Advances & Insights: Neurosciences
What the news means for you
Gregory A. Jicha, MD, PhD
New tool is an important step in early Alzheimer’s detection
I am super-fond of the approach taken by this study. In my opinion, the development and testing of the TYM is a very important step in helping us find a reliable screening tool that will help us detect the early signs of Alzheimer’s disease.
“Early treatment [of Alzheimer’s disease] can buy people months or even years of time they wouldn’t have had otherwise.”
Currently, we have no mandates for any type of screening for memory and thinking problems, including Alzheimer’s disease. We have guidelines for other diseases such as getting a colonoscopy after age 50 for finding colon and rectal cancer, or a mammogram for finding breast cancer, or doing Pap smears to find cervical cancer. But in the field of memory and thinking problems, we’ve really fallen behind.
Early detection buys time
Part of the hesitation to recommend routine screenings of people as they age has been a general consensus that there was nothing we could do for people who might be developing memory problems or diseases such as Alzheimer’s. That may have been true 10 years ago, but the story today is quite different. While we don’t have a cure for Alzheimer’s or other related disorders, we do have good medicines that are readily available and can help slow down memory decline. Early treatment can buy people months or even years of time they wouldn’t have had otherwise.
Our active clinical trials program at UK is searching for cures today, and we are currently testing several potential important experimental medicines that may be able to actually slow or stop Alzheimer’s in its tracks. While such breakthroughs are exciting, without the ability to identify those in the population who may suffer from the early stages of Alzheimer’s disease, simply finding a cure will never defeat the disease.
Validity of the test
Developing valid screening tests such as the TYM to screen the elderly population is a critical issue in the field. None of the currently available screening methods have ecological validity, that is, they cannot be easily incorporated into the primary care doctor’s office setting. I’ve been working with area doctors to develop a tool that can be easily administered in the existing family practice setting, one that is quick to take and easy to score. Family practice doctors are too busy taking care of everything, including blood pressure, cholesterol, diabetes, osteoporosis; they have no time left to administer a lengthy memory test.
TYM appears to accomplish the goal of being short and practical and appears to have ecological validity. This study also demonstrates it has medical validity, it works in detecting cognitive dysfunction. While the negative predictive value was high, the positive predictive value was quite low. This means that if you take the TYM and score in the normal range, we can comfortably say you are OK. But if you score poorly, for whatever reason, we can’t say you actually have Alzheimer’s disease.
Interpretation of test scores is also a struggle in the older population. When the study participants were over the age of 70, the validity of the test fell apart, the patient’s low scores may have been more indicative of normal age-related changes than Alzheimer’s disease. Generalizability is also an issue. We’d have to do additional testing of the TYM to determine if a screening tool created in the United Kingdom would work in Kentucky or with people of different ethnic backgrounds.
Screening vs. diagnosis
The bigger question is whether we need to find tests that can be used to actually diagnose Alzheimer’s or just recognize the value of the TYM and other similar tests as screening tools that throw up a red flag and tell the doctor more testing is needed to determine a diagnosis. It’s a slippery slope to link the results of a screening tool to a diagnosis; telling someone they have Alzheimer’s when they don’t can have serious social, psychological, financial and legal implications.
The most important point to remember is screening tests such as TYM are useful for looking at symptoms, but these tests cannot identify the biologic cause of memory disorders nor can they provide a definitive diagnosis that can guide appropriate treatment.
Dr. Jicha is a neurologist with the Kentucky Neuroscience Institute, seeing patients in the Memory Disorders Clinic. He is also director of the Telemedicine Cognitive/Memory Clinic serving all of Kentucky, clinical core director of the Alzheimer ’s Center at UK ’s Sanders-Brown Center for Aging, and an assistant professor of neurology in the UK College of Medicine. He is listed among the Best Doctors® in America.
Fast, simple test detects early Alzheimer’s disease
A new test that is quick to take, easy to use and simple to analyze appears to be much better at detecting early signs of Alzheimer’s disease than other widely used tests. This was the finding reported recently in the journal BMJ by neurologist Jeremy Brown, MD, of Addenbrooke’s Hospital in the United Kingdom, and other researchers.
“[The test] detected 93 percent of cases of Alzheimer’s disease compared with 52 percent detected by the mini-mental state examination.”
