I Project Name:

ALZHEIMERS DISEASE
SUBJECT: CLINICAL PHARMACY INSTRUCTER: MISS SANA

HANIF
Prepared by:

ASAD ULLAH DP106-047 JAWAD SALEEM DP-106070 ADNAN SHAUKAT DP-106051

Pharm-D (10th A)

Department of Pharmacy
UNIVERSITY OF LAHORE

ALZHEIMER` S DISEASE

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Description
Introduction of Alzheimers disease Epidemiology Pathophysiology of AD Types of AD Symptoms Diagnosis

Page Number 3 4 5 6 7 7

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7 8 9 10 11 12 13 14 15

Lab Test Treatment Management Plan Prognosis Complication References & Sources Case No 01 Case No 02 Case No 03

8 10 13 14 14 15 16 19 22

ALZHEIMER'S DISEASE (AD)

INTRODUCTION: Alzheimers disease (AD) is an irreversible, progressive brain disease that slowly destroys memory and thinking skills and, eventually, the ability to carry out the simplest tasks of daily living. In most people with AD, symptoms first appear after age 60.

Alzheimer's disease is characterized by the formation of large numbers of abnormal features in the brain called

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plaques and tangles. Plaques are dense deposits of protein that build up over time between brain cells. Tangles are twisted fibers of protein that develop inside brain cells. It is believed that plaques and tangles can block communication between brain cells and play a role in brain cell degeneration and brain cell death. What is dementia? Dementia is a general term that refers to a decline in cognitive function so extensive that it interferes with daily life and activities. This loss in the ability to think, remember, and reason is not a disease itself, but a group of symptoms that often accompanies a disease or condition. AD is the most common type of dementia accounts for 60-80 percent of cases.

EPIDEMIOLOGY:
Advancing age is the most significant risk factor. Three percent of the US population aged 65 to 74 years old suffers from AD. Nearly 20% of those aged 75 to 84 have AD.

And that number approaches 50% among the population aged 85 and older. AD affects more than 4 million Americans. One in 10 people over the age of 65 are affected. Nearly 50% of all people age 85 and older may have symptoms of AD. African Americans and Hispanic Americans may have higher overall risk. Alzheimer prevalence was estimated to be 1.6% in 2000 both overall and in the 6574 age groups, with the rate increasing to 19% in the 7584 groups and to 42% in the greater than 84 group. The World Health Organization estimated that in 2005, 0.379% of people worldwide had dementia, and that the prevalence would increase to 0.441% in 2015 and to 0.556% in 2030. The disease prevalence is more in women as compared to men.

Etymology:
1912, title of article by S.C. Fuller published in "Journal of Nervous and Mental Diseases;" named for Ger. neurologist Alois Alzheimer (18641915). The name was not common before 1970s; shortened form Alzheimer's first recorded 1954.

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History:
AD is named after Dr. Alois Alzheimer, a German doctor. In 1906, Dr. Alzheimer described changes in the brain tissue of a woman who had died of an unusual mental illness. Her symptoms included memory loss, language problems, and unpredictable behavior. After she died, he examined her brain and found many abnormal clumps (now called amyloid plaques) and tangled bundles of fibers (now called neurofibrillary tangles). He noted following features of AD
Plaques in the brain Tangles in the brain The loss of connections between nerve cells (neurons) in the brain.

Damage to the brain begins as many as 10 to 20 years before any obvious signs of forgetfulness appear. As nerve cells die throughout the brain, affected regions begin to shrink. By the final stage of AD, damage is widespread, and brain tissue has shrunk significantly.

Pathology/Pathophysiology of AD:
Pathophysiology studies changes in function of an organ or tissue caused by a disease or an injury. Two main pathophysiological changes in the brain found in Alzheimer's disease: plaques and tangles.

Plaques Plaques are abnormal accumulations of the protein beta-amyloid in the brain, inflammation around these plaques leads to the death of nearby brain cells. Causes Plaques may be caused by a problem in processing beta-amyloid. Risk factors for the development of plaques include high blood pressure and high cholesterol; there is probably also a genetic component of plaque formation. Tangles Tangles occur when strands of the protein tau, which gives brain cells their shape, becomes twisted; this pathophysiological change causes affected cells to die. Some people are genetically predisposed to developing tau that twists. Features It is not known, whether the processes that causes plaques and tangles are related. Effects The pathophysiological changes of the brain in Alzheimer's disease lead to dementia, the slow, progressive (increasingly worse over time) loss of brain function. This affects memory, learning and behavior.

