New Test May Detect Early Alzheimer's Disease

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From Medscape Medical News

New Test May Detect Early Alzheimer's Disease

News Author: Allison Gandey
CME Author: Laurie Barclay, MD

CME Released: 06/22/2009; Valid for credit through 06/22/2010

June 22, 2009 — Researchers have developed a new cognitive test that is quick to use, examines 10 skills, and reportedly detects 93% of cases of Alzheimer's disease. Published online June 10 in BMJ, investigators suggest the new self-administered test is a powerful and valid screening tool.

"If a patient completes the test while in the waiting area supervised by the receptionist, it can be scored and analyzed by the doctor in 2 minutes," explain the researchers, led by Jeremy Brown, MD, from Addenbrooke's Hospital, in Cambridge, the United Kingdom. "If there is time during the consultation to observe the patients filling in the test, this can also be a useful aid to diagnosis."

Dr. Brown is a neurologist, but his team found that with 10 minutes' training and a scoring sheet, a nurse without experience working in memory clinics was able to evaluate the test as accurately as a specialist.

In an accompanying editorial, Claire Nicholl, MD, also at Addenbrooke’s Hospital, pointed out that the study showed that the new test was more sensitive than the Mini-Mental State Examination (MMSE) in this patient population (93% vs 52%).

More Sensitive Than Mini-Mental State Examination

"Longer scales are used in specialist settings," Dr. Nicholl notes, "but the test is not designed to replace these."

In this cross-sectional study, investigators evaluated subjects from 3 hospitals including a memory clinic. They looked at 540 control participants and 139 patients with dementia or amnesic mild cognitive impairment.

In the diagnosis of early Alzheimer's disease with a cut-off point of <42/50, the test had good sensitivity (93%), specificity (86%), and interrater reliability.

The test requires participants to write 10 answers on a double-sided card. The requested tasks evaluate a range of areas, including the patient's semantic knowledge, ability to calculate and name objects, and recall.

"If the memory test is to be adopted more widely, it must be validated in a range of settings and different populations," Dr. Nicholl writes. "Until then, the most important message is that clinicians should identify a test that suits their clinical setting, use it to screen or case find as appropriate, and develop experience in its use to improve the identification of patients with early dementia."

Must Be Validated

Dr. Nicholl points out that the authors do not comment on the ethnicity of the study participants, but the local population is mainly white and some of the items on the test likely show some cultural bias.

Elizabeth Gould, director of quality care programs at the Alzheimer's Association, echoed similar concerns to Medscape Neurology. Speaking during a recent interview, she emphasized the importance of taking cultural differences into account as much as possible. She also stressed the importance of early detection.

A Web site is being developed for clinicians to download the new test, scoring sheets, and further instructions.

The researchers and editorialist have disclosed no relevant financial relationships.

BMJ. 2009;338:b2030 Abstract, b1176. Abstract
Clinical Context

Worldwide, approximately 24 million people have dementia, and it is estimated that the prevalence will double every 20 years. The prevalence of mild cognitive impairment is even greater.

Cognitive tests are useful to diagnose dementia and to evaluate functional ability, and a quick, sensitive test will be even more important once there are effective treatments of Alzheimer's disease. Currently available cognitive tests do not satisfy criteria for widespread use by nonspecialists (minimal operator time to administer, testing of a broad variety of cognitive functions, and sensitivity to mild Alzheimer's disease).
Study Highlights

    * This cross-sectional study evaluated the performance of a self-administered cognitive screening test ("test your memory" [TYM]) for detection of Alzheimer's disease.
    * The TYM was designed for quick administration and suitability for use by general practitioners.
    * It consists of a series of 10 tasks on a double-sided sheet or card with blanks for the patient to complete.
    * The tasks include orientation (10 points), ability to copy a sentence (2 points), semantic knowledge (3 points), calculation (4 points), verbal fluency (4 points), similarities (4 points), naming (5 points), and visuospatial abilities (2 tasks, total 7 points),
    * Ability to complete the TYM is considered as an additional task.
    * At the outpatient departments of 3 hospitals, 139 patients seen at a memory clinic for dementia or amnestic mild cognitive impairment and 540 control participants aged 18 to 95 years were tested with the TYM.
    * Of the 139 patients with dementia or amnestic mild cognitive impairment, 108 had Alzheimer's disease or amnestic mild cognitive impairment, and 31 had non-Alzheimer's degenerative dementias.
    * The performance on the TYM of patients with Alzheimer's disease (n = 94) was compared vs age-matched control subjects (n = 282).
    * Interrater reliability was excellent, determined by 3 scorers of differing backgrounds marking 100 tests.
    * The TYM was validated against 2 standard tests, the MMSE and the Addenbrooke's cognitive examination-revised (ACE-R).
    * Sensitivity and specificity of the TYM in the diagnosis of Alzheimer's disease were calculated.
    * Average TYM score was 33 of 50 for patients with Alzheimer's disease vs 39 of 50 in 31 patients with non-Alzheimer's dementias, 45 of 50 for patients with mild cognitive impairment, and 47 of 50 for control subjects.
    * Control subjects completed the test in an average time of 5 minutes.
    * The average TYM score remained constant between the ages of 18 and 70 years and decreased slightly thereafter.
    * Men and women had similar TYM scores, as did subjects with various geographic backgrounds.
    * Scores on the TYM score correlated well with scores on the MMSE and ACE-R.
    * The TYM takes less time to administer than the MMSE and tests a broader range of cognitive domains.
    * Although the ACE-R tests a similar number of cognitive domains to the TYM and is sensitive to mild Alzheimer's disease, it takes 20 minutes to administer and score.
    * Both the TYM and the ACE-R require specially printed sheets, but a Web site is being developed to address this limitation of the TYM.
    * Using a cutoff score of less than or equal to 42 of 50, the TYM was 93% sensitive and 86% specific in the diagnosis of Alzheimer's disease.
    * The TYM was more sensitive in the detection of Alzheimer's disease vs the MMSE (sensitivity, 93% vs 52%).
    * Assuming a prevalence of Alzheimer's disease of 10%, the negative predictive value of the TYM (with a cutoff point of ≤ 42) was 99%, and the positive predictive value was 42%.
    * The investigators concluded that the TYM can be completed quickly and accurately by healthy control subjects and that it is a powerful and valid screening test for the detection of Alzheimer's disease.

Clinical Implications

    * The TYM, which tests a broad range of cognitive domains, was designed for quick administration (approximately 5 minutes for control subjects to complete) and suitability for use by nonspecialists. Interrater reliability was excellent. Score on the TYM score correlated well with score on the MMSE and ACE-R.
    * With use of a cutoff score of less than or equal to 42 of 50, the TYM was 93% sensitive and 86% specific in the diagnosis of Alzheimer's disease. The investigators concluded that the TYM is a powerful and valid screening test for the detection of Alzheimer's disease.