1,721,019 research outputs found
Major adverse cardiovascular and cerebral events in hypothyroid patients undergoing percutaneous coronary intervention
No full textZhang et al. (1) carried out a large prospective naturalistic study on patients who underwent percutaneous coronary intervention (PCI) evaluating the role of thyroid hypo-function on major clinical outcomes from in-hospital stay up to 10 years of follow up with a median observation of 3 years. The enrolled population was representative of adult patients (mean age of the whole cohort 64.6 years) with several traditional risk factors (previous cardiovascular events or coronary artery disease, hypertension, diabetes mellitus, obesity, dyslipidemia and smoking status), which accounted for high risk of cardiovascular events. The diagnosis of hypothyroidism, only defined by the presence of serum TSH level above 5 mIU/L at PCI time-point, was associated with underlying clinical features at baseline [age, female gender, history of myocardial infarction (MI), diabetes mellitus, heart failure (HF), hypertension, hyperlipidemia, arteriopathy as well as ACE/ARB and amiodarone administration] and a worse clinical composite outcome during follow up [cardiac death, MI, HF events, repeat vascularization (TRV) and stroke]. The risk of composite endpoint in hypothyroid patients remained significantly higher even after adjusting for several potential confounding factors, and accounted for about 30% of the increased risk. In detail, the greatest correlation between hypothyroidism and single endpoints was observed for MI, HF, TRV and stroke. By stratifying hypothyroid patients on the basis of serum TSH value (≥5<10 mIU/L and ≥10 mIU/L), the authors demonstrated that even a mild increase of serum TSH (≥5<10 mIU/L) was significantly associated to the composite endpoint and the occurrence of MI, although to a lesser extent as compared to patients with TSH ≥10 mIU/L, while the statistical significance was not reached for the other single endpoints. On the other hand, patients with a marked increase of serum TSH (≥10 mIU/L, defined as affected by overt hypothyroidism independently from analyzing the level of serum free thyroxin) presented a greater risk of either the composite endpoint or all the single endpoints as compared to euthyroid patients. It is noteworthy that patients receiving adequate L-thyroxin replacement therapy (TRT) showed a significant reduction of composite or single endpoints while, those with inadequate TSH target value (≥5 mIU/L) maintained a risk profile similar to hypothyroid patients not receiving any TRT. Finally, in a nested group of patients randomly selected with a ratio of 1/3 from the two cohorts (euthyroid and hypothyroid patients at baseline) and evaluated in single blind by coronary angiogram at follow-up, the authors documented a significant worsening of target vessel diseases in hypothyroid as compared to euthyroid patients
Endocrine Disorders and Cognitive Function in the Elderly
Full text linkA direct link between cognition and endocrine function has been established at several levels, from preclinical models to
large clinical surveys. In this regard, international guidelines suggest performing a screening test for thyroid function (circulating
TSH level) in subjects with cognitive impairment in order to exclude a possible reversible cause of dementia [1]. Moreover,
marked cognitive changes have been observed in patients with severe hypercortisolism [2]. Apart from the full-blown manifestations
of hypothyroidism and hypercortisolism that may account for secondary causes of dementia, either subclinical thyroid
dysfunction or mild adrenal hyper-function along with several other endocrine diseases including testosterone deficit, obesity
and glucose metabolism alterations, have been observed in patients with neurodegenerative diseases, suggesting a potential role
of these clinical entities on Alzheimer (AD) or Parkinson Disease (PD) development [3-8]. Moreover, we have to mention the
possible link between cognition and neuro-endocrine alterations associated with cardiovascular dysfunction. In this regard, the
adrenergic system seems to play a key role in the cognitive alterations observed in heart failure [9]. However, given that all
these clinical conditions increase the cardiovascular risk and the consequent risk of vascular dementia, it is very difficult to distinguish
their possible direct role on the neurodegenerative process from that consequent to chronic cerebrovascular disease. In
any case, when analyzing the scientific literature regarding the association between mild endocrine or metabolic disorders and
neurodegeneration, conflicting results are still present making the interpretation of reported results very complex. In fact, we
have to consider different settings and different age ranges of the available studies along with the time of onset and the duration
of the analyzed endocrine dysfunction. An increasing body of evidence suggests a possible concurrent effect of several endocrine
disorders and the ageing process on the pathophysiology of neurodegenerative diseases and, in general, on cognitive function
[3, 4-8, 10]. This thematic issue of the Journal “Recent Patents on Endocrine, Metabolic & Immune Drug Discovery” is
aimed to explore these complex relationships and provide an updated review of the literature reporting also on most recent patents
that may have an impact on the development and progress of neurodegenerative disease
Why are so few antipsychotic drugs licensed for Alzheimer's disease related behavioral and psychological symptoms?
