apolipoproteine e4 allelic variant cognitive decline and psychosis in alzheimer disease a review of the literature and suggestions for upcoming studies

Apolipoprotein E (ApoE) e4 allele represents a well known vascular risk factor for developing Alzheimer disease (AD) and differences in ApoE genotypes may explain a part of the variability in AD phenotypes. In fact, ApoE e4 allele possession seems to be associated with a more precocious age of onset, greater episodic memory impairment, and psychotic symptoms. The first question we discuss regards the role of ApoE e4 on cognitive progression of AD. In fact, while a general agreement exists about the role played by ApoE e4 on the precocious onset of AD, cognitive decline has been differently associated with ApoE e4 allele possession in AD patients in a continuum of faster decline, no effect, and slower decline. An attemptable interpretation is that the biological processes leading to the onset of AD are different from those involved in determining its clinical course. The second question regards the possible relationship between the presence of the degenerative pathological hallmarks of the disease in specific cerebral areas and different cognitive or behavioural symptoms. In fact, there is evidence that degenerative pathology in hippocampal formation and frontal cortex reflects the progression of cognitive deficits in brain aging and AD and that hypometabolism in right frontal lobe and greater frontal neuropsychological deficits occur in AD patients with psychosis in comparison to those without. The third question regards, specifically, the relationship between ApoE e4 variant and behavioural symptoms. In fact, there is evidence supporting the link between being carriers of ApoE e4 allele and severity of delusions, mostly at the early stage of the illness. In an interpretative challenge, we suggest that the link between being carriers of ApoE e4 allele and suffering from delusions in AD may be explained by frontal lobe dysfunctions. Finally, we hypothesize that the most precocious onset of AD illness, described in carriers of ApoE e4 allelic variant, may also be related to the precocious onset of psychotic symptoms, which produces caregiver and patient distress and requires immediate assessment and treatment

Evaluating the metabolic approach to treatment of diabetic coronary patients

Diabetic patients with coronary artery disease have an altered myocardial metabolism of glucose and free fatty acids (FFA) and accelerated and diffuse atherogenesis with involvement of peripheral coronary segments that causes chronic hypoperfusion and hibernation. Therefore, in coronary diabetic patients the ischaemic metabolic changes that occur as a consequence of the mismatch between blood supply and cardiac metabolic requirements are heightened by the diabetic metabolic alterations. Important metabolic alterations in diabetic patients are the decreased utilization of glucose and the increase in muscular and myocardial FFA uptake and oxidation. These metabolic changes are responsible for the increased susceptibility of the diabetic heart to myocardial ischaemia and to a greater decrease of myocardial performance for a given amount of ischaemia compared to non diabetic hearts. A therapeutic approach aimed at an improvement of cardiac metabolism through manipulations of the utilization of metabolic substrates should result in an improvement of myocardial ischaemia and of left ventricular function. The inhibition of FFA oxidation improves cardiac metabolism at rest, increases the cardiac resistance to ischaemia and therefore reduces the decline of left ventricular function due to chronic hypoperfusion and repetitive episodes of myocardial ischaemia in patients with and without diabetes. Modulation of myocardial FFA metabolism should be the key target for metabolic interventions in diabetic patients with coronary artery disease

Metabolic approach to heart failure: The role of metabolic modulators

Abstract Heart failure (HF) is a systemic and multiorgan syndrome with metabolic failure as fundamental mechanism. As a consequence of its impaired metabolism, other processes are activated in the failing heart, further exacerbating the progression of HF. Metabolic agents are a relatively new class of drugs that act through optimisation of cardiac substrate metabolism. Among the metabolic modulators, Trimetazidine (TMZ) and perhexiline are the only two agents with proven anti-ischaemic effect currently available. However, due to its major side effects, perhexiline is not yet approved in the US or Europe. Clinical trials have demonstrated that the adjunct of TMZ to optimal medical therapy improves symptoms and prognosis of HF without exerting negative hemodynamic effects. Due to its anti-ischaemic/anti-anginal effect and excellent tolerability, the modulation of cardiac metabolism with TMZ represents a promising approach for the treatment of patients with HF

Post-percutaneous coronary intervention angina: From physiopathological mechanisms to individualized treatment

Chronic ischemic heart disease (IHD) is a multifactorial disease with different underlying pathogenetic mechanisms. Percutaneous coronary intervention (PCI) is widely used in patients with IHD in order to reduce angina recurrence. However, after complete or incomplete revascularization procedures, patients may still present anginal symptoms, with a detrimental impact on quality of life and prognosis. This review summarizes the pathogenic mechanisms and the main challenges encountered in the diagnosis and management of post-PCI angina

The combination of nutraceutical and simvastatin enhances the effect of simvastatin alone in normalising lipid profile without side effects in patients with ischemic heart disease

