CAN METFORMIN BE USED TO TREAT DEMENTIA WITH OUT DIABETES?

WHAT IS DEMENTIA Dementia is cause by abnormal brain changes which has a great impact on people thinking, memory and language. Impact of dementia is persistent and there is disabling decline in cognitive function (the core skills your brain uses to think, read, learn, remember, reason and pay attention) which significantly interfere with patient daily life activities. As the disorder of dementia progress, it is continues to get worse. It affects behaviors, feelings and relationships and due to this quality of patient life become compromised. There are limited option available to slow down the process of cognitive decline associated with dementia. According to WORLD HEALTH ORGANIZATION (WHO) estimation of 2017, there are about 47 millions people affected with dementia and per year there is increase of about 10 million people of the world. RISK FACTORS FOR DEMENTIA • Obesity • High BP • Diabetes • Age (dementia mostly affect older people but can also affects younger generation. Due to advancement in medical science, life span of people increase and we have significant older people population in the world) • Inflammation and oxidative stress. HOW DIABETES IS RISK FACTOR FOR DEMENTIA                                                            Diabetic patients are at two fold increase risk of developing dementia as compare to those with out disease. Diabetes cause cerebral damage which results in loss of memory. The following are possible theories which show link between diabetes and dementia • Diabetes affects the heart health which in turn affects the brain health. Increase BP increases the risk of stroke which can lead to dementia. However, patients with out the history of stroke are also at risk of developing dementia which show that stroke is not only the cause of dementia in diabetic patients. • Chronic diabetes cause narrowing of small arteries and capillaries which has a very important role in delivering oxygen and nutrition to brain and other parts of body. Elevated lipids and high BP which mostly happened in diabetic patients can lead to cerebrovascular damage due to cerebral atherosclerosis and vascular dementia. • Hypoglycemia can damage the hippocampus which has important role in memory. Hypoglycemia may be due to tight control of sugar levels which prevent from heart disease and stroke on long term basis but can damage the brain. • Insulin play a very important role in the synthesis of amyloid beta protein which is sticky in nature. Increase sugar level lead to increase formation of amyloid protein which coagulate with each other and form a plaque which is known as amyloid beta deposition. This plaques are the hall marks of a very common type of dementia which is Alzheimer disease. (neuro degenerative disease). • Brain insulin resistance with hyperinsulinemia (a condition in which there is increase release of insulin from pancreas for managing blood sugar level. To normal insulin concentration body cell show resistance for uptake of glucose that’s why pancreas release more insulin for maintaining sugar level). METFORMIN USE IN DIABETES AND DEMENTIA According to GARVAN INSTITUTE OF MEDICAL RESEARCH use of Metformin in diabetic patients slower the cognitive decline and lower the rates of dementia. According to PUB MED Metformin should continue to be used as a first line therapy for diabetes in patients at risk of developing dementia or Alzheimer disease. According to DIABETIC JOURNAL, older people using Metformin over 6 years have lessen cognitive decline and lower rate of dementia as compare to older people who are not taking Metformin. HOW METFORMIN IMPROVE DEMENTIA IN DIABETIC PATIENTS                                            As we know that, high sugar level impair cerebral functions and diabetic patients are at great risk of developing dementia. Beneficial effects of metformin for dementia in diabetic patients is not clear one but possible mechanism of action are listed below • Metformin inhibits hepatic gluconeogenesis and also decrease blood glucose level by activating Liver kinase beta 1 or AMPK pathway (a pathway which exert neuroprotective effects). • Metformin improve effects of insulin by increasing insulin receptor expressions which in turn decrease insulin resistance and improve impaired insulin signaling and glucose metabolism which in turn improve cognitive function in CSF (cerebral spinal fluid ). • Inflammation and oxidative stress cause changes in brain and responsible for dementia. Metformin through vascular protection show beneficial effects against dementia. CAN METFORMIN BE USED AS A DRUG OF CHOICE IN DEMENTIA WITH OUT DIABETE  As we all know that, dementia is a syndrome which is characterized by worsening in memory and loss of daily care ability. With the above mentioned discussion, it is clear that Metformin slower the rates of cognitive decline and dementia in diabetic patients. That’s why it has STRONG POTENTIAL FOR ANTI AGING EFFECTS. • Due to this strong evidence AUSTRALIA RESEARCHER are currently planning a large, randomized, control trail to access the effects of Metformin on non -diabetic subjects at risk of dementia. • Similar study is also being planned in EUROPE including many countries and recruiting 600 subjects to find out whether Metformin can delay the onset of Alzheimer disease. • Researcher with the GARVAN INSTITUTE OF MEDICAL RESEARCH have recently launched a phase 3 clinical trial to find out how the Metformin could be used to lower the progress of dementia in non diabetic patients. • According to FRONTIER, cerebral small vascular disease (CSVD) cause the dementia and Metformin slow the rate of dementia. Therefore, to fully understand the beneficial effects of Metformin on cognitive functions further clinical trial are required which prove us that drug has potential to be useful in clinical treatment of cognitive impairment and cerebral small vascular disease irrespective of diabetes. CONCLUSION We can say that Metformin not only use to manage sugar level in diabetic patients but also improve diabetic associated cognitive decline. If clinical trial result establish the use of Metformin for dementia and cognitive functions irrespective of diabetes then we will be able to translate into direct clinical practice.