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Diagnostic Center for Alzheimer’s Disease

Table of Contents (click on topics below to navigate this page) Mission of the Center Alzheimer's Disease Causes of Alzheimer's Disease Symptoms of Alzheimer's Disease How Alzheimer's Disease is Diagnosed Treatments for Alzheimer's Disease Statistics Regarding Alzheimer's Disease Diagnostic Center for Alzheimer's Disease Autopsy Future Needs - How You Can Help Alzheimer's Information and Research Sites

Mission of the Center

The Diagnostic Center for Alzheimer's Disease and Neuropathology Laboratory at the University of Oklahoma Health Sciences Center in Oklahoma City is dedicated to the study of Alzheimer's disease.  Today, Alzheimer's disease can only be positively diagnosed by brain autopsy following the death of the affected individual.  The Diagnostic Center performs brain autopsies for any Oklahoman resident suspected of dying of Alzheimer's disease at no cost to the family. The brains are studied using the latest techniques to establish the diagnosis and to understand the disease process. As an additional service, families are given the opportunity to visit the Diagnostic Center upon completion of the brain evaluation and to discuss (in a counseling session) the results and underlying implications for family members. Approximately 10% of the brains from supposed Alzheimer's patients show some other brain disease.  Our goal at the Center is ultimately to develop ways to make early diagnosis of this debilitating disease and to develop treatments that prevent further progression of the disease. 

Alzheimer's disease was first recognized in a 51-year old woman in the early 1900's by Alois Alzheimer, a physician practicing in Frankfurt-am-Main, Germany.  It was Alzheimer's mentor, Emil Kraepelin, who first used  the term "Alzheimer's disease" to describe this condition in his textbook on mental illness.  Alzheimer's disease is a devastating brain disorder in which nerve cells  in memory areas of the brain and eventually other areas begin to die at an accelerated rate. Its primary symptom involves progressive memory loss, but difficulties with vision, speech, and emotions are also common. Deterioration in cognitive skills may continue for five to ten years. While progress of the disease is generally very gradual and symptoms are slow to appear, the course of Alzheimer's disease can vary tremendously from one individual to another.  Most cases of Alzheimer's Disease occur in individuals aged 65 and over, but a small percentage of cases (1 to 10%) develop symptoms in  their fifties, forties, or even  their thirties.  Eventually, the victim requires almost constant attention, unable to care for themselves in the most minor of tasks, such as eating, dressing, or toiletry. The disease slowly robs its victims of dignity, livelihood, and savings.  Because the impact of the disease is so great, it profoundly affects not only the patient but also the family members; family members feel powerless as they reluctantly relinquish their loved ones to a form of mental bondage for which there is no cure. In addition to watching helplessly as a parent, grandparent, or other relative slowly fades away, family members suffer another form of slow torture, as they wonder if they too will one day be the victims of this merciless disease.

Alzheimer's disease is a hereditary disorder in which nerve cells in the brain, called neurons, die, making it difficult for the brain to work properly. Neuron death begins insidiously, many years before the onset of memory loss or other symptoms of the disease.  During this pre-symptomatic period, there are no obvious symptoms because remaining nerve cells compensate for the net loss.  In fact, the brain can lose nearly four-out-of-five nerve cells and still function almost normally. Only when those last remaining nerve cells begin to die do symptoms really become pronounced - and at that point, the process is irreversible. Alzheimer's Disease specifically affects the cerebral cortex (gray matter) of the temporal lobe (controlling memory, hearing, language), parietal lobe (language and senses of touch, pain, space, and temperature), and frontal lobe (reasoning, judgment, personality, movement, speech) of the brain, but also deeper structures of the brain, such as the hippocampus (short-term memory) and amygdala (emotional drives).  For further information on the mechanisms of dementia follow the hyperlink Mechanisms of Dementia.

