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The Effects of Metformin on Dementia Patients

  • 13 Pages
  • Published On: 28-11-2023
Introduction

Metformin is a medication that is majorly used in the control of high blood sugar. In most occasions, the drug is used with patients with type 2 diabetes. Metformin is used with a proper diet and exercise program and possibly other medications to control the high blood sugar levels (Scherrer et al., 2019). Metformin restores the body's response to the hormone insulin that is naturally produced by the body. The medication reduces the amount of sugar made by the liver, and the stomach absorbs levels (Orkaby et al., 2017). The use of this medication presents with various side effects that are experienced by the patient. This summative assessment aims to explore the impacts that metformin has on dementia patients. Dementia is a syndrome characterized by memory loss, deterioration in thinking, behavior, and worsening of the ability to perform the daily activities of one's living (Lin et al., 2018). The essay aims to critically discuss the effects of metformin on dementia patients as an area of improvement for a nursing student. The report also aims to reflect on change or modification of practice due to this essay's learning. This paper is thus of utmost significance to the improvement of nursing practice in ensuring improved patient outcomes.

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Critical Discussion

According to Chin-Hsiao T (2019), the use of metformin in type 2 diabetes patients is linked to a reduced risk of dementia. According to the study, metformin has been noted to inhibit the process of gluconeogenesis in the liver, thus lowering the blood glucose levels through the activation of the liver kinase B1 /AMPK pathway via the inhibition of the mitochondrial respiratory chain complex (Bridges et al., 2014). Various studies have been conducted in the past, and activation of the AMPK-dependent pathway in the brain causes neuroprotective effects. Besides, insulin resistance with impaired signaling of insulin and glucose metabolism reduction has been noted in dementia patients (Chin-Hsiao, 2019). Also, the study notes that the use of metformin improves insulin resistance through an increase in the expression of the insulin receptor and improvement of the activity of tyrosine kinase enzyme (Bridges et al., 2014). Metformin also has an impact that is associated with an improvement in cognitive functionality. In patients with dementia, other effects such as increased inflammation and oxidative stress have been reported besides pathophysiological changes in the brain of dementia patients (Cameron et al., 2016). Metformin also increases the amyloid-beta's biogenesis in the neural cells associated with potential harm to the neuronal cells. The medication has been termed a neuroprotective agent against amyloid-beta-induced mitochondrial dysfunction in humans' neuronal stem cells through the AMPK-dependent pathway (Campbell et al., 2017). Besides, research has also noted that medication can reduce the formation of AGEs. Metformin does this by improving glycemic control. Other researchers have detailed that metformin exerts scavenging effects on AGEs. In dementia patients with diabetes, dysregulation of the lipid metabolism and microbiota dysbiosis has been reported (Campbell et al., 2017). Also, the medication reverses insulin resistance in some instances. Through this, metformin improves insulin signaling, thus disabling lipid dysmetabolism. According to Campbell et al. (2017), metformin can change the gut microbiota's composition, thus increasing Akkermansia species and improving insulin resistance, and lowering the tissue's inflammation. From UK based studies, metformin has also been noted to possess cardioprotective effects due to a reduction in the atherosclerosis events in diabetic individuals. Through this, the medication lowers the chances of dementia. From the study by Chin-Hsiao, (2019), it is noted that metformin has beneficial effects on dementia patients through vascular and neuronal protection. This author's findings are similar to those by Campbell al (2018), who notes that metformin use is linked to reduced risks of dementia. Metformin prevents or delays the development of dementia. From the study by Campbell al, metformin has been noted o have a protective effect against dementia (2018). Metformin induces vitamin B12 deficiency, a factor that contributes to cognitive impairment. Thus, metformin exerts an impact on mental health to counteract the neurodegenerative effects of diabetes (Scherrer et al., 2019). Further, this harms patients that are vulnerable to vitamin B12 deficiency. In a study by Kuan et al. (2017), the researchers note that long-term metformin exposure in patients with T2DM leads to the development of neurodegenerative conditions such as dementia.

In comparison, an older population who use metformin for the management of type 2 diabetes has been reported to have lower risks of dementia amongst other cognitive declines relative to those that do not use the medication (Campbell et al., 2017). Metformin mitigates the effects of diabetes on cognitive decline in older people. The risk of developing dementia has been noted to increase with age resulting in impaired thinking, behavior, and ability to undertake daily activities (Scherrer et al., 2019).

