by Edmund Howe, MD, JD

Dr. Howe is Professor, Department of Psychiatry, and Director, Programs in Medical Ethics, Uniformed Services University of the Health Sciences, Bethesda, Maryland

Introduction

Patients often bring concerns of memory loss to psychiatrists first, making it imperative that psychiatrists know how to screen these patients who present with initial memory loss for Alzheimer’s disease (AD). This is especially true since AD is now understood to be a diagnosis that can be made with proper testing, as opposed to a diagnosis of exclusion.[1]

Early diagnosis is also important because AD is now viewed as a progressive disorder, and not one that occurs all at once.[2–5] It is believed that cognitive reserves in the brains of people with AD become overwhelmed, usually later in life. Thus, preventive measures in individuals as early as in their 20s may help reduce the onset and intensity of AD later on in life. These endeavors may involve optimal earlier treatment of hypertension, diabetes, elevated cholesterol, and taking preventive medications, such as folic acid.[6–9]

Since early treatment of AD is clearly beneficial, early screening also is clinically most important. This update will review some of the more useful outpatient screening approaches psychiatrists can use in their office practices.

Minimal Cognitive Impairment

Minimal cognitive impairment (MCI) is defined as a condition in which individuals have greater memory problems than people normally do at a particular age but whose memory problems do not significantly affect their functioning. Emerging data suggests, on the other hand, that the effect on their functioning may be more than previously assumed.[10]

MCI is an exceedingly important condition of which to be aware because of the associated risk to later develop dementia. The prevalence of MCI in adults over 65 is 3 to 19 percent, and over half of persons with MCI go on to develop dementia after five years.[2]

A difficulty with treating MCI is that some MCI patients go on to develop AD, while others do not and may even get better. Therefore, even if it were known that treatments at this time would help (e.g., prescribing a cholinesterase inhibitor), it is unclear which patients with MCI should be treated and which should not. Therefore, at this time, the most important reason for making the diagnosis of MCI is to identify and follow these patients early on so that if and when their problems progress and become AD, they can be treated as early as possible.

Brief Diagnostic Approaches

When patients complain of problems with memory, psychiatrists should in general initiate testing immediately so that if AD is indicated, a cholinesterase inhibitor may be initiated right away to slow the disease progression.[1]

There are several tests psychiatrists can perform in their offices that do not take an exorbitant amount of time and still have clinically significant sensitivity and specificity. Based on the results of these tests, psychiatrists can then decide when and whether to refer these patients on for further, more formal testing. The following tests are brief and among the most effective.

The “WORLD” test. The first test is to ask a patient to spell the word “world” forward and backward and then list the letters in “world” in alphabetical order. This test is scored as wholly correct or incorrect and has been found to have a sensitivity of 85 percent and a specificity of 88 percent for AD.[11] Leopold and Borson assert that that when a highly educated patient fails this test, a strong suggestion of impaired cognition is made and more formal testing should be carried out.[11]

The one-minute naming test. A second brief test is to ask a patient to name as many objects in a category (e.g., animals) as he or she can within one minute. If a patient can generate the names of more than 21 objects, he or she is probably “ok.” If he or she cannot name 15 or more objects, the patient is likely to be cognitively impaired, and the likelihood that he or she has AD may be 20 times higher than if a patient can name 15 animals or more.[12,13]

Patients naming as many words as they can in one minute that start with the letter F may also be revealing, but to a lesser extent. Combining the two “naming” tests may help differentiate, however, the kind of dementia a patient has. For example, if a patient is less able to generate letter F words than to generate names within a specified group, he or she may be more likely to have vascular dementia.[12] In a study by Duff, et al., after controlling for severity, only the vascular dementia group generated fewer letter F words compared to the normal control group. Only animal fluency was found to contribute to discrimination of patients with AD from normal elderly control subjects. The overall correct classification using letter F fluency was 75 percent using an optimal cutoff of 13 with sensitivity of 0.76 and specificity of 0.74.12 Persons should be able to name at least 13 F words within a minute, but while this cutoff number can help significantly to discriminate patients with vascular dementia, it cannot help significantly to discriminate patients with AD.

