on Defeating Alzheimer's Disease and other dementias: a priority for European science and society Dementia includes a range of neurological disorders characterized by memory loss and cognitive impairment. The most common early symptom is difficulties remembering recent events. With the development of the disease, symptoms occur such as disorientation, mood swings, confusion, more serious memory loss, behavioural changes, difficulties in speaking and swallowing, as well as walking. Alzheimer Disease (AD) is the most common form of dementia (50-70% of dementia cases). Increasing age is the most important risk factor for AD.In 2012 and 2015, the World Health Organization (WHO) presented reports suggesting that Alzheimer Disease and other dementias (ADOD) should be regarded as a global public health priority 1,2 . Similar policy declarations have been presented by the European Union 3 , as well as by some individual countries. These policy declarations acknowledge trends that sometimes are described in terms of an epidemic or a "time-bomb". In 2015, the number of people affected by dementia worldwide is estimated to be almost 47 million and the numbers are expected to reach 75 million by 2030 and 131 million by 2050, with the greatest increase in low and middle income countries. The main reason for the increase is the global aging trend, since dementias are associated with a high age-specific prevalence, i.e., increasing prevalence with higher age. The global economic costs of dementia were estimated to be more than 600 billion USD in 2010 6 and 818 billion USD in 2015 5 . The direct costs in the medical and social care sectors, 487 billion USD, represent 0.65% of the aggregated global gross domestic products (GDP), which is an enormous economic impact of a single group of disorders, especially considering that 87% of the costs occur in high income countries. Care of people with dementia impacts several sectors in the society with the social care (long term care and home services) and informal care sectors constituting the greatest proportions -even greater than direct medical care 6 . In cost of illness studies, European cost estimates in 2010 ranged between 238,6 billion USD 6 and 105,6 billion € 7 .However, the economic and societal burden of ADOD corresponds to the aggregate burden of people with dementia and their next of kin. The progressive nature of dementia can influence the whole life situation for families over many years. So far, no cure or substantial symptom relieving treatment is available for ADOD. Thus, the impact of this terminal disease is already today enormous, and given the predictions for the future, ADOD represents an enormous challenge for any society, and particularly to the ageing European society.Further knowledge is needed regarding the causes of ADOD. A more complete understanding of the disease mechanisms is required for new diagnostic and therapeutic strategies. There is also a need to establish new cell-based and animal models representing, as far as possible, major clinical component...
In the 12 years since the publication of the first Consensus Paper of the WFSBP on biomarkers of neurodegenerative dementias, enormous advancement has taken place in the field, and the Task Force takes now the opportunity to extend and update the original paper. New concepts of Alzheimer's disease (AD) and the conceptual interactions between AD and dementia due to AD were developed, resulting in two sets for diagnostic/research criteria. Procedures for pre-analytical sample handling, biobanking, analyses and post-analytical interpretation of the results were intensively studied and optimised. A global quality control project was introduced to evaluate and monitor the inter-centre variability in measurements with the goal of harmonisation of results. Contexts of use and how to approach candidate biomarkers in biological specimens other than cerebrospinal fluid (CSF), e.g. blood, were precisely defined. Important development was achieved in neuroimaging techniques, including studies comparing amyloid-b positron emission tomography results to fluid-based modalities. Similarly, development in research laboratory technologies, such as ultra-sensitive methods, raises our hopes to further improve analytical and diagnostic accuracy of classic and novel candidate biomarkers. Synergistically, advancement in clinical trials of anti-dementia therapies energises and motivates the efforts to find and optimise the most reliable early diagnostic modalities. Finally, the first studies were published addressing the potential of cost-effectiveness of the biomarkers-based diagnosis of neurodegenerative disorders. ARTICLE HISTORY
AimsTreatment of chronic heart failure (CHF) guided by natriuretic peptides has been studied in clinical trials with conflicting results. The aim of this study was to investigate if N-terminal pro-B-type natriuretic peptide (NT-proBNP)-guided therapy in symptomatic heart failure patients in primary care would improve clinical outcomes over and above treatment according to guidelines. Methods and resultsSIGNAL-HF was a 9 month, randomized, single-blind, parallel group study in patients with CHF in NYHA class II -IV, ejection fraction (EF) ,50% and elevated NT-proBNP levels (males .800, females .1000 ng/L). All investigators underwent a pre-study educational programme about current CHF guidelines. A control group managed by nontrained investigators was considered not possible for ethical and practical reasons. Patients were randomized to structured treatment of CHF according to guidelines with or without NT-proBNP monitoring. The choice and dose of therapy for CHF was at the investigator's discretion. The primary outcome variable was the composite endpoint of days alive, days out of hospital, and symptom score from the Kansas City Cardiomyopathy Questionnaire.In all, 252 patients were randomized. The allocation groups were well balanced with regards to age, NT-proBNP, and EF. Treatment doses of beta-blockers and blockers of the renin -angiotensin-aldosterone system were markedly increased towards target doses and to a similar degree in both groups. There were no differences between the groups concerning either the primary endpoint (P ¼ 0.28) or its components [cardiovascular (CV) death, P ¼ 0.93; CV hospitalization, P ¼ 0.88; or symptom score, P ¼ 0.28]. ConclusionNT-proBNP-guided CHF treatment did not result in important improvements in clinical outcomes in patients with CHF in primary care above and beyond what could be achieved by education and structured CHF treatment according to guidelines.--
Loera-Valencia R, Cedazo-Minguez A, ). Current and emerging avenues for Alzheimer's disease drug targets (Review). J Intern Med 2019; 286: 398-437.Alzheimer's disease (AD), the most frequent cause of dementia, is escalating as a global epidemic, and so far, there is neither cure nor treatment to alter its progression. The most important feature of the disease is neuronal death and loss of cognitive functions, caused probably from several pathological processes in the brain. The main neuropathological features of AD are widely described as amyloid beta (Ab) plaques and neurofibrillary tangles of the aggregated protein tau, which contribute to the disease. Nevertheless, AD brains suffer from a variety of alterations in function, such as energy metabolism, inflammation and synaptic activity. The latest decades have seen an explosion of genes and molecules that can be employed as targets aiming to improve brain physiology, which can result in preventive strategies for AD. Moreover, therapeutics using these targets can help AD brains to sustain function during the development of AD pathology. Here, we review broadly recent information for potential targets that can modify AD through diverse pharmacological and nonpharmacological approaches including gene therapy. We propose that AD could be tackled not only using combination therapies including Ab and tau, but also considering insulin and cholesterol metabolism, vascular function, synaptic plasticity, epigenetics, neurovascular junction and blood-brain barrier targets that have been studied recently. We also make a case for the role of gut microbiota in AD. Our hope is to promote the continuing research of diverse targets affecting AD and promote diverse targeting as a near-future strategy. ReviewInsoluble Ab fibrils are taken into consideration as the main responsible for spine pathology. On the other hand, in both transgenic mouse models of AD and human AD brain, synapse defects and memory loss correlate weakly with the presence of Ab Current and novel Alzheimer´s disease therapy targets / R. Loera-Valencia et al.
Group counseling for mothers after emergency cesarean section did not influence their views on the recent delivery or prevent symptoms of posttraumatic stress or postnatal depression. It was, however, appreciated and did no harm. In future studies, other outcomes should be measured.
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