Reliability and precision of pseudo‐continuous arterial spin labeling perfusion MRI on 3.0 T and comparison with 15O‐water PET in elderly subjects at risk for Alzheimer's disease

Arterial spin labeling (ASL) offers MRI measurement of cerebral blood flow (CBF) in vivo, and may offer clinical diagnostic utility in populations such as those with early Alzheimer's disease (AD). In the current study, we investigated the reliability and precision of a pseudo‐continuous ASL (pcASL) sequence that was performed two or three times within one hour on eight young normal control subjects, and 14 elderly subjects including 11 with normal cognition, one with AD and two with Mild Cognitive Impairment (MCI). Six of these elderly subjects including one AD, two MCIs and three controls also received ¹⁵O‐water positron emission tomography (PET) scans 2 h before their pcASL MR scan. The instrumental reliability of pcASL was evaluated with the intraclass correlation coefficient (ICC). The ICCs were greater than 0.90 in pcASL global perfusion measurements for both the young and the elderly groups. The cross‐modality perfusion imaging comparison yielded very good global and regional agreement in global gray matter and the posterior cingulate cortex. Significant negative correlation was found between age and the gray/white matter perfusion ratio (r = –0.62, p < 0.002). The AD and MCI patients showed the lowest gray/white matter perfusion ratio among all the subjects. The data suggest that pcASL provides a reliable whole brain CBF measurement in young and elderly adults whose results converge with those obtained with the traditional ¹⁵O‐water PET perfusion imaging method. pcASL perfusion MRI offers an alternative method for non‐invasive in vivo examination of early pathophysiological changes in AD. Copyright © 2009 John Wiley & Sons, Ltd.     

Feasibility of detection and intervention for alcohol-related liver disease in the community: the Alcohol and Liver Disease Detection study (ALDDeS)

Background

In the past 15 years mortality rates from liver disease have doubled in the UK. Brief alcohol advice is cost effective, but clinically meaningful reductions in alcohol consumption only occur in around 1 in 10 individuals.

Aim

To provide evidence that detecting early liver disease in the community is feasible, practical, and that feedback of liver risk can increase the proportion of subjects reducing alcohol consumption.

Design and setting

A community feasibility study in nine general practice sites in Hampshire.

Method

Hazardous and harmful drinkers were identified by WHO AUDIT questionnaire and offered screening for liver fibrosis.

Results

In total, 4630 individuals responded, of whom 1128 (24%) hazardous or harmful drinkers were offered a liver fibrosis check using the Southampton Traffic Light (STL) test; 393 (38%) attended and test results were returned by post. The STL has a low threshold for liver fibrosis with 45 (11%) red, 157 (40%) amber, and 191 (49%) green results. Follow-up AUDIT data was obtained for 303/393 (77%) and 76/153 (50%) subjects with evidence of liver damage reduced drinking by at least one AUDIT category (harmful to hazardous, or hazardous to low risk) compared with 52/150 (35%, P<0.011) subjects without this evidence; in the subset of harmful drinkers patterns (AUDIT >15), 22/34 (65%) of STL positives, reduced drinking compared with 10/29 (35%, P<0.017) STL negatives.

Conclusion

Detection of liver disease in the community is feasible, and feedback of liver risk may reduce harmful drinking.     

Psychosocial Stress and Cardiovascular Disease Part 2: Effectiveness of the Transcendental Meditation Program in Treatment and Prevention

Abstract

Psychosocial stress is a nontraditional risk factor for cardiovascular morbidity and mortality that may respond to behavioral or psychosocial interventions. To date, studies applying such interventions have reported a wide range of success rates in treatment or prevention of cardiovascular disease (CVD). The authors focus on a natural medicine approach that research indicates reduces both psychosocial and traditional risk factors for cardiovascular disease—the Transcendental Meditation (TM) program. Randomized controlled trials, meta-analyses, and other controlled studies indicate this meditation technique reduces risk factors and can slow or reverse the progression of pathophysiological changes underlying cardiovascular disease. Studies with this technique have revealed reductions in blood pressure, carotid artery intimamedia thickness, myocardial ischemia, left ventricular hypertrophy, mortality, and other relevant outcomes. The magnitudes of these effects compare favorably with those of conventional interventions for secondary prevention.     