An estimated 24 million persons worldwide have dementia, and that number is expected to double every 20 years, the study notes. Alzheimer’s is the most common form of dementia.
The researchers wanted to see if this new screening tool, Test Your Memory or TYM, met three requirements that would make it easily used by nonspecialists:
- Takes minimal time to administer;
- Tests a reasonable range of cognitive functions; and
- Is sensitive to mild or early signs of Alzheimer’s disease.
Results of TYM were compared with two widely recognized screening tools, the mini-mental state examination (MMSE) and Addenbrooke’s cognitive examination-revised (ACE-R).
TYM has patients complete 10 questions on a two-sided sheet of paper to examine a patient’s semantic (word) knowledge, ability to calculate and name objects, and recall. The 11th task is completing the test. The maximum possible score is 50 points.
In our study it (TYM) detected 93 percent of cases of Alzheimer’s compared with 52 percent detected by the mini-mental state examination, concluded the researchers. The TYM can be completed quickly and accurately by normal controls. It is a powerful and valid screening test for the detection of Alzheimer’s disease.
Control participants completed the test within an average of five minutes with minimal supervision from a receptionist or nurse. For ages 18 to 70, the average score was 47 out of 50, with a small decline for older patients.
In patients with Alzheimer’s disease, the average score was 33 out of 50. A score of 42 or lower detected 93 percent of the cases of mild Alzheimer’s disease; a score of 44 or lower detected 96 percent of patients with mild Alzheimer’s disease. The TYM also tested a wide range of cognitive functions and it was sensitive to the signs of mild Alzheimer’s, thus fulfilling the researcher’s goals.
In comparison, the MMSE, the standard short test for the last 30 years, took longer to complete (an average of eight minutes) and was insensitive to aiding in the diagnosis of mild Alzheimer’s disease, finding only 52 percent of those cases. ACE-R took at least 20 minutes to administer and score. However, researchers found that this test looked at a similar number of cognitive functions as the TYM and was as sensitive to detecting mild Alzheimer’s.
How study was conducted
The investigators looked at subjects from three hospitals, including a memory clinic. There were 540 control participants ages 18-95 and 139 patients from a memory clinic (108 with Alzheimer’s disease or amnestic mild cognitive impairment, which is similar to Alzheimer’s disease, and 31 with non- Alzheimer’s degenerative dementias). The patients were seen at the clinic between March and December 2007. The control participants were recruited from relatives of memory clinic patients and of patients of neurology and medical outpatient clinics at two other hospitals, as well as from dermatology outpatients.
The effectiveness of the TYM tool in detecting Alzheimer’s disease was determined by comparing the scores of 94 patients (average age of 69) who have Alzheimer’s disease with the scores of 282 age-matched control participants. Three age-matched controls were randomly selected from the 540 controls to compare with each patient already diagnosed with Alzheimer’s disease. Three people with different backgrounds scored 100 of the tests to assure there were no differences based on scoring (inter-rater reliability). To validate the TYM tool, comparisons were made with scores from the MMSE and the Addenbrooke’s cognitive examination-revised (ACE-R).
The investigators note that while the TYM was successful in serving as a screening tool for detecting signs of early Alzheimer’s disease, the test alone cannot be used to diagnose Alzheimer’s disease. It may incorrectly predict the presence of the disease in some people, especially those over the age of 70 who may have other memory problems.
Also, in an editorial accompanying the study findings, Claire Nicholl, MD, from Addenbrooke’s Hospital, notes that ethnicity of the study participants is not reported, though the local population is generally white. Thus some of the items on the TYM may show cultural bias. The researchers do note that the TYM would need to be revised if used in different countries (e.g., a question about the prime minister would need to be revised to president for use in the United States). The test is already being translated into four languages for those patients who do not speak English as their first language.
- Editorial: Diagnosis of dementia, BJM, June 9, 2009
- Author’s reply: TYM and Alzheimer’s disease, BJM, July 15, 2009
- Alzheimer’s disease, Health Information, UK HealthCare
- Alzheimer’s disease, MedlinePlus, National Library of Medicine
- Understanding stages and symptoms of Alzheimer’s disease, National Institute on Aging, National Institutes of Health
- Memory Disorders Clinic, Kentucky Neuroscience Institute, UK HealthCare
- Faculty among Top 100 Alzheimer’s researchers, Press Information, UK HealthCare
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