Background
Mechanical Thrombectomy (MT) has improved outcomes in acute ischemic stroke (AIS) due to Large Vessel Obstruction (LVO). However, there is limited data on the safety and outcomes of MT in ...AIS patients with thrombocytopenia. This study aims to assess the efficacy and safety of MT in this population.
Methods
Following the PRISMA guidelines, a comprehensive systematic review was conducted using PubMed, Embase, Web of Science, and Scopus. Studies meeting inclusion criteria underwent rigorous risk of bias assessment using the ROBINS-I tool. We compared outcomes between patients with and without thrombocytopenia undergoing MT. Using the R software version 4.3.1, meta-analyses were conducted employing random-effect models.
Results
This meta-analysis encompassed data from 5 studies. Thrombocytopenic AIS patients who underwent MT (n = 974) exhibited lower rates of functional independence (OR 0.83, 95% CI 0.71–0.98; p = 0.030) compared to patients with normal platelet counts (n = 2036). In addition, the thrombocytopenic group experienced higher mortality as compared to the group with normal platelet counts (OR 1.76, 95% CI 1.26–2.45; p < 0.001). Rates of sICH were found to be similar between groups (OR 1.20, 95% CI 0.74–1.93; p = 0.456), as were rates of successful recanalization (OR 0.94, 95% CI 0.47–1.87; p = 0.863). Lastly, no significant differences were observed in procedure times between thrombocytopenic and non-thrombocytopenic groups.
Conclusion
As compared to patients without thrombocytopenia, thrombocytopenic AIS patients undergoing MT displayed lower functional independence and higher mortality rates, with no significant differences in sICH or successful recanalization.
The pathology-based classification of Alzheimer’s disease (AD) and other neurodegenerative diseases is a work in progress that is important for both clinicians and basic scientists. Analyses of large ...autopsy series, biomarker studies, and genomics analyses have provided important insights about AD and shed light on previously unrecognized conditions, enabling a deeper understanding of neurodegenerative diseases in general. After demonstrating the importance of correct disease classification for AD and primary age-related tauopathy, we emphasize the public health impact of an underappreciated AD “mimic,” which has been termed “hippocampal sclerosis of aging” or “hippocampal sclerosis dementia.” This pathology affects >20% of individuals older than 85 years and is strongly associated with cognitive impairment. In this review, we provide an overview of current hypotheses about how genetic risk factors (GRN, TMEM106B, ABCC9, and KCNMB2), and other pathogenetic influences contribute to TDP-43 pathology and hippocampal sclerosis. Because hippocampal sclerosis of aging affects the “oldest-old” with arteriolosclerosis and TDP-43 pathologies that extend well beyond the hippocampus, more appropriate terminology for this disease is required. We recommend “cerebral age-related TDP-43 and sclerosis” (CARTS). A detailed case report is presented, which includes neuroimaging and longitudinal neurocognitive data. Finally, we suggest a neuropathology-based diagnostic rubric for CARTS.
ABSTRACT
BACKGROUND AND PURPOSE
Interpreting the clinical significance of moderate‐to‐severe global cerebral atrophy (GCA) is a conundrum for many clinicians, who visually interpret brain imaging ...studies in routine clinical practice. GCA may be attributed to normal aging, Alzheimer's disease (AD), or cerebrovascular disease (CVD). Understanding the relationships of GCA with aging, AD, and CVD is important for accurate diagnosis and treatment decisions for cognitive complaints.
METHODS
To elucidate the relative associations of age, moderate‐to‐severe white matter hyperintensities (WMHs), and moderate‐to‐severe medial temporal lobe atrophy (MTA), with moderate‐to‐severe GCA, we visually rated clinical brain imaging studies of 325 participants from a community based sample. Logistic regression analysis was conducted to assess the relations of GCA with age, WMH, and MTA.
RESULTS
The mean age was 76.2 (±9.6) years, 40.6% were male, and the mean educational attainment was 15.1 (±3.7) years. Logistic regression results demonstrated that while a 1‐year increase in age was associated with GCA (OR = 1.04; P = .04), MTA (OR = 3.7; P < .001), and WMH (OR = 8.80; P < .001) were strongly associated with GCA in our study population. Partial correlation analysis showed that the variance of GCA explained by age is less than the variance attributed to MTA and WMH (r = .13, .21, and .43, respectively).
CONCLUSIONS
Moderate‐to‐severe GCA is most likely to occur in the presence of AD or CVD and should not be solely attributed to age when evaluating clinical imaging findings in the workup of cognitive complaints. Developing optimal diagnostic and treatment strategies for cognitive decline in the setting of GCA requires an understanding of its risk factors in the aging population.
White matter hyperintensities (WMH), associated with both dementia risk and progression, can individually progress, remain stable, or even regress influencing cognitive decline related to specific ...cerebrovascular-risks. This study details the development and validation of a registration protocol to assess regional, within-subject, longitudinal WMH changes (ΔWMH) that is currently lacking in the field.