Concepts for the treatment of Alzheimer's disease: molecular mechanisms and clinical application

To date, various strategies have been developed in order to prevent or to slow down the progression of Alzheimer's disease (AD). Despite the medical need for an effective therapeutic treatment of AD, progress towards this goal is painstakingly slow. Although AD is the most common neurodegenerative disorder and a large amount of primary basic and clinical research has been performed already, it appears very difficult to identify appropriate targets, which would promise fast, effective and safe strategies to combat the disease onset and progression. In this review, we present some of clinically applied treatment options, which may improve AD symptoms for a short period but so far lack the ability to prevent or halt this devastating disease. Additionally, we summarize some of the experimental approaches in AD therapy, which might lead to the development of more promising drugs in the future.     

Long-term exposure to magnetic fields and the risks of Alzheimer's disease and breast cancer: Further biological research

Objective: Extremely low frequency (ELF) and radio frequency (RF) magnetic fields (MFs) pervade our environment. Whether or not these magnetic fields are associated with increased risk of serious diseases, e.g., cancers and Alzheimer's disease, is thus important when developing a rational public policy. The Bioinitiative Report was an effort by internationally recognized scientists who have spent significant time investigating the biological consequences of exposures to these magnetic fields to address this question. Our objective was to provide an unbiased review of the current knowledge and to provide our general and specific conclusions. Results: The evidence indicates that long-term significant occupational exposure to ELF MF may certainly increase the risk of both Alzheimer's disease and breast cancer. There is now evidence that two relevant biological processes (increased production of amyloid beta and decreased production of melatonin) are influenced by high long-term ELF MF exposure that may lead to Alzheimer's disease. There is further evidence that one of these biological processes (decreased melatonin production) may also lead to breast cancer. Finally, there is evidence that exposures to RF MF and ELF MF have similar biological consequences. Conclusion: It is important to mitigate ELF and RF MF exposures through equipment design changes and environmental placement of electrical equipment, e.g., AC/DC transformers. Further research related to these proposed and other biological processes is required.     

MHD患者血清NT-proBNP、leptin和血浆Hcy的变化和心血管疾病的关系

目的:探讨维持性血液透析 (MHD)患者血中N端脑利钠肽前体(NT-proBNP)、瘦素(leptin)和同型半胱氨酸(Hcy)的变化及其和心血管疾病的关系.方法:将69例MHD患者分为心血管疾病组(CVD)和非心血管疾病组(NCVD),另选取30例健康人为对照组,检测其血清NT-proBNP、leptin和Hcy的水...     

Progression of Alzheimer's disease and effect of scFv‐h3D6 immunotherapy in the 3xTg‐AD mouse model: An in vivo longitudinal study using Magnetic Resonance Imaging and Spectroscopy

