Alzheimer's Disease

Description

Diagnosis

A definitive test to diagnose Alzheimers disease, even in patients showing signs of dementia, has not yet been devised. A number of expert groups have developed criteria to help diagnose Alzheimer's disease and rule out other disorders. Often a diagnosis involves answering the following questions about the patient:

• Do psychologic tests indicate dementia?
• Does the patient have deficits in two or more areas of mental functioning (such as language, motor skills, and perceptions)?
• Has memory and mental functions gotten progressively worse?
• Is consciousness disturbed? (It is not in Alzheimer's disease.)
• Is the patient over 40?
• Are other medical or physical conditions present that could account for the same symptoms?
• Are daily activity impaired or has the behavior changed?
• Is there a family history of Alzheimer's disease?
• Are there other symptoms, such as depression, insomnia, incontinence, delusions, hallucinations, dramatic verbal, emotional or physical outbursts, sexual disorders, and weight loss?

Other steps involved in making a decision include laboratory tests (EEG and possibly tests to rule out other diseases) and psychological testing to determine the presence of dementia.

Ruling out Conditions of Normal Aging that Can Cause Alzheimer's-like Symptoms

Although some memory impairment occurs in many people as they age, only some of these people develop Alzheimer's disease. Many similar symptoms can occur in healthy older individuals from other conditions associated with aging, such as the following:

• Fatigue.
• Grief or depression.
• Illness.
• Vision or hearing loss.
• The use of alcohol or certain medications.
• Simply the burden of too many details to remember at once.

Ruling Out Other Causes Memory Loss or Dementia

The first step in diagnosing Alzheimer's disease is to rule out other conditions that might be causing memory loss or dementia. There are a number of causes for dementia in the elderly:

• Alzheimer's disease.
• Vascular dementia (abnormalities in the vessels that carry blood to the brain).
• Lewy bodies variant (LBV), also called dementia with Lewy bodies.
• Parkinson's disease.
• Frontotemporal dementia

Experts currently believe that 60% of cases of dementia are due to Alzheimer's, 15% to vascular injuries, and the rest are a mixture of the two or caused by other factors. Specialists can usually clearly identify patients who have Alzheimer's by using criteria developed by expert groups. (It is much more difficult to diagnose a patient whose dementia is caused by a mixture of Alzheimer's disease and stroke-related injury.) Other diseases, many common in the elderly, can also cause symptoms that resemble Alzheimer's disease.

Vascular Dementia. Vascular dementia is primarily caused by either multi-infarct dementia (multiple small strokes) or Binswanger's disease (which affects tiny arteries in the midbrain). One major analysis suggests that patients with vascular dementia have better long term verbal memory than Alzheimer's patients, but poorer executive function (less ability to integrate and organize).

Lewy Bodies Variant. Lewy bodies are abnormalities found in the brains of patients with both Parkinson's disease and Alzheimer's. They can also be present in the absence of either disease; in such cases, the condition is called Lewy bodies variant (LBV). In all cases, the presence of Lewy bodies is highly associated with dementia. LBV was defined in 1997 and some experts believe it may be responsible for about 20% of people who have been diagnosed with Alzheimer's. They can be difficult to distinguish. Compared to Alzheimer's disease patients, those with LBV may be more likely to have hallucinations and delusions early on, to walk with a stoop (similar to Parkinson's disease), to have more fluctuating attention problems, and to perform better than Alzheimer's disease patients on verbal recall but less well with organizing objects.

Parkinson's Disease. Dementia is about six times more common in the elderly Parkinson patient than in the average older adult. It is most likely to occur in older patients who have had major depression. Unlike in Alzheimer's, language is not usually affected in Parkinson's related dementia. Visual hallucinations occur in about a third of people on long-term medications.

Parkinsons disease is a slowly progressive disorder that affects movement, muscle control, and balance. Part of the disease process develops as cells are destroyed in certain parts of the brain stem, particularly the crescent-shaped cell mass known as the substantia nigra. Nerve cells in the substantia nigra send out fibers to tissue located in both sides of the brain. There the cells release essential neurotransmitters that help control movement and coordination.

