• Article on Alzheimers

• Scientists raise possibility of vaccine for Alzheimer's disease  Deborah Josefson, San Francisco

• Brain drugs of the future Susan Greenfield, professor. 

• Other Information

by National Foundation for Brain Research
Alzheimer's disease is a neurodegenerative disorder characterized by a progressive decline in memory, judgement and the ability to reason and sustain intellectual function. The cause of Alzheimer's disease is unknown, and no cure is available.

Early symptoms may include memory loss, difficulty with abstract thinking and disorientation in time and place. (2) As the disease progresses, changes in behaviour and personality occur. Complications associated with Alzheimer's disease usually result in death within two to 10 years of onset.

Alzheimer's disease was first described in 1907 by the German physician Alois Alzheimer, who found, at autopsy, abnormalities in the brain of a 51-year-old patient hew was treating for dementia. The abnormalities, now known as plaques and tangles, are characteristic histopathological findingsof Alzheimer's disease.

These features are associated with the neuronal degeneration. A definitive diagnosis of Alzheimer's disease cannot be made without identifying the presence of these lesions by brain biopsy or at autopsy. A diagnosis of "probable Alzheimer's disease" is usually arrived at by excluding the possibility that the patient is suffering from other conditions that have features similar to Alzheimer's disease.

Symptoms
The onset of Alzheimer's disease is gradual and seems to progress in three stages, according to the National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS/ADRDA).

The earliest stage can last from two to four years (leading up to and including diagnosis) and is usually characterized by levels of impairment such as confusion about names and places, decreased ability to readily recall information, difficulty handling money and paying bills, poor decisions, loss of initiative, and anxiety about symptoms, which may lead to avoiding people.

The second stage of the illness (moderate), is the longest and can last from two to 10 years after diagnosis. This stage is characterized by moderate symptoms, such as: increasing memory loss and confusion, restlessness, difficulty recognizing close friends and family, perceptual and motor problems, loss of language facility, problems thinking logically, and disintegrating social skills.

The disease's terminal stage (severe) can last from one to three years or more. Symptoms typical of this stage include: inability to recognize self or family, weight loss, little capacity for care for oneself, incontinence,aphasia, mood changes (anxiety, agitation, depression), difficulty swallowing, and seizures.

Although there appear to be three stages, an individual patient may vary from this profile and not exhibit all symptoms.

Diagnosis
There is no simple diagnostic test for Alzheimer's disease. Rather, a diagnosis of probable Alzheimer's disease is typically made by excluding other likely causes of dementia. When symptoms are noticed, a complete physical, psychiatric and neurologic evaluation should be performed by a physician experienced in the area of dementia.

Such an examination will include a detailed medical history, physical (including laboratory examination) and neurological examination, neuropsychological testing and mental status test(s). Computerized Tomography (CT scan) or magnetic resonance imaging (MRI), and electroencephalography (EEG) may also be indicated.

After a thorough examination is completed, a diagnosis of probable Alzheimer's disease can be made accurately in up to 90 percent of patients.

Only a histopathologic examination of brain tissue, which is often done at autopsy to check for the presence of tangles and plaques, will confirm a diagnosis of Alzheimer's disease. Neurofibrillary tangles are bundles of twisted fibers that accumulate in the cell bodies of neurons. Neuritic plaques are round or oval lesions consisting of an amyloid protein core surrounded by fragments of damaged neurons. These types of lesions occur in the cerebral cortex and hippocampus, the regions of the brain which govern such higher intellectual functions as memory, thinking, reasoning and sensory perception.

Related Disorders
Other conditions have Alzheimer's-disease-like symptoms and need to be ruled out by a physician during the process of diagnosis. These include:

Multi-Infarct Dementia (MID) - a dementing disorder caused by multiple strokes (infarcts) Parkinson's disease - a neurodegenerative disorder characterized by tremors, stiffness in the limbs and joints, speech impediment and, sometimes, dementia late in the course of the disease Huntington's disease - an inherited, neurodegenerative disease whose symptoms include intellectual decline and irregular and involuntary movements of the facial muscles and limbs Creutzfeldt-Jacob disease - a rare and fatal neurodegenerative disorder caused by an infectious transmissible organism that leads to rapid and pronounced mental deterioration Pick's disease - a rare neurodegenerative disorder producing dementia involving the frontal and temporal cortex in which personality and behaviour are more notably affected earlier and more prominently than Alzheimer's disease.

