Alzheimers AND pioglitazone

Modern longitudinal studies collect multiple outcomes as the primary endpoints to understand the complex dynamics of the diseases. Oftentimes, especially in clinical trials, the joint variation among the multidimensional responses plays a significant role in assessing the differential characteristics between two or more groups, rather than drawing inferences based on a single outcome. We develop a projection-based two-sample significance test to identify the population-level difference between the multivariate profiles observed under a sparse longitudinal design...

Oxidative stress and neuroinflammation play a pivotal role in triggering the neurodegenerative pathological cascades which characterize neurodegenerative disorders, such as Alzheimer's and Parkinson's diseases. In search for potential efficient treatments for these pathologies, that are still considered unmet medical needs, we started from the promising properties of the antidiabetic drug pioglitazone, which has been repositioned as an MAO-B inhibitor, characterized by promising neuroprotective properties. Herein, with the aim to broaden its neuroprotective profile, we tried to enrich pioglitazone with direct and indirect antioxidant properties by hanging polyphenolic and electrophilic features that are able to trigger Nrf2 pathway and the resulting cytoprotective genes' transcription, as well as serve as radical scavengers...

Alzheimer's disease (AD) is the main cause of dementia in older age. The prevalence of AD is growing worldwide, causing a tremendous burden to societies and families. Due to the complexity of its pathogenesis, the current treatment of AD is not satisfactory, and drugs acting on a single target may not prevent AD progression. This review summarizes the multi-target pharmacological effects of thiazolidinediones (TZDs) on AD. TZDs act as peroxisome proliferator-activated receptor gamma (PPARγ) agonists and long-chain acyl-CoA synthetase family member 4 (ACSL4) inhibitors...

BACKGROUND: The 523 poly-T length polymorphism (rs10524523) in TOMM40 has been reported to influence longitudinal cognitive test performance within APOE ε3/3 carriers. The results from prior studies are inconsistent. It is also unclear whether specific APOE and TOMM40 genotypes contribute to heterogeneity in longitudinal cognitive performance during the preclinical stages of AD. OBJECTIVES: To determine the effects of these genes on longitudinal cognitive change in early preclinical stages of AD, we used the clinical trial data from the recently concluded TOMMORROW study to examine the effects of APOE and TOMM40 genotypes on neuropsychological test performance...

AIMS: The objective of this umbrella review and meta-analysis was to evaluate the effect of diabetes on risk of dementia, as well as the mitigating effect of antidiabetic treatments. MATERIALS AND METHODS: We conducted a systematic umbrella review on diabetes and its treatment, and a meta-analysis focusing on treatment. We searched MEDLINE/PubMed, Embase, PsycINFO, CINAHL and the Cochrane Library for systematic reviews and meta-analyses assessing the risk of cognitive decline/dementia in individuals with diabetes until 2 July 2023...

BACKGROUND: Pharmacotherapy for most psychiatric conditions was developed from serendipitous observations of benefit from drugs prescribed for different reasons. An algorithmic approach to formulating pharmacotherapy is proposed, based upon which combination of changed activities by brain cell-types is dominant for any particular condition, because those cell-types contain and surrogate for genetic, metabolic and environmental information, that has affected their function. The algorithm performs because functions of some or all the affected cell-types benefit from several available drugs: clemastine, dantrolene, erythropoietin, fingolimod, fluoxetine, lithium, memantine, minocycline, pioglitazone, piracetam, and riluzole PROCEDURES/FINDINGS: Bipolar disorder, major depressive disorder, schizophrenia, Alzheimer's disease, and post-traumatic stress disorder, illustrate the algorithm; for them, literature reviews show that no single combination of altered cell-types accounts for all cases; but they identify, for each condition, which combination occurs most frequently, i...

The goal of treatment for Alzheimer's dementia (AD) is the restoration of normal cognition. No drug regimen has ever achieved this. This article suggests that curing AD may be achieved by combination therapy as follows. First, with intranasal insulin to augment the body's natural counter-reaction to the changes in brain cell-types that produced the dementia. Second, with edaravone to decrease free radicals, which are increased and causal in AD. Third, as described elsewhere, with one or two drugs from among pioglitazone, fluoxetine, and lithium, which address the brain cell-types whose changed functions cause the dementia...

Pioglitazone is an insulin resistance inhibitor widely used as monotherapy or combined with metformin or insulin in treating type 2 diabetes mellitus (T2DM). This study further investigated the relationship between pioglitazone use and the risk of developing Alzheimer's disease (AD) in patients newly diagnosed with T2DM, and examined the potential impact of insulin use on this association. Data were extracted from the National Health Insurance Research Database (NHIRD) of Taiwan. Our data exhibited that the risk of developing AD in the pioglitazone group was 1...

Multiple genetic, metabolic, and environmental abnormalities are known to contribute to the pathogenesis of Alzheimer's dementia (AD). If all of those abnormalities were addressed it should be possible to reverse the dementia; however, that would require a suffocating volume of drugs. Nevertheless, the problem may be simplified by using available data to address, instead, the brain cells whose functions become changed as a result of the abnormalities, because at least eleven drugs are available from which to formulate a rational therapy to correct those changes...

