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Metformin Alzheimer's Clinical Trial

Link Between Type 2 Diabetes And Alzheimers Disease: From Epidemiology To Mechanism And Treatment

Link Between Type 2 Diabetes And Alzheimers Disease: From Epidemiology To Mechanism And Treatment

Link between type 2 diabetes and Alzheimers disease: from epidemiology to mechanism and treatment 3Division of Geriatric Medicine and Gerontology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA 1Dalian Medical University, Dalian, Peoples Republic of China 2Department of Geriatrics, Qingdao Municipal Hospital, Qingdao, Peoples Republic of China 3Division of Geriatric Medicine and Gerontology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA Correspondence: Dalin Song, Department of Geriatrics, Qingdao Municipal Hospital, 5 Donghoi Middle Road, Qingdao 266071, Peoples Republic of China, Tel +86 185 6172 8001, Email [email protected]_yllib Author information Copyright and License information Disclaimer Copyright 2015 Li et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution Non Commercial (unported, v3.0) License The full terms of the License are available at . Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. This article has been cited by other articles in PMC. The aim of this paper is to provide a comprehensive review of the epidemiological evidence linking type 2 diabetes mellitus and its related conditions, including obesity, hyperinsulinemia, and metabolic syndrome, to Alzheimers disease (AD). Several mechanisms could help to explain this proposed link; however, our focus is on insulin resistance and deficiency. Studies have shown that insulin resistance and deficiency can interact with amyloid- protein and tau protein phosphorylation, each leading to the onset and development of AD. Based on those epidemiological data and basic research, i Continue reading >>

Metformin A Future Therapy For Neurodegenerative Diseases

Metformin A Future Therapy For Neurodegenerative Diseases

, Volume 34, Issue12 , pp 26142627 | Cite as Metformin a Future Therapy for Neurodegenerative Diseases Theme: Drug Discovery, Development and Delivery in Alzheimer's Disease Guest Editor: Davide Brambilla Drug Discovery, Development and Delivery in Alzheimer's Disease Type 2 diabetes mellitus(T2DM) is a complex, chronic and progressive metabolic disease, which is characterized by relative insulin deficiency, insulin resistance, and high glucose levels in blood. Esteemed published articles and epidemiological data exhibit an increased risk of developing Alzheimers disease(AD) in diabetic pateints. Metformin is the most frequently used oral anti-diabetic drug, which apart from hypoglycaemic activity, improves serum lipid profiles, positively influences the process of haemostasis, and possesses anti-inflammatory properties. Recently, scientists have put their efforts in establishing metformins role in the treatment of neurodegenerative diseases, such as AD,amnestic mild cognitive impairment and Parkinsons disease. Results of several clinical studies confirm that long term use of metformin in diabetic patients contributes to better cognitive function, compared to participants using other anti-diabetic drugs. The exact mechanism of metformins advantageous activity in AD is not fully understood, but scientists claim that activation of AMPK-dependent pathways in human neural stem cells might be responsible for the neuroprotective activity of metformin. Metformin was also found to markedly decease Beta-secretase 1(BACE1) protein expression and activity in cell culture models and in vivo, thereby reducing BACE1 cleavage products and the production of A(-amyloid). Furthermore, there is also some evidence that metformin decreases the activity of acetylcholinesterase(AChE), which Continue reading >>

Could A Diabetes Drug Help Beat Alzheimer's Disease?

Could A Diabetes Drug Help Beat Alzheimer's Disease?