Contrary to these findings, other researchers have linked an increase in cognitive impairment in patients with diabetes to metformin. For instance, Moore et al. (2013) note that metformin is linked to impaired cognitive performance. Notably, the results are related to vitamin B12 deficiency. In a different study, results indicated a significant impact of insulin resistance in cognitive decline and dementia, which protects against cognitive decline by the insulin sensitizers such as metformin (Campbell et al., 2018).

Type 2 diabetes is a significant risk factor for dementia. Campbell et al. (2017) note that insulin is associated with a 50% increase in the risk of dementia relative to other treatments for diabetes. On the other hand, metformin is not associated with an increased risk of dementia. The researchers have noted that metformin, a biguanide, lower insulin-mediated hepatic glucose production and improves glucose's peripheral disposal (Scherrer et al., 2019). Due to its neuroprotection role in decreasing insulin resistance, the medication is significant in preventing dementia (Orkaby et al., 2017). Studies have suggested metformin use and slower cognitive decline as well as lower dementia rates. Metformin helps the body effectively use the hormone insulin since it is an insulin sensitizer, as initially mentioned. Insulin ushers sugar into the body cells to be used for energy genesis (Campbell et al., 2017). Besides being an insulin-sensitizing medication, metformin has been noted to have other effects in the cells that allow them to be metabolically healthy, inclusive in reducing the risk of cognitive decline and dementia (Orkaby et al., 2017). Insulin resistance contributes significantly to the brain nerves' degeneration and the nerve tissues leading to dangerous deviations in the blood vessels (Campbell et al., 2017). Metformin thus boosts the working of insulin in the body, thus reducing the risk of cognitive damage and the occurrence of dementia. The biguanide metformin antidiabetic medication reduces the blood glucose by increasing the glucose uptake by the muscles while decreasing the liver gluconeogenesis by activating the AMP-activated protein kinase pathway.

Despite these reports, other studies have suggested a potential increase in the rate of dementia due to the detrimental effects of the use of metformin in older people. This indicates a controversy in the relationship between metformin and vitamin B12 levels (Campbell et al., 2018). Just as previously mentioned, the lower cognitive function has been associated with the deficiency with vitamin B12 deficiency, causing cognitive impairment. In efforts to alleviate the controversy, studies have been undertaken, which have reported that metformin use has reduced the incidence of dementia (Orkaby et al., 2017). Metformin does not cause dementia. It helps reduce a person's risk of dementia. Memory loss in patients who take metformin may be the underlying disease, diabetes but not the medication itself (Farr et al., 2019).

Apart from the health effects of metformin, the medication has been noted to have various side effects that are harmful to dementia patients and diabetes patients. One of the side effects of using the drug has been reported as lactic acidosis. This life-threatening condition occurs due to dangerous build-up of lactic acid, decreasing the PH, and causing electrolyte disturbances in the body (Farr et al., 2019). This condition results from the kidney's inability to excrete metformin due to malfunctioning of the organ, thus causes a build-up of the medication and creating lactic acidosis (Wu et al., 2020). In dementia patients, this condition causes tiredness, weakness, unusual muscle pain, breathing complications, stomach pains, nausea, vomiting, dizziness, and irregular heart rate. Since dementia has been linked to a deficiency in vitamin B12 due to metformin, a low blood count has been a reported occurrence that results in anemia (Weinstein et al., 2019). The use of the drug with an inadequate diet has also been linked to hypoglycemia. The condition also results if the patient of dementia using metformin to undertake strenuous exercise, drink too much alcohol, or use other antidiabetic drugs (Farr et al., 2019). In a study that evaluated the effects of metformin on dementia patients, Wu et al. note in cognitively normal older adults, the use of metformin has been linked to better memory performance that occurs gradually (2020). Besides, metformin has been associated with a decreased hazard of the occurrence of dementia.

Similar to most researchers' findings, Farr et al. (2019) note that glucose metabolism and brain insulin resistance as a result of diabetes significantly impact the occurrence of dementia. Metformin affects the central nervous system by crossing the blood-brain barrier. Metformin treatments between 2-4 years or more have been shown to impact the risk reduction of dementia in patients with type 2 diabetes relative to patients with non-metformin treatment. More than four years of exposure to metformin has been linked to lower instances of PD and AD.

Metformin is associated with a change in brain metabolism (Lin et al., 2018). The clinical dose of metformin that has been applied in the management of type 2 diabetes is linked with hypermetabolic variations in the white matter of the bilateral cerebral hemispheres and with hypometabolic changes in the semantic memory system (Kenawy et al., 2017). Metformin is linked to slowed cognitive decline in dementia patients. The medication has been noted as life-changing for patients at the risk of dementia (Lin et al., 2018). Metformin adds extra to standard glucose to diabetic patients, thus benefiting the cognitive health. The drug has also been termed as an anti-aging agent for dementia patients. Metformin improves glycemic control by enhancing insulin sensitivity in the liver and the muscle (Lin et al., 2018). The medication does not stimulate the process of insulin secretion.

