Commentary on “A roadmap for the prevention of dementia II. Leon Thal Symposium 2008.” Centers of excellence in Alzheimer's disease: It is time to better integrate patient care and clinical research to improve the prevention and treatment of Alzheimer's disease

Despite enormous worldwide public and private interest in improving the prevention and treatment of Alzheimer's disease (AD), we have not made as much of an impact as we would like, and the number of affected individuals continues to grow. Even more alarmingly, whereas global efforts to identify AD cases and to develop new treatments are increasing, patient-care options are disappearing, so that even if a highly efficacious therapy or prevention approach arose, it would not be used effectively. As a first step toward organizing a better way forward, we should establish AD centers of excellence that mandate both patient care and research in the same setting. These centers would benefit from changes in public health policies related to chronic-disease surveillance, Center for Medicare and Medicaid Services funding for the care of chronic diseases, institutional review boards, good clinical practice guidelines, National Institutes of Health regulations for the use of research funds, Food and Drug Administration guidelines for the approval of AD drugs, and Department of Commerce regulations related to patent protection of AD diagnostic aids and treatments. This new form of AD centers of excellence would also provide direct care to many patients and their families, model care for communities and medical trainees, enhance the voluntary recruitment of AD patients to clinical trials, and improve our understanding of AD and its management.     

Unemployment, social isolation, achievement–expectation mismatch and psychosis: findings from the ÆSOP Study

INTRODUCTION: In this study, we aimed to establish: (1) whether social isolation modifies the effect of unemployment on first episode psychosis and duration of untreated psychosis (DUP); and (2) whether the gap between high employment expectations and perceived poor employment achievement is associated with first-episode psychosis; and (3) whether the relationship of this achievement-expectation gap and first-episode psychosis is strongest in the African-Caribbean population. METHOD: All patients with a first episode of psychosis presenting to specialist mental health services within tightly defined catchment areas in south-east London and Nottingham over a 2-year period were included in the study. A random sample of healthy participants living within the same catchment areas was also recruited. Data were collected on socio-demographic and clinical characteristics, DUP, social contacts, and perceived levels of employment achievement and expectation. Analysis was conducted on data of 546 participants (224 cases, 322 controls) from the AESOP study. RESULTS: The relationship between unemployment and risk of non-affective psychosis was moderated by social contacts (unemployed/low social contacts, OR 7.52, 95% CI 2.97-19.08; unemployed/medium social contacts, OR 3.27, 95% CI 1.66-6.47; unemployed/high social contacts, OR 1.36, 95% CI 0.47-3.93). Unemployed patients experienced a longer DUP when having reported lower levels of social contacts. Participants whose employment achievement was lower than their expectations were more likely to be cases than those in whom achievement matched or exceeded expectations (adjusted OR 1.84, 95% CI 1.13-3.02). This applied equally to both African-Caribbean and White British participants (the Mantel-Haenszel test for homogeneity of odds ratios, chi (2 )= 0.96, P = 0.33). CONCLUSIONS: This study suggests that unemployment, social isolation, employment achievement and expectations are important environmental factors associated with risk of psychosis. More attention needs to be focused on interactions between environmental factors as well as subjective experience of those factors in future research on the aetiology of psychosis.     

The effect of a physical activity education programme on physical activity, fitness, quality of life and attitudes to exercise in obese females

Obesity has reached epidemic proportions worldwide. Decline in physical activity has occurred simultaneously or before the increase in obesity. The aim of this pilot study was to investigate the effect of a physical activity group-based education programme delivered by a Physiotherapist on weight, physical activity, cardiovascular fitness, quality of life and attitudes to exercise in obese females. A sample of 18 obese Irish females (mean age 37.6 years, mean weight 117.9kg), took part in this study. The participants attended four physical activity education sessions in groups of 6-8, 1 month apart. Outcome measures were Cardiorespiratory fitness (CRF) measured by the Incremental Shuttle Walk test (ISWT) International Physical Activity Questionnaire-Short Form (IPAQ-Short) Impact of Weight on Quality of Life Questionnaire-Short Form (IWQOL-Lite), and a questionnaire adapted from the EU survey on Consumer Attitudes to Physical Activity. There were no significant decreases in participants' weight (p=0.444) and there were no significant improvements in IPAQ (p=0.496) and IWQOL-Lite scores (p=0.337). There were significant improvements in CRF (p<0.0002). Attitudes towards exercise improved as shown by decreased barriers to exercise, i.e. decreased shyness (17%) and increased energy (22%) and increased enjoyment (22%). A group education programme focusing on physical activity alone demonstrated a significant increase in CRF (ISWT) and had a positive influence on attitudes to exercise. Longer duration interventions may allow participants to make the necessary lifestyle changes to achieve weight loss.     

Commentary on “A roadmap for the prevention of dementia II. Leon Thal Symposium 2008.” Recruitment of participants for Alzheimer's disease clinical trials: The role of trust in caregivers,clinical researchers,regulatory authorities,and industry sponsors

A major barrier to progress in Alzheimer's disease treatment research is the increasingly difficult task of recruiting elderly participants into clinical trials. We conducted an anonymous online survey of 676 adults (average age, 50 years) to examine perceived trust in different components of our healthcare-delivery and clinical-research systems, as well as willingness to participate in clinical trials. Respondents indicated the greatest amount of trust in family members, followed by family physicians. Only 3% of respondents “completely” trusted clinical researchers, whereas 62% of respondents trusted them “somewhat” to care for them during the course of a clinical trial. Trust in clinical researchers was modestly negatively correlated with income (r = ?0.165, P < .001), but was not significantly related to sex, race, or education. Respondents indicated the least amount of trust in industry sponsors, followed by regulatory authorities.     

T-cell protein tyrosine phosphatase is a key regulator in immune cell signaling: lessons from the knockout mouse model and implications in human disease

Summary:  The immune system requires for its proper ontogeny, differentiation, and maintenance the function of several tyrosine kinases and adapters that create and modify tyrosine phosphorylation sites. Tyrosine phosphorylation is a crucial protein modification in immune cell signaling and can be reversed by protein tyrosine phosphatases (PTPs). Much progress has been made in identifying and understanding PTP function in the immune system. In this review, we present one of these proteins, named T-cell PTPs (TC-PTP) (gene name PTPN2 ), a classical, non-receptor PTP that is ubiquitously expressed with particularly high expression in hematopoietic tissues. TC-PTP is remarkable not only by the fact that it appears to influence most, if not all, cells involved in the development of the immune system, from stem cells to differentiated lineages, but also recent findings have positioned it at the core of several human diseases from autoimmune disease to cancer.