ByM. MeenakshiSivapriyaXII B3School: Shrishti Vidyashram Year: 2014-2015

What are we going to learn?

Acknowledgement What is Alzheimer’s disease? Stages of Alzheimer’s disease Causes of Alzheimer’s disease How is Alzheimer’s disease diagnosed? Alzheimer’s vs. Parkinson’s disease Preventive measures Treatments and cures Some interesting facts Conclusion Bibliography

Acknowledgement

Firstly, I would like to thank my parents for encouraging and enabling me to collect facts for this project. Also, I thank the almighty for giving me interest

and joy in completing this work.

I also express my heart felt gratitude to my biology teachers Mrs. Anuradha and Mrs. Susan Philip for giving me this wonderful opportunity and guiding

me throughout.

I sincerely thank our assistant teacher Mrs. Vijayakumari for her valuable suggestions and constant encouragement.

What is Alzheimer ’s Disease?

Alzheimer’s disease (AD), also known in medical literature as Alzheimer disease, is the most common form of dementia. There is no cure for the

disease, which worsens as it progresses, and eventually leads to death. It was first described by German psychiatrist and neuropathologist Alois Alzheimer in 1906 and was named after him. Most often, AD is diagnosed in people over 65 years of age, although the less-prevalent early-onset Alzheimer’s can occur much earlier. In 2006, there were 26.6 million people worldwide with AD. Alzheimer’s is predicted to affect 1 in 85 people globally by 2050.Although Alzheimer’s disease develops differently for every individual, there are many common symptoms. Early symptoms are often mistakenly thought to be 'age-related' concerns, or manifestations of stress.In the early stages, the most common symptom is difficulty in remembering recent events, known as short term memory loss. When AD is suspected, the diagnosis is usually confirmed with tests that evaluate behavior and thinking abilities, often followed by a brain scan if available. However, examination of brain tissue is required for a definitive diagnosis. As the disease advances, symptoms can include confusion, irritability, aggression, mood swings, trouble with language, and long-term memory loss. As the person's condition declines they often withdraw from family and society. Gradually, bodily functions are lost, ultimately leading to death.

Since the disease is different for each individual, predicting how it will affect the person is difficult. AD develops for an unknown and variable amount of time before becoming fully apparent, and it can progress undiagnosed for years. On average, the life expectancy following diagnosis is approximately seven years. Fewer than 3% of individuals live more than 14 years after diagnosis.Current treatments only help with the symptoms of the disease. There are no available treatments that stop or reverse the progression of the disease. Mental stimulation, exercise, and a balanced diet have been suggested as ways to delay cognitive symptoms in healthy older individuals, but there is no conclusive evidence supporting an effect. Thus, AD is one of the most costly diseases to society.

Stages of Alzheimer’s Disease We must not confuse aging effects with Alzheimer’s disease. The following stages of AD will help us understand the differences.Effects due to aging:

Forgetting things occasionally. Misplacing items sometimes. Minor short-term memory loss. Forgetting that memory lapses happened.

Early stage Alzheimer’s:

Absent-mindedness. Forgetting appointments. Slight changes seen by close loved ones. Some confusion in situations outside the familiar.

Middle stage Alzheimer’s:

Deeper difficulty remembering recently learned information. Deepening confusion in many circumstances. Speech impairment. Repeatedly initiating the same conversation.

Late stage Alzheimer’s

More aggressive or passive. Some loss of self-awareness. Debilitating cognitive deficit. More abusive, anxious, or paranoid.

CAUSES OF ALZHEIMER’S

The cause for most Alzheimer’s cases is still mostly unknown except for 1% to 5% of cases where genetic differences have been identified. Several competing hypotheses exist trying to explain the cause of the disease.

GeneticsAround 0.1% of the cases are familial forms of autosomal dominant inheritance, which usually have an onset before age 65. This form of the disease is known as early onset familial Alzheimer’s disease. Most of autosomal dominant familial AD can be attributed to mutations in one of three genes: those encoding amyloid precursor protein (APP) and presenilins 1 and 2. Most mutations in the APP and presenilin genes increase the production of a small protein called Aβ42, which is the main component of Senile plaques. Some of the mutations merely alter the ratio between Aβ42 and the other major forms without increasing Aβ42 levels. 

CHOLINERGIC HYPOTHESIS

The oldest, on which most currently available drug therapies are based, is the cholinergic hypothesis, which proposes that AD is caused by reduced synthesis of the neurotransmitter acetylcholine. The cholinergic hypothesis has not maintained widespread support, largely because medications intended to treat acetylcholine deficiency have not been very effective. Other cholinergic effects have also been proposed, for example, initiation of large-scale aggregation of amyloid, leading to generalized neuroinflammation.

Also, there is tentative evidence that exposure to air pollution may be a contributing factor to the development of Alzheimer’s disease.

How is AD diagnosed?

