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  • 1
    Keywords: Germany ; DISEASE ; RISK ; METABOLISM ; PATIENT ; BLOOD-FLOW ; DEFICITS ; PATTERNS ; positron emission tomography ; POSITRON-EMISSION-TOMOGRAPHY ; tomography ; DEMENTIA ; PREDICTION ; PET ; AD ; MILD COGNITIVE IMPAIRMENT ; DECLINE ; IMPAIRMENT ; conversion ; FDG-PET ; EMISSION ; AACD ; aging-associated cognitive decline
    Abstract: While significantly reduced glucose metabolism in fronto-temporo-parietal and cingulate cortices has been demonstrated in Alzheimer's disease (AD) compared with controls, cerebral glucose metabolism in patients with mild cognitive impairment who subsequently develop AD is less well-defined. In the present study we measured cerebral glucose metabolism by positron emission tomography (PET) with F-18-2-fluoro-2-deoxy-D-glucose in 14 patients with aging-associated cognitive decline (AACD), 44 patients with AD, and 14 healthy control subjects at baseline. The AACD patients were clinically followed up, and conversion to AD was determined. Compared with controls, AACD patients had significantly reduced glucose metabolism in the right precuneus, posterior cingulate, right angular gyrus, and bilateral middle temporal cortices, while the respective deficits were more pronounced in AD patients and also involved the frontal cortices. AACD patients who subsequently converted to AD (AACD-converters) showed more extended metabolic changes which also involved the frontal and temporal cortices, right cingulate gyrus, right thalamus, and bilateral precuneus. (c) 2006 Elsevier Ireland Ltd. All rights reserved
    Type of Publication: Journal article published
    PubMed ID: 17524628
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  • 2
    Keywords: COHORT ; EPIDEMIOLOGY ; POPULATION ; RISK ; RISKS ; PATIENT ; FAMILY ; BIOLOGY ; SCHIZOPHRENIA ; AGE ; SWEDEN ; POPULATIONS ; familial risk ; molecular biology ; sibling risk ; SIBLINGS ; FAMILIES ; heritability ; familial aggregation ; GENDER ; TWINS ; DEVELOPMENTAL EXPRESSION ; ONSET ; population-based ; FAMILIAL RISKS ; GENDER-DIFFERENCES ; SWEDISH ; HOSPITALIZATIONS ; WINTER
    Abstract: Familial risks of psychotic disorders and schizophrenia have been assessed in previous studies. However, the degree of familial clustering in large population datasets remains to be established. We conducted a study on familial risks of psychotic disorders and schizophrenia by linking the Multigeneration Register to the nationwide Swedish Hospital Discharge Register. All patients Younger than 72 years hospitalized for psychotic disorders or schizophrenia between 1987 and 2004 were included. Standardized incidence ratios (SIRs) were calculated for individuals with affected singleton siblings, twins or Spouses compared with individuals whose siblings or spouses had no hospitalization for psychotic disorders or schizophrenia. A total of 40,228 hospitalized cases were identified of which 3006 were affected sibling pairs. The overall significant familial SIRs were 4.82 for psychotic disorders and 7.34 for schizophrenia. The highest SIRs were found in the younger ages. There were no significant gender differences. The significant SIR for psychotic disorders among twin pairs was 6.40 and the significant SIRs for psychotic disorders among spouses varied between 3.17 and 3.29. Age difference between siblings had no effect on the magnitude of the SIRs. The findings of the present large-scale study suggest that heritable factors have a stronger effect on psychotic disorders and schizophrenia than environmental factors. Future studies could coordinate epidemiological studies of large populations with molecular biology resources. (c) 2007 Elsevier Ireland Ltd. All rights reserved
    Type of Publication: Journal article published
    PubMed ID: 19208442
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  • 3
    Keywords: SYSTEM ; RATS ; cytokines ; INVOLVEMENT ; PHARMACOKINETICS ; BEHAVIOR ; ANIMAL-MODEL ; forced swimming test ; CHRONIC HEPATITIS-C ; Anhedonia ; Dexamethasone suppression test ; Forced swim test ; IMMOBILITY
    Abstract: Interferon (IFN) alpha proteins are proinflammatory cytokines having immunomodulating and antiviral properties. States during which cytokine systems are activated (e.g., during viral infection or during treatment of chronic hepatitis C and various malignancies with IFN alpha, etc.) can be associated with depression-like syndromes or even full-blown depressive episodes. Therefore, the role of IFN alpha and other cytokines in the pathogenesis of depressive disorder ("cytokine hypothesis of depression") has been assessed for many years with contradictory results. We have investigated whether intraperitoneal administration of high doses (up to 600microg/kg body weight) of pegylated, recombinant human IFN alpha 2a in mice induces changes known to be associated with depression using three different readouts: behavior in a model of despair (Porsolt swim test), presence of anhedonia (sucrose preference test), and sensitivity of the hypothalamic-pituitary-adrenal system (dexamethasone suppression test). We also assessed potential IFN-induced changes in gene expression in the liver. In none of the performed experiments, depression-associated effects could be found despite very high serum levels of IFN-induced antiviral activity compared to levels measured in hepatitis C virus (HCV) patients treated routinely with pegylated recombinant human IFN alpha 2a. The lack of such expected effects is probably due to the fact that pegylated human recombinant IFN alpha 2a does not activate the murine class I IFN receptor. Our results do not support the hypothesis that administration of recombinant pegylated human IFN alpha to mice produces a robust model of depression.