 

While death of brain cells is a normal process of aging and can cause mild forgetfulness and slowed reflexes as we age, what causes the accelerated death of brain cells in Alzheimer's Disease patients is currently unknown.  What is clear is that the disease does not  have a single underlying cause, but rather is due to a number of factors – both environmental and genetic. However, we are gradually beginning to understand exactly what are the factors involved.  Multiple studies have shown that the risk for acquiring the disease is age-dependent.  The risk is also increased in the presence of family history, indicating that genetic factors play a strong role. However, the nature of this genetic contribution has been difficult to dissect, due to a variety of technical reasons, including the absence of definitive antemortem diagnostic tools.  Inheritance patterns also appear to differ between the early-onset and late-onset varieties of the disease; the former resembles an autosomal dominant inheritance with age-dependent penetrance while the latter has a pattern resembling a high-frequency, low-penetrance, single gene disorder or a multifactorial model with multiple genes and/or non-genetic factors. The genetic component in the etiology of the disease also appears to be variable for different families - strong in some and weak in others.  

Researchers have identified at least four different genes that appear to confer inherited risk for Alzheimer's disease.  A variation on chromosome 19, called Apolipoprotein E4, is associated with a dose-dependent increase in risk and decrease in age-of-onset of both sporadic and late-onset Alzheimer's disease. Conversely, the E2 form of the gene appears to confer a protective effect.  However, because many people with the E4 variation never develop Alzheimer's, and as many as 40 % of patients with late-onset Alzheimer's do not have the E4 form of the gene, and individuals with E2 form are not immune to developing Alzheimer's, genetic testing for this marker is usually not  recommended.  Mutations within the Presenilin 1 gene (unknown function) on chromosome 14 are associated with approximately 50-70% of cases of a particularly aggressive form of early onset Alzheimer's (30-60 years of age). Mutations in a homologous gene on chromosome 1, Presenilin 2, have also been associated with later onset Alzheimer's in several families of European ancestry.  Mutations within the β-amyloid precursor protein (β-APP) gene on chromosome 21, the protein of which gives rise to β-amyloid (Aβ) peptide (a main constituent of the neuritic plaques seen in post-mortem brains of Alzheimer's patients), were the first gene mutations to be described in association with early-onset (45-60 years) Alzheimer's disease.  These mutations are presumed to give rise to longer isoforms of the Aβ peptide (derived by cleavage of  β-APP) which may be neurotoxic and lead to neuronal death.  This may explain the fact that Down's syndrome patients, who have an extra copy of chromosome 21 (trisomy 21) and thus an extra copy of the β-APP gene, almost invariably develop the neuropathologic attributes of Alzheimer's by the age of 30-40 years. It seems highly likely that other Alzheimer's disease susceptibility genes will be revealed in the near future.

Alzheimer's patients who have at least one other family member with the disease are categorized as "familial", but this does not mean that the disease has a purely genetic cause in that family; family members may have been exposed to something in their common environment.  Some studies have shown that the risk for Alzheimer's disease may be increased by exposure to heavy metals such as aluminum, by depression, hyperthyroidism, lower levels of education, and even head trauma.  If an Alzheimer's patient has no other family members with the disease, then they are said to have "sporadic" Alzheimer's Disease, but again this does not rule-out inheritable factors, given our present knowledge of the disease.

 The symptoms of Alzheimer's disease become more numerous and apparent with progression of the disease.  They can be arranged into the categories of early, middle or late stages of the disease with the following examples of symptoms:  

 How Alzheimer's Disease is Diagnosed

There is no simple test to diagnose the disease; definitive diagnosis relies on examination of the brain, usually at autopsy.  At autopsy, Alzheimer's patients will show extensive extracellular deposits of a substance called amyloid and vacuolar fluid-filled spaces and tangles of fibrillary material within the neurons.   

Examples of some of the histopathologic features include:

• Neurofibrillary tangles
• Neuritic (senile) plaques
• Hirano bodies
• Granulovacuolar bodies of Simchowicz
• Pick bodies
• Lewy bodies

It is important to see a physician when symptoms of the disease are recognized or suspected.  Alzheimer's disease shares the symptoms found in other forms of dementia and only a physician can make the proper diagnosis with a comprehensive medical and neurological evaluation, which may include:  

• History from patient, relative, or friend
• Mental status examination (including Blessed-Folstein Mini Mental State Exam)
• Physical examination with vital signs
• Neurological examination
• CAT, MRI, and/or SPECT scan (brain scan)
• Thyroid function tests
• Serum vitamin B12 and folic acid levels
• Chest x-ray, electrocardiogram (EKG)
• Complete blood count, urinalysis, VDRL and FTA-ABS, blood glucose, BUN, calcium, phosphate, albumin, HIV titer, Lyme titer, electrolytes, alkaline phoshatase, ESR, SGOT, SGPT
• Drug levels
• Toxic Screen (including heavy metals)
• Electroencephalogram
• Lumbar puncture

