Diffusion Weighted Imaging (DWI) permits a robust visualization of lesions just a few minutes after the onset of cerebral ischemia, Diffusion Tensor Imaging (DTI) measures the magnitude and direction of diffusion, leading to the characterization of cerebral white matter (WM) microstructural integrity. In this paper, the potential role of MRI techniques, particularly DTI, for the study of the relationship between changes in the microstructural integrity of WM and cognitive impairment in the context of cerebrovascular disease are discussed. Significant correlations between scores of behavioral measures of cognitive function and regional anisotropy values are an example of the potential efficacy of DTI for in vivo studies of brain connectivity in vascular neurodegenerative conditions.

scholarly journals High-resolution MRI: in vivo histology?

2005 ◽  
Vol 361 (1465) ◽  
pp. 137-146 ◽  
Author(s):  
Holly Bridge ◽  
Stuart Clare
Keyword(s):  
Magnetic Resonance Imaging ◽  
High Resolution ◽  
Post Mortem ◽  
Resonance Imaging ◽  
Brain Surface ◽  
High Resolution Mri ◽  
Magnetic Resonance Imaging Mri ◽  
The Brain ◽  
Very High

For centuries scientists have been fascinated with the question of how the brain works. Investigators have looked at both where different functions are localized and how the anatomical microstructure varies across the brain surface. Here we discuss how advances in magnetic resonance imaging (MRI) have allowed in vivo visualization of the fine structure of the brain that was previously only visible in post-mortem brains. We present data showing the correspondence between definitions of the primary visual cortex defined anatomically using very high-resolution MRI and functionally using functional MRI. We consider how this technology can be applied to allow the investigation of brains that differ from normal, and what this ever-evolving technology may be able to reveal about in vivo brain structure in the next few years.

scholarly journals Spatial inhibition of return is impaired in mild cognitive impairment and mild Alzheimer’s disease

2020 ◽  
Author(s):  
Xiong Jiang ◽  
James H. Howard ◽  
G. Wiliam Rebeck ◽  
R. Scott Turner
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Medial Temporal Lobe ◽  
Inhibition Of Return ◽  
Memory Performance ◽  
Brain Regions ◽  
List Type ◽  
Older Individuals

ABSTRACTSpatial inhibition of return (IOR) refers to the phenomenon by which individuals are slower to respond to stimuli appearing at a previously cued location compared to un-cued locations. Here we provide evidence supporting that spatial IOR is mildly impaired in individuals with mild cognitive impairment (MCI) or mild Alzheimer’s disease (AD), and the impairment is readily detectable using a novel double cue paradigm. Furthermore, reduced spatial IOR in high-risk healthy older individuals is associated with reduced memory and other neurocognitive task performance, suggesting that the novel double cue spatial IOR paradigm may be useful in detecting MCI and early AD.SIGNIFICANCE STATEMENTNovel double cue spatial inhibition of return (IOR) paradigm revealed a robust effect IOR deficits in individuals with mild cognitive impairment (MCI) or mild Alzheimer’s disease (AD)Spatial IOR effect correlates with memory performance in healthy older adults at a elevated risk of Alzheimer’s disease (with a family history or APOE e4 allele)The data suggests that double cue spatial IOR may be sensitive to detect early AD pathological changes, which may be linked to disease progress at the posterior brain regions (rather than the medial temporal lobe)

scholarly journals Evaluation and Treatment of Vascular Cognitive Impairment by Transcranial Magnetic Stimulation

2020 ◽  
Vol 2020 ◽  
pp. 1-17
Author(s):  
Mariagiovanna Cantone ◽  
Giuseppe Lanza ◽  
Francesco Fisicaro ◽  
Manuela Pennisi ◽  
Rita Bella ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Synaptic Plasticity ◽  
Transcranial Magnetic Stimulation ◽  
Magnetic Stimulation ◽  
Cortical Excitability ◽  
Disease Process ◽  
Vascular Cognitive Impairment ◽  
Future Research ◽  
Disease Modifying Drugs

The exact relationship between cognitive functioning, cortical excitability, and synaptic plasticity in dementia is not completely understood. Vascular cognitive impairment (VCI) is deemed to be the most common cognitive disorder in the elderly since it encompasses any degree of vascular-based cognitive decline. In different cognitive disorders, including VCI, transcranial magnetic stimulation (TMS) can be exploited as a noninvasive tool able to evaluate in vivo the cortical excitability, the propension to undergo neural plastic phenomena, and the underlying transmission pathways. Overall, TMS in VCI revealed enhanced cortical excitability and synaptic plasticity that seem to correlate with the disease process and progression. In some patients, such plasticity may be considered as an adaptive response to disease progression, thus allowing the preservation of motor programming and execution. Recent findings also point out the possibility to employ TMS to predict cognitive deterioration in the so-called “brains at risk” for dementia, which may be those patients who benefit more of disease-modifying drugs and rehabilitative or neuromodulatory approaches, such as those based on repetitive TMS (rTMS). Finally, TMS can be exploited to select the responders to specific drugs in the attempt to maximize the response and to restore maladaptive plasticity. While no single TMS index owns enough specificity, a panel of TMS-derived measures can support VCI diagnosis and identify early markers of progression into dementia. This work reviews all TMS and rTMS studies on VCI. The aim is to evaluate how cortical excitability, plasticity, and connectivity interact in the pathophysiology of the impairment and to provide a translational perspective towards novel treatments of these patients. Current pitfalls and limitations of both studies and techniques are also discussed, together with possible solutions and future research agenda.

scholarly journals Identification and Distribution of Novel Metabolites of Lolitrem B in Mice by High-Resolution Mass Spectrometry

Molecules ◽  
2020 ◽  
Vol 25 (2) ◽  
pp. 372 ◽  
Author(s):  
Priyanka Reddy ◽  
Aaron Elkins ◽  
Joanne Hemsworth ◽  
Kathryn Guthridge ◽  
Simone Vassiliadis ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
High Resolution ◽  
High Resolution Mass Spectrometry ◽  
Brain Regions ◽  
High Resolution Mass ◽  
Metabolic Products ◽  
Severe Intoxication ◽  
Lolitrem B ◽  
Resolution Mass

Lolitrem B is the most potent indole-diterpene mycotoxin produced by Epichloë festucae var. lolii (termed LpTG-1), with severe intoxication cases reported in livestock. To date, there are no in vivo metabolism studies conducted for the mycotoxin. A mouse model assay established for assessing toxicity of indole-diterpenes was used to investigate metabolic products of lolitrem B. Mice were administered lolitrem B at 0.5 and 2.0 mg/kg body weight (b.wt) intraperitoneally before body and brain tissues were collected at 6 h and 24 h post-treatment. Samples were cryoground and subjected to a biphasic or monophasic extraction. The aqueous and lipophilic phases were analysed using liquid chromatography high-resolution mass spectrometry (LC–HRMS); data analysis was performed with Compound Discoverer™ software. A total of 10 novel phase I metabolic products were identified in the lipophilic phase and their distribution in the liver, kidney and various brain regions are described. The biotransformation products of lolitrem B were found to be present in low levels in the brain. Based on structure–activity postulations, six of these may contribute towards the protracted tremors exhibited by lolitrem B-exposed animals.

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.

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