TYPES OF AD:
1. Mild Alzheimers Disease

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As Alzheimers disease progresses, memory loss continues and changes in other cognitive abilities appear. Problems can include getting lost, trouble handling money and paying bills, repeating questions, taking longer to complete normal daily tasks, poor judgment, and small mood and personality changes. People often are diagnosed in this stage. 2. Moderate Alzheimers Disease In this stage, damage occurs in areas of the brain that control language, reasoning, sensory processing, and conscious thought. Memory loss and confusion increase, and people begin to have problems recognizing family and friends. They may be unable to learn new things, carry out tasks that involve multiple steps (such as getting dressed), or cope with new situations. They may have hallucinations, delusions, and paranoia, and may behave impulsively. 3. Severe Alzheimers Disease By the final stage, plaques and tangles have spread throughout the brain and brain tissue has shrunk significantly. People with severe Alzheimers cannot communicate and are completely dependent on others for their care. Near the end, the person may be in bed most or all of the time as the body shuts down.

Causes:
We dont yet fully understand what causes AD, but it is clear that it develops because of a complex series of events that take place in the brain over a long period of time. Genetics play a role in some people with AD. A rare type of AD, called early-onset AD, affects people ages 30 to 60. Some cases of early-onset AD, called familial AD, are inherited. Familial AD is caused by mutations (permanent changes) in three genes. Offspring in the same generation have a 50-50 chance of developing familial AD if one of their parents had it. Genetic factors do appear to increase a persons risk of developing the disease. This increased risk is related to the apoliprotein E (APOE) gene. Nutritious diet, exercise, social engagement, and mentally stimulating pursuits.

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Symptoms of Alzheimers disease:

Alzheimers disease can affect different people in different ways, but the most common symptom pattern begins with Gradually, thinking and judgment become more difficult. Progressive difficulty in communication and severe deterioration in memory, language, and motor function result in a loss of coordination and an inability to write or speak. Personality changes (restlessness, irritability) and nocturnal awakenings are common. Patients also exhibit loss of eye contact, a fearful look, wringing of the hands, and other signs of anxiety.

In advanced Alzheimers, people need help with bathing, dressing, using the bathroom, eating and other daily activities. In the final stages of the disease lose their ability to communicate, fail to recognize loved ones and become bed-bound and reliant on 24/7 care.

Diagnosis/Diagnostic Tests
No specific test that can detect AD. Variety of tests evaluates the brain and can rule out other causes of Alzheimer's disease symptoms, such as vascular dementia or depression. The diagnostic process begins with Taking a thorough personal and family history, including symptoms, and completing a physical examination. A neurological exam evaluates the nerves and nervous system and such functions as reflexes, sensation, movement, balance, coordination, vision, and hearing. Mini-mental state examination (MMSE), evaluates mental function by assessing the answers provided to a series of questions. Imaging tests CT and MRI provide information about the structure of the brain.

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Diagnostic Criteria for Delirium, Dementia, Alzheimer's Disease and Vascular Dementia
Diagnostic criteria for delirium 1. A change in cognition or development of a perceptual disturbance is present and not explained by a preexisting, established or evolving dementia. 2. The disturbance developed over a short period of time (usually hours to days) and tends to fluctuate. 3. The level of consciousness (awareness of the environment) is disturbed or fluctuates. 4. There is evidence that a drug, acute illness or metabolic disturbance is present that could explain the change in cognition. Diagnostic criteria for dementia 1. Cognitive impairment is present, as demonstrated by: (1) memory loss and (2) impairment of language, praxis, recognition or abstract thinking. 2. The cognitive impairment is chronic and progressive and has resulted in functional decline. 3. Delirium has been ruled out. Diagnostic criteria for Alzheimer's disease 1. Dementia is present. 2. History, physical and mental status examinations are consistent with Alzheimer's disease. 3. Screening blood tests (CBC, BUN, calcium, liver function, thyroid function, vitamin B and others as indicated) and review of medications do not reveal any major untreated cause of cognitive impairment. 4. Brain imaging study (CT or MRI) is normal or shows atrophy (some authorities do not recommend neuroimaging studies except in uncertain cases).
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Diagnostic criteria for vascular dementia 1. Dementia is present. 2. Two or more of the following are present: (1) focal neurologic signs on physical examination; (2) an onset that was abrupt, stepwise or stroke-related; (3) brain imaging study (CT or MRI) shows multiple strokes.