Consequently, it is not linked to hypoglycemia (Kenawy et al., 2017). When metformin is used in the improvement of metabolic control, weight gained is not induced; instead, the use of the medication sometimes causes weight loss. (Malin & Kashyap, 2014) Besides, for dementia patients, medicine has various beneficial effects on several cardiovascular risk factors. These risk factors include dyslipidemia, elevated plasminogen activator inhibitor one level, other fibrinolytic abnormalities, hyperinsulinemia, and insulin resistance (Kenawy et al., 2017). Metformin enhances the muscle and the adipocyte's insulin receptor number and affinity, increasing insulin receptor tyrosine kinase activity. The medication stimulates the process of glucose transport and glycogen synthesis, lowering both hepatic gluconeogenesis and glycogenesis. According to Kenawy et al. (2017), metformin reduces lipid oxidation besides plasma-free fatty acid levels. This results in an inhibition of the overactive Randle cycle (Malin & Kashyap, 2014). Monotherapy of metformin lowers the plasma glucose concentration. The addition of the medication enhances insulin and glycemic control sensitivity, as mentioned earlier, thus enabling the reduction in the daily insulin dose. Gastrointestinal tract discomforts have been noted as some of the most prevalent side effects of metformin use (Lin et al., 2018).

Critical Reflection

Understanding the effects of metformin on dementia is an impeccable knowledge that is inevitable for practicing nurses. Metformin is essential in the management of type 2 diabetes (Lin et al., 2018). The learning is critical to practicing nurses since dementia is equally a significant and life-threatening condition. The nurses need to understand the clinical implications as well as the causes of dementia. As detailed in the essay, nurses need to understand that dementia refers to the loss of memory, language, problem-solving, and thinking abilities (Lu et al., 2018). These conditions severely interfere with the daily lives of individuals. Consequently, the essay is ultimately essential as it is crucial to understanding the metformin's contribution to dementia. Nurses need to understand that abnormal brain changes cause dementia and trigger a decline in cognitive abilities, behavior, and feelings (Samaras et al., 2020). The signs of dementia start out and gradually magnify over time. Applying this practice in future practice would involve metformin in the reduction of the risk of dementia amongst other cognitive disabilities. From the essay, metformin impacts significantly on the presentation and occurrence of dementia. Since metformin's effects reduce damage to brain cells, the medication thus effectively would reduce the potential risk of dementia in future practice should a patient present with the initially noted signs and symptoms of dementia (Lin et al., 2018). Metformin would ensure that the brain cells usually communicate, ensuring that thinking, behavior, and feelings are not affected (Salas et al., 2020). Through this practice, managing patients with dementia would be more superficial relative to a situation where the learning would not have been incorporated into practice. The teaching will enhance the practice and evidence base and the acre that a student nurse would give. The evidence from the essay supports the previous nursing on the chosen nursing practice. Following the concept of continued personal and professional development (CPPD), the practicing nurse would ensure the Maintenance and documentation of the identified nursing practice (Scherrer et al., 2019). The course would also provide an ongoing, voluntary, and self-motivated pursuit of knowledge for professional importance (Salas et al., 2020). The nursing practice would thus ensure personal development, competitiveness as well as self-sustainability.

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Conclusion

The essay has adequately discussed the effects that metformin has on dementia patients. The study has reviewed various articles and papers and journals on the topic from which evidence has been attained to achieve the learning need ad the nursing practice. From a review of the existing data, the essay has noted that the use of metformin reduces the risk of dementia and other cognitive disabilities. The report first introduced the nursing practice's learning need before synthesizing evidence relevant to the learning need. The study identified metformin as a biguanide drug that has been used in the management of type 2 diabetes and has proven to be successful. The drug curbs insulin resistance by improving insulin sensitivity and has thus been termed an insulin sensitizer. Through its effects, metformin ensures that abnormal changes in the brain do not occur, thus reducing the risk of dementia and other cognitive complications. After the critical discussion, the essay has critically reflected on the learning need before detailing how the practice would enhance practice in a future context. Further research is necessary to understand the effects of metformin on dementia patients adequately.

References

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Cameron, A. R., Morrison, V. L., Levin, D., Mohan, M., Forteath, C., Beall, C., ... & Rena, G. (2016). Anti-inflammatory effects of metformin irrespective of diabetes status. Circulation research, 119(5), 652-665.

