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HISTORY OF ALZHEIMER'S DISEASE[1] In 1906's, Alois Alzheimer (1864-1915), a German Neurologist and Psychiatrist, described a patient who experienced progressive problems with memory, language and behavior. After her death, from brain autopsy studies, Alzheimer found dense deposits surrounding the nerve cells (neuritic plaques) and within the neuronal cells he observed twisted bands of fibers (neurofibrillary tangles). In this new age of medicine, this degenerative brain disorder bears his name and the two features he observed are said to be Hallmarks of the disease. IMPACT OF ALZHEIMER'S DISEASE ON LIFESTYLE OF PATIENT... Once considered a rare disorder, now Alzheimer's disease is seen as a major public health problem that is seriously affecting millions of older people and their families around the world. It is not only burden to the patient but also to the patient's family. The patient fails to perform his daily activities like brushing, bathing, having his food etc, which poses a substantial burden on his/her family. WHAT IS ALZHEIMER'S DISEASE?? Alzheimer's disease is a neurodegenerative brain disease. It is irreversible, progressive and slowly destroys memory and thinking skills. It mostly affects people of age group 60years and progresses as the age increases. PREVALENCE...[2][3] * AD is the most common cause of dementia among people aged 60 and older. * In last year's report (WORLD ALZHEIMER REPORT-2010) submitted by the ALZHEIMER'S DISEASE INTERNATIONAL, it is estimated that there are 35.6 million people living with AD worldwide in 2010, increasing to 65.7 million by 2030 and 115.4 million by 2050. * The number of people affected will be over 115.4 million by 2050. * In 2010, there are 3.7 million Indians with dementia. ALZHEIMER'S AND THE BRAIN...[4] Plaques and Tangles: The Hallmarks of AD * Beta-amyloid plaques are dense deposits made up of protein and cellular material that accumulate outside and around nerve cells. These amyloid plaques are made up of aggregates of Av containing 40 or 42 residues of amino acids. * Neurofibrillary tangles are twisted fibers that build up inside the nerve cell. These deposits are protein aggregates that result from misfolding of native proteins. How Deposition of beta-amyloid plaques takes place?? Amyloid precursor protein (APP) is the precursor of amyloid plaque. It is a membrane protein which is expressed in normal conditions by many cells including CNS neurons. 1. APP sticks through the neuron membrane. 2. Enzymes (Secretases- type of proteases) cut the APP into fragments of protein, including beta amyloid. 3. Beta-amyloid fragments clumps to form plaques. In AD, many of these clumps form, disrupting the work of neurons. Initially, these are primarily seen in the hippocampus region and areas of the cerebral cortex. How formation of neurofibrillary tangles takes place?? Usually neurons have an internal support structure partly made up of microtubules. Tau protein helps to stabilize these microtubules. In AD, tau is formed abnormally in which it gets phosphorylated and loses its nature, causing microtubules to collapse, and tau proteins clump together as paired helical filaments to form neurofibrillary tangles with characteristic microscopic appearance. Other mechanisms that leads to AD are[3] * Excitotoxicity * Oxidation * Inflammation POTENTIAL RISK FACTORS OF ALZHEIMER'S DISEASE[2] * Age * Family history of dementia * Head injury * Depression * Hypothyroidism * Increased aluminium concentration in drinking water * Tobacco consumption * Alcohol abuse * Vascular risk factors * Early and late parental age SYMPTOMS[2] Memory loss Language problems Difficulty in making decisions Depression Loss of interest Forgetfulness of people's names and recent events Becomes dependent on family and care givers Difficulty in walking, eating and communication Breathing difficulties, respiratory infections DIAGNOSIS OF ALZHEIMER'S DISEASE[5] Physicians in specialized AD centers diagnose AD with up to 90 percent accuracy. Early diagnosis has advantages. There are a number of tools to diagnose AD: * A detailed patient history * Information from family and friends * Physical and neurological exams and lab tests * Neuropsychological tests * CT scan or magnetic resonance imaging (MRI). PET scans are used primarily for research purposes. CURRENT TREATMENT AVAILABLE[5] Drugs that are recommended by for treating the cognitive symptoms of Alzheimer's disease. ADMENTA(r) Generic Name: Memantine GALAMER(r) Generic Name: Galantamine EXELON(r) Generic Name: Rivastigmine ARICEP(r) Generic Name: Donepezil TREATMENTS CURRENTLY UNDER INVESTIGATION[6] Researchers are also looking at other treatments, including: * Cholesterol-lowering drugs called 'Statins' * Anti-oxidants (vitamins) and folic acid * Anti-inflammatory drugs * Substances that prevent formation of beta-amyloid plaques * Nerve growth factor to keep neurons healthy GUIDELINES FOR CARETAKERS[5] 70 to 90% of people with Alzheimer's eventually develop behavioral symptoms, including sleeplessness, wandering and pacing, aggression, agitation, anger, depression, and hallucinations and delusions. * Stay calm and be understanding. * Be patient and flexible. Don't argue or try to convince. * Acknowledge requests and respond to them. * Try not to take behaviors personally. Remember: it's the disease talking, not your loved one. DO YOU KNOW??? Ronald Regan the 40th American president suffered from AD which ultimately lead to his death.[7] References:: 1. on 13-02-2011) 2. on 13-02-2011) 3. on 13-02-2011) 4.Rang and Dale PHARMACOLOGY, 6th Edition, Elsevier Publications, Pg:514,515 5. on 14-02-2011) 6. on 13-02-2011) 7. on 14-02-2011) This work contains no plagiarized material

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Gangadhar Hari's picture
Author: Gangadhar Hari


K Rajakrishna's picture

Hi hari. You have presented the topic very well. Can you please explain the mechanism of action of drugs used in the treatment of AD.
Gangadhar Hari's picture

Memantine: Memantine is a NMDA receptor antagonist. It reduces the excitotoxicity produced by the glutamate in the brain via NMDA receptors. This is one of the mechanisms involved for the neuronal degeneration in Alzheimer's Disease. Link: One of the main characteristics of AD is the Loss of Choline acetyl transferase activity, acetylcholine content, and acetylcholinesterase and choline transport in the cortex and hippocampus which leads to the so called memory loss and thought impairment in AD patients. So use of cholinesterase inhibitors proved useful in relieving these symptoms and slight improvement in cognitive functions. These act by inhibiting the acetylcholinesterase at the synaptic vesicles. These drugs do not cure the disease completely. The mechanisms underlying the loss of these cholinergic neurons are not yet known. Following are the Cholinesterase inhibitors Used in the treatment of Alzheimer's disease Galantamine: Reversible, Non-selective Duration 8hrs Rivastigmine: Slowly reversible, affects both AChE and BuChE Duration 8hrs Donepezil: Short acting, reversible AChE selective Duration 24hrs Reference: Rang and Dale PHARMACOLOGY, 6th Edition, Elsevier Publications, Pg: 515, 516.
Venkata Ram Sudhir Kakarlapudi's picture

its nice topic , can you tell me the specific test for AD . i require information on drug-drug interaction and food-drug interactions from kvr sudhir mail id :


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