LAB TEST: Diagnostic tests use in the diagnosis of Alzheimer's disease includes: Urine tests Blood tests Neuropsycholo gical tests Memory tests Cognitive tests Brain scans o Brain CT scan o Brain MRI scan

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o Brain PET scan

Differential Diagnosis:
Diagnosis may be delayed or missed because early symptoms develop gradually and are often associated with the normal aging process. In addition, symptoms of Alzheimer's disease can mimic symptoms of a variety of diseases, disorders or conditions. These include TIA, depression, vascular dementia, Creutzfeldt-Jacob disease,bovine spongiform encephalopathy, brain tumor, hydrocephalus, or advanced syphilis or AIDS.

The following conditions can be alternative diagnoses to consider during the diagnostic process for Alzheimer's Disease:

Aging - some level of memory and concentration lapse is normal. Emotional problems like depression, fatigue etc. Dementia - and various underlying causes of dementia and causes of dementia symptoms Brain conditions like Head injury ,Subdural hematoma,Brain tumors,Brain blood vessel disease Chronic hypothermia - may cause confusion or slowing down in elderly living with poor heating. Pneumonia - may cause confusion in the elderly. Vitamins deficiency Thyroid problems Idiopathic Parkinson's disease Cortico-basal ganglionic degeneration Huntington's disease High -dose glucocorticosteroid therapy

Antihypertensive drug intoxication Benzodiazepine intoxication

Management And Treatment:

Pharmacologic Therapy While no drug has been shown to completely protect neurons, agents that inhibit the degradation of acetylcholine within the synapse are the mainstay of treatment for Alzheimer's disease.

1.0 ACETYLCHOLINESTERASE INHIBITORS The cholinesterase inhibitor tacrine (Cognex) is used rarely because of potential liver toxicity and the need for frequent laboratory monitoring. The acetylcholinesterase inhibitors donepezil (Aricept), rivastigmine (Exelon), and galantamine (Reminyl) have been proved effective in clinical trials. Acetylcholinesterase Inhibitors Used in the Treatment of Alzheimer's Disease
Drug Donepezil (Aricept)
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Pharmacologic actions Acetylcholinesterase inhibitor

Rivastigmine Acetylcholinesterase (Exelon) inhibitorButyrylcholinesterase inhibitor

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Dosage Start at 5 mg once daily, taken at bedtime; after 6 weeks, increase to 10 mg once daily. Start at 1.5 mg twice 6 mg twice 3 mg twice daily, taken with food; daily daily at 2-week intervals, increase each dose by

Minimum Target therapeutic dosage* dosage 10 mg 5 mg daily once daily

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Drug

Dosage 1.5 mg, up to a dosage of 6 mg twice daily. Galantamine Acetylcholinesterase Start at 4 mg twice 12 mg 8 mg twice (Reminyl) inhibitorNicotinic receptor actions daily with food; at 4- twice daily daily week intervals, increase each dose by 4 mg, up to a dosage of 12 mg twice daily.
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Pharmacologic actions

Target dosage*

Minimum therapeutic dosage

Others drugs that are claimed for the treatment of AD are as follows

2. VITAMIN E Vitamin E, an antioxidant, is thought to mitigate the inflammatory effects of plaque formation in the brain. In vitro, vitamin E protects nerve cells from the effects of b; -amyloid, but it does not protect against other CNS diseases such as Parkinson's disease. 3. ESTROGEN Post-menopausal women who take estrogen have a lower incidence of Alzheimer's disease. Estrogen improves cerebral metabolism in women. Although estrogen may have a neuroprotective effect but it does not improve function in patients with AD and the combination of estrogen and progestin actually may increase the risk for dementia and stroke. 4. ANTI-INFLAMMATORY DRUGS NSAID `s can resolve Inflammation surrounding -amyloid plaques with resultant destruction of neurons which is a key factor in the pathogenesis of Alzheimer's disease.

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5. GINKGO BILOBA Four trials using ginkgo-biloba found a modest therapeutic benefit, but some reports associated with side effects of commercially available ginkgo, including coma, bleeding, and seizures.

Behavioral Management:

Use the five "P's" for effective assessment and planning Describe the problem accurately--what happens, who is involved, when it occurs, what precedes the behavior and what consequences result for the patient and caregivers. Assess the patient--are there unmet needs that may be triggering the behavior? Is an undetected medical problem present (e.g., pain)? What stresses are acting on the patient? Are delusions or other psychotic signs present? Is the patient depressed? Brainstorm possible causes--an interdisciplinary team meeting is the best setting in which to do this. Develop a plan. Implement the plan, reassess it, modify it if necessary and pass it on to all caregivers if it is successful.

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MANAGEMENT PLAN FOR ALZHEIMER `S DISEASE:

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Prognosis: AD is a progressive disease. The course of the disease varies from person to person. Some people have the disease only for the last 5 years of life, while others may have it for as many as 20 years. The most common cause of death in AD patients is infection. Death Rates:
53,852 deaths in USA 2001 (CDC); 44,536 annual deaths (NVSR Sep 2001) Cause of death rank: 8th leading cause of death in 1999 and 2000 (CDC)

1.3% (ratio of deaths to prevalence).

Complications: Complications of Alzheimer's Disease may include: Memory loss Sleeplessness Agitation Wandering (see Disorganization) Anxiety Chronic brain failure

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References:

http://www.aafp.org/afp/981101ap/sloane.html http://www.wrongdiagnosis.com/a/alzheimers_disease /intro.htm

http://www.pitt.edu/~super1/lecture/lec9341/021.htm http://www.alz.org/national/documents/report_alzfactsfigur es2009.pdf

http://www.ehow.com/facts_5780227_pathophysiolog y-alzheimer_s-disease.html http://www.aafp.org/afp/2003/1001/p1365.html

Physicians' desk reference. Accessed May 2003 (with password) at: www.pdr.net.

http://www.etymonline.com/index.php? term=Alzheimer's+disease
NICE issues guidance on drugs for Alzheimer's disease. National Institute for Clinical Excellence. Accessed April 2003 at: www.nice.org.uk/article.asp?a=14406

http://www.caalz.org/PDF_files/GuidelineFullReport-CA.pdf http://www.vhct.org.

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CASE NO.1
Pharmacist: ASAD ULLAH DP-106-047
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10th A

CASE NO 01

Alzheimers disease
Patient Name: Samina Arif Address: 14-shadman Lahore 72 yrs Height: Race: Known

Age: 5 4 Gender: Female Asian Weight: 132lbs Allergies: Penicillin

Chief complaint: Samina is a retired lecturer and a slim lady. She has loss her personal history, difficulty in reading or writing, forget recent event of her life, difficulty in dressing and has trouble in recognizing his family members. History of Present Illness: She is loosing her abilities to carryout daily activities gradually. She has such symptoms from last 4-5 years but now these become more intense.

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Past medical History: She has Mild Hypertension and use Lisinoprill 5mg daily for that. No other important medical history. Family History: Father was died at age 70 by Brain Hemorrhage due to CVA Social History: Tobacco use: Never Caffeine use: 3 cup of tea daily. Review of Symptoms: Patient has impaired cognitive function and loss his short and long term memory. Physical Exam: General: Under weight modern old women, with White hair cut lying on bed with Temp 97.5 `C, CVS: BP 150/95, HR 78/min. Resp. Sys: Mild wheezing sound with RR 22/min, CNS: reflexes and sensation are poor in body extremities. Mental Status: Impaired judgments, Unable to follow a command like hair combing etc. Carnial Nerves: Intact Gait: Walking in a shuffling manner. Laboratory Diagnostics Test: CBC: Hb 11.2g/dl, WBC 9500cu/mm3, ESR 38mm/h Thyroid hormone: T3 170ug/dl, T4 8.4ug/dl (Normal) Vitamin B12: 340pg/mL (Normal) Serum Electrolytes: Sodium 140mmol/L, Potassium 4.0mmol/L,

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Chloride 102mmol/L, Bicarbonate 25 mmol/L CT scan: Brain scan show cortical atrophy. Diagnosis: Primary: Dementia due to aging Secondary: Moderate Alzheimers disease

CASE
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NO.2
Pharmacist: JAWAD SALEEM DP-106-070 10th A

CASE NO 02

Alzheimers disease
Patient Name: Naema Address: 25-Iqbal town Lhr

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Age: 5 6 Gender: Asian Weight: Allergies: None

67 yrs Female 145lbs

Height: Race: Known

Chief complaint: Naema is a house wife lying on bed with confused face. She has problem in remembering things, operating household machine, paying bills, money counting etc. Also she feels difficulty in remembering the way of her house. History of Present Illness: She becomes depressive and did not behave normally. She also felt difficulty in speech and repeats her questions. Past medical History: Moderate Pneumonia 15yrs before.She has moderate asthma and use salbutamol inhaler occasionally. Moderate Hypertension but not used medicine regularly. Occasionally use Propyphenazone and herbel remedies. Family History: Her Mother had unsound mind but her father died at age 70 without any known disease. Social History: Tobacco use: Never Caffeine use: 4 cup of tea daily. Review of Symptoms: Patient has confused talk, mild impairment in daily life activities and loss of short term memory. Physical Exam: General: Febrile with Temp 99C CVS: BP 160/100, HR 82/min.

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Resp. Sys: Moderate wheezing sound with RR 28/min, CNS: reflexes and pricking sensation are normal in body extremities. Mental Status: Impaired judgment skills, does not know about her dress. Carnial Nerves: Intact. Laboratory Diagnostics Test: CBC: Hb 10.8g/dl, WBC 10,500cu/mm3, ESR 55mm/h Thyroid hormone: T3 162ug/dl, T4 8.0ug/dl (Normal) Vitamin B12: 380pg/mL (Normal) Serum Electrolytes: Sodium 136mmol/L, Potassium 4.6mmol/L, Chloride 98mmol/L, Bicarbonate 23 mmol/L Chest X-Ray: X-Ray reveals no deformity. CT scan: Shows atrophy of brain. Diagnosis: Primary: Brochitis with dementia Secondary: Mild Alzheimers disease

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CASE NO.3

Pharmacist: ADNAN SHAUKAT DP-106-051 10th A

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CASE NO 03

Alzheimers disease
Patient Name: Shafaqat ALi Address: 25-Iqbal town Lhr Age: 82 yrs 6 0 Gender: male Asian Weight: 140lbs Allergies: Nil

Height: Race: Known

Chief complaint: Shafqat is a retired bank officer. His family members complaint, that he does not recognize them and unable to sense day or night. He feels Hallucinations and considers dreams reality. General weakness and pains in lower limbs. History of Present Illness: He is inclined in bed from last 1 year, has memory problem might be related to aging. Past medical History: He is asthmatic from adolescent, use Xaltide inhaler. Use Slipping pills to get calmness. Illicit use Cough depressants syrups. Family History: Not Known.

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Social History: Tobacco use: 2 packs/day Caffeine use: 3 cup of tea daily. Review of Symptoms: Patient has loss his short and long term memory, Unable to perform his routine tasks. Physical Exam: General: Febrile with Temp 99C CVS: BP 130/90, HR 72/min. Resp. Sys: Moderate wheezing sound with RR 26/min, CNS: reflexes and pricking sensation are minor in body extremities. Mental Status: no judgment skills, need an attendant everytime.

Laboratory Diagnostics Test: CBC: Hb 9.8g/dl, WBC 9,350cu/mm3, ESR 48mm/h Thyroid hormone: T3 154ug/dl, T4 7.7ug/dl (Normal) Vitamin B12: 410pg/mL (Normal) Serum Electrolytes: Sodium 122mmol/L, Potassium 3.6mmol/L, Chloride 96mmol/L, Bicarbonate 24 mmol/L CT scan: Shows moderate atrophy of brain. Diagnosis: Primary: Vascular dementia and asthma Secondary: Alzheimers disease

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