Pathophysiology of Alzheimer's Disease - Coursework Example

Name: Tutor: Title: Alzheimer ’s disease Institution: Date: Introduction Alzheimer's disease is the most common form of dementia which is mainly experienced by older people. It is a slow progression of the brain that is characterized by impaired memory which eventually results in poor reasoning, planning, language and perception. Various scientists believe that the disease is caused by buildup of a specific protein known as beta-amyloid protein in the brain which results to death of the nerve cells. Increased age is one of the main risk factors of the disease. Other risk factors for Alzheimer disease include genetic factors where a child of a person who experiences early onset of Alzheimer has a higher risk of developing it at the same age. Other risk factors include high blood pressure, diabetes, and coronary artery disease (Burns, Winter & Page, 2006). PATHOPHYSIOLOGY OF ALZHEIMER'S DISEASE The typical neuropathologic findings in Alzheimer’s disease include amyloid plaques, neurofibrillary tangles and neurological and synaptic cell death (Lau, Brodney, & Bhat, 2008). Granulovacuolar degeneration in the hippocampus and the deposition of amyloid in the blood vessels may also be observed during examination of the tissues as shown in figure 1, 2 and 3 below. The pathological criteria used to diagnose Alzheimer’s disease at autopsy are based on demonstration of adequate number of neuritic plaques and neurofibrillary tangles when examined under the microscope (Cutler & Sramek, 2004).  Figure 1.  Figure 2.  Figure 3. Diagrammatic representation of a normal brain and one affected with Alzheimer’s disease Amyloid plaques Amyloid plaques, also referred to as senile plaques may be further grouped according to their composition but they all contain forms of beta-amyloid protein. The beta-amyloid protein is a 39- to 42-amino acid peptide which is formed as a result of proteolytic cleavage of beta-amyloid precursor protein. This is found in the extracellular deposits in the entire central nervous system as shown below. Beta-amyloid protein is known to disrupt the activities of the neurons because it stimulates the release of free radicals which results to oxidative stress and death of the neuronal cells (Tavee & Sweeney, 2011). Diagrammatic representation of amyloid plaques in the brain Neurofibrillary tangles These are helical filaments which are paired and made up of tau protein. The tau protein is in normal cells important for the growth and development of the axonal. However, when the tau protein is hyperphosphorylated, it forms tangles which are then deposited within the neurons that are found in the hippocampus and medial temporal region, also in the frontal association cortices. Their deposition results to death of the cells in these areas (Dash, & Villemarette-Pittman, 2005). Neuron and synapse loss Areas that are affected by the death of the neuronal cells are found throughout and are distributed in a pattern that is similar to that of neorofibrillary tangles. They however greatly affect the neurotransmitter pathways. When the cholinergic neurons in the basalis nucleus of Meynert die, there is a deficit in acetylcholine which is the main transmitter which is involved in memory. Loss of serotoninergic neurons in the median raphe results in deficits in serotonin while loss in the adrenergic neurons results to deficit in norepinephrine. Serotonin and norepinephrine are neurotransmitters whose death may impair attention and memory of the person affected (Tavee & Sweeney, 2011). Chromosomal mutations Chromosomes 21, 14 and 1 undergo genetic mutation and this has been shown to cause early onset of Alzheimer’s disease which may be inherited in a family line. This is inherited in an autosomal-dominant pattern and the mutations are however responsible for just less than five percent of all the cases of Alzheimer’s disease. The chromosomal mutation results in excess production and deposition of beta-amyloid protein (Lim, 2009). Inflammation Inflammation occurs in the regions of the Alzheimer’s disease brain that are pathologically vulnerable. It also occurs with full complexity of local periphery inflammatory response. The typical stimulants of inflammation are the degenerating tissues and the deposition of highly insoluble abnormal materials (Jones, 2001). Case study on Pathophysiology of Alzheimer’s disease This study was conducted in Swedish Medical University Karolinska Institute to investigate the pathological course of Alzheimer’s disease. The case showed much of what has been discussed above on Pathophysiology of Alzheimer’s disease. The first PET scan to be conducted in the world of amyloid plaque was performed in a living patient by the use of amyloid-binding compound 11C-PIB by Professor Agneta Nordberg in 2002. The Alzheimer’s patient was monitored through regular PET scans and conduction tests on the memory as the disease continued to develop. When the patient died, pathological and neurochemical analysis of the brain was carried out. The combined tests were aimed at showing how the disease develops. The results showed that amyloid plaques were discovered in high concentrations at the early stage of the disease when the patient experienced just a slight memory loss. However, the concentration of the plaques did not change even as the disease progressed and energy metabolism in the brain declined. Another discovery in the study was that the high concentration of the plaque was accompanied by lowering levels of neuronal nicotinic receptors in the brain. These are the receptors which play the main role in brain functioning. This case study demonstrated