Cause
The cause or causes of Alzheimer's disease are unknown. However, scientific research has begun to point in several directions. Neurotransmitter deficits have been implicated, with a deficiency of the neurotransmitter acetylcholine being a prominent and consistently identified deficit. Acetylcholine is one of several chemicals that carry nerve impulses from one neuron to another in the brain's communication system. It is not yet known, however, whether destruction of the cells that make acetylcholine is a cause or a consequence of Alzheimer's disease.
In addition, there is evidence to suggest that a defect in a single gene on Chromosome 21 has been linked to a form of the disease called Familial or Early Onset Alzheimer's disease. For most patients, however, genetic involvement is less clear. Scientists are also exploring the importance of theories such as a slow virus, environmental toxins, amyloid and other physical conditions that can trigger the disease.

Treatment
Researchers worldwide are working to develop psychosocial and medical interventions to help sustain or raise the functional capabilities of persons with Alzheimer's disease. Studies show that stimulating, non- challenging activities, planned according to an affected individual's remaining capabilities can be successful in raising the quality of life for Alzheimer's patients.

Approval in the United States and France of the drug tacrine for mild to moderate Alzheimer's disease is a significant milestone. It is the first drug to have an effect on cases of mild to moderate Alzheimer's disease, and has provided some Alzheimer's patients with improved cognitive performance and the ability to perform many activities of daily living. Studies on the efficacy of tacrine were reported in the Journal of the American Medical Association (JAMA), April 6, 1994; Vol. 271, No. 13.

Recently, 3  drugs have been approved by the U.S. Food and Drug Administration for treating Alzheimer's disease. All have been shown to help only in the early stages of the disease. They work on some symptoms, slowing memory loss and decreasing agitation; they do nothing to attack the cause or to slow the progression of the disease.

At the recent World Alzheimer Congress, researchers released results of a study of a drug, Memantine, that helped with moderate to severe cases of the disease. The drug is the leading prescription for dementia in Germany, where it has been available for more than a decade.

Memantine does not slow the disease, but it helps patients with tasks of daily living: eating, dressing, bathing. It also improves a patient's sense of well-being for a few months. The drug's benefits are limited, and it is known to help for only a short time.

Research and Development
Drugs currently being studied include those relating to nerve growth factor, which prevent the loss of neuronal activity; calcium channel blockers, which have been reported to improve memory in older animals ; drugs that increase the level of acetylcholine; and those that augment the release of dopamine, serotonin and other neurotransmitters that seem to be associated with Alzheimer's disease.

Advances are also being made in genetic studies of Alzheimer's disease. Researchers are investigating protein thought to create neurofibrillary tangle associated with the disease and the gene related to the production of that protein. Dr. Alan Roses at Duke University found that 80 percent of Alzheimer's patients may have developed the disease due to a gene related to the production of apolipoprotein E4.

Contacts:
Rachel Billington, Alzheimer's Disease International, 312-335-5777.

1. Alzheimer's Disease Fact Sheet. Alzheimer's Association, 1990, p. 1.
2. Ibid.
3. Ibid., p. 2.
4. Alzheimer's Disease Learning Program. Parke-Davis, pp. 2.2 - 11 - 15.
5. Stages of Symptom Progression in Alzheimer's Disease. Alzheimer's Association, pp. 1-2.
6. Alzheimer's Disease: An Overview. Alzheimer's Association, p. 2.
7. Alzheimer's Disease Learning Program. Parke-Davis, pp. 2.2 - 10.
8. Alzheimer's Disease and Related Disorders Fact Sheet. 1990, pp. 1-2.
9. Alzheimer's Disease: An Overview. Alzheimer's Association, p. 4.
10. In Development: Alzheimer's Medicine. Pharmaceutical Manufacturing Association, November 1989, p. 1.
11. Starr, Cynthia, R. Ph.D., "Alzheimer's Drug Research: Where is it headed?" Drug Topics, December 14, 1992, p. 38.

Other Information

• In Italy

Associazione Malattia Di Alzheimer Milano

• Alzheimer's Disease Review 

• Brain Disorders Network / Index  

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