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Diagnosis of Alzheimer's Disease

Impact of Alzheimer's Disease (AD or DAT, Dementia of Alzheimer Type)

Year after year people grow old but their memory banks grow richer. So much happens every day and so much to reminisce each day. We make deposits to our memory bank through our deeds and interactions with others. In the journey of life, it is not the bank account that matters. It is the memory bank that represents one's life and its significance in terms of deposits. In the end, everyone gets a fair dividend paid by his or her memory bank. Unfortunately, there is a bank robber at large. AD is the meanest bank robber in the history of time as we shall see below.

Alzheimer Disease, frequently occurring with older people shows symptoms of memory and other cognitive function impairment (age-associated memory impairment) and progressively develops to become helpless. In fact, people can develop mild cognitive impairment (MCI) at younger age (50 or younger). Medically, it is best to treat the AD symptoms early rather than regarding them as a result of normal aging process. However, early diagnosis is difficult and treatment at later stage of the disease is ineffective. AD patients and their families endure much more pain and cost than other terminal diseases due to its lack of cure and prolonged illness (average of 8-10 years, as long as 20 years). According to the Karolinska Institute of Sweden, the world-wide cost of Alzheimer Disease is estimated at $248 B (2006 figure), an astonishing figure greater than the gross domestic product (GDP) of 198 countries in the world. Indeed, AD is the meanest bank robber in the history of time. 

Diagnosis of AD from Its Symptoms

AD usually begins slowly. At first, the only symptom may be mild forgetfulness which may be forgettable since every one young or old does forget things from time to time. Parents forget errands and kids forget doing homework. In the early stage of AD, people may have trouble remembering recent events, activities, or the names of familiar people or things. They may not be able to solve simple math problems. Such difficulties may be a bother, but usually they are not serious enough to cause alarm. However, as the disease progresses, symptoms are more easily noticed by others or patients themselves. When the symptoms become serious enough, the patients or their family members may then seek medical help. The seriousness of the symptoms, for example for people in the middle stages of AD, may be forgetting how to do simple tasks, like brushing their teeth or combing their hair. Patients can no longer think clearly and/or begin to have problems speaking, understanding, reading, or writing, later on developing behavior problems acting anxious or aggressive, or wander away from home. In the late stage, AD patients need total care.

Since there is no treatment that can stop AD at present time, an early, accurate diagnosis of AD can help patients and their families plan for the future. It gives them time to discuss care while the patient can still take part in making decisions. Early diagnosis also offers the best chance to treat the symptoms of the disease.

Unfortunately, the only definite way to diagnose AD is to find out whether there are plaques and tangles in brain tissue. To look at brain tissue, however, doctors must wait until they do an autopsy, which means an examination of the body done after a person dies. Therefore, doctors can only make a diagnosis of "possible" or "probable" AD while the person is still alive. At specialized AD treatment centers, doctors can use several tools to diagnose "probable" AD with high accuracy, these tools include:

These test results help the doctor to eliminate other possible causes of the person's symptoms, for example, thyroid problems, drug reactions, depression, brain tumors, and blood vessel disease in the brain which can cause AD-like symptoms. Some of these other conditions can be treated successfully.

Therefore, it is extremely desirable to find a method of diagnosing AD at its early stage and be able to differentiate normal aging, mild cognitive impairment (MCI) and Alzheimer's Disease (AD). Scientists have been diligently focusing on their research on this problem.  

Possible Early Detection of Alzheimer's Disease

Since the concrete evidence of Alzheimer's Disease is exhibited by the plaque ( clumps of protein) observed in the brain tissues, advanced imaging technologies (Laser, MRI, PET and others) have been explored for early detection of Alzheimer's disease as well as for monitoring treatments or therapies or effects of new drugs for AD.

The 10th International Conference on Alzheimer's Disease and Related Disorders (ICAD), held in Madrid, 2006, has raised some new hope for early diagnosis of AD.  In one study, scientists use a new laser technology for detecting AD in the lens of mice's eyes engineered to produce lesions in their brains similar to that observed in AD patients. A second study describes an experimental magnetic resonance imaging (MRI) technique that presents more information about the cause of Alzheimer's Disease. A third study shows that MRI may be able to track changes in brain size that correlate with the results of cognitive tests, in the course of a treatment trial in mild cognitive impairment (MCI). Using different marker chemical, two additional studies applied positron emission tomography (PET) to differentiate people with MCI from people with AD, and suggesting possibility of identifying which people with MCI may get worse.

Since definitive diagnosis of AD currently requires autopsy analysis of brain tissue of a deceased patient, the above diagnostic tools added to the conventional diagnostic methods make it possible for physicians to diagnose MCI and AD with more accuracy -- raising new hope for early diagnosis and treatment of them.

The scientists at Brigham & Women's Hospital and Harvard Medical School, Boston, (Lee E. Goldstein, MD, PhD et al) based on their discovery that people with AD have Beta-amyloid deposits that appear as unusual cataracts in the lens of the eye, have developed a new, non-invasive, laser technology to detect AD at its earliest stages.

The plaques accumulated outside the brain's nerve cells in people with AD are clumps of abnormal Beta-amyloid protein. Goldstein and colleagues previously reported in the British medical journal, The Lancet, that these same Beta-amyloid clumps also were collected in the lens of the AD patient's eyes as unusual "supranuclear cataracts." These Alzheimer's cataracts can be differentiated from common, age-related cataracts. Hence the laser imaging technique may be used as a tool to find evidence of AD through observing Beta-amyloid outside of the brain, that is in the eye.

