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Viagra For Alzheimer’s Dosage

Benefits Of Sildenafil In Ad

New studies show Viagra as candidate to treat, prevent Alzheimers

Since most doses of sildenafil/cGMP activate PGC1 and PGC1signaling induces mitochondrial biogenesis , upregulates antioxidant enzymes , and suppresses BACE1 expression , sildenafil should provide significant benefits to patients with AD. In addition to its PGC1-specific benefits, sildenafil promotes smooth muscle relaxation and vasodilation via cGMP , which might provide additional benefit to patients with AD since hypoperfusion is also a significant impairment in AD patients brains . Sildenafil suppresses apoptosis in hypoxic neurons and promotes neurogenesis , so it might slow the loss of AD neurons and promote the replenishment of new ones. Furthermore, sildenafil improves insulin sensitivity and endothelial inflammation in patients , so sildenafil might also promote insulin sensitivity and suppress inflammation in AD brains. Since cGMP/PKG signaling mediates long-term potentiation via CREB phosphorylation , sildenafil should improve the learning and memory impairments associated with AD. Therefore, in theory, most doses of sildenafil should improve multiple hallmarks of AD, including excessive A generation, impaired mitochondrial biogenesis, oxidative stress, neuroinflammation, hypoperfusion, insulin resistance, neuron loss, insufficient neurogenesis, and memory deficits.

Sildenafil And Ad Comorbidities And Risk Factors

It is also important to consider the effects of sildenafil on common AD comorbidities and/or risk factor conditions, such as type II diabetes, cardiovascular diseases, and depression, since many AD patients suffer from one or more of these conditions.

Regarding the effect of sildenafil in depression, NOS/NO/sGC/cGMP and serotonin signaling tend to oppose each other. cGMP triggers cerebral vasodilation , whereas serotonin induces cerebral vasoconstriction . NOS/NO/sGC/cGMP/PKG signaling activates the serotonin transporter , inducing serotonin reuptake . For this reason, sildenafil might be expected to make selective serotonin reuptake inhibitor antidepressants less effective. However, there do not appear to be any reports of this being the case, and sildenafil has been used safely and successfully to treat erective dysfunction in patients taking SSRIs . Moreover, sildenafil itself has been shown to exert an antidepressant effect in mice .

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Expert Reaction To Study Identifying Sildenafil As A Candidate Drug For Alzheimers Disease

A study published in Nature Aging identifies sildenafil as a candidate drug for Alzheimers disease.

Prof Tara Spires-Jones, Deputy Director of the Centre for Discovery Brain Sciences, University of Edinburgh, said:

This study by Dr Cheng and colleagues used computer modelling and data from insurance claims from over 7 million people to look for potential drugs that may prevent Alzheimers disease. This study looks at data from a very large number of people, but there are several important limitations to consider. The data from insurance claims are not very detailed and did not include information on other important risk factors for Alzheimers like risk genes and level of education. Women are at greater risk of Alzheimers than men and as this drug, sildenafil , is most commonly used for erectile dysfunction, there were fewer women taking sildenafil in this study and the effect on women taking the drug was not as strong. Sildenafil is more often prescribed to wealthy people and low socioeconomic status is associated with higher risk of Alzheimers.

As the authors point out, this type of data cannot determine whether this drug, actually prevents Alzheimers disease. There are other possible explanations for these findings for example, we know that brain changes start decades before dementia symptoms and it is possible that these early Alzheimers changes reduce sex drive .

Prof Robert Howard, Professor of Old Age Psychiatry, UCL Division of Psychiatry, said:

Sildenafil Shows Potential For Drug Repurposing

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byJudy George, Senior Staff Writer, MedPage Today December 6, 2021

Sildenafil may be a candidate drug to prevent or treat Alzheimer’s disease, new research suggested.

Across 6 years of follow-up, sildenafil users were 69% less likely to develop Alzheimer’s disease than non-sildenafil users , a large case-control analysis of insurance claims showed.