Most of the 20 million people diagnosed with type 2 diabetes in the U.S. take metformin to help control their blood glucose. The drug is ultrasafe: millions of diabetics have taken it for decades with few side effects beyond gastrointestinal discomfort. And it is ultracheap: a month's supply costs $4 at Walmart. And now new studies hint that metformin might help protect the brain from developing diseases of aging, even in nondiabetics. Diabetes is a risk factor for neurodegenerative diseases, but using metformin is associated with a dramatic reduction in their incidence. In the most comprehensive study yet of metformin's cognitive effects, Qian Shi and her colleagues at Tulane University followed 6,000 diabetic veterans and showed that the longer a patient used metformin, the lower the individual's chances of developing Alzheimer's disease, Parkinson's disease, and other types of dementia and cognitive impairment. In line with some of the previous, smaller studies of long-term metformin use, patients in the new study who used the drug longer than four years had one quarter the rate of disease as compared with patients who used only insulin or insulin plus other antidiabetic drugs—bringing diabetics' risk level to that of the general population. The findings were presented in June at the American Diabetes Association's Scientific Sessions meeting. Even in the absence of diabetes, Alzheimer's patients often have decreased insulin sensitivity in the brain, says Suzanne Craft, a neuroscientist who studies insulin resistance in neurodegenerative disease at the Wake Forest School of Medicine. The association has led some people to call Alzheimer's “type 3 diabetes.” Insulin plays many roles in the brain—it is involved in memory formation, and it helps to keep synapses Continue reading >>

Forget The Blood Of Teens. This Pill Promises To Extend Life For A Nickel A Pop

Forget The Blood Of Teens. This Pill Promises To Extend Life For A Nickel A Pop

Nir Barzilai has a plan. It’s a really big plan that might one day change medicine and health care as we know it. Its promise: extending our years of healthy, disease-free living by decades. And Barzilai knows about the science of aging. He is, after all, the director of the Institute for Aging Research at the Albert Einstein College of Medicine in the Bronx. And, as such, he usually talks about his plan with the caution of a seasoned researcher. Usually. Truth is, Barzilai is known among his colleagues for his excitability—one author says he could pass as the older brother of Austin Powers—and sometimes he can’t help himself. Like the time he referred to his plan—which, among other things, would demonstrate that human aging can be slowed with a cheap pill—as “history-making.” In 2015, he stood outside of the offices of the Food and Drug Administration, flanked by a number of distinguished researchers on aging, and likened the plan to a journey to “the promised land.” Last spring, Barzilai traveled to the Vatican to discuss the plan at a conference on cellular therapies. It was the second time he’d been invited to the conference, which is a pretty big deal in the medical world. At the last one, in 2013, he appeared alongside a dwarf from Ecuador, a member of a community of dwarfs whose near immunity to diabetes and cancer has attracted the keen interest of researchers. The 2016 conference featured a number of the world’s top cancer scientists and included addresses from Pope Francis and Joe Biden. That Barzilai was invited was a sign not only of his prominence in his field but also of how far aging research, once relegated to the periphery of mainstream science, has come in recent years. That progress has been spurred by huge investments from Sil Continue reading >>

Worlds First Anti-ageing Drug Could See Humans Live To 120

Worlds First Anti-ageing Drug Could See Humans Live To 120

Worlds first anti-ageing drug could see humans live to 120 Pensioners could be as healthy as 50 year olds in the future if tests on metformin perform as well as expectedCredit:ALAMY The worlds first anti-ageing drug will be tested on humans next year in trials which could see diseases like Alzheimers and Parkinsons consigned to distant memory. Scientists now believe that it is possible to actually stop people growing old as quickly and help them live in good health well into their 110s and 120s. Although it might seem like science fiction, researchers have already proven that the diabetes drug metformin extends the life of animals, and the Food and Drug Administration in the US has now given the go ahead for a trial to see if the same effects can be replicated in humans. This would be the most important medical intervention in the modern era, an ability to slow ageing Dr Jay Olshansky, University of Illinois Chicago If successful it will mean that a person in their 70s would be as biologically healthy as a 50 year old. It could usher in a new era of geroscience where doctors would no longer fight individual conditions like cancer, diabetes and dementia, but instead treat the underlying mechanism ageing. Scottish ageing expert Professor Gordon Lithgow of the Buck Institute for Research on Ageing in California, is one of the study advisors. If you target an ageing process and you slow down ageing then you slow down all the diseases and pathology of ageing as well, he said Thats revolutionary. Thats never happened before. I have been doing research into ageing for 25 years and the idea that we would be talking about a clinical trial in humans for an anti-ageing drug would have been though inconceivable. But there is every reason to believe its possible. The future is taki Continue reading >>