Alzheimer’s disease is usually diagnosed based on the person's history, and observations of the person's behaviors. The presence of characteristic neurological and neuropsychological features and the absence of alternative conditions is supportive. Advanced medical imaging with computed tomography (CT) or magnetic resonance imaging (MRI), and with single-photon emission computed tomography (SPECT) or positron emission tomography(PET) can be used to

help exclude other cerebral pathology or subtypes of dementia. Moreover, it may predict conversion from prodromal stages (mild cognitive impairment) to Alzheimer’s disease.

Assessment of intellectual functioning including memory testing can further characterize the state of the disease. Medical organizations have created diagnostic criteria to ease and standardize the diagnostic process for practicing physicians. The diagnosis can be confirmed with very high accuracy post-mortem when brain material is available and can be examinedhistologically.

The criteria requires that the presence of cognitive impairment, and a suspected dementia syndrome, be confirmed by neuropsychological testing for a clinical diagnosis of possible or probable AD. A histopathologic confirmation including a microscopic examination of brain tissue is required for a definitive diagnosis. Eight cognitive domains are most commonly impaired in AD—memory, language, perceptual skills, attention, constructive abilities, orientation, problem solving and functional abilities.

EARLY DIAGNOSIS

Emphasis in Alzheimer’s research has been placed on diagnosing the condition before symptoms begin. A number of biochemical tests have been developed to allow for early detection. One such test involves the analysis of cerebrospinal fluid for beta-amyloid or tau proteins. Searching for these proteins using a spinal tap can predict the onset of Alzheimer’s with a sensitivity of between 94% and 100%. When used in conjunction with existing neuroimaging techniques, doctors can identify people with significant memory loss who are already developing the disease.

Alzheimer’s vs. Parkinson’s disease

Similarities:The two diseases are not related but they do share some similarities. Both Alzheimer’s and Parkinson’s disease have a late onset in life, usually after the age of 50. Both diseases are neurodegenerative, meaning that brain cells (neurons) become damaged and die during the course of the disease. They are also both progressive, so they get worse over time.

In the late stages of both diseases, the neurodegeneration can ultimately lead to dementia – a severe impairment in memory, judgment, orientation, and executive functioning. Approximately two out of every three dementia cases are caused by Alzheimer’s disease, making it by far the most common cause. Meanwhile, dementia due to Parkinson’s accounts for a much smaller portion of all dementia cases.Differences:

Parkinson’s disease is primarily a movement disorder that can eventually result in memory problems and dementia in about 50% of patients. Many individuals with Parkinson’s may never have memory problems during the course of their illness.

Parkinson’s disease results from the loss of dopamine-producing neurons in an area of the brain called the substantia nigra. Dopamine is needed in that part of the brain to control movement and coordination, and it is estimated that it takes a 60-80% loss of these dopaminergic neurons before symptoms become outwardly apparent. These symptoms include a resting tremor (shaking at rest), muscle rigidity, slowed movements, and impaired coordination. Over time, as the disease progresses, the benefits of the drugs often diminish or become less consistent.

Now with Alzheimer’s disease, the initially affected brain areas are the hippocampus and the entorhinal cortex, which are critical for learning and memory. Therefore it follows that the early symptoms of Alzheimer’s are cognitive in nature. In Alzheimer’s it is the neurotransmitter acetylcholine that is progressively diminished over the course of the disease. This worsening of memory and general intellect can progress and become severe without any effect on the patient’s coordination or movement ability.

Preventive Measures

At present, there is no definitive evidence to support that any particular measure is effective in preventing AD. Global studies of measures to prevent or delay the onset of AD have often produced inconsistent results. Epidemiological studies have proposed relationships between certain modifiable factors, such as diet, cardiovascular risk, pharmaceutical products, or intellectual activities among others, and a population's

likelihood of developing AD. Only further research, including clinical trials, will reveal whether these factors can help to prevent AD.

MEDICATION

Although cardiovascular risk factors, such as hypercholesterolaemia, hypertension, diabetes, and smoking, are associated with a higher risk of onset and course of AD, statins, which are cholesterol lowering drugs, have not been effective in preventing or improving the course of the disease.

Long-term usage of non-steroidal anti-inflammatory drugs (NSAIDs) is associated with a reduced likelihood of developing AD. Human postmortem studies, in animal models, or in vitro investigations also support the notion that NSAIDs can reduce inflammation related to amyloid plaques. However, trials investigating their use as palliative treatment have failed to show positive results, apparently because the brain NSAID concentration after an oral NSAID dose is exceedingly small. 

No prevention trial has been completed. Hormone replacement therapy, although previously used, may increase the risk of dementia.

LIFESTYLE

People who engage in intellectual activities such as reading, playing board games, completing crossword puzzles, playing musical instruments or regular social interaction show a reduced risk for Alzheimer’s disease. This is compatible with the cognitive reserve theory, which states that some life experiences result in more efficient neural functioning providing the individual a cognitive reserve that delays the onset of dementia manifestations. Education delays the onset of AD syndrome, but is not related to earlier death after diagnosis. Learning a second language even

later in life seems to delay getting Alzheimer disease. Physical activity is also associated with a reduced risk of AD.