Sildenafil also emerged as a potential disease risk modifier in an analysis of drugs that might be repurposed for Alzheimer’s, reported Feixiong Cheng, PhD, of the Cleveland Clinic Genomic Medicine Institute, and co-authors.

Moreover, the phosphodiesterase 5 inhibitor, which is approved to treat erectile dysfunction and pulmonary arterial hypertension, increased neurite growth and decreased phospho-tau expression in neuron models derived from induced pluripotent stem cells, Cheng and colleagues wrote in Nature Aging.

Understanding endophenotypes may uncover common underlying mechanisms and lead to drugs that could be repurposed for diseases like Alzheimer’s, the researchers noted.

“Recent studies show that the interplay between amyloid and tau is a greater contributor to Alzheimer’s than either by itself,” Cheng said in a statement. “Therefore, we hypothesized that drugs targeting the molecular network intersection of amyloid and tau endophenotypes should have the greatest potential for success.”

Disclosures

Primary Source

Nature Aging

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Common Side Effects People Have Besides Dementia Alzheimer’s Type *:

  • Drug Ineffective: 10 people, 24.39%
  • Memory Loss: 8 people, 19.51%
  • Neuropathy Peripheral : 4 people, 9.76%
  • Hearing Loss: 4 people, 9.76%
  • Otorrhea : 4 people, 9.76%
  • Tinnitus : 4 people, 9.76%
  • Tendonitis : 4 people, 9.76%
  • Muscle Aches : 3 people, 7.32%
  • Arthritis : 3 people, 7.32%
  • Rotator Cuff Syndrome : 3 people, 7.32%
  • Findings Show A 69% Reduced Likelihood Of Developing The Disease

    Date:
    Cleveland Clinic
    Summary:
    A new study has identified sildenafil — an FDA-approved therapy for erectile dysfunction and pulmonary hypertension — as a promising drug candidate to help prevent and treat Alzheimer’s disease. Researchers determined that sildenafil is associated with 69% reduced incidence of Alzheimer’s.

    A new Cleveland Clinic-led study has identified sildenafil — an FDA-approved therapy for erectile dysfunction and pulmonary hypertension — as a promising drug candidate to help prevent and treat Alzheimer’s disease.

    According to findings published in Nature Aging, the research team, led by Feixiong Cheng, Ph.D., of Cleveland Clinic’s Genomic Medicine Institute, used computational methodology to screen and validate FDA-approved drugs as potential therapies for Alzheimer’s disease. Through a large-scale analysis of a database of more than 7 million patients, they determined that sildenafil is associated with 69% reduced incidence of Alzheimer’s disease, indicating the need for follow-up clinical trial testing of the drug’s efficacy in patients with the disease.

    “Recent studies show that the interplay between amyloid and tau is a greater contributor to Alzheimer’s than either by itself,” said Dr. Cheng. “Therefore, we hypothesized that drugs targeting the molecular network intersection of amyloid and tau endophenotypes should have the greatest potential for success.”

    Story Source:

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    Icipants Were Nearly 70% Less Likely To Develop Alzheimers Disease

    After a 6-year follow-up, Cleveland Clinic researchers found that people who took sildenafil were 69 percent less likely to develop Alzheimers disease than those who didnt take the medication.

    To further examine the drugs potential to treat Alzheimers disease, Cheng and team created a lab model that showed sildenafil targeted tau protein and increased brain cell growth, revealing how the drug might work against the degenerative condition.

    Its important to note the study did not find sildenafil actually reduced the risk of Alzheimers disease. It was only associated with it. Cheng admitted there were limiting factors that indicate a need for more research.

    Although we adjusted many confounding factors in our patient data analysis based on our sizeable efforts, possible confounding factors may exist by our limited clinical knowledge of this complex disease, he said.

    Cheng emphasized that the findings must be confirmed in clinical trials before sildenafil can be used as a treatment for Alzheimers disease.

    We are working hard to pursue a RCT in the next step, said Cheng.