The Mini-Cog test. A third test, known as the Mini-Cog, takes 2 to 4 minutes to administer and involves asking patients to recall three words after drawing a picture of a clock. If a patient shows no difficulties recalling the words, it is inferred that he or she does not have dementia. If the patient can recall one or two words, the level of accuracy of his or her clock drawing then becomes definitive. If the patient is unable to recall any of the words, it is inferred that he or she has dementia, and more formal testing should be initiated.[14]

The interpretation of the clock drawing is all or none. It has been found that untrained examiners assess this test essentially as well in a clinical context as those who are trained.[15]

An important additional point here is that if a patient does not recall the words, psychiatrists can prompt him or her by revealing the general categories of the words to the patient, such as “a flower,” or by going further and giving the patient several specific choices, including the right one. If the patient can recall the right word, he or she retains some capacity for recall.[16]

The Mini-Cog’s sensitivity and specificity approaches that of the Mini-Mental Status Exam (MMSE), a traditional gold standard of psychiatrists that takes seven minutes to administer and includes 30 measures.[14] Though considered by many to be the psychiatrist’s traditional “follow-up test,” the MMSE is not ideal. It has been criticized for having limited sensitivity and specificity and allowing patients’ education levels to affect the results too much.[17] Its overall sensitivity is 79 percent.[14] On the other hand, in a highly diverse sample, the Mini-Cog reportedly surpasses the MMSE on brevity, sensitivity, and acceptability to those taking it.[14] The Mini-Cog is especially helpful in early detection of AD.[18] It may also be more effective in identifying patients with AD who have less education.[19]

The Montreal Cognitive Assessment test. Finally, the Montreal Cognitive Assessment test (MoCA), a more recently developed test, takes 10 minutes to administer and, like the MMSE, involves 30 measures. It is available at www.mocatest.org at no cost. It involves several additional tests. The tests, along with instructions for administering and scoring, are available in 11 languages, including Spanish, Chinese, and Arabic. The MoCa has been shown to detect mild AD with 100-percent sensitivity and 87-percent specificity.[20] The MoCA, however, is most effective in detecting MCI. In fact, it was developed for this purpose, and Nasreddine, et al., state it is now the only screening tool available to distinguish between persons who have MCI and those who are considered “normal.”[20]

MCI is considered a preclinical stage of AD and may extend over decades.[2–4] During this preclinical stage, most patients with MCI score at least 26 out of 30 on the MMSE, which is within the normal range for elderly patients.[20] Nasreddine, et al, suggest that when patients present with cognitive complaints and functional impairment, psychiatrists should first administer the MMSE. If the MMSE is normal (greater than or equal to 26), psychiatrists should administer the MoCA, since its sensitivity is greater (mild AD: MoCA sensitivity 100% vs MMSE 78%). If a patient presents with only memory complaints, psychiatrists should administer the MoCA first, because the MMSE is more likely to be normal (MoCA sensitivity for detecting MCI 90% vs MMSE 18%).[20]

Conclusion

Psychiatrists should explore patient memory complaints aggressively whether the complaints come from the patient or the patient’s families.[21–23] Even individuals with only subjective initial memory complaints have a five-fold increase of developing AD later in life.[5] While currently there are no evidence-based options outside of research settings for defining subtypes of MCI that will progress into AD and that will respond to treatment, these options should be available in the near future. Especially promising are the use of structural and functional imaging, such as amyloid imaging, and cerebrospinal fluid (CSF) biomarkers.[24–26] Multiple pharmacological and nonpharmacalogical treatments may be forthcoming as well.[27,28]

Over the past decade, the goal of psychiatrists caring for patients with Alzheimer’s disease (AD) has changed profoundly from palliation to treatment.[29] Psychiatrists now can investigate memory concerns of their patients more reasonably in an outpatient office setting. Early treatment of AD improves outcomes, and since treatment options for initial memory problems are now emerging, the psychiatrist may soon be able to offer these patients greater hope for better outcomes.

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