Genetically engineered Alzheimer's mice were used by the Harvard research group to test this new, non-invasive molecular diagnostic technology. Goldstein and his team directed a brief pulse of infrared light into the eye of each of four non-anesthetized Alzheimer mice and four age-matched normal mice every month starting from five months of age. The scientists were able to Analyze how the light bounced back from the lens differently allowing them to completely separate the two types of mice by 10 months of age. At tenth months, usually the amyloid lesions were not detectable in the brain or eye by conventional means. Therefore, scientists believe that this laser technology, known as quasi-elastic light scattering (QLS), may serve as a pathological tool for detecting the very early stages of AD by observing Beta-amyloid in human eyes.

Possibility of Outcome Measurement of MCI Drug Trial

The above mentioned MRI experiment (called Susceptibility Weighted Imaging (SWI)) was conducted by Wolff M. Kirsch, MD, of Loma Linda University, Loma Linda, Calif., and colleagues over 3 years with MCI subjects. SWI images revealed that five of these individuals had small bleeds in important brain areas that the researchers say may account for their neurological problems. A small blood vessel disease characterized by tiny brain bleeds is believed to be a major cause for sporadic late-onset dementia.

Research has shown that vitamin E slows the progress of some consequences of AD by about 7 months. Hence scientists now are studying vitamin E to learn whether it can prevent or delay AD in patients with MCI.

Leon Thal, MD, of the University of California, San Diego, Clifford R. Jack, Jr., MD, from the Mayo Clinic, Rochester, Minn., and colleagues used MRI to analyze brain atrophy over three years in 131 participants in a clinical trial of vitamin E and donepezil for the treatment of MCI. The researchers measured volume changes in four different brain locations: hippocampus, entorhinal cortex (ERC), whole brain, and ventricle. Rates of hippocampal atrophy were reduced in those participants with the APOE4 gene (a known risk factor for AD), who were treated with donepezil. No treatment effect was seen for vitamin E. The authors conclude that observing brain shrinkage by MRI may be used as an outcome measurement of disease progression in drug trials for MCI.

Possibility of Differentiating MCI, AD and Normal Aging

Gary W. Small, MD, of  UCLA, reported at ICAD that they could use PET scans to clearly differentiate MCI from normal aging and AD. Sixty people participated in their study -- 20 with Alzheimer's, 20 with MCI, and 20 cognitively normal controls. The investigators injected the participants with a chemical marker called FDDNP, which binds to Alzheimer's plaques and tangles in a test tube. Using a PET scan to detect the FDDNP, the researchers found that global FDDNP-PET binding was lowest for the control group, higher for the MCI group and highest for the AD group with better cognitive test results correlated with lower FDDNP binding values. Two years later, the researchers performed follow-up PET scans on 12 participants, including eight with normal aging and four with MCI. Patients who got worse, declining from normal to MCI or from MCI to AD, showed an increase of FDDNP binding of between five and 11 percent compared with their previous brain scans. Hence PET may be another useful tool for early diagnosis and for monitoring of the effectiveness of a new therapy.

Steven T. DeKosky, MD, from the University of Pittsburgh, and colleagues used PET and a different marker known as Pittsburgh Compound (PIB) to visualize Beta- amyloid plaque deposition over the continuum of normal cognition to MCI to AD. Among 47 (13 MCI, 22 Normal, and 12 AD) with a few exceptions, cognitively normal participants showed little or no significant PIB retention in their brains whereas People with AD in the study doubled that of the controls. People with MCI retained PIB at levels ranged from that of  control and AD, a somewhat expected result.

These PET experiments discussed here clearly raise hopes for early AD diagnosis with ability to differentiate normal aging, MCI and AD and possibility to track their progression in declining brain function.

Conclusions

The main purpose of this paper  is to report the recent progress in the area of early diagnosis of AD. Based on the reports presented at ICAD, we are hopeful that diagnostic tools are emerging for detecting the onset of AD. 

In an earlier paper, Human Memory, Alzheimer's Disease and Drug in Development, we have discussed how human memory functions and what treatment and prevention of MCI and AD there are. Two points worth repeating here are: first, frequent brain stimulation (brain exercise) is good for the brain and helpful in MCI and AD prevention and second, fatty diets are not good for the brain since the plaque observed in AD brains bear some similarity with plaques found in arteries caused by a high cholesterol diet.  

AD is a slow disease, starting with mild memory problems which may be ignored until it becomes a severe brain damage. While we are hoping that very soon we shall have a low-cost diagnostic tool for early detection of MCI and AD, in the mean time, let's protect our brain by exercising it. Playing brain stimulating games are probably the most enjoyable therapy for preventing MCI and AD. For this reason, the author has created a set of brain-stimulating games called Scrammble Games.

References 

Related article by Dr. Chang and be accessed by clicking Human Memory, Alzheimer's Disease and Drug in Development

Brain-Stimulating game Invented by Dr. Chang, http://www.scrammble.com 

Written by Ifay Chang, Ph.D. on August 19, 2006

Dr. Chang is the co-founder of Medical World Search which offers an intelligent medical search engine, called MWSearch. MWSearch is an independent search service without affiliation with any healthcare organization or drug companies. Medical World Search ( www.mwsearch.com ) has been offered for public use since 1996.

In early 90's, while working as a research scientist at IBM T. J. Watson Research Center, Dr. Chang led a group of researchers developing an advanced clinic information system with the purpose of supporting efficient and reliable healthcare practice. The system has been adopted by Kaiser Permanente and other healthcare organizations. Dr. Chang writes articles for MWSearch from time to time.

This article is copyrighted but you may use it or reproduce it in part or in whole with proper acknowledgement made. The author can be reached at ifay@mwsearch.com

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