Strategies And Challenges In Clinical Trials Targeting Human Aging

Strategies And Challenges In Clinical Trials Targeting Human Aging

Strategies and Challenges in Clinical Trials Targeting Human Aging Division of Geriatrics, University of California San Francisco *These authors contributed equally to this work. Search for other works by this author on: Department of Medicine, Division of Endocrinology Institute for Aging Research, Albert Einstein College of Medicine *These authors contributed equally to this work. Search for other works by this author on: Department of Hematology and Transplant Center, Mayo Clinic Department of Biology, University of Alabama at Birmingham Robert and Arlene Kogod Center on Aging, Mayo Clinic Geriatrics Center and Institute of Gerontology, University of Michigan Department of Medicine, Division of Endocrinology Institute for Aging Research, Albert Einstein College of Medicine The Journals of Gerontology: Series A, Volume 71, Issue 11, 1 November 2016, Pages 14241434, John C. Newman, Sofiya Milman, Shahrukh K. Hashmi, Steve N. Austad, James L. Kirkland, Jeffrey B. Halter, Nir Barzilai; Strategies and Challenges in Clinical Trials Targeting Human Aging, The Journals of Gerontology: Series A, Volume 71, Issue 11, 1 November 2016, Pages 14241434, Interventions that target fundamental aging processes have the potential to transform human health and health care. A variety of candidate drugs have emerged from basic and translational research that may target aging processes. Some of these drugs are already in clinical use for other purposes, such as metformin and rapamycin. However, designing clinical trials to test interventions that target the aging process poses a unique set of challenges. This paper summarizes the outcomes of an international meeting co-ordinated by the NIH-funded Geroscience Network to further the goal of developing a translational pipeline to move candid Continue reading >>

Possible Alzheimer's Drug Also Slows Aging

Possible Alzheimer's Drug Also Slows Aging

Possible Alzheimer's drug also slows aging Dave Schubert, Professor and Laboratory Head of Cellular Neurobiology Laboratory at the Salk Institute Dave Schubert, Professor and Laboratory Head of Cellular Neurobiology Laboratory at the Salk Institute (Joe Belcovson) A potential Alzheimers drug works by reducing the rate of aging at the molecular level, according to a new study led by Salk Institute scientists . The study explains how the drug both improves cognition and reduces the rate of aging, when given to very old mice. Study authors say a drug that inhibits aging may succeed where drugs specifically aimed at Alzheimers have failed. Getting the drug into human clinical trials will require a little over $1 million. Possible Alzheimer's drug affects aging: Heres the full story A potential Alzheimers drug works by reducing the rate of aging at the molecular level, according to a new study led by Salk Institute scientists. The study provides an explanation for previously observed signs of improved cognition and rejuvenation, when the drug was given to very old mice. It found that the drug, called J147, protects the cells energy factories, called mitochondria. Brain cells consume enormous amounts of energy, about 25 percent of all energy used in the human body. And mitochondrial dysfunction has been implicated in Alzheimers as well as aging-associated deterioration. Knowledge of the drug target and how it works may help persuade drug companies and investors to fund human studies of the drug, said the studys senior author, Dave Schubert. Moreover, a relatively small amount of money will be needed to start human trials, Schubert said. About $150,000 is needed to complete an FDA application to begin trials, with about $1 million more to actually start human testing. An addi Continue reading >>

Diabetes Drug Could Work Against Alzheimer's, Animal Study Suggests

Diabetes Drug Could Work Against Alzheimer's, Animal Study Suggests

Follow all of ScienceDaily's latest research news and top science headlines ! Diabetes drug could work against Alzheimer's, animal study suggests Helmholtz Association of German Research Centres The diabetes drug metformin has an effect against one of the main causes of the Alzheimer's disease, according to new research in animal models. Metformin, a drug used in type 2-diabetes might have the potential to also act against Alzheimer's disease. This has been shown in a study from scientists of the German Center for Neurodegenerative Diseases (DZNE), the University of Dundee and the Max-Planck-Institute for Molecular Genetics. The researchers have found out that the diabetes drug metformin counteracts alterations of the cell structure protein Tau in mice nerve cells. These alterations are a main cause of the Alzheimer's disease. Moreover, they uncovered the molecular mechanism of metformin in this process. "If we can confirm that metformin shows also an effect in humans, it is certainly a good candidate for an effective therapy on Alzheimer's diseases," says Sybille Krau from DZNE. Their results have been published in the Proceedings of the National Academy of Sciences (Nov. 22, 2010). Alzheimer's disease is a form of dementia that affects almost exclusively elderly people. Today, about 700,000 people are suffering from Alzheimer's disease in Germany. Neurons in their brains die, leading to cognitive impairment. At the molecular level, the disease is characterized amongst others by the formation of Tau protein deposits in nerve cells. Tau is a molecule that usually binds to the supportive cytoskeleton and performs a function in the transport system of the cell. In Alzheimer's disease, Tau is tipped too strongly with phosphate groups. This phosphorylation causes removal o Continue reading >>

