47 research outputs found
Colocalization of Tau but Not β-Amyloid with Cortical Superficial Siderosis in a Case with Probable CAA.
No full textCortical superficial siderosis (cSS) is a common feature in patients with cerebral amyloid angiopathy (CAA). The correlation between β-amyloid and/or tau pathology and the occurrence of cSS is unclear. We report on an 80-year-old male patient who was diagnosed with probable CAA according to modified Boston criteria and underwent longitudinal magnetic resonance imaging, amyloid positron emission tomography (PET), and additional tau PET imaging. Amyloid deposition presented predominantly in the contralateral hemisphere not affected by cSS. In contrast, tau deposition was predominantly overlapping with brain regions affected by cSS. Amyloid deposition was not different in the vicinity of cSS whereas tau depositions were elevated in the vicinity of CSS-affected regions compared to non-cSS-affected brain regions. This case of probable CAA suggests that cSS may be associated with a locally elevated tau pathology but not with increased fibrillary amyloid deposition
Regional Associations of Cortical Superficial Siderosis and β-Amyloid-Positron-Emission-Tomography Positivity in Patients With Cerebral Amyloid Angiopathy.
No full textObjective
This is a cross-sectional study to evaluate whether β-amyloid-(Aβ)-PET positivity and cortical superficial siderosis (cSS) in patients with cerebral amyloid angiopathy (CAA) are regionally colocalized.
Methods
Ten patients with probable or possible CAA (73.3 ± 10.9 years, 40% women) underwent MRI examination with a gradient-echo-T2*-weighted-imaging sequence to detect cSS and 18F-florbetaben PET examination to detect fibrillar Aβ. In all cortical regions of the Hammers Atlas, cSS positivity (MRI: ITK-SNAP segmentation) and Aβ-PET positivity (PET: ≥ mean value + 2 standard deviations of 14 healthy controls) were defined. Regional agreement of cSS- and Aβ-PET positivity was evaluated. Aβ-PET quantification was compared between cSS-positive and corresponding contralateral cSS-negative atlas regions. Furthermore, the Aβ-PET quantification of cSS-positive regions was evaluated in voxels close to cSS and in direct cSS voxels.
Results
cSS- and Aβ-PET positivity did not indicate similarity of their regional patterns, despite a minor association between the frequency of Aβ-positive patients and the frequency of cSS-positive patients within individual regions (r s = 0.277, p = 0.032). However, this association was driven by temporal regions lacking cSS- and Aβ-PET positivity. When analyzing all composite brain regions, Aβ-PET values in regions close to cSS were significantly higher than in regions directly affected with cSS (p < 0.0001). However, Aβ-PET values in regions close to cSS were not different when compared to corresponding contralateral cSS-negative regions (p = 0.603).
Conclusion
In this cross-sectional study, cSS and Aβ-PET positivity did not show regional association in patients with CAA and deserve further exploitation in longitudinal designs. In clinical routine, a specific cross-sectional evaluation of Aβ-PET in cSS-positive regions is probably not useful for visual reading of Aβ-PETs in patients with CAA
Ghrelins, obestatin, nesfatin-1 and leptin levels in pregnant women with and without hyperemesis gravidarum
No full textCatak, Zekiye/0000-0003-1973-3645; KUMRU, Selahattin/0000-0001-6615-7666; CITIL, Cihan/0000-0002-3006-4035WOS: 000319549100025PubMed: 23380589Objectives: The goal of this study was to compare levels of acyl and des-acyl ghrelin, obestatin, nesfatin-1 and leptin in healthy gravidas to hyperemesis gravidarum (HG) patients. Design and methods: Twenty pregnant women with HG and twenty healthy pregnant women all of similar ages, BMI and all at similar pregnancy development comprised the study cohort. Fasting serum samples were obtained and measured for acyl and des-acyl ghrelin, leptin, obestatin and nesfatin-1. Results: Nesfatin-1 concentrations in the HG group were higher compared to the control group whereas; leptin concentrations during pregnancy were lower in the HG group as compared to the control group. The two groups did not differ with regard to acyl and des-acyl ghrelin and obestatin. Conclusion: This pilot study suggests a possible role of leptin and nesfatin-1, which might be involved in the pathology of the disease. (C) 2013 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.Firat UniversityFirat University [1929]The authors would like to extend their thanks to Firat University for their financial support (project no: 1929)
Deep learning based Sequential model for malware analysis using Windows exe API Calls
No full textMalware development has seen diversity in terms of architecture and features. This advancement in the competencies of malware poses a severe threat and opens new research dimensions in malware detection. This study is focused on metamorphic malware, which is the most advanced member of the malware family. It is quite impossible for anti-virus applications using traditional signature-based methods to detect metamorphic malware, which makes it difficult to classify this type of malware accordingly. Recent research literature about malware detection and classification discusses this issue related to malware behavior. The main goal of this paper is to develop a classification method according to malware types by taking into consideration the behavior of malware. We started this research by developing a new dataset containing API calls made on the windows operating system, which represents the behavior of malicious software. The types of malicious malware included in the dataset are Adware, Backdoor, Downloader, Dropper, spyware, Trojan, Virus, and Worm. The classification method used in this study is LSTM (Long Short-Term Memory), which is a widely used classification method in sequential data. The results obtained by the classifier demonstrate accuracy up to 95% with 0.83 -score, which is quite satisfactory. We also run our experiments with binary and multi-class malware datasets to show the classification performance of the LSTM model. Another significant contribution of this research paper is the development of a new dataset for Windows operating systems based on API calls. To the best of our knowledge, there is no such dataset available before our research. The availability of our dataset on GitHub facilitates the research community in the domain of malware detection to benefit and make a further contribution to this domain.publishedVersion© 2020 Catak et al. Licence This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ Computer Science) and either DOI or URL of the article must be cited
Neuronal injury biomarkers for assessment of the individual cognitive reserve in clinically suspected Alzheimer's disease
No full textOBJECTIVES:
Many predictive or influencing factors have emerged in investigations of the cognitive reserve model of patients with Alzheimer's disease (AD). For example, neuronal injury, which correlates with cognitive decline in AD, can be assessed by [18F]-fluorodeoxyglucose positron-emission-tomography (FDG-PET), structural magnetic resonance imaging (MRI) and total tau in cerebrospinal fluid (CSFt-tau), all according to the A/T/N-classification. The aim of this study was to calculate residual cognitive performance based on neuronal injury biomarkers as a surrogate of cognitive reserve, and to test the predictive value of this index for the individual clinical course.