    Type of Publication: Journal article published
    PubMed ID: 20580843
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  • 4
    Keywords: OPTIMIZATION ; IMAGES ; DISEASE ; AGE ; REGISTRATION ; WHITE-MATTER ; ATROPHY ; ACCURATE ; microstructure ; ROBUST
    Abstract: Magnetic resonance imaging (MRI) and brain volumetry allow for the quantification of changes in brain volume using automatic algorithms which are widely used in both, clinical and scientific studies. However, studies comparing the reliability of these programmes are scarce and mainly involved MRI derived from younger healthy controls. This study evaluates the reliability of frequently used segmentation programmes (SPM, FreeSurfer, FSL) using a realistic digital brain phantom and MRI brain acquisitions from patients with manifest Alzheimer's disease (AD, n=34), mild cognitive impairment (MCI, n=60), and healthy subjects (n=32) matched for age and sex. Analysis of the brain phantom dataset demonstrated that SPM, FSL and FreeSurfer underestimate grey matter and overestimate white matter volumes with increasing noise. FreeSurfer calculated overall smaller brain volumes with increasing noise. Image inhomogeneity had only minor, non- significant effects on the results obtained with SPM and FreeSurfer 5.1, but had effects on the FSL results (increased white matter volumes with decreased grey matter volumes). The analysis of the patient data yielded decreasing volumes of grey and white matter with progression of brain atrophy independent of the method used. FreeSurfer calculated the largest grey matter and the smallest white matter volumes. FSL calculated the smallest grey matter volumes; SPM the largest white matter volumes. Best results are obtained with good image quality. With poor image quality, especially noise, SPM provides the best segmentation results. An optimised template for segmentation had no significant effect on segmentation results. While our findings underline the applicability of the programmes investigated, SPM may be the programme of choice when MRIs with limited image quality or brain images of elderly should be analysed.
    Type of Publication: Journal article published
    PubMed ID: 26211622
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  • 5
  • 6
    Keywords: Germany ; DIAGNOSIS ; FOLLOW-UP ; imaging ; DISEASE ; PROTEIN ; PATIENT ; IMPACT ; CONTRAST ; MRI ; MAGNETIC-RESONANCE ; magnetic resonance imaging ; DIFFERENCE ; AGE ; STABILITY ; PROTEIN LEVELS ; DEMENTIA ; AD ; ATROPHY ; VASCULAR DEMENTIA ; CLINICAL-DIAGNOSIS ; DIFFERENTIAL-DIAGNOSIS ; A-BETA-1-42(43) ; APOLIPOPROTEIN-E GENOTYPE ; BIOCHEMICAL MARKER ; CSF-TAU ; dementia,differential diagnosis,CSF tau,volumetric MRI ; DIAGNOSTIC-ACCURACY ; E4 ALLELE ; TAU-PROTEIN
    Abstract: Increased tau levels are a well-established finding in Alzheimer's disease (AD). In contrast, the potential value of tau levels in the differential diagnosis of AD, vascular dementia (VD) and major depression warrants further investigation. The potential impact of psychotropic medication also needs to be established. We investigated cerebrospinal fluid (CSF) tau protein concentrations in 88 patients with AD, 23 patients with VD, 25 patients with major depression and 17 age-paralleled controls without cognitive impairment with respect to important clinical variables. type and dosage of psychotropic medication and cerebral changes as assessed by magnetic resonance imaging (MRI). The AD patients showed significantly elevated tau levels compared with patients with VD or major depression and controls. Tau levels obtained in the VD group were intermediate, with significant differences from both AD patients and patients with major depression and controls. Within the AD group, no significant correlation between tau levels, severity of dementia, age, duration of disease, type and dosage of psychotropic medication or MRI volumetric changes arose. A subgroup of AD patients without increased tau levels was characterized by a significantly larger percentage of patients with presenile onset. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved
    Type of Publication: Journal article published
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  • 7
    Keywords: ALZHEIMERS-DISEASE ; IMAGE REGISTRATION ; TEMPORAL-LOBE ; GRAY-MATTER ; AGE-RELATED-CHANGES ; CEREBRAL-CORTEX ; VOXEL-BASED MORPHOMETRY ; WHITE-MATTER CHANGES ; AGING HIPPOCAMPUS ; APOE GENOTYPE
    Abstract: Studying the distribution and chronological sequence of brain morphological changes that occur in normal aging is crucial for understanding the mechanisms underlying these alterations and for distinguishing them from pathological processes. Whether the hippocampal formation is subjected to or spared from age-related shrinkage still remains controversial. We used magnetic resonance imaging (MRI) in order to assess hippocampal and entorhinal morphology in two population-based cognitively unimpaired cohorts (aged 53-55 years and 73-75 years, respectively) matched for gender, education, handedness, and apolipoprotein E status. Voxel-based morphometry (VBM-DARTEL) and shape analysis (FSL-FIRST) revealed significant bihemispheric age-related shrinkage of subiculum and cornu ammonis as well as of the entorhinal cortex (investigated with VBM only). The results lend further support to an effect of aging on medial temporal lobe morphology and thus may be of importance for the interpretation of structural imaging findings, especially in those diseases that are typically related to advancing age, as well as for the interpretation of functional imaging studies, where age-related differences in hippocampal activation may--to a locally varying degree--be explained by morphometric alterations.
