A Possible New Test to Distinguish between Alzheimer's Disease and Major Depressive Disorder

The Pocket Smell Test (UPSIT)-Alzheimer's Disease-Part X of a XXVIII Series

(10/12//17)- A study conducted on 2906 men and women ages 57 to 85 tested their ability to identify 5 odors-orange, leather, peppermint, rose and fish, who were examined 5 years later, diagnosed that 4.1% were suffering from dementia. Of all the factors the researchers measured, only cognitive disability at the start of the study and poor performance on the “ smell test” were associated with an increased risk for dementia.

The study was published in the Journal of the American Geriatrics Society. Risk increased with the number of odors the subjects failed to recognize. Those individuals with the smell problem had more than twice the likelihood of developing dementia five years later.

Dr. Jayant M. Pinto, a specialist in sinus and nasal diseases at the University of Chicago was the lead author for the study.

Poor performance on a simple odor identification test was associated with a significantly increased risk of developing dementia years later, in a study of more than 2,400 older black and white adults led by Kristine Yaffe, MD, a UC San Francisco professor of psychiatry, neurology and epidemiology and biostatistics.

The study, that was published in Neurology, analyzed the medical records of 2,428 community-dwelling adults enrolled in the prospective Health, Aging, and Body Composition study conducted by the National Institutes of Health. The participants were between 70 and 79 years old when they enrolled in the study, and none had developed dementia.

(7/15/14)- A study conducted in 2004 to 2006 of some 1,000 individuals without Alzheimer’s disease, using a simple scratch-and-sniff smell test, that we described in our item dated 6/11/00 below, showed that lower scores on the test were associated with a greater risk of developing AD, even if the individual was cognitively normal at the beginning of the study.

When scratched, an odor is released. There are 4 possible responses involved in the test, and if 2 or more errors are made, the probability of AD developing in that individual is increased, as opposed to the individual being “depressed”.

Davangere Devanand, a Columbia University psychology and psychiatry professor, was the lead author of the study.

(6/11/00)- A full-page ad in the Journal of The American Geriatric Society suggests a new test to discriminate between Alzheimer’s disease and major depressive disorder. The ad actually reads that the test will "discriminate between probable Alzheimer’s disease and depression better than the Mini-Mental State Examination". Cursory reading might imply that this was a test for Alzheimer’s disease. The ad refers to a study in the Journal of Neuropsychiatry and Clinical Neuroscience (2000; 12:29-33), whose lead author was Robert McCaffrey.

Reviewing the McCaffrey study indicated that the "test" was a three-item microencapsulated "scratch and sniff" measure derived from a test called the "University of Pennsylvania Smell Identification Test". On each item an odor is released and you choose one of four response alternatives. Two or more errors clearly distinguished individuals with probable Alzheimer’s disease as opposed to depressed subjects.

The theory behind this test is that the first area affected by neurotangle fibers, a distinguishing marker for Alzheimer’s disease, is the entorhinal cortex, one of the major components of the olfactory (smell) system. In depression, this area is not affected. The study also implies that age, gender and education do not systematically affect the Pocket Smell Test.

The authors of this study stress that PST "should not be used as the sole indication in the differential diagnosis of Alzheimer’s disease versus major depression". They go on to declare that "The PST is a brief, portable, inexpensive and user friendly measure that has been used successfully to discriminate between these two groups".

Since, up to now, no definitive diagnosis of Alzheimer’s disease can be made until a pathological examination of brain tissue after death is completed, and depression is a confounding variable in making a diagnosis of Alzheimer’s disease, the Pocket Smell Test may prove a valuable tool in the entire diagnostic process. It requires further clinical testing in groups that are not at the severe end of the scale of the two particular disorders and should be done in a double-blind manner with a control group and matched age groups. We will be on the lookout for further research studies in this area.

Harold Rubin, MS, ABD, CRC, Guest Lecturer

June 11, 2000

A recent review (April 2002) of the research literature has turned up new information about the olfactory test for Alzheimer’s disease. This information can be summarized, citing the conclusion of the Schiffman et al (8) research report: "Among chemosensory tasks, tests combining both olfactory and memory demands may be especially sensitive to changes occurring in Alzheimer’s disease. Areas of the entorhinal cortex and hippocampus are vulnerable to early neuroanantomical and metabolic changes occurring in Alzheimer’s disease. These areas are also involved with olfactory processing and with memory. Therefore, olfactory tests with a memory component can be uses as an additional tool for predicting Alzheimer’s disease." They were discussing familial risk evaluation for Alzheimer’s disease and were careful to use the words "additional tool" for prediction.

The present clinical diagnosis for possible Alzheimer’s disease makes use of a battery of neuropsychological tasks, clinical competence of the diagnostician, neuroimaging, and physical examination to rule out other possible diagnoses and can only be confirmed via autopsy. The need is to develop a screening device that may indicate early on the potential for Alzheimer’s disease. Interventions can then be started at an earlier stage of the disease and clinical support can be provided at this early stage.

There have been scattered reports of evidence suggesting that a diminished sense of smell is associated with Alzheimer’s disease. In 1987, Rezek (7) reported on olfactory deficits as a neurological sign in dementia of the Alzheimer type. Talamo (9) and his group examined changes in olfactory neurons in patients with Alzheimer’s disease. They indicated that there were histopathological changes in olfactory epithelium. In 1991, Hyman and colleagues (2) suggested that neuroanatomical and neurochemical changes related to Alzheimer’s disease occur in the olfactory bulb of the brain, confirming prior studies. Other areas that exhibited degeneration included the anterior olfactory nucleus, the olfactory tubercle, the uncus and the subiculum. These studies could be challenged on methodological grounds, but still carry some weight. It should be noted that Feldman and his associates (1) found that olfactory deficits are not the result of rhinologic pathology.

Mesholam et al (5), in 1998, did a meta-analysis of published papers on olfactory functioning in neurodegenerative disease including Alzheimer’s and Parkinson’s disease. The conclusion was that deficits occur in three olfactory domains: identification, recognition and threshold. This referred to the type of olfactory test performed. In an identification olfactory task, subjects are asked to identify odors form a list or those named by the experimenter. In a recognition/discrimination task, the goal is to recognize the presence of an odor or to determine if pairs of odors are identical, similar or different. In a threshold task, the lowest concentration at which odors could be detected was determined. (4, 6, 7).