METHODS:
110 initially mild cognitive impaired and demented subjects (age 71 ± 8 years) with a final diagnosis of AD dementia were assessed at baseline by clinical mini-mental-state-examination (MMSE), FDG-PET, MRI and CSFt-tau. All neuronal injury markers were tested for an association with clinical MMSE and the resulting residuals were correlated with years of education. We used multiple regression analysis to calculate the expected MMSE score based on neuronal injury biomarkers and covariates. The residuals of the partial correlation for each biomarker and the predicted residualized memory function were correlated with individual cognitive changes measured during clinical follow-up (27 ± 13 months).
RESULTS:
FDG-PET correlated highly with clinical MMSE (R = -0.49, p < .01), whereas hippocampal atrophy to MRI (R = -0.15, p = .14) and CSFt-tau (R = -0.12, p = .22) showed only weak correlations. Residuals of all neuronal injury biomarker regressions correlated significantly with education level, indicating them to be surrogates of cognitive reserve. A positive residual was associated with faster cognitive deterioration at follow-up for the residuals of stand-alone FDG-PET (R = -0.36, p = .01) and the combined residualized memory function model (R = -0.35, p = .02).
CONCLUSIONS:
These findings suggest that subjects with higher cognitive reserve had accumulated more pathology, which subsequently caused a faster cognitive decline over time. Together with previous findings suggesting that higher reserve is associated with slower cognitive decline, we propose a biphasic reserve effect, with an initially protective phase followed by more rapid decompensation once the protection is overwhelmed
Design and first baseline data of the DZNE multicenter observational study on predementia Alzheimer's disease (DELCODE)
No full textBACKGROUND: Deep phenotyping and longitudinal assessment of predementia at-risk states of Alzheimer's disease (AD) are required to define populations and outcomes for dementia prevention trials. Subjective cognitive decline (SCD) is a pre-mild cognitive impairment (pre-MCI) at-risk state of dementia, which emerges as a highly promising target for AD prevention.METHODS: The German Center for Neurodegenerative Diseases (DZNE) is conducting the multicenter DZNE-Longitudinal Cognitive Impairment and Dementia Study (DELCODE), which focuses on the characterization of SCD in patients recruited from memory clinics. In addition, individuals with amnestic MCI, mild Alzheimer's dementia patients, first-degree relatives of patients with Alzheimer's dementia, and cognitively unimpaired control subjects are studied. The total number of subjects to be enrolled is 1000. Participants receive extensive clinical and neuropsychological assessments, magnetic resonance imaging, positron emission tomography, and biomaterial collection is perfomed. In this publication, we report cognitive and clinical data as well as apolipoprotein E (APOE) genotype and cerebrospinal fluid (CSF) biomarker results of the first 394 baseline data sets.RESULTS: In comparison with the control group, patients with SCD showed slightly poorer performance on cognitive and functional measures (Alzheimer's Disease Assessment Scale-cognitive part, Clinical Dementia Rating, Functional Activities Questionnaire), with all mean scores in a range which would be considered unimpaired. APOE4 genotype was enriched in the SCD group in comparison to what would be expected in the population and the frequency was significantly higher in comparison to the control group. CSF Aβ42 was lower in the SCD group in comparison to the control group at a statistical trend with age as a covariate. There were no group differences in Tau or pTau concentrations between the SCD and the control groups. The differences in all measures between the MCI group and the AD group were as expected.CONCLUSIONS: The initial baseline data for DELCODE support the approach of using SCD in patients recruited through memory clinics as an enrichment strategy for late-stage preclinical AD. This is indicated by slightly lower performance in a range of measures in SCD in comparison to the control subjects as well as by enriched APOE4 frequency and lower CSF Aβ42 concentration.TRIAL REGISTRATION: German Clinical Trials Register DRKS00007966 . Registered 4 May 2015.</p
Cognitive reserve hypothesis in frontotemporal dementia: A FDG-PET study.