    Type of Publication: Journal article published
    PubMed ID: 23168382
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  • 8
    Abstract: The results of research about the influences of impulsivity on decision-making in situations of risk have been inconsistent. In this study, we used functional magnetic resonance imaging to examine the neural correlates of decision-making under risk in 12 impulsive, as defined by the Barratt Impulsiveness Scale-11, and 13 normal men. Although both groups showed similar decision-making behavior, neural activation regarding decision-making processes differed significantly. Impulsive persons revealed stronger activation in the (ventro-) medial prefrontal cortex and less deactivation of the orbitofrontal cortex while playing for potential gains. These brain regions might be associated with the emotional components of decision-making processes. Significant differences in brain areas linked to cognitive decision-making components were not found. This activation pattern might be seen as an indication for a hypersensitivity to rewarding cues in impulsive persons and might be linked to the propensity for inappropriate risk-taking behavior in persons with more extreme impulsivity levels, especially in situations in which they have a strong emotional involvement in the decision process.
    Type of Publication: Journal article published
    PubMed ID: 26786151
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  • 9
    Keywords: Germany ; DISEASE ; METABOLISM ; PATIENT ; IMPACT ; ASSOCIATION ; PATTERNS ; WOMEN ; statistics ; positron emission tomography ; POSITRON-EMISSION-TOMOGRAPHY ; tomography ; GLUCOSE ; PET ; AD ; immunoassay ; 17 beta-estradiol,Alzheimer's disease,positron emission tomography,Hippocampus ; POSTMENOPAUSAL WOMEN
    Abstract: Animal studies indicate that estrogens, such as 17beta-estradiol (EA may enhance hippocampal metabolism and function. In postmenopausal Alzheimer's disease (AD) patients, cerebrospinal fluid (CSF) E-2 levels were significantly lower than in non-demented controls. This finding was inversely correlated with CSF beta-amyloid levels. To address the potential impact of this finding, E-2 levels in CSF were correlated with regional cerebral [F-18]2-fluoro-2-deoxy-D-glucose (FDG) uptake as measured using positron emission tomography (PET) in six postmenopausal AD patients. CSF E-2 levels were determined using an electro-chemiluminescence-immunoassay on the Roche Elecsys 2010 immunoassay analyzer. Basic image processing was done by MEDx, using SPM routines for spatial normalization and statistics. CSF E-2 levels were significantly correlated with cerebral glucose metabolism in the left hippocampus. This is the first clinical study indicating an association between CSF E-2 concentration and hippocampal glucose metabolism in postmenopausal women with AD. (C) 2003 Elsevier Ireland Ltd. All rights reserved
    Type of Publication: Journal article published
    PubMed ID: 14561431
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  • 10
    Keywords: brain ; DISEASE ; MRI ; ALZHEIMERS-DISEASE ; SCHIZOPHRENIA ; REGION ; Alzheimer's disease ; multicenter studies ; HEALTHY-VOLUNTEERS ; HUNTINGTONS-DISEASE ; Diffusion Tensor Imaging ; DTI ; early diagnosis ; FRACTIONAL ANISOTROPY ; MEAN DIFFUSIVITY ; DIAGNOSTIC UTILITY ; Effect size estimation ; Physical phantom ; TRACT INTEGRITY
    Abstract: Diffusion tensor imaging (DTI) detects white matter damage in neuro-psychiatric disorders, but data on reliability of DTI measures across more than two scanners are still missing. In this study we assessed multicenter reproducibility of DTI acquisitions based on a physical phantom as well as brain scans across 16 scanners. In addition, we performed DTI scans in a group of 26 patients with clinically probable Alzheimer's disease (AD) and 12 healthy elderly controls at one single center. We determined the variability of fractional anisotropy (FA) measures using manually placed regions of interest as well as automated tract based spatial statistics and deformation based analysis. The coefficient of variation (CV) of FA was 6.9% for the physical phantom data. The mean CV across the multicenter brain scans was 14% for tract based statistics, and 29% for deformation based analysis. The degree of variation was higher in less organized fiber tracts. Our findings suggest that a clinical and physical phantom study involving more than two scanners is indispensable to detect potential sources of bias and to reliably estimate effect size in multicenter diagnostic trials using DTI.
    Type of Publication: Journal article published
    PubMed ID: 22078796
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