Metformin: An Old But Still The Best Treatment For Type 2 Diabetes

Metformin: An Old But Still The Best Treatment For Type 2 Diabetes

Abstract The management of T2DM requires aggressive treatment to achieve glycemic and cardiovascular risk factor goals. In this setting, metformin, an old and widely accepted first line agent, stands out not only for its antihyperglycemic properties but also for its effects beyond glycemic control such as improvements in endothelial dysfunction, hemostasis and oxidative stress, insulin resistance, lipid profiles, and fat redistribution. These properties may have contributed to the decrease of adverse cardiovascular outcomes otherwise not attributable to metformin’s mere antihyperglycemic effects. Several other classes of oral antidiabetic agents have been recently launched, introducing the need to evaluate the role of metformin as initial therapy and in combination with these newer drugs. There is increasing evidence from in vivo and in vitro studies supporting its anti-proliferative role in cancer and possibly a neuroprotective effect. Metformin’s negligible risk of hypoglycemia in monotherapy and few drug interactions of clinical relevance give this drug a high safety profile. The tolerability of metformin may be improved by using an appropiate dose titration, starting with low doses, so that side-effects can be minimized or by switching to an extended release form. We reviewed the role of metformin in the treatment of patients with type 2 diabetes and describe the additional benefits beyond its glycemic effect. We also discuss its potential role for a variety of insulin resistant and pre-diabetic states, obesity, metabolic abnormalities associated with HIV disease, gestational diabetes, cancer, and neuroprotection. Introduction The discovery of metformin began with the synthesis of galegine-like compounds derived from Gallega officinalis, a plant traditionally em Continue reading >>

Diabetes Drug May Someday Repair Alzheimer's Damage

Diabetes Drug May Someday Repair Alzheimer's Damage

Diabetes Drug May Someday Repair Alzheimer's Damage By Susan E. Matthews, MyHealthNewsDaily Staff Writer | The diabetes drug metformin may spur the growth of new brain cells, which could have benefits for Alzheimer's patients, a new Canadian study on mice suggests. The study showed that metformin caused brain cells to divide, producing new cells. The diabetes medication was intended to target a specific pathway in liver cells. In the new study, researchers found that the drug activated that same pathway in brain cells, prompting new cell growth, said study researcher Freda Miller, a stem cell biologist and molecular geneticist at the Hospital for Sick Children Research Institute in Toronto. The new cells that are produced could help to repair the effects of neurodegenerative disorders, such as Alzheimers disease , Miller told MyHealthNewsDaily. The concept that new cell growth could repair the brain is also driving research into neural stem cells, she added. The research on metformin's effects on the brain is still in early stages, and the findings have yet to be shown in people. Still, the researchers found that new brain cells grew in both living mice and in human brain cell cultures growing in lab dishes . They are now working to set up clinical trials, Miller said. The researchers decided to test metformin's effects on brain cells after it was found that the pathway targeted by the drug in liver cells was also operating in brain cells. A 2008 study found that patients with both diabetes and Alzheimers who began taking metformin experienced improvements in their Alzheimer's symptoms after starting on the drug. It was thought that treating the patients' diabetes had effects on the body that helped improve their Alzheimers , but the new study suggests the change in br Continue reading >>

Metformin & Your Brain | Cognitive Vitality | Alzheimer's Drug Discovery Foundation

Metformin & Your Brain | Cognitive Vitality | Alzheimer's Drug Discovery Foundation