3D-FLAIR images (baseline and one-year-visit) were used for protocol development and validation. The method was validated by assessing the correlation between forward and reverse longitudinal registration, and between summated regional progression-regression volumes and Global ΔWMH. The clinical relevance of growth-regression ΔWMH were explored in relation to an executive function test.
MRI scans for 79 participants (73.5 ± 8.8 years) were used in this study. Global ΔWMH vs. summated regional progression-regression volumes were highly associated (r2 = 0.90; p-value < 0.001). Bi-directional registration validated the registration method (r2 = 0.999; p-value < 0.001). Growth and regression, but not overall ΔWMH, were associated with one-year declines in performance on Trial-Making-Test-B.
This method presents a unique registration protocol for maximum tissue alignment, demonstrating three distinct patterns of longitudinal within-subject ΔWMH (stable, growth and regression).
These data detail the development and validation of a registration protocol for use in assessing within-subject, voxel-level alterations in WMH volume. The methods developed for registration and intensity correction of longitudinal within-subject FLAIR images allow regional and within-lesion characterization of longitudinal ΔWMH. Assessing the impact of associated cerebrovascular-risks and longitudinal clinical changes in relation to dynamic regional ΔWMH is needed in future studies.
Tracking dynamic changes in white matter hyperintensities (WMH) is critical for the assessment of longitudinal degenerative and vascular disease related injury. WMHs have been shown to progress, remain stable, or even regress over time. The present study sought to develop and validate a registration protocol that will allow the assessment of regional, within-subject, longitudinal WMH changes over periods as short as one-year, necessary for use in future clinical trials of disease modifying therapies that hope to limit, stabilize, or even reverse deleterious WMH injury. Display omitted
•Midpoint co-registration of FLAIR images can be used to assess longitudinal WMH changes.•Image intensity z-score corrections minimize co-registration T2 signal artifacts.•Dynamic intra-subject WMH volume changes include a mix of both progression and regression.•WMH progression is associated with a decline in executive function.•This standardized protocol can accurately detect such changes over a short one-year interval.
Significant variability in white matter hyperintensity quantification can occur as a result of variability in standardizing selection of the image center of gravity, software package, thresholding ...techniques, and manual editing procedures. Controlling for such variables can reduce the interscan post-acquisition processing variability to less than 0.5%.
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•Current protocols for WMH volumetric quantification have substantial variability.•Selection of image center, software, threshold, and manual editing introduce variability.•Methods to address these sources-of-variability can be developed and are essential for reliable interpretation of data.•Standardizing techniques can reduce intra-scan variability to less than 0.5%.
Disparate research sites using identical or near-identical magnetic resonance imaging (MRI) acquisition techniques often produce results that demonstrate significant variability regarding volumetric quantification of white matter hyperintensities (WMH) in the aging population. The sources of such variability have not previously been fully explored.
3D FLAIR sequences from a group of randomly selected aged subjects were analyzed to identify sources-of-variability in post-acquisition processing that can be problematic when comparing WMH volumetric data across disparate sites. The methods developed focused on standardizing post-acquisition protocol processing methods to develop a protocol with less than 0.5% inter-rater variance.
A series of experiments using standard MRI acquisition sequences explored post-acquisition sources-of-variability in the quantification of WMH volumetric data. Sources-of-variability included: the choice of image center, software suite and version, thresholding selection, and manual editing procedures (when used). Controlling for the identified sources-of-variability led to a protocol with less than 0.5% variability between independent raters in post-acquisition WMH volumetric quantification.
Post-acquisition processing techniques can introduce an average variance approaching 15% in WMH volume quantification despite identical scan acquisitions. Understanding and controlling for such sources-of-variability can reduce post-acquisition quantitative image processing variance to less than 0.5%.
Considerations of potential sources-of-variability in MRI volume quantification techniques and reduction in such variability is imperative to allow for reliable cross-site and cross-study comparisons.
Alzheimer's disease (AD) pathology and hypertension (HTN) are risk factors for development of white matter (WM) alterations and might be independently associated with these alterations in older ...adults.
To evaluate the independent and synergistic effects of HTN and AD pathology on WM alterations.
Clinical measures of cerebrovascular disease risk were collected from 62 participants in University of Kentucky Alzheimer's Disease Center studies who also had cerebrospinal fluid (CSF) sampling and MRI brain scans. CSF Aβ1-42 levels were measured as a marker of AD, and fluid-attenuated inversion recovery imaging and diffusion tensor imaging were obtained to assess WM macro- and microstructural properties. Linear regression analyses were used to assess the relationships among WM alterations, cerebrovascular disease risk, and AD pathology. Voxelwise analyses were performed to examine spatial patterns of WM alteration associated with each pathology.
HTN and CSF Aβ1-42 levels were each associated with white matter hyperintensities (WMH). Also, CSF Aβ1-42 levels were associated with alterations in normal appearing white matter fractional anisotropy (NAWM-FA), whereas HTN was marginally associated with alterations in NAWM-FA. Linear regression analyses demonstrated significant main effects of HTN and CSF Aβ1-42 on WMH volume, but no significant HTN×CSF Aβ1-42 interaction. Furthermore, voxelwise analyses showed unique patterns of WM alteration associated with hypertension and CSF Aβ1-42.