Campbell, J. M., Stephenson, M. D., de Courten, B., Chapman, I., Bellman, S. M., & Aromataris, E. (2017). Metformin and Alzheimer's disease, dementia and cognitive impairment: a systematic review protocol. JBI Database of Systematic Reviews and Implementation Reports, 15(8), 2055-2059.

Campbell, J. M., Stephenson, M. D., De Courten, B., Chapman, I., Bellman, S. M., & Aromataris, E. (2018). Metformin use associated with reduced risk of dementia in patients with diabetes: A systematic review and meta-analysis. Journal of Alzheimer's Disease, 65(4), 1225-1236.

Chin-Hsiao T. (2019). Metformin and the Risk of Dementia in Type 2 Diabetes Patients. Aging and disease, 10(1), 37–48. https://doi.org/10.14336/AD.2017.1202

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Farr, S. A., Roesler, E., Niehoff, M. L., Roby, D. A., McKee, A., & Morley, J. E. (2019). Metformin improves learning and memory in the SAMP8 mouse model of Alzheimer’s disease. Journal of Alzheimer's Disease, 68(4), 1699-1710.

Kenawy, S., Hegazy, R., Hassan, A., El-Shenawy, S., Gomaa, N., Zaki, H., & Attia, A. (2017). Involvement of insulin resistance in D-galactose-induced age-related dementia in rats: Protective role of metformin and saxagliptin. PloS one, 12(8), e0183565.

Kuan, Y. C., Huang, K. W., Lin, C. L., Hu, C. J., & Kao, C. H. (2017). Effects of metformin exposure on neurodegenerative diseases in elderly patients with type 2 diabetes mellitus. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 79, 77-83.

Lee, J. H., Kim, T. I., Jeon, S. M., Hong, S. P., Cheon, J. H., & Kim, W. H. (2012). The effects of metformin on the survival of colorectal cancer patients with diabetes mellitus. International journal of cancer, 131(3), 752-759.

Lin, Y., Wang, K., Ma, C., Wang, X., Gong, Z., Zhang, R., ... & Cheng, Y. (2018). Evaluation of metformin on cognitive improvement in patients with non-dementia vascular cognitive impairment and abnormal glucose metabolism. Frontiers in Aging Neuroscience, 10, 227.

Lu, C. H., Yang, C. Y., Li, C. Y., Hsieh, C. Y., & Ou, H. T. (2018). Lower risk of dementia with pioglitazone, compared with other second-line treatments, in metformin-based dual therapy: a population-based longitudinal study. Diabetologia, 61(3), 562-573.

Malin, S. K., & Kashyap, S. R. (2014). Effects of metformin on weight loss: potential mechanisms. Current Opinion in Endocrinology, Diabetes and Obesity, 21(5), 323-329.

Moore, E. M., Mander, A. G., Ames, D., Kotowicz, M. A., Carne, R. P., Brodaty, H., ... & Watters, D. A. (2013). Increased risk of cognitive impairment in patients with diabetes is associated with metformin. Diabetes care, 36(10), 2981-2987.

Orkaby, A. R., Cho, K., Cormack, J., Gagnon, D. R., & Driver, J. A. (2017). Metformin vs sulfonylurea use and risk of dementia in US veterans aged≥ 65 years with diabetes. Neurology, 89(18), 1877-1885.

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Samaras, K., Makkar, S., Crawford, J. D., Kochan, N. A., Wen, W., Draper, B., ... & Sachdev, P. S. (2020). Of n 5 1,037, 123 had diabetes; 67 received metformin (DM1MF) and were demographically similar to those who did not (DM-noMF) and participants without diabetes (no-DM). DM1MF had significantly slower global cognition and executive function decline compared with DM-noMF. Incident dementia was significantly higher in DM-noMF compared with DM1MF (odds ratio 5.29 [95% CI 1.17–23.88]. Diabetes Care, 43, 2691.

Scherrer, J. F., Morley, J. E., Salas, J., Floyd, J. S., Farr, S. A., & Dublin, S. (2019). Association Between Metformin Initiation and Incident Dementia Among African American and White Veterans Health Administration Patients. The Annals of Family Medicine, 17(4), 352-362.

Scherrer, J. F., Salas, J., Floyd, J. S., Farr, S. A., Morley, J. E., & Dublin, S. (2019, August). Metformin and sulfonylurea use and risk of incident dementia. In Mayo Clinic Proceedings (Vol. 94, No. 8, pp. 1444-1456). Elsevier.

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