1 meta-analysis for Alzheimer's prevention 2 small clinical studies in patients with mild cognitive impairment or mild Alzheimer's disease 6 observational studies for future Alzheimer's risk in patients with type-2 diabetes Multiple observational studies have reported varying results on whether metformin may be beneficial for preventing Alzheimer's disease in type 2 diabetes patients. Three studies reported a decreased risk for cognitive impairment or dementia in diabetic patients taking metformin compared to those not taking medication or taking other diabetes drugs [1] [2] [3] . Additionally, one meta-analysis suggested a trend for reduced risk of dementia with metformin use in diabetics [4] . Three other studies, however, reported an increased risk for impaired cognitive performance, dementia, or Alzheimer's disease with metformin use compared to those taking other medications [5] [6] [7] . One study reported that longer metformin use was associated with an increasing risk for dementia [6] . Several factors could account for the varying results. Many of these studies do not account for diabetes duration, severity, or how well diabetes is controlled [8] . Also, metformin is often used to treat mild diabetes, so patients taking other drugs may have more severe diabetes. Additionally, long-term metformin use can decrease vitamin B12 levels, which may be a potential risk factor for Alzheimer's disease. One study reported that when controlling for vitamin B12 levels, metformin was no longer significantly associated with increased risk of Alzheimer's [7] [9] . It is currently unknown whether metformin would prevent Alzheimer's disease in non-diabetic patients. Whether with metformin or another method, controlling diabetes is important for reducing your risk for Alzheimer' Continue reading >>

Metformin Linked To Dementia, Parkinson's In Patients With T2dm

Metformin Linked To Dementia, Parkinson's In Patients With T2dm

Metformin Use Linked to Increased Dementia, Parkinson's Risk in Patients With Diabetes VIENNA, Austria — Long-term use of the diabetes medication metformin may increase the risk for neurodegenerative disease in patients with type 2 diabetes mellitus (T2DM), new research suggests. In a cohort study that followed about 9300 patients with T2DM in Taiwan for up to 12 years, the risk for Parkinson's disease (PD) or Alzheimer's dementia was more than double during a 12-year period for those who took metformin vs those who did not — even after adjusting for multiple confounders. In addition, outcome risks increased progressively with higher dosage and longer duration of treatment. The results were presented here at AD/PD 2017: The 13th International Conference on Alzheimer's and Parkinson's Diseases by Yi-Chun Kuan, MD, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan. Interestingly, recent research has suggested that use of metformin may protect against neurodegenerative diseases. When asked about that, Dr Kuan told Medscape Medical News that "some studies have actually found positive [outcomes] but some have been negative ." So the researchers wanted to look into this using their own data. "We'd heard about a possible protective effect from metformin. However, we found the reverse," she said, but stressed that large-scale, prospective studies in other countries are needed to clarify the results. The investigators note that past research has shown a link between T2DM and increased risk for neurodegenerative diseases, but there's been "some question" about the association with specific diabetes medications. They examined records for patients with T2DM from the National Health Insurance research database of Taiwan, including 4651 who had metformin pre Continue reading >>

Metformin In Amnestic Mild Cognitive Impairment: Results Of A Pilot Randomized Placebo Controlled Clinical Trial.

Metformin In Amnestic Mild Cognitive Impairment: Results Of A Pilot Randomized Placebo Controlled Clinical Trial.