Frontotemporal Dementia (FTD). Once considered rare, FTD is now considered to be the second most common cause of early-onset dementia. People who develop this condition tend to be in their mid-fifties although it can develop later on. It results in greater behavioral impairment (e.g., apathy, reduced empathy, poor self-care, unrestrained behavior) than with Alzheimer's disease. It may also be marked by speech problems and early incontinence. Brain imaging scans can help diagnose this problem.

Other Conditions that Cause Similar Symptoms. Some elderly people have a condition called mild cognitive impairment, which involves more severe memory loss than normal but no other symptoms of Alzheimer's. A number of conditions, including many medications, can produce symptoms similar to Alzheimer's:

• Severe depression.
• Drug abuse.
• Thyroid disease.
• Severe vitamin B12 deficiency.
• Blood clots.
• Hydrocephalus (excessive accumulation of spinal fluid in the brain).
• Syphilis.
• Huntingtons disease.
• Creutzfeldt-Jakob disease.
• Brain tumors.

It is important that the physician recognize any treatable conditions that might be causing symptoms or worsening existing dementia caused by Alzheimer's or vascular abnormalities.

Psychological Testing

A number of psychologic tests are used or being developed to assess difficulties in attention, perception, and memory and problem-solving, social, and language skills. Experts are researching specific tests for mental impairment that may help identify early on people with mild memory impairment who are at high risk for Alzheimer's disease.

• Two commonly used tests that are very useful in identifying individuals who may be at risk for Alzheimer's are the Mini-Mental State Exam (MMSE) and the Mattis Dementia Rating Scale. Still, these tests have limitations.
• A clock drawing test is also a good test for Alzheimer's disease. The patient is given a piece of paper with a circle on it and is first asked to write the numbers in the face of a clock and then to show "10 minutes after 11. The score is based on spacing between the numbers and the positions of the hands. In the study, scoring eight or less identified 71% of Alzheimer's patients and correctly ruled out 82% of subjects without the disease.

Electroencephalography

Electroencephalography (EEG) traces brain-wave activity; in some Alzheimers patients this test reveals "slow waves. Although other diseases may evidence similar abnormalities, EEG data helps distinguish a potential Alzheimers patient from a severely depressed person, whose brain waves are normal.

Imaging Tests

Imaging tests include computed tomography (CT) and magnetic resonance imaging (MRI and the more advanced techniques single photon emission computed tomography (SPECT), and positron-emission tomographic (PET). They are sometimes used to rule out other disorders such as multi-infarct dementia, stroke, blood clots, tumors, or hydrocephalus.

Click the icon to see an image of a CT scan.

Click the icon to see an image of a MRI of the brain.

Eventually imaging techniques, particularly PET or SPECT, may be able to specifically detect Alzheimer's disease in early stages. For example, imaging studies of Alzheimer's disease brains nearly always detect between 20% and 52% reductions in the hippocampus, the part of the brain associated with memory. Recent PET scan research has focused on developing tracer molecules that target early-stage amyloid plaques and brain lesions. At this time, however, using imaging tests for diagnosing Alzheimer's disease are limited to trials. The National Institute on Aging is funding the Alzheimer's Disease Neuroimaging Initiative to help identify biomarkers for early Alzheimer's diagnosis and accelerate the drug development process.

Investigative Tests.

Blood Tests. High blood levels of a substance called p97 may prove to help detect the presence of Alzheimer's, but more research is needed. Other blood tests may rule out metabolic abnormalities.

Cerebrospinal Fluid Test. A screening test the detects high levels of beta-amyloid proteins in the cerebrospinal fluid is expected to be approved in 2002 in Europe. The manufacturers are hoping to eventually develop a blood test that can give similar results.

Odor Test. Investigators are also using the impairment of smell in Alzheimer's disease to develop tests that require patients to distinguish between odors.

Determining Severity after a Diagnosis Has Been Made

Once a diagnosis has been made, some experts observe that certain factors at the time of diagnosis indicate a higher risk for a more rapid decline:

• Older age.
• Being male.
• The presence of high blood pressure.
• Signs of loss of motor control and coordination.
• Tremor.
• Social withdrawal.
• Loss of appetite and severe weight loss.
• Accompanying sensory problems, such as hearing loss and a decline in reading ability.
• General physical debility.