No full textBACKGROUND AND OBJECTIVE
Reserve is defined as the ability to maintain cognitive functions relatively well at a given level of pathology. Early life experiences such as education are associated with lower dementia risk in general. However, whether more years of education guards against the impact of brain alterations also in frontotemporal dementia (FTD) has not been shown in a large patient collective. Therefore, we assessed whether education is associated with relatively high cognitive performance despite the presence of [18F]-fluorodeoxyglucose positron-emission-tomography (FDG-PET) hypometabolism in FTD.
METHODS
Sixty-six FTD subjects (age 67 ± 8 years) and twenty-four cognitively healthy controls (HC) were evaluated. Brain regions with FTD-related glucose hypometabolism in the contrast against HC and brain regions that correlate with the cognitive function were defined by a voxel-based analysis and individual FDG-PET values were extracted from all frontotemporal brain areas. Linear regression analysis served to test if education is associated with residualized cognitive performance and regional FDG-PET hypometabolism after controlling for global cognition.
RESULTS
Compared to healthy controls, patients with FTD showed glucose hypometabolism in bilateral frontal and temporal brain areas whereas cognition was only associated with deteriorated glucose metabolism in the left temporal lobe. The education level was significantly correlated with the residualized cognitive performance (residuals from regression analysis between hypometabolism and cognitive function as a quantitative index of reserve) and also negatively correlated with left temporal FDG-PET hypometabolism after controlling for cognition.
CONCLUSIONS
In patients with FTD, the education level predicts the existing left temporal FDG-PET hypometabolism at the same cognition level, supporting the cognitive reserve hypothesis in FTD
Tau plasma levels in subjective cognitive decline: Results from the DELCODE study
No full textPrevious studies have demonstrated increased tau plasma levels in patients with Alzheimer’s disease (AD) and mild cognitive impairment (MCI) due to AD. Much less is known whether increased tau plasma levels can already be detected in the pre-MCI stage of subjective cognitive decline (SCD). In the present study we measured tau plasma levels in 111 SCD patients and 134 age- and gender-matched cognitively healthy controls participating in the DZNE (German Center for Neurodegenerative Diseases) longitudinal study on cognition and dementia (DELCODE). Tau plasma levels were measured using ultra-sensitive, single-molecule array (Simoa) technology. We found no significant different tau plasma levels in SCD (3.4 pg/ml) compared with healthy controls (3.6 pg/ml) after controlling for age, gender, and education (p = 0.137). In addition, tau plasma levels did not correlate with Aβ42 (r = 0.073; p = 0.634), tau (r = −0.179; p = 0.240), and p-tau181 (r = −0.208; p = 0.171) cerebrospinal fluid (CSF) levels in a subgroup of 45 SCD patients with available CSF. In conclusion, plasma tau is not increased in SCD patients. In addition, the lack of correlation between tau in plasma and CSF in the examined cohort suggests that tau levels are affected by different factors in both biofluids
Clinical Routine FDG-PET Imaging of Suspected Progressive Supranuclear Palsy and Corticobasal Degeneration: A Gatekeeper for Subsequent Tau-PET Imaging?
No full textBackground: F-18-fluordeoxyglucose positron emission tomography (FDG-PET) is widely used for discriminative diagnosis of tau-positive atypical parkinsonian syndromes (T+APS). This approach now stands to be augmented with more specific tau tracers. Therefore, we retrospectively analyzed a large clinical routine dataset of FDG-PET images for evaluation of the strengths and limitations of stand-alone FDG-PET. Methods: A total of 117 patients (age 68.4 ± 11.1 y) underwent an FDG-PET exam. Patients were followed clinically for a minimum of one year and their final clinical diagnosis was recorded. FDG-PET was rated visually (positive/negative) and categorized as high, moderate or low likelihood of T+APS and other neurodegenerative disorders. We then calculated positive and negative predictive values (PPV/NPV) of FDG-PET readings for the different subgroups relative to their final clinical diagnosis. Results: Suspected diagnoses were confirmed by clinical follow-up (≥1 y) for 62 out of 117 (53%) patients. PPV was excellent when FDG-PET indicated a high likelihood of T+APS in combination with low to moderate likelihood of another neurodegenerative disorder. PPV was distinctly lower when FDG-PET indicated only a moderate likelihood of T+APS or when there was deemed equal likelihood of other neurodegenerative disorder. NPV of FDG-PET with a low likelihood for T+APS was high. Conclusions: FDG-PET has high value in clinical routine evaluation of suspected T+APS, gaining satisfactory differential diagnosis in two thirds of the patients. One third of patients would potentially profit from further evaluation by more specific radioligands, with FDG-PET serving gatekeeper function for the more expensive methods