J Alzheimers Dis. 2016;51(2):501-14. doi: 10.3233/JAD-150493. Metformin in Amnestic Mild Cognitive Impairment: Results of a Pilot Randomized Placebo Controlled Clinical Trial. Department of Medicine, Columbia University Medical Center, New York, NY, USA. Department of Epidemiology, Columbia University Medical Center, New York, NY, USA. Department of Statistics, Mt. Sinai Medical Center, New York, NY, USA. New York Institute for Basic Research, Staten Island, NY, USA. Gertrude H. Sergievsky Center, Columbia University, New York, NY, USA. Department of Psychiatry, Columbia University Medical Center, New York, NY, USA. Department of Radiology, Columbia University Medical Center, New York, NY, USA. Division of Geriatric Psychiatry, New York State Psychiatric Institute, New York, NY, USA. Diabetes and hyperinsulinemia may be risk factors for Alzheimer's disease (AD). We conducted a pilot study of metformin, a medication efficacious in treating and preventing diabetes while reducing hyperinsulinemia, among persons with amnestic mild cognitive impairment (aMCI) with the goal of collecting preliminary data on feasibility, safety, and efficacy. Participants were 80 men and women aged 55 to 90 years with aMCI, overweight or obese, without treated diabetes. We randomized participants to metformin 1000 mg twice a day or matching placebo for 12 months. The co-primary clinical outcomes were changes from baseline to 12 months in total recall of the Selective Reminding Test (SRT) and the score of the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog). The secondary outcome was change in relative glucose uptake in the posterior cingulate-precuneus in brain fluorodeoxyglucose positron emission tomography. Change in plasma A42 was an exploratory outcome. The mean age of p Continue reading >>

The Many Faces Of Metformin

The Many Faces Of Metformin

In 2004, Clifford Bailey of the Diabetes Group from Aston University in Birmingham, United Kingdom described metformin, the most widely prescribed drug for treating diabetes, as ironic: In our high-tech era of drug discovery and development this first-line treatment for type 2 diabetes is little removed from an herbal remedy of the Middle Ages. Despite its chemical simplicity and detailed investigation, metformin continues to evade a complete exposé of its cellular activity (Pract Diab Int April 2004 Vol.21 No. 3) Now, almost a decade later, a team led by Morris Birnbaum, M.D., Ph.D. from the Institute for Diabetes, Obesity and Metabolism, is getting closer to a clear picture of how this drug works, which, in addition to its widespread use for diabetes, is being tested for treating dementia and cancer. The Birnbaum lab and colleagues found that metformin works in a different way than previously understood. They found that in mice it suppresses the liver hormone glucagon’s ability to generate an important signaling molecule, which points to new drug targets. For fifty years, one of the few classes of therapeutics effective in reducing the overactive glucose production associated with diabetes has been the biguanides, which includes metformin. The inability of insulin to keep liver glucose output in check is a major factor in the high blood sugar of type 2 diabetes and other diseases of insulin resistance. “Overall, metformin lowers blood glucose by decreasing liver production of glucose,” says Birnbaum. “But we didn’t really know how the drug accomplished that.” Birnbaum’s Nature study describes a novel mechanism by which metformin antagonizes the action of glucagon, thus reducing fasting glucose levels. The team showed that metformin leads to the accumula Continue reading >>

Metformin And Alzheimer’s: A Potential New Therapy?

Metformin And Alzheimer’s: A Potential New Therapy?

The diabetes drug may have a beneficial effect on neurodegenerative diseases. Metformin, a biguanide, is an oral diabetes medicine used to improve blood glucose levels in people with type 2 diabetes. There have been various studies on other uses of metformin. It may be beneficial in Alzheimer’s disease, stroke and other degenerative brain cell diseases. An animal study found that metformin helps neurogenesis and enhances hippocampus, a key pathway (aPKC-CBP). Type 2 diabetes doubles the risk of having dementia; though some studies show metformin helps reduce risk, other studies show antidiabetic medications like insulin are linked to increased risk of having dementia. Animal studies show that metformin recruits endogenous neural stem cells and also promotes the genesis of new neurons. Metformin, however, needs to have been used for a longer period before a drastic reduction in neurodegenerative disease and its neuroprotective nature is seen. The purpose of this study is to find a link between antidiabetic medications, especially metformin and other neurodegenerative diseases. Also, to know how long one has to be on these antidiabetics before the neuroprotective nature kicks in. A cohort study of type 2 diabetes patients who are 55 years and above and being managed on a monotherapy antidiabetic drug of either metformin, sulfonylurea (SU), thiazolidinedione (TZD) or insulin were observed in a period of 5 years. In the course of 5 years, dementia was identified in 9.9% of the patients. Comparing those taking metformin to those taking sulfonylurea, there was a 20% reduction in dementia in those taking metformin. The hazard ratio 0.79%, a 95% confidence interval of 0.65-0.95. For TZD, metformin had a 23% reduction in having dementia as compared to TZD with hazard ratio of Continue reading >>

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