    Multiphasic Regulation Of Pgc1 By Sildenafil And Cgmp

    Viagra may help treat Alzheimers disease: Study

    NOS/NO/sGC/cGMP signaling upregulates PGC1 in diverse cell types, including not only renal proximal tubular cells , but also brown adipocytes, U937 monocytic cells, HeLa cervical cancer-derived cells, white 3T3-L1 adipocytes , and probably neurons . In mice, subcortical brain tissue responded to hypoxia with PGC1 upregulation in a manner that depended on nNOS expression , so the nNOS/NO/cGMP/PGC1 pathway does appear to be active in neurons.

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    Sildenafil For The Treatment Of Alzheimers Disease: A Systematic Review

    Article type: Review Article

    Authors: Sanders, Owen *

    Affiliations: Portland State University, Portland, OR, USA

    Correspondence: Correspondence to: Owen Sanders, 1777 NW 173rd Ave, #610, Beaverton, OR 97006, USA. Tel.: +1 503 809 1333 E-mail: .

    Keywords: Alzheimers disease, cyclic GMP, mitochondrial biogenesis, peroxisome proliferator-activated receptor gamma coactivator 1-alpha, sildenafil citrate

    DOI: 10.3233/ADR-200166

    Journal: Journal of Alzheimer’s Disease Reports, vol. 4, no. 1, pp. 91-106, 2020

    Abstract

    Too Soon To Claim It A Treatment

    To further explore sildenafils effect on Alzheimers disease, the researchers developed an Alzheimers patient-derived brain cell model using stem cells.

    In the model, they found that sildenafil increased brain cell growth and decreased hyperphosphorylation of tau proteins – a build-up of which is a hallmark of Alzheimers. Researchers believe this offers biological insights into how sildenafil may influence disease-related brain changes.

    Because our findings only establish an association between sildenafil use and reduced incidence of Alzheimers disease, we are now planning a mechanistic trial and a phase II randomised clinical trial to test causality and confirm sildenafils clinical benefits for Alzheimers patients, said Cheng.

    We also foresee our approach being applied to other neurodegenerative diseases, including Parkinsons disease and amyotrophic lateral sclerosis, to accelerate the drug discovery process.

    Randomised clinical trials involving both sexes with a placebo control are still needed to determine the effectiveness of sildenafil, Cheng added.

    Additional sources University of Cleveland

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    What We Dont Know

    What caused the drop in Alzheimers. The study was observational, meaning it cannot determine causes and only establishes an association between sildenafil use and a lower risk of Alzheimers disease. Buoyed by the findings, lead researcher Dr. Feixiong Cheng said the team is planning clinical trials to test causality and confirm sildenafils clinical benefits for Alzheimers patients.

    A Guide To Men’s Health Fifty And Forward

    Malegra 120 (Sildenafil Citrate): Dosage, Uses

    This Special Health Report, A Guide to Men’s Health Fifty and Forward, offers steps and strategies to lessen or prevent threats to a man’s well-being and longevity. It provides a wide-ranging, clear-eyed look at the leading causes of death for men at midlife and beyond. It examines those factors that put them at risk for a variety of health problems and explains the important measures that can be taken to reduce risk and live a longer, healthier life.

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    Study Looked At Over 1000 Fda Approved Drugs

    The study used insurance data, a large gene-mapping network, and integrated genetic and other information to discover which of about 1,600 Food and Drug Administration approved drugs showed effectiveness against Alzheimers disease.

    Researchers focused on drugs that target two proteins considered markers of Alzheimers disease, amyloid and tau, compared with drugs that only target one of them.

    According to Cheng, many drug discovery projects targeting either protein alone failed in the past 20 years.

    But for this project, they tested a new theory that dual targeting both amyloid and tau at the same time may provide better clinical benefits for people with Alzheimers.

    He explained that Alzheimers disease is a complex disease caused by many factors, and multi-target drugs or combination therapy to target more than one disease pathway might offer greater benefits in treating the disease.

    By testing this novel hypothesis, we identified sildenafil as potential treatment of AD, said Cheng.