Only after other potential causes have been identified, treated, or eliminated can a diagnosis of Alzheimer's Disease be made. Many forms of dementia, which can show Alzheimer's-like symptoms, are treatable.  Some of these are listed below:

• Deficiencies of vitamin B12, folate, niacin (pellagra), thiamine (Wernicke-Korsakoff syndrome), or other vitamins
• Zinc and/or copper deficiency
• Endocrine disorders (hypo- or hyperthyroidism, hypo- or hyper-parathyroidism)
• Neurosyphilis, tertiary Borellia infection, HIV infection (AIDS)
• Electrolyte imbalance
• Normal pressure hydrocephalus
• Cerebrovascular disease ("multi-infarct dementia")
• Hypoglycemia
• Renal or hepatic failure
• Lupus cerebritis (systemic lupus erythematosus)
• Pulmonary disease with chronic hypoxia and/or hypercarbia
• Drug or medication-induced mental disturbances
• Neoplasms (primary or secondary tumors or as a remote effect)
• Affective disorder (depressive pseudodementia)
• Epilepsy
• Subdural hematoma
• Toxin exposure (lead, arsenic, mercury, manganese, organic toxins)

At the present time, there are no accurate tests available that can be used to predict who will get this tragic disease.  Because a combination of factors are believed to be responsible for most cases of Alzheimer's Disease, genetic testing is not usually a routine part of a diagnosis workup. 

What are the Treatments for Alzheimer's Disease? 

At present, there are no effective treatments to prevent or stop the insidious nerve cell death process once the disease begins. However, there are some treatments that can be used to help manage and ease the symptoms in some patients.  For instance, several FDA-approved drugs are designed to inhibit the breakdown of a chemical neurotransmitter, called acetylcholine, in the brain, which appears to be in short supply in Alzheimer's patients.  Medications can also be prescribed to help alleviate the symptoms of depression, anxiety, and delusions.

Several drug companies are in the process of developing drugs to block amyloid production, but progress has been slow.  However, the recent discovery of the gene that encodes for the enzyme beta-secretase, one of two enzymes (the other is gamma-secretase) that snips the amyloid fragments from the harmless β-amyloid precursor protein (β-APP), offers some hope for the discovery of new drugs that can slow or stop the build-up of amyloid and thus stemming the relentless progression of Alzheimer's Disease.  

Statistics of Alzheimer's Disease

Of all the patients diagnosed as suffering from dementia, (defined as deterioration of intellectual, cognitive, and reasoning abilities), approximately 50% have a treatable condition.  The remaining approximately 50% have a neurodegenerative disease (a disease that progressively and irreversibly destroys the brain) which may include one of the following:

• Alzheimer's disease
• Pick's disease
• Huntington's disease
• Parkinson's disease
• Multi-system atrophy
• Binswanger's disease/multi-infarct
• Cerebral amyloid angiopathy
• Granulomatous angiitis
• Creutzfeldt-Jakob disease
• Progressive multi-focal leukoencephalopathy
• Polyglucosan body disease
• Diffuse Lewy body disease

The latter can only be diagnosed definitely by autopsy examination of the brain. Up to 90% of these individuals with neurodegenerative disease will have Alzheimer's disease.

Statistics indicate that most Americans have either a relative or an acquaintance with Alzheimer's disease. The prevalence (i.e., the total) of Alzheimer's disease in the US is as follows:

• general population = 1-2%
• individuals over 65 years old = 5-10%
• individuals over 80 years old= 20-30%

In Oklahoma, with a population of 3.2 million, 15% are over 65 years old which amounts to about 500,000 elderly individuals. Considering a prevalence on the low end of only 5% for Alzheimer's disease in individuals over age 65 years, that means that at any given time at least 25,000 people state-wide are afflicted with this disorder!