Diabetes mellitus (DM) is known to be a risk factor for dementia, especially in the elderly population, and close associations between diabetes and Alzheimer disease (AD) have been determined. Peroxisome proliferator-activated receptor-gamma (PPAR-γ) agonists are insulin-sensitising drugs. In addition to their anti-diabetic properties, their effectiveness in preventing and decreasing cognitive impairment are the most recent characteristics that have been studied. For this study, we conducted a systematic review and meta-analysis to critically analyse and evaluate the existing data on the effects of PPAR-γ agonist therapy on the cognitive status of patients...

BACKGROUND: The onset of mild cognitive impairment (MCI) is an essential outcome in Alzheimer's disease (AD) prevention trials and a compelling milestone for clinically meaningful change. Determining MCI, however, may be variable and subject to disagreement. Adjudication procedures may improve the reliability of these determinations. We report the performance of an adjudication committee for an AD prevention trial. METHODS: The TOMMORROW prevention trial selected cognitively normal participants at increased genetic risk for AD and randomized them to low-dose pioglitazone or placebo treatment...

Pioglitazone, a peroxisome proliferator-activated receptor gamma (PPARγ) agonist, is known to have anti-inflammatory and anti-oxidant effects on the brain, and its clinical potential in the treatment of cognitive impairment in diseases such as Alzheimer's disease (AD) and Parkinson disease (PD) is currently being explored. This review focused on the reported beneficial effects of pioglitazone on cognitive dysfunction and summarized the associated mechanisms associated with pioglitazone-induced improvement in cognitive dysfunction...

Alzheimer's (AD) and Parkinson's Diseases (PD) are common neurodegenerative disorders growing in incidence and prevalence and for which there are no disease-modifying treatments. While there are considerable complexities in the presentations of these diseases, the histological pictures of these pathologies, as well as several rare genetic predispositions for each, point to the involvement of maladaptive protein processing and inflammation. Importantly, the common presentations of AD and PD are connected to aging and to dysmetabolism, including common co-diagnosis of metabolic syndrome or diabetes...

BACKGROUND: Alzheimer's Disease (AD) is the most rampant neurodegenerative disorder which has caused havoc worldwide. More than a century has passed since the first case of AD was reported, but still no stable treatment is known to mankind. The available medications only provide temporary relief and are not a cure for the disease. The hunt for advanced techniques in drug development has paved the way for drug repurposing, i.e., repositioning or reutilizing drugs as an innovative approach...

The present study aimed to evaluate the role of diosmetin in alleviating advanced glycation end products (AGEs)-induced Alzheimer's disease (AD)-like pathology and to clarify the action mechanisms. Before stimulation with AGEs (200 μg/mL), SH-SY5Y cells were treated with diosmetin (10 μmol/L), increasing cell viability. The induction of AGEs on the reactive oxygen species overproduction and downregulation of antioxidant enzyme activities, including superoxide dismutase, glutathione peroxidase, and catalase, were ameliorated by diosmetin...

Pioglitazone hydrochloride (PGZ), a nuclear receptor peroxisome proliferator-activated receptor gamma (PPAR- γ ) agonist, is a universally adopted oral agent for the treatment of type 2 diabetes (T2D). Previous studies reported that PGZ could ameliorate the symptoms of aging-related diseases and Alzheimer's disease. However, whether PGZ participates in aging regulation and the underlying mechanism remain undetermined. Here, we found that PGZ significantly prolonged the lifespan and healthspan of Caenorhabditis elegans ( C ...

Type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD) commonly co-occur. T2DM increases the risk for AD by approximately twofold. Animal models provide one means of interrogating the relationship of T2DM to AD and investigating brain insulin resistance in the pathophysiology of AD. Animal models show that persistent hyperglycaemia results in chronic low-grade inflammation that may contribute to the development of neuroinflammation and accelerate the pathobiology of AD. Epidemiological studies suggest that patients with T2DM who received treatment with specific anti-diabetic agents have a decreased risk for the occurrence of AD and all-cause dementia...

BACKGROUND: Genome-wide association studies (GWAS) have identified numerous susceptibility loci for Alzheimer's disease (AD). However, utilizing GWAS to identify high-confidence AD risk genes (ARGs) that can guide development of new therapeutics for patients suffering from AD has heretofore not been successful. METHOD: To address this critical problem in the field, we have developed a genotype-informed, network-based methodology that interrogates pathogenesis to identify new therapeutics...

BACKGROUND: Genome-wide association studies (GWAS) have identified numerous susceptibility loci for Alzheimer's disease (AD). However, utilizing GWAS and multi-omics data to identify high-confidence AD risk genes (ARGs) and druggable targets that can guide development of new therapeutics for patients suffering from AD has heretofore not been successful. METHODS: To address this critical problem in the field, we have developed a network-based artificial intelligence framework that is capable of integrating multi-omics data along with human protein-protein interactome networks to accurately infer accurate drug targets impacted by GWAS-identified variants to identify new therapeutics...

Alzheimer's disease (AD) is the leading cause of dementia that has remained a major medical, sociocultural and economical challenge globally. Previously developed treatments like anticholinesterase inhibitors (AChEIs) and N-methyl-D-aspartate receptor (NMDAR) antagonists only provide short-term symptomatic improvement and do not prevent progression. Repeated setbacks and failures over the past 25 years in AD clinical trials have hindered efforts to develop effective AD treatments. Fortunately, Aducanumab, a specific anti-amyloid β antibody, has shown promising clinical results and was recently approved by the Food and Drug Administration (FDA) through an accelerated approval pathway...