that the receptors are affected at the early stages of the disease. Changes in inflammation were also checked in the regions of the brain where levels of plaques were low. It showed that neuroinflammation which is related to Alzheimer’s disease may be caused by something else and it evolves at a different stage of the disease compared to the accumulation of amyloid (Kadir, 2010). DRUG TREATMENT FOR ALZHEIMER’S DISEASE There are no specific drugs that have been developed to cure Alzheimer’s disease but there are those which have been developed to manage the symptoms of slow down the disease progression. The main drugs used are divided into two: Cholinesterase inhibitors and memantine (Geldmacher & Whitehouse, 1997). Cholinesterase inhibitors These are donepezil (Aricept), rivastigmine (Exelon) and galantamine (Reminyl). These drugs prevent the enzyme involved in the process by which acetyl cholinesterase breaks down to acetylcholine in the brain thus allowing concentration of acetylcholine in the brain. Increased concentration of acetylcholine leads to improved communication between the nerve cells and this may stabilize the symptoms for about 6 to 12 months (Alzheimer’s Society 2012). Memantine Memantine acts in a complex and different way from that of the Cholinesterase inhibitors. It blocks glutamate, a messenger chemical which is produced in excess in the brain cells that are damaged by Alzheimer’s disease. Excessive release of Glutamate leads to further damage of the brain cells (Alzheimer’s Society 2012). Other drugs that are used in treatment of Alzheimer’s disease include: Anti-psychotic drugs These are used in treatment of agitation, aggressiveness and delusions. However, these drugs should not be used for a long period and should only be used during severe symptoms. Their use should also be carefully monitored since their prolonged use may lead to death of a patient (National institute of Mental Health, 2006). Risperidone This drug is used to treat psychosis in Alzheimer’s disease, a condition that is characterized by hallucinations, delusions and misidentifications. Risperidone works in elderly patients who have moderate to severe psychosis in Alzheimer’s disease (Alzheimer’s Society 2012). Anti-depressants Depression is very common to Alzheimer’s patients. Meta analysis studies have proved that antidepressants can safely and efficiently treat the depression which is mainly due to low levels of norepinephrine, serotonin and dopamine in the central nervous system. Therefore some of the antidepressants used include sertaline, tianeptine, fluvoxamine, bupropion, and mirtazapine. Trazodone This is a serotonergic antidepressant with alpha 2-adrenergic blocking activity used to treat irritability, restlessness and anxiety in Alzheimer’s patients. Trazodone corrects disturbances in the behavior of Alzheimer’s patient caused by depletion of serotonin (Alzheimer’s Society 2012). Hypnotics These are also known as “sleepers”. They include Ambien and Lunesta which are used to treat sleep problems in Alzheimer’s patients. Insomnia is a common problem in Alzheimer’s patients during the moderate stages. Treatment with the hypnotics is referred to as hypnotherapy. Zopiclone is one of the newest hypnotics which do not make people feel unwell (Alzheimer’s Society 2012). Experimental therapy for treatment of Alzheimer’s disease These are some of the current experimental therapies for treatment of Alzheimer’s disease. β-secretase inhibitors β-secretase is the first protein involved in the processing of amyloid precursor protein that results in the release of amyloid-β (Aβ) in the brain. Amyloid-β (Aβ) is the protein that is believed to cause Alzheimer’s disease if its levels are high in the brain. β-secretase inhibitors are drugs that are meant to stop the production of Amyloid-β (Citron, 2004). ϒ secretase inhibitor ϒ secretase is involved in the production of Amyloid Precursor Protein (APP), a protein that is a protein involved in development of Alzheimer's disease. ϒ secretase inhibitor will therefore prevent the production APP (Chen, Zhang, Li & Le, 2007). Non Steroidal Anti-Inflammatory Ibobrufen and Indomenthacin have demonstrated clinical benefits in the treatment of Alzheimer’s disease. Indomethacin slows the cognitive decline in Alzheimer’s patients. Long term use of drugs that are known to reduce aches and pains such as ibuprofen are also known to lower the risks for Alzheimer’s disease (Feldmand, & Tabet, 2003). Generally, the Non Steroidal Anti-Inflammatory plays a role in conditions that are characterized by inflammation such as Alzheimer’s disease (Veld, Ruitenberg, Hofman, 2001) Immunized Aβ-Protein This is being considered in the development of a vaccine for Alzheimer’s disease. This involves immunizing Alzheimer’s patients with Aβ peptides to enable them generate antibodies that binds Aβ protein leading to its removal form the brain (Boche & Nicoll, 2008). NON DRUG THERAPY FOR MANAGING ALZHEIMER’S DISEASE In addition to drugs, a wide range of non-drug treatment has also been invented and is also being used. The primary goals for treating Alzheimer include improving the quality of life of the person suffering from the Alzheimer disease and also the life of the person’s caregivers. The treatment therefore takes three approaches which are interrelated. These are: Slowing the progression, managing the behavioral symptoms and educating and supporting the caregivers (Richter, 2007). Some of the non drug therapies for managing Alzheimer’s disease include: Non drug treatment for sleeping problems This form of treatment is aimed at improving the sleep routine and also the sleeping environment. A comfortable sleeping