Associations of HTN and lower CSF Aβ1-42 with WM alteration were statistically and spatially distinct, suggesting independent rather than synergistic effects. Considering such spatial distributions may improve diagnostic accuracy to address each underlying pathology.
Subcortical white matter hyperintensities (WMHs) in the aging population frequently represent vascular injury that may lead to cognitive impairment. WMH progression is well described, but the factors ...underlying WMH regression remain poorly understood. A sample of 351 participants from the Alzheimer's Disease Neuroimaging Initiative 2 (ADNI2) was explored who had WMH volumetric quantification, structural brain measures, and cognitive measures (memory and executive function) at baseline and after approximately 2 years. Selected participants were categorized into three groups based on WMH change over time, including those that demonstrated regression (
= 96; 25.5%), stability (
= 72; 19.1%), and progression (
= 209; 55.4%). There were no significant differences in age, education, sex, or cognitive status between groups. Analysis of variance demonstrated significant differences in atrophy between the progression and both regression (
= 0.004) and stable groups (
= 0.012). Memory assessments improved over time in the regression and stable groups but declined in the progression group (
= 0.003;
= 0.018). WMH regression is associated with decreased brain atrophy and improvement in memory performance over two years compared to those with WMH progression, in whom memory and brain atrophy worsened. These data suggest that WMHs are dynamic and associated with changes in atrophy and cognition.
New nanophenolic oxime complexes of the type M(κ2‐Saly)2 {where HSaly = salicyl‐aldoxime; M = Co(1), Ni(2), Cu(3), Pd(4), Pt(5), Zn(6), Cd(7), and Hg(8)} were prepared and characterized by different ...spectroscopic methods. The surface morphology and the micrographs of the investigated complexes were checked by the scanning electron microscopy (SEM) and X‐ray diffraction (XRD) analysis. The results indicate the successful preparation of nanocomplexes with nanoparticles size. In addition, the antibacterial activity was studied against three different pathogenic bacteria, and the Pt(II) complex displayed the highest activity compared with free salicylaldoxime ligand and other complexes. Magnetic susceptibility and ultraviolet (UV)–visible spectroscopic measurements were used to deduce the geometry of the complexes, which was then validated by density functional theory (DFT) calculations. The in vitro antitumor activity was investigated by MTT assays against HepG‐2 cell lines. The Zn(II) and Pt(II) complexes displayed good activity with IC50 values at 17.31 ± 0.95 and 11.78 ± 0.54 μM, respectively. In contrast, the Cu(Saly)2 and Ni(Saly)2 complexes showed the lowest activity against tested cells.
We have reported synthesis of M(II) salicylaldoxime complexes and the prepared compounds were characterized by spectroscopic methods. The anticancer activity of complexes 1–6 were tested against human hepatoma carcinoma HepG‐2 cell line using MTT. In addition, the biological activity was tested against three pathogenic bacteria. Also, the nanoproperties were studied using SEM and XRD, and the results indicate the successful preparation of nanocomplexes with nanoparticles size. Furthermore, DFT was used to analyze the structural properties of the compounds.
Small cerebral vascular disease (SCeVD) demonstrated by white matter hyperintensity (WMH) on MRI contributes to the development of dementia in Alzheimer's disease (AD), but it has not been possible ...to correlate onset, severity, or protein components of SCeVD with characteristics of WMH in living patients. Plasma endothelial‐derived exosomes (EDEs) were enriched by two‐step immunoabsorption from four groups of participants with no clinical evidence of cerebrovascular disease: cognitively normal (CN) without WMH (CN without SCeVD, n = 20), CN with SCeVD (n = 22), preclinical AD (pAD) + mild cognitive impairment (MCI) without SCeVD (pAD/MCI without SCeVD, n = 22), and pAD/MCI with SCeVD (n = 16) for ELISA quantification of cargo proteins. Exosome marker CD81‐normalized EDE levels of the cerebrovascular‐selective biomarkers large neutral amino acid transporter 1 (LAT‐1), glucose transporter type 1 (Glut‐1), and permeability‐glycoprotein (p‐GP, ABCB1) were similarly significantly higher in the CN with SCeVD and pAD/MCI with SCeVD groups than their corresponding control groups without SCeVD. CD81‐normalized EDE levels of Aβ40 and Aβ42 were significantly higher in the pAD/MCI with SCeVD group but not in the CN with SCeVD group relative to controls without SCeVD. Levels of normal cellular prion protein (PrPc), a receptor for amyloid peptides, and phospho‐181T‐tau were higher in both CN and pAD/MCI with SCeVD groups than in the corresponding controls. High EDE levels of Aβ40, Aβ42, and phospho‐181T‐tau in patients with WMH suggesting SCeVD appear at the pre‐clinical or MCI stage of AD and therapeutic lowering of neurotoxic peptide levels may delay progression of AD angiopathy.
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