Average survival of patients with Alzheimer's disease after a diagnosis of dementia ranges from 4 to 8 years. The disease claims more than 100,000 lives per year – the fourth leading cause of deaths for adults. Younger patients die more quickly, because the disease tends to be more severe. Average stay in nursing home after diagnosis until death ranges from 3 years in younger patients to 6 years in older patients. Estimated cost of custodial care (nursing homes) for Alzheimer's disease victims in Oklahoma is $1,000,000,000 [one billion dollars]. This disease is also a major financial drain on families, costing upwards of $20,000 per year per victim in medical and nursing expenses alone.

Diagnostic Center for Alzheimer's Disease

The Diagnostic Center for Alzheimer's Disease and Neuropathology Laboratory was established at the University of Oklahoma Department of Pathology through contract with the Oklahoma State Department of Health to provide a free-of-charge neuropathologic confirmation of the clinical diagnosis of dementia in autopsy material. Brain specimens that are removed at autopsy by pathologists throughout the state of Oklahoma can be submitted to the Diagnostic Center, where exhaustive neuropathologic assessment is undertaken. A formal written report of the neuropathologic analysis is provided to the family and attending physician. The Diagnostic Center also serves as a tissue bank, providing research material to scientists working in the area of Alzheimer's disease.

Autopsy Assistance Network

Arrangements for autopsies to obtain brain specimens for evaluation by the Diagnostic Center for Alzheimer's Disease are coordinated through the Autopsy Assistance Network, sponsored by the Alzheimer's Association. The Autopsy Assistance Network was established in response to the increasing awareness by the lay-public that diagnosis of Alzheimer's disease and related disorders, can only be confirmed by close examination of the brain after death. Planning ahead helps families with relatives potentially suffering from Alzheimer's disease in making the difficult decision for autopsy; they need support and guidance in making this decision and in taking the necessary steps for arranging this procedure. The primary purpose of the Autopsy Assistance Network is to provide families with information and support regarding autopsy and assistance in arranging for this outcome. It is prudent to make such arrangements, well in advance of the death of the Alzheimer's patient. 

His est locus ubimors gaudet succurrere vitae - "this is the place where death rejoices to come to the aid of life"

 

Future Needs - How You Can Help

Despite limited resources, the physician scientists at the Diagnostic Center for Alzheimer's Disease have employed ingenuity and perseverance to study Alzheimer's disease. Unfortunately, without sufficient future funds it will not be possible to continue the many efforts of the Diagnostic Center. As the focus of an urgent campaign to stem the tide of this tragic disease, the Diagnostic Center for Alzheimer's Disease seeks gifts in the form of equipment and financial support. Contributions of all types will help to advance studies directed at a disease that affects at least 25,000 Oklahomans. More and more families are finding themselves dealing with a loved one afflicted with this terrible condition. In order to speed critical studies, the Diagnostic Center for Alzheimer's Disease is in urgent need of additional funding.

The future of tomorrow's potential Alzheimer's patients and their families can be much brighter than the present reality of today's Alzheimer's victim, if the secrets underlying brain nerve cell death can be unlocked and therapies instituted.

The scientists at the University of Oklahoma Health Sciences Center invite you to join this initiative by promising a gift to support their efforts. Giving to this cause is an investment in the future of your family and your loved ones. Your donation will help meet the challenge of finding a cure for this devastating illness that affects not only its victims and their families, but society as a whole. With your contribution, the potential exists to stem the tide of this insidious disease so that tomorrow's generations can continue to lead useful and meaningful lives.

If you would like to make a tax-deductible contribution to our efforts at the Diagnostic Center for Alzheimer's Disease, please write donation checks payable to: University of Oklahoma Foundation, Inc.  Indicate on the check (memo) or in an attached letter that the gift is for the Diagnostic Center for Alzheimer's Disease.  We would also appreciate that you include your name and address in the attached letter, so that we have the opportunity to thank you for your donation.

Alzheimer's Disease Information and Research Sites

Center for Memory Loss and Dementia (OUHSC)
Center for Alzheimer's and Neurodegenerative Disorders (CANDO) of the V.A.
Alzheimer's Association (Central Oklahoma Office)
Mayo Clinic Alzheimer's Page
University-Presbyterian Neurological Institute
Agenet - National and International Alzheimer's organizations
Oklahoma Center of  Neuroscience (OCNS)

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