environment promotes rest for an Alzheimer’s patient. The non drug treatment for sleep problems involves maintaining regular meal times before and after sleeping, exposing to the morning sunlight, daily regular exercises, maintaining a comfortable bedroom temperature and discouraging watching of television when one is awake at night (Alzheimer’s Association, 2012). Non drug therapy for managing behavior symptoms Non drug therapy for managing behavior symptoms are aimed at promoting physical and emotional comfort. This involves three steps. The first step is to recognize that the behavior of the person is a symptom of Alzheimer’s disease, secondly, to identify how the symptoms may relate to the experience of the person with Alzheimer and finally to change the environment so as to overcome the challenges and other factors hindering the comfort, security and ease of the person’s mind. A calm environment is very important for behavior change (Alzheimer’s Association, 2012). Non drug treatment for depression Non drug treatment for depression in Alzheimer’s patient involves making a list of activities or places that the person likes most and scheduling for them regularly, encouraging the person to exercise regularly especially in the morning, celebrating the person’s small successes and occasions, pampering the person with his or her favorite foods and recognizing every effort of the person. It is also important to keep reassuring the person that he or she will never be left alone (Alzheimer’s Association, 2012). Current research in Alzheimer’s disease There is intense research that is being carried out in the prevention, causes and treatment for Alzheimer’s disease. On the pathogenesis, a lot of research is being carried as some researchers are disagreeing on the importance of tau protein and beta-amyloid as the main cause of Alzheimer’s. Another research that is underway is on the role of inflammation in Alzheimer’s. Some researchers believe that inflammation damages the neurons while others believe that it is beneficial in helping clear away the plaques. Another research that is underway on the possibility for screening against Alzheimer so that it can be diagnosed before symptoms start showing up. Other researches are on neuroimaging and functional imaging as means of detecting structural changes in the brains of those suffering from Alzheimer’s disease (Joel & Jessica, 2008) Relevant studies Studies to compare the benefits of non-drug interventions as compared to drug interventions were carried out on 33 studies that involved a total of 3800 patients with Alzheimer’s disease. The studies classified the three treatment approaches as activity based interventions, caregiver training and emotion oriented interventions. The drug interventions that were compared with were ginkgo compounds, cholinesterase inhibitors and memantine. Patients on non drug treatment approaches were found to improve better on symptoms such as depression, restlessness and agitation (Light & Lebowitz, 2007). Conclusion Further research is however going on to find out more about Pathophysiology of Alzheimer’s disease. A lot of attention has also been put on the disease due to its increasing number of cases in the world. Non drug therapy has however been found to do well for many patients. Bibliography Alzheimer’s Association, 2012, Treatments for Alzheimer’s Disease, retrieved on 16th April 2012 from Alzheimer’s Society, 2012, Symptoms and Diagnosis, Retrieved on 16th April 2012 from Boche, D., & Nicoll, J., 2008, The role of the immune system in clearance of Aβ from the brain. Brain Pathology, vol 18, 267-278. Burns, A., Winter, J., & Page, S., 2006, Alzheimer's Disease and Memory Loss Explained: A Guide for Patients and Carers, Altman Publishing, London. Chen, S., Zhang, X., Li, L., & Le, W., 2007, Current experimental therapy for Alzheimer’s disease. Bentham Science Publishers Ltd., Sharjah , UAE. Citron, M., 2004, Beta-secretase inhibition for the treatment of Alzheimer's disease--promise and challenge. Trends Pharmacologic Sci.;25(2):92-7. Cutler, N., & Sramek, J., 2004, Understanding Alzheimer's Disease, Univ. Press of Mississippi. Dash, P., & Villemarette-Pittman, N., 2005, Alzheimer's Disease, Demos Medical Publishing, New York. Lau, L., Brodney, M., & Bhat, R., 2008, Alzheimer's Disease, Springer, New York. Feldmand, H., & Tabet, N., 2003, Ibuprofen for Alzheimer’s disease. Bentham Science Publishers Ltd., Sharjah , UAE. Geldmacher, D., & Whitehouse, P.1997, Differential diagnosis of Alzheimer's disease. Neurology, 48: (S6): S2-S9. Joel, D., & Jessica, E., 2008, Recent Research and Developments in Alzheimer’s disease. Retrieved on 28th April 2012 from Jones, R. 2001, Inflammation and Alzheimer's disease. Lancet,358: 436-437. Kadir, A., et al., 2010, Press Release on PET imaging and clinical progression in relation to molecular pathology in first PIB PET AD Patient, retrieved on 8th April 2012 from Light, E., & Lebowitz, B., 2007, Alzheimer's Disease Treatment and Family Stress: Directions for Research, Taylor and Francis, New York. Lim, Y., 2009, Pathophysiology of Alzheimer's Disease, University of Sydney. National institute of Mental Health, 2006, Antipsychotic Medications Used to Treat Alzheimer’s Patients Found Lacking. Retrieved on 26th April 2012 from Richter, B., 2007, Alzheimer's Disease: A Physician's Guide to Practical Management, Humana Press, New Jersey. Tavee, J., & Sweeney, P., 2011, Alzheimer’s disease, retrieved on 16th April 2012 from Veld, A., Ruitenberg, A., Hofman, A., et al. 2001, Nonsteroidal anti-inflammatory drugs and the risk of Alzheimer's disease. New England Journal of Medicine, 345: 1515-1521. Read More