Alzheimer's disease (AD) is an incurable disease that affects most of the 47 million people estimated as living with dementia worldwide. The main histopathological hallmarks of AD are extracellular β‐amyloid (Aβ) plaques and intracellular neurofibrillary tangles (NFTs) composed of hyperphosphorylated tau protein. In recent years, Aβ‐immunotherapy has been revealed as a potential tool in AD treatment. One strategy consists of using single‐chain variable fragments (scFvs), which avoids the fragment crystallizable (Fc) effects that are supposed to trigger a microglial response, leading to microhemorrhages and vasogenic edemas, as evidenced in clinical trials with bapineuzumab. The scFv‐h3D6 generated by our research group derives from this monoclonal antibody, which targets the N‐terminal of the Aβ peptide and recognizes monomers, oligomers and fibrils. In this study, 3xTg‐AD mice were intraperitoneally and monthly treated with 100 μg of scFv‐h3D6 (a dose of ~3.3 mg/kg) or PBS, from 5 to 12 months of age (?mo), the age at which the mice were sacrificed and samples collected for histological and biochemical analyses. During treatments, four monitoring sessions using magnetic resonance imaging and spectroscopy (MRI/MRS) were performed at 5, 7, 9, and 12 months of age. MRI/MRS techniques are widely used in both human and mouse research, allowing to draw an in vivo picture of concrete aspects of the pathology in a non‐invasive manner and allowing to monitor its development across time. Compared with the genetic background, 3xTg‐AD mice presented a smaller volume in almost all cerebral regions and ages examined, an increase in both the intra and extracellular Aβ_1–42 at 12‐mo, and an inflammation process at this age, in both the hippocampus (IL‐6 and mIns) and cortex (IL‐6). In addition, treatment with scFv‐h3D6 partially recovered the values in brain volume, and Aβ, IL‐6, and mIns concentrations, among others, encouraging further studies with this antibody fragment.     

Prevention of tobacco use among medically at-risk children and adolescents: clinical and research opportunities in the interest of public health

OBJECTIVE: Cigarette smoking and other forms of tobacco use are addictive and harmful. Though no level of smoking is safe, children and adolescents who are medically at-risk due to the presence of a chronic or life-threatening disease may be especially vulnerable to these dangers. This article provides an overview of considerations in the prevention of tobacco use in this special population. METHODS: This article summarizes medical aspects of childhood chronic disease and the impact of cigarette smoking, the prevalence of tobacco screening in pediatric healthcare, and levels of prevention for individuals, families, schools, and healthcare. Recommendations for clinical services and research are also included. RESULTS: There are a number of reasons to prevent and interrupt the onset of smoking in medically at-risk youth. Subspecialty clinics appear to be the most likely point of entry for prevention-based work in this area. However, no one single setting will be effective in preventing and deterring use without due consideration of other settings, perspectives, and influences on smoking uptake. CONCLUSIONS: The promise of smoking prevention to improve the health and outlook of children and adolescents with chronic or life-threatening disease is high, and additional efforts are needed for this population.     

Intranasal immunotherapy for the treatment of Alzheimer's disease: Escherichia coli LT and LT(R192G) as mucosal adjuvants

Alzheimer’s disease (AD) is the most common form of dementia worldwide, yet there is currently no effective treatment or cure. Extracellular deposition of amyloid-β protein (Aβ) in brain is a key neuropathological characteristic of AD. In 1999, Schenk et al. first reported that an injected Aβ vaccine given to PDAPP mice, an AD mouse model displaying Aβ deposition in brain, led to the lowering of Aβ levels in brain. In 2000, we demonstrated that intranasal (i.n.) immunization with human synthetic Aβ1–40 peptide for 7 months led to a 50–60% reduction in cerebral Aβ burden in PDAPP mice; serum Aβ antibody titers were low (26 μg/ml). More recently, we have optimized our i.n. Aβ immunization protocol in wild-type (WT) mice. When low doses Escherichia coli heat-labile enterotoxin (LT) were given as a mucosal adjuvant with Aβ i.n., there was a dramatic 12-fold increase in Aβ antibody titers in WT B6D2F1 mice treated two times per week for 8 weeks compared to those of mice receiving i.n. Aβ without adjuvant. A non-toxic form of LT, designated LT(R192G), showed even better adjuvanticity; anti-Aβ antibody titers were 16-fold higher than those seen in mice given i.n. Aβ without adjuvant. In both cases, the serum Aβ antibodies recognized epitopes within Aβ1–15 and were of the immunoglobulin (Ig) isotypes IgG2b, IgG1, IgG2a and low levels of IgA. This new and improved Aβ vaccine protocol is now being tested in AD mouse models with the expectation that higher Aβ antibody titers may be more effective in reducing cerebral Aβ levels.