Alzheimer's disease pathology:pathways between central norepinephrine activity, memory, and neuropsychiatric symptoms

The locus coeruleus (LC) supplies norepinephrine to the brain, is one of the first sites of tau deposition in Alzheimer's disease (AD) and modulates a variety of behaviors and cognitive functions. Transgenic mouse models showed that norepinephrine dysregulation after LC lesions exacerbates inflammatory responses, blood-brain barrier leakage (BBB), and cognitive deficits. Here, we investigated relationships between central norepinephrine metabolism, tau and beta-amyloid (Aβ), inflammation, BBB-dysfunction, neuropsychiatric problems, and memory in-vivo in a memory clinic population (total n = 111, 60 subjective cognitive decline, 36 mild cognitively impaired, and 19 AD dementia). Cerebrospinal fluid (CSF) and blood samples were collected and analyzed for 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG), CSF/plasma albumin ratio (Q-alb), Aβ, phosphorylated tau, and interleukins. The verbal word learning task and the neuropsychiatric inventory assessed memory functioning and neuropsychiatric symptoms. Structural equation models tested the relationships between all fluid markers, cognition and behavior, corrected for age, education, sex, and clinical dementia rating score. Our results showed that neuropsychiatric symptoms show strong links to both MHPG and p-tau, whereas memory deficits are linked to MHPG via a combination of p-tau and inflammation-driven amyloidosis (30-35% indirect effect contribution). These results suggest that the LC-norepinephrine may be pivotal to understand links between AD pathology and behavioral and cognitive deficits in AD

Separate and combined effects of individual and neighbourhood socio-economic disadvantage on health-related lifestyle risk factors:a multilevel analysis

BACKGROUND: Socio-economic disadvantage at both individual and neighbourhood levels has been found to be associated with single lifestyle risk factors. However, it is unknown to what extent their combined effects contribute to a broad lifestyle profile. We aimed to (i) investigate the associations of individual socio-economic disadvantage (ISED) and neighbourhood socio-economic disadvantage (NSED) in relation to an extended score of health-related lifestyle risk factors (lifestyle risk index); and to (ii) investigate whether NSED modified the association between ISED and the lifestyle risk index. METHODS: Of 77 244 participants [median age (IQR): 46 (40-53) years] from the Lifelines cohort study in the northern Netherlands, we calculated a lifestyle risk index by scoring the lifestyle risk factors including smoking status, alcohol consumption, diet quality, physical activity, TV-watching time and sleep time. A higher lifestyle risk index was indicative of an unhealthier lifestyle. Composite scores of ISED and NSED based on a variety of socio-economic indicators were calculated separately. Linear mixed-effect models were used to examine the association of ISED and NSED with the lifestyle risk index and to investigate whether NSED modified the association between ISED and the lifestyle risk index by including an interaction term between ISED and NSED. RESULTS: Both ISED and NSED were associated with an unhealthier lifestyle, because ISED and NSED were both positively associated with the lifestyle risk index {highest quartile [Q4] ISED beta-coefficient [95% confidence interval (CI)]: 0.64 [0.62-0.66], P < 0.001; highest quintile [Q5] NSED beta-coefficient [95% CI]: 0.17 [0.14-0.21], P < 0.001} after adjustment for age, sex and body mass index. In addition, a positive interaction was found between NSED and ISED on the lifestyle risk index (beta-coefficient 0.016, 95% CI: 0.011-0.021, Pinteraction < 0.001), which indicated that NSED modified the association between ISED and the lifestyle risk index; i.e. the gradient of the associations across all ISED quartiles (Q4 vs Q1) was steeper among participants residing in the most disadvantaged neighbourhoods compared with those who resided in the less disadvantaged neighbourhoods. CONCLUSIONS: Our findings suggest that public health initiatives addressing lifestyle-related socio-economic health differences should not only target individuals, but also consider neighbourhood factors

Attenuation-Corrected vs. Nonattenuation-Corrected 2-Deoxy-2-[F-18]fluoro-d-glucose-Positron Emission Tomography in Oncology, A Systematic Review

Purpose: To perform a systematic review and meta-analysis to determine the diagnostic accuracy of attenuation-corrected (AC) vs. nonattenuation-corrected (NAC) 2-deoxy-2-[F-18] fluoro-D-glucose-positron emission tomography (FDG-PET) in oncological patients. Procedures: Following a comprehensive search of the literature, two reviewers independently assessed the methodological quality of eligible studies. The diagnostic value of AC was studied through its sensitivity/specificity compared to histology, and by comparing the relative lesion detection rate reported with NAC-PET vs. AC, for full-ring and dual-head coincidence PET (FRand DH-PET, respectively). Results: Twelve studies were included. For FR-PET, the pooled sensitivity/specificity on a patient basis was 64/97 % for AC and 62/99 % for NAC, respectively. Pooled lesion detection with NAC vs. AC was 98 % [95 % confidence interval (95 % CI): 96Y99%, n=1,012 lesions] for FR-PET, and 88 % (95 % CI:81Y94%, n=288 lesions) for DH-PET. Conclusions: Findings suggest similar sensitivity/specificity and lesion detection for NAC vs. AC FR-PET and significantly higher lesion detection for NAC vs. AC DH-PET

Sparse Asymmetry in Locus Coeruleus Pathology in Alzheimer's Disease.