    Common Conditions People Have *:

  • High Blood Pressure: 10 people, 24.39%
  • Neuropathy Peripheral : 6 people, 14.63%
  • Arthritis : 5 people, 12.20%
  • Sleep Disorder: 4 people, 9.76%
  • Glaucoma : 4 people, 9.76%
  • Joint Pain: 2 people, 4.88%
  • Emphysema in the lungs): 2 people, 4.88%
  • Epididymitis : 2 people, 4.88%
  • Abnormal Behavior: 2 people, 4.88%
  • Prostatic Disorder: 2 people, 4.88%
  • * Approximation only. Some reports may have incomplete information.

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    Low And High But Not Moderate Cgmp Levels Activate Pgc1

    Consistent with the dose-dependent effect of sildenafil and cGMP on PGC1, 10M of 8-Br-cGMP treatment for 24 hours upregulated PGC1 mRNA expression and mitochondrial biogenesis in renal proximal tubular cells . By contrast, in endothelial cells, 100M 8-Br-cGMP treatment for 624 hours downregulated PGC1 . In addition, treatment for less than 12 hours with NO donors decreased PGC1 expression, whereas treatment for 24 hours or more increased PGC1 expression . NO-triggered PGC1 downregulation and consequent reactive oxygen species production were required for endothelial cell migration, an effect that was mediated by NO-activated PI3K/Akt signaling and Akt phosphor-inhibition of Foxo3a .

    Surprisingly though, much higher dosages of cGMP than 100M upregulate PGC1 like lower doses do: for example, PGC1 was upregulated in brown adipocytes treated with 1mM 8-Br-cGMP for 4 days . In human monocytic U937 cells, rat L6 myotubes, and rat PC12 neurosecretory cells, 3mM 8-Br-cGMP treatment every day for 6 days upregulated PGC1, as well as Nrf1 and Tfam, mitochondrial proteins Cox IV and Cytochrome C, and mitochondrial DNA content . Furthermore, 6 days of 3mM 8-Br-cGMP in these three cell types resulted in increased oxidative phosphorylation-coupled oxygen consumption .

    PGC1 post-translational regulation.

    Sildenafil In Ad Patients

    Viagra playing new role in fight against Alzheimer’s disease

    In 10 AD patients, a single 50mg dose of sildenafil significantly decreased spontaneous neural activity in the right hippocampus as shown by the fractional amplitude of low-frequency fluctuations recorded on functional magnetic resonance imaging of the blood oxygen level-dependent signal, a parameter that had been shown to be aberrantly increased in AD patients hippocampi and parahippocampal gyri . In 12 elderly patients with AD, a single dosage of 50mg of sildenafil significantly increased the cerebral metabolic rate of oxygen and cerebral blood flow . In 8 AD patients, it decreased cerebrovascular reactivity .

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    Study Had Significant Limitations

    This study looks at data from a very large number of people, but there are several important limitations to consider, Professor Tara Spires-Jones, DPhil, deputy director of the Centre for Discovery Brain Sciences at the University of Edinburgh, said in a statement.

    According to Spires-Jones, study data came from insurance claims, arent very detailed, and did not include information on other important risk factors for Alzheimers, like sex, risk genes, and socioeconomic status.

    Spires-Jones pointed out there are other possible explanations for these findings.

    For example, we know that brain changes start decades before dementia symptoms and it is possible that these early Alzheimers changes reduce sex drive, thus people wouldnt ask for a prescription for erectile dysfunction, she explained.

    is a recently FDA approved drug to treat Alzheimers disease. So far, its the only drug approved for this purpose.

    It was granted accelerated FDA approval . This program allows for earlier approval of drugs to treat serious conditions and fill an unmet medical need based on a marker, such as laboratory measurement, physical sign, or other measure that might predict clinical benefit.

    Aducanumab is not a cure for Alzheimer disease, Dr. Winston Chiong, member of the American Academy of Neurology Ethics, Law, and Humanities Committee, told the Psychiatric Times.

    The condition involves brain bleeding, brain swelling, or both.

    The behaviors were:

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