Abstract Background hyperlipidemia is one of the most important cardiovascular risk factors. Statins at high doses are commonly prescribed to lower LDL-cholesterol, but are often poorly tolerated. In particular, muscle pain and increase of creatine phosphokinase are frequent side effects. The purpose of this study was to assess whether the addition of a nutraceutical to simvastatin may result in the achievement of the therapeutic target (LDL-cholesterol less than 70mg/dL) without side effects in patients with ischemic heart disease. Methods Sixty-four patients with ischemic heart disease treated with simvastatin 20mg who had not achieved the therapeutic target were enrolled. Patients were randomised 1:1. Patients of group A (n=32) were given simvastatin 40mg per day and patients of group B (n=32) were given simvastatin 20mg plus 2 tablets of a nutraceutical composed of bergamot, phytosterols, artichoke, vitamin C. Results After 3months, patients in both groups showed a significant reduction from baseline in total cholesterol, LDL-c and tryglicerides. However, in group A, 4 patients reported myalgia (9,7%) with an increase in creatine phosphokinase; whereas no adverse events occurred in group B. Conclusions The association of a nutraceutical and simvastatin 20mg may be a valid therapeutic option for the treatment of hyperlipidemia in patients with ischemic heart disease intolerant to statin at high doses, in the absence of side effects. Further studies are needed to clarify the mechanisms of action of nutraceuticals

Implantable devices for heart failure monitoring: the CardioMEMS™ system.

Several devices have been developed for heart failure (HF) treatment and monitoring. Among device-based monitoring tools, CardioMEMS™ has received growing research attention. This document reflects the key points of an ESC consensus meeting on implantable devices for monitoring in HF, with a particular focus on CardioMEMS™

Who approves/pays for additional monitoring?

Major considerations in the provision of healthcare are availability, affordability, accessibility, and appropriateness, especially in the setting of heart failure where disease burden is growing, developments have been rapid and newer biomarkers, diagnostic and imaging techniques, monitoring systems, devices, procedures, and drugs have all been developed in a relatively short period of time. Many monitoring and diagnostic systems have been developed but the disproportionate cost of conducting trials of their effectiveness has limited their uptake. There are added complexities, in that the utilization of doctors for the supervision of the monitoring results may be optimal in one setting and not in another because of differences in the characteristics of organization of healthcare provision, making even interpretation of the trials we have had, still difficult to interpret. New technologies are continuously changing the approach to healthcare and will reshape the structure of the healthcare systems in the future. Mobile technologies can empower patients and carers by giving them more control over their health and social care needs and reducing their dependence on healthcare professionals for monitoring their health, but a significant problem is the integration of the multitude of monitored parameters with clinical data and the recognition of intervention thresholds. Digital technology can help, but we need to prove its cost/efficacy and how it will be paid for. Governments in many European countries and worldwide are trying to establish frameworks that promote the convergence of standards and regulations for telemedicine solutions and yet simultaneously health authorities are closely scrutinizing healthcare spending, with the objective of reducing and optimizing expenditure in the provision of health services. There are multiple factors to be considered for the reimbursement models associated with the implementation of physiological monitoring yet it remains a challenge in cash-strapped health systems

Monitoring of biomarkers in heart failure.

The role of biomarkers is increasingly recognized in heart failure (HF) management, for diagnosis, prognostication, and screening of high-risk patients. Beyond natriuretic peptides and troponins, the utility of novel, emerging biomarkers is less established. This document reflects the key points of a Heart Failure Association of the European Society of Cardiology (ESC) consensus meeting on biomarker monitoring in HF

Monitoring functional capacity in heart failure.

This document reflects the key points of a consensus meeting of the Heart Failure Association of European Society of Cardiology (ESC) held to provide an overview the role of physiological monitoring in the complex multimorbid heart failure (HF) patient. This article reviews assessments of the functional ability of patients with HF. The gold standard measurement of cardiovascular functional capacity is peak oxygen consumption obtained from a cardiopulmonary exercise test. The 6-min walk test provides an indirect measure of cardiovascular functional capacity. Muscular functional capacity is assessed using either a 1-repetition maximum test of the upper and lower body or other methods, such as handgrip measurement. The short physical performance battery may provide a helpful, indirect indication of muscular functional capacity

Superiority of the new sex-adjusted models to remove the female disadvantage restoring equity in liver transplant allocation

Background and Aims: Model for End-stage Liver Disease (MELD) and MELDNa are used worldwide to guide graft allocation in liver transplantation (LT). Evidence exists that females are penalized in the present allocation systems. Recently, new sex-adjusted scores have been proposed with improved performance respect to MELD and MELDNa. GEMA-Na, MELD 3.0, and sex-adjusted MELDNa were developed to improve the 90-day dropout prediction from the list. The present study aimed at evaluating the accuracy and calibration of these scores in an Italian setting. Methods: The primary outcome of the present study was the dropout from the list up to 90 days because of death or clinical deterioration. We retrospectively analysed data from 855 adults enlisted for liver transplantation in the Lazio region (Italy) (2012–2018). Ninety-day prediction of GEMA-Na, MELD 3.0 and sex-adjusted MELDNa with respect to MELD and MELDNa was analysed. Brier score and Brier Skill score were used for accuracy, and the Greenwood-Nam- D'Agostino test was used to evaluate the calibration of the models. Results: GEMA-Na (concordance = .82, 95% CI = .75–. 89), MELD 3.0 (concordance = .81, 95% CI = .74–. 87) and sex-adjusted MELDNa (concordance = .81, 95% CI = .74–.88) showed the best 90-day dropout prediction. GEMA-Na showed a higher increase in accuracy with respect to MELD (p = .03). No superiority was shown with respect to MELDNa. All the tested scores showed a good calibration of the models. Using GEMA-Na instead of MELD would potentially save one in nine dropouts and could save one dropout per 285 patients listed