No full textAlzheimer’s disease is the most common type of dementia. The
progressive nature of the disease represents a challenge for
clinicians, aiming to ensure an adequate treatment and support
to the patient and the caregivers. Together with the impairment
in several cognitive domains, progressively worsening, behavioral
symptoms frequently occur. Among them, agitation and
aggression pose great management difficulty; the therapeutic
approach could be nonpharmacological and/or pharmacological.
Unfortunately, even though the non-pharmacological
approach is safer for the patient, the data about efficacy are
sparse and limited. The pharmacological approach with antipsychotic
drugs, together with heterogeneous results about efficacy,
leads to higher rate of complications. For this reason,
antipsychotic drugs are not licensed for the use in behavioral
disturbances in dementia, apart from Risperidone; other drugs
are usually prescribed off-label. All considered, the treatment of
behavioral symptoms in dementia represents a great challenge
for clinicians, especially when treating complex or frail patients
Coenzyme Q10 in neuromuscular and neurodegenerative disorders
No full textCoenzyme Q10 (CoQ10, or ubiquinone) is an electron carrier of the mitochondrial respiratory chain (electron transport chain) with antioxidant properties. In view of the involvement of CoQ10 in oxidative phosphorylation and cellular antioxidant protection a deficiency in this quinone would be expected to contribute to disease pathophysiology by causing a failure in energy metabolism and antioxidant status. Indeed, a deficit in CoQ10 status has been determined in a number of neuromuscular and neurodegenerative disorders. Primary disorders of CoQ10 biosynthesis are potentially treatable conditions and therefore a high degree of clinical awareness about this condition is essential. A secondary loss of CoQ10 status following HMG-Coa reductase inhibitor (statins) treatment has be implicated in the pathophysiology of the myotoxicity associated with this pharmacotherapy. CoQ10 and its analogue, idebenone, have been widely used in the treatment of neurodegenerative and neuromuscular disorders. These compounds could potentially play a role in the treatment of mitochondrial disorders, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, Friedreich's ataxia, and other conditions which have been linked to mitochondrial dysfunction. This article reviews the physiological roles of CoQ10, as well as the rationale and the role in clinical practice of CoQ10 supplementation in different neurological and muscular diseases, from primary CoQ10 deficiency to neurodegenerative disorders. We also briefly report a case of the myopathic form of CoQ10 deficiency
Neuroprotective effects of tetracyclines: molecular targets, animal models and human disease
No full textTetracyclines are a class of antibiotics which could play a therapeutic role in several neurological disorders. Minocycline, extensively studied in animal models, decreased the size of ischaemic and haemorrhagic infarct. In Parkinson's disease models minocycline protected the nigrostriatal pathway, and in Huntington's disease and motoneuron disease models delayed the progression of disease extending the lifespan. Finally, in human diseases such as stroke and multiple sclerosis tetracyclines seem to play some neuroprotective role. The main biological effects of tetracyclines are the inhibition of microglial activation, the attenuation of apoptosis, and the suppression of reactive oxygen species production. These mechanisms are involved in the pathogenesis of several neurodegenerative disorders. Several reports showed that minocycline reduced mitochondrial Ca(2+) uptake, stabilized mitochondrial membranes, and reduced the release into the cytoplasm of apoptotic factors. Other effects include up-regulation of mitochondrial bcl-2 (an antiapoptotic protein), direct scavenging of reactive oxygen species, and inhibition of mitogen activated protein kinases. It is still unclear which of these mechanisms plays the pivotal role in neuroprotective properties of tetracyclines. The anti-apoptotic effect of tetracyclines probably involves the mitochondrion. The major target for tetracyclines in neurodegeneration could lie within the complex network that links mitochondria, oxidative stress, poly (ADP-ribose) polymerase-1 and apoptosis. Here, we review the neuroprotective effects of tetracyclines in animal models and in human disease, and we focus on their possible mechanism(s) of action, with special regard to mitochondrial dysfunction in neurodegeneration
.Is there a primary role of the mitochondrial genome in Alzheimer's disease?
No full textThe "mitochondrial cascade hypothesis" could explain many of the biochemical, genetic and pathological features of sporadic Alzheimer's disease (AD). Somatic mutations in mitochondrial DNA (mtDNA) could cause energy failure, increased oxidative stress and accumulation of amyloid beta, which in a vicious cycle reinforces mtDNA damage and oxidative stress. Despite the evidence of mitochondrial dysfunction in AD, and despite the cognitive impairment frequently reported in patients with mtDNA mutation, no causative mutation in the mtDNA have been linked to AD. Indeed, results of studies on the role of mtDNA polymorphisms or haplogroups in AD are controversial. In this minireview, we summarize the actual knowledge about the involvement of mtDNA in AD pathology
Potential drug–drug interactions in alzheimer patients with behavioral symptoms
Full text linkThe use of multi drug regimens among the elderly population has increased tremendously over the last decade although the benefits of medications are always accompanied by potential harm, even when prescribed at recommended doses. The elderly populations are particularly at an increased risk of adverse drug reactions considering comorbidity, poly-therapy, physiological changes affecting the pharmacokinetics and pharmacodynamics of many drugs and, in some cases, poor compliance due to cognitive impairment and/or depression. In this setting, drug-drug interaction may represent a serious and even life-threatening clinical condition. Moreover, the inability to distinguish drug-induced symptoms from a definitive medical diagnosis often results in addition of yet another drug to treat the symptoms, which in turn increases drug-drug interactions. Cognitive enhancers, including acetylcholinesterase inhibitors and memantine, are the most widely prescribed agents for Alzheimer's disease (AD) patients. Behavioral and psychological symptoms of dementia, including psychotic symptoms and behavioral disorders, represent noncognitive disturbances frequently observed in AD patients. Antipsychotic drugs are at high risk of adverse events, even at modest doses, and may interfere with the progression of cognitive impairment and interact with several drugs including anti-arrhythmics and acetylcholinesterase inhibitors. Other medications often used in AD patients are represented by anxiolytic, like benzodiazepine, or antidepressant agents. These agents also might interfere with other concomitant drugs through both pharmacokinetic and pharmacodynamic mechanisms. In this review we focus on the most frequent drug-drug interactions, potentially harmful, in AD patients with behavioral symptoms considering both physiological and pathological changes in AD patients, and potential pharmacodynamic/pharmacokinetic drug interaction mechanisms
Cognitive function and quality of life in mild thyroid hormone deficiency
No full textSubclinical hypothyroidism (sHT) is very common in general population, especially in women and older people. sHT individuals may experience symptoms that resemble those observed in overt hypothyroidism, resulting in impaired quality of life (QOL). Asymptomatic patients may suffer a reduction in perceived health status due to the awareness of disease. Cognitive function represents one of the most important domains of the QOL questionnaires. Given the intrinsic relationship between cognitive status and QOL it is worth to address these topics together, in a systematic review of the literature. Thus, we reviewed the English scientific literature available on National Library of Medicine (www.pubmed.com) sine 1980 regarding hypothyroidism, sHT, elderly, L-thyroxine (LT4) therapy, QOL, cognition, brain. We supplemented the search with records from personal files, textbooks, and relevant articles. The possible link, at molecular level, between cognition and thyroid failure was also assessed. Conflicting results on the association between sHT and cognitive and health related QOL impairment are still present, although the most recent, naturalistic studies did not find any significant relationship. Interestingly, a reduction in health related QOL is frequently reported in patients with thyroid autoimmune diseases regardless of thyroid dysfunction. We also report most significant patents on the topic
The Use of Antipsychotic Drugs for Treating Behavioral Symptoms in Alzheimer’s Disease
Full text linkAccording to the World Alzheimer’s report, dementia was estimated to affect 50 million worldwide in 2018, number expected to increase to more than 150 million within 30 years. Alzheimer’s disease is the most common type of dementia, accounting on its own for 2/3 of all dementia cases. The initial signs and symptoms of Alzheimer’s disease relate to progressive cognitive decline, inexorably progressing until the loss of independence. Neuropsychiatric and behavioral symptoms may occur during the progression of the disease; around 20% of patients without any behavioral symptoms at the diagnosis will experience some of them within 2 years. Consequences are early institutionalization, lower quality of life, of both patients and carers, and more severe cognitive impairment. Treatment options for behavioral symptoms include pharmacological and nonpharmacological approaches. The latter are usually preferred, since antipsychotic therapy is not free from several, and often serious, adverse events. However, behavioral symptoms are not always controllable with non-pharmacological intervention. The psychotropic class of medication more frequently prescribed for behavioral symptoms are atypical antipsychotics; among them, risperidone is the only one licensed for the treatment of aggression, in Europe but not in the USA. On that regard, the use of antipsychotic drugs should be limited, due to the increased risk of mortality, stroke, hallucination, and higher risk of relapse after discontinuation. Some new agents are under evaluation, such as pimavanserin and lumateperone. In this review, we are evaluating the current available pharmacological options to treat behavioral symptoms as well as the forthcoming new agents
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