peer reviewed Tau accumulation in and neurodegeneration of locus coeruleus (LC) neurons is observed in Alzheimer's disease (AD). We investigated whether tangle and neuronal density in the rostral and caudal LC is characterized by an asymmetric pattern in 77 autopsy cases of the Rush Memory and Aging Project. We found left-right equivalence for tangle density across individuals with and without AD pathology. However, neuronal density, particularly in the caudal-rostral axis of the LC, is asymmetric among individuals with AD pathology. Asymmetry in LC neuronal density may signal advanced disease progression and should be considered in AD neuroimaging studies of LC neurodegeneration

Cost-effectiveness of a screening strategy for Q fever among pregnant women in risk areas: a clustered randomized controlled trial

Contains fulltext : 87399.pdf (publisher's version ) (Open Access)BACKGROUND: In The Netherlands the largest human Q fever outbreak ever reported in the literature is currently ongoing with more than 2300 notified cases in 2009. Pregnant women are particularly at risk as Q fever during pregnancy may cause maternal and obstetric complications. Since the majority of infected pregnant women are asymptomatic, a screening strategy might be of great value to reduce Q fever related complications. We designed a trial to assess the (cost-)effectiveness of a screening program for Q fever in pregnant women living in risks areas in The Netherlands. METHODS/DESIGN: We will conduct a clustered randomized controlled trial in which primary care midwife centres in Q fever risk areas are randomized to recruit pregnant women for either the control group or the intervention group. In both groups a blood sample is taken around 20 weeks postmenstrual age. In the intervention group, this sample is immediately analyzed by indirect immunofluorescence assay for detection of IgG and IgM antibodies using a sensitive cut-off level of 1:32. In case of an active Q fever infection, antibiotic treatment is recommended and serological follow up is performed. In the control group, serum is frozen for analysis after delivery. The primary endpoint is a maternal (chronic Q fever or reactivation) or obstetric complication (low birth weight, preterm delivery or fetal death) in Q fever positive women. Secondary aims pertain to the course of infection in pregnant women, diagnostic accuracy of laboratory tests used for screening, histo-pathological abnormalities of the placenta of Q fever positive women, side effects of therapy, and costs. The analysis will be according to the intention-to-screen principle, and cost-effectiveness analysis will be performed by comparing the direct and indirect costs between the intervention and control group. DISCUSSION: With this study we aim to provide insight into the balance of risks of undetected and detected Q fever during pregnancy. TRIAL REGISTRATION: ClinicalTrials.gov, protocol record NL30340.042.09

Definitions and incidence of cardiac syndrome X: review and analysis of clinical data

There is no consensus regarding the definition of cardiac syndrome X (CSX). We systematically reviewed recent literature using a standardized search strategy. We included 57 articles. A total of 47 studies mentioned a male/female distribution. A meta-analysis yielded a pooled proportion of females of 0.56 (n = 1,934 patients, with 95% confidence interval: 0.54–0.59). As much as 9 inclusion criteria and 43 exclusion criteria were found in the 57 articles. Applying these criteria to a population with normal coronary angiograms and treated in 1 year at a general hospital, the attributable CSX incidence varied between 3 and 11%. The many inclusion and exclusion criteria result in a wide range of definitions of CSX and these have large effects on the incidence. This shows the need for a generally accepted definition of CSX

Update of the fdg pet search strategy

The comprehensive search strategy for identification of FDG PET literature in the electronic databases MEDLINE and EMBASE, published in 2000, has been updated for PubMed. The new search strategy presented here is freely available at the VU website and can be easily copied from there and pasted into the PubMed search window. In addition, the strategy can be stored using the ‘Cubby’ feature on the PubMed interface and run whenever needed in a minimum of time. It can therefore be used for quick searches during clinical practice as well as extensive searches for systematic reviews. To increase sensitivity, new search terms and term combinations for ‘PET’ and ‘FDG’ were added. The existing truncations and field qualifications had to be changed for PubMed. The new strategy is even more sensitive than the previous and therefore identifies more articles without affecting precision (proportion of the retrieved articles that are relevant). Since 2000, MeSH indexing of FDG and PET has hardly improved. Our proposal to introduce the MeSH ‘positron emission tomography’ as a narrower term of the current ‘Tomography, emission-computed’ and to replace the current MeSH ‘Fludeoxyglucose F-18’ by ‘18F-Fluorodeoxyglucose’ has been accepted by the National Library of Medicine. The new MeSH terms will be included in the MeSH edition for 2004-2005

Systematic review on recovery specific quality-of-life instruments.

Contains fulltext : 70895.pdf (publisher's version ) (Closed access)BACKGROUND: Postoperative recovery is a considerable issue in studies comparing operative techniques of similar effectiveness. In recent years, a shift has occurred toward patient-centered study outcomes such as quality-of-life questionnaires. The objective of this article is to provide a systematic review of the literature on general postoperative, recovery-specific quality-of-life instruments and their measurement properties. METHODS: We searched the databases EMBASE.com, Cinahl, PsycINFO, and PubMed for articles reporting on postoperative, recovery-specific quality-of-life instruments. A checklist was used to assess the revealed studies and instruments. Existing quality criteria were applied to the measurement properties to compare the instruments. RESULTS: The search strategy identified 620 studies, of which 18 studies reported on 12 different postoperative, recovery-specific quality-of-life instruments. None of the instruments had been validated completely in line with the 8 quality criteria, which were used to assess the measurement properties. Two instruments were clearly superior, which were the Postdischarge surgical recovery scale and the Quality of recovery-40. CONCLUSIONS: No fully validated instrument is available for the assessment of general postoperative recovery. We advise to use the Postdischarge surgical recovery scale and the Quality of recovery-40 in future validation and application studies on short-term postoperative recovery