DIET

People who eat a Mediterranean diet have a lower risk of AD, and it may improve outcomes in those with the disease. Those who eat a diet high in saturated fats and simple carbohydrates have a higher risk. The Mediterranean diet's beneficial cardiovascular effect has been proposed as the mechanism of action. There is limited evidence that light to moderate use of alcohol, particularly red wine, is associated with lower risk of AD. There is tentative evidence that caffeine may be protective. A number of foods high in flavonoids such as cocoa, red wine, and tea may decrease the risk of AD.

Treatments & CuresFive medications are currently used to treat the cognitive problems of AD:Acetylcholinesteraseinhibitors (tacrine, rivastigmine, galantamine and donepezil) and the other is an NMDA receptor antagonist. The benefit from their use is small. No medication has been clearly shown to delay or halt the progression of the disease.

Reduction in the activity of the cholinergic neurons is a well-known feature of Alzheimer’s disease. Acetylcholinesterase inhibitors are employed to reduce the rate at which acetylcholine (ACh) is broken down, thereby increasing the concentration of ACh in the brain and combating the loss of

ACh caused by the death of cholinergic neurons. There is evidence for the efficacy of these medications in mild to moderate Alzheimer’s disease and some evidence for their use in the advanced stage.

Only donepezil is approved for treatment of advanced AD dementia. The use of these drugs in mild cognitive impairment has not shown any effect in a delay of the onset of AD. 

The most common side effects are nausea and vomiting, both of which are linked to cholinergic excess. These side effects arise in approximately 10–20% of users and are mild to moderate in severity. Less common secondary effects include muscle cramps, decreased heart rate (bradycardia), decreased appetite and weight, and increased gastric acid production.

Glutamate is a useful excitatory neurotransmitter of the nervous system, although excessive amounts in the brain can lead to cell death through a process called excitotoxicity which consists of the overstimulation of glutamate receptors. Excitotoxicity occurs not only in Alzheimer’s disease, but also in other neurological diseases such as Parkinson's disease and multiple sclerosis. 

Memantine is a noncompetitive NMDA receptor antagonist first used as an anti-influenza agent. It acts on the glutamatergic system by blocking NMDA

receptors and inhibiting their overstimulation by glutamate. Memantine has been shown to be moderately efficacious in the treatment of moderate to severe Alzheimer’s disease. Its effects in the initial stages of AD are unknown. 

Reported adverse events with Memantine are infrequent and mild, including hallucinations, confusion, dizziness, headache and fatigue. The combination of Memantine and donepezil has been shown to be "of statistically significant but clinically marginal effectiveness".

Antipsychotic drugs are modestly useful in reducing aggression and psychosis in Alzheimer’s disease with behavioral problems, but are associated with serious adverse effects, such as stroke, movement difficulties or cognitive decline, that do not permit their routine use. When used in the long-term, they have been shown to associate with increased mortality.

Huperzine A, while promising requires further evidence before it use can be recommended.

Some interesting facts

Nearly half of adults aged 85 and over have Alzheimer’s disease. Out of approximately 5.4 million Americans with Alzheimer’s, more than

half may not know they have it. More women than men have Alzheimer’s disease. Early-onset Alzheimer’s can develop in people as young as age 30. In America, a new case of Alzheimer’s develops every 68 seconds; by

2050, the incidence will increase to every 33 seconds.

Alzheimer’s is the 6th-leading cause of death in the U.S., and the 5th-leading cause of death in adults aged 65 and over.

Over 15 million Americans are unpaid caregivers for someone with Alzheimer’s disease or another form of dementia.

In 2012, the average annual cost of health care and ltc services for someone with Alzheimer’s was $43,847.

An estimated 800,000 Americans with Alzheimer’s are living alone.

Conclusion

So to conclude Alzheimer’s is a disease that remains a mystery with the cause and the cure yet to be found. Though Alzheimer’s can’t be cured or reversed at present much can be done to help the patient and their family live through the course of the illness with less discomfort and more dignity.

From our part, just as we exercise and keep our body healthy and fit, we must take up brain games like crosswords or chess to keep our brains fresh. There are proven results that confirm this. Cures are being investigated and

hopefully one day this disease will be cured and if not better understood.

Bibliography

Cohen. E (1999) ALZHEIMER’S DISEASE McGraw-Hill Professional publishing

Strock. M (1996) ALZHEIMER’S DISEASE, DIAGNOSIS, CURE AND TREATMENT DIANE Publishing

ALZHEIMER’S DISEASE 2007 [online] (http://www.Alzheimer’s.org.uk/

ALZHEIMER’S DISEASE INTERNATIONAL 2007 [online] http://www.alz.co.uk/Alzheimer’s/

http://www.cartoonstock.com/lowres/jdo0864l.jpg

http://www.colorado.edu/kines/Class/IPHY3730/image/figure4-9.jpg

http://en.wikipedia.org/wiki/Alzheimer’s_disease