β-Amyloid (1–42) Levels in Cerebrospinal Fluid and Cerebral Atrophy in Mild Cognitive Impairment and Alzheimer's Disease

Background: Recent studies consistently reported Alzheimer’s disease (AD) and, to a lower extent, mild cognitive impairment (MCI) to be accompanied by reduced cerebrospinal fluid (CSF) levels of β-amyloid. However, how these changes are related to brain morphological alterations is so far only partly understood. Methods: CSF levels of β-amyloid (1–42) were examined with respect to cerebral atrophy in 23 subjects with MCI, 16 patients with mild-to-moderateAlzheimer’s disease (AD) and 15 age-matched controls by using magnetic resonance imaging and voxel-based morphometry (VBM). Results: When contrasted with the controls, β-amyloid (1–42) levels were significantly lower (p Conclusion: Our finding confirms the results of previous studies and suggests that both the decrease in β-amyloid (1–42) and the development of hippocampal atrophy coincide in the disease process

Activation of the tryptophan/serotonin pathway is associated with severity and predicts outcomes in pneumonia: results of a long-term cohort study

As part of the immune defense during infection, an increase in enzyme activity of indoleamine 2,3-dioxygenase (IDO) leads to a breakdown of tryptophan to kynurenine. In previous animal studies, therapeutic antagonism of IDO resulted in reduced sepsis mortality. We investigated the prognostic ability of tryptophan, serotonin, kynurenine and IDO (represented by the ratio of kynurenine/tryptophan) to predict adverse clinical outcomes in patients with community-acquired pneumonia (CAP).; We measured tryptophan, serotonin and kynurenine on admission plasma samples from CAP patients included in a previous multicenter trial by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). We studied their association with inflammation (C-reactive protein), infection (procalcitonin) and clinical outcome.; Mortality in the 268 included patients was 45% within 6 years of follow-up. IDO and kynurenine showed a strong positive correlation with markers of infection (procalcitonin) and inflammation (C-reactive protein) as well as sepsis and CAP severity scores. Tryptophan showed similar, but negative correlations. In a multivariate regression analysis adjusted for age and comorbidities, higher IDO activity and lower tryptophan levels were strongly associated with short-term adverse outcome defined as death and/or ICU admission within 30 days with adjusted odds ratios of 9.1 [95% confidence interval (CI) 1.4-59.5, p=0.021] and 0.11 (95% CI 0.02-0.70, p=0.021). Multivariate analysis did not reveal significant associations for kynurenine and serotonin.; In hospitalized CAP patients, higher IDO activity and lower tryptophan levels independently predicted disease severity and short-term adverse outcome. Whether therapeutic modulation of IDO has positive effects on outcome needs further investigation

Reduced Gray to White Matter Tissue Intensity Contrast in Schizophrenia

BACKGROUND: While numerous structural magnetic resonance imaging (MRI) studies revealed changes of brain volume or density, cortical thickness and fibre integrity in schizophrenia, the effect of tissue alterations on the contrast properties of neural structures has so far remained mostly unexplored. METHODS: Whole brain high-resolution MRI at 3 Tesla was used to investigate tissue contrast and cortical thickness in patients with schizophrenia and healthy controls. RESULTS: Patients showed significantly decreased gray to white matter contrast in large portions throughout the cortical mantle with preponderance in inferior, middle, superior and medial temporal areas as well as in lateral and medial frontal regions. The extent of these intensity contrast changes exceeded the extent of cortical thinning. Further, contrast changes remained significant after controlling for cortical thickness measurements. CONCLUSIONS: Our findings clearly emphasize the presence of schizophrenia related brain tissue changes that alter the imaging properties of brain structures. Intensity contrast measurements might not only serve as a highly sensitive metric but also as a potential indicator of a distinct pathological process that might be independent from volume or thickness alterations

Altered Markers of Brain Development in Crohn's Disease with Extraintestinal Manifestations - A Pilot Study.

Alterations of brain morphology in Crohn's disease have been reported, but data is scarce and heterogenous and the possible impact of disease predisposition on brain development is unknown. Assuming a systemic course of the disease, brain involvement seems more probable in presence of extraintestinal manifestations, but this question has not yet been addressed. The present study examined the relationship between Crohn's disease and brain structure and focused on the connection with extraintestinal manifestations and markers of brain development.In a pilot study, brains of 15 patients with Crohn's disease (of which 9 had a history of extraintestinal manifestations, i.e. arthritis, erythema nodosum and primary sclerosing cholangitis) were compared to matched healthy controls using high resolution magnetic resonance imaging. Patients and controls were tested for depression, fatigue and global cognitive function. Cortical thickness, surface area and folding were determined via cortical surface modeling.The overall group comparison (i.e. all patients vs. controls) yielded no significant results. In the patient subgroup with extraintestinal manifestations, changes in cortical area and folding, but not thickness, were identified: Patients showed elevated cortical surface area in the left middle frontal lobe (p<0.05) and hypergyrification in the left lingual gyrus (p<0.001) compared to healthy controls. Hypogyrification of the right insular cortex (p<0.05) and hypergyrification of the right anterior cingulate cortex (p<0.001) were detected in the subgroup comparison of patients with against without extraintestinal manifestations. P-values are corrected for multiple comparisons.Our findings lend further support to the hypothesis that Crohn's disease is associated with aberrant brain structure and preliminary support for the hypothesis that these changes are associated with a systemic course of the disease as indicated by extraintestinal manifestations. Changes in cortical surface area and folding suggest a possible involvement of Crohn's disease or its predisposition during brain development

Feasibility of an Intervention Delivered via Mobile Phone and Internet to Improve the Continuity of Care in Schizophrenia: A Randomized Controlled Pilot Study

Schizophrenia is a severe mental illness associated with a heavy symptom burden and high relapse rates. Digital interventions are increasingly suggested as means to facilitate continuity of care, relapse prevention, and long-term disease management for schizophrenia spectrum disorders. In order to investigate the feasibility of a mobile and internet-based aftercare program, a 2-arm randomized controlled pilot study was conducted. The program could be used by patients for six months after inpatient treatment and included psychoeducation, an individual crisis plan, optional counseling via internet chat or phone and a supportive monitoring module. Due to the slow pace of enrollment, recruitment was stopped before the planned sample size was achieved. Reasons for the high exclusion rate during recruitment were analyzed as well as attitudes, satisfaction, and utilization of the program by study participants. The data of 25 randomized patients suggest overall positive attitudes towards the program, high user satisfaction and good adherence to the monitoring module. Overall, the results indicate that the digital program might be suitable to provide support following discharge from intensive care. In addition, the study provides insights into specific barriers to recruitment which may inform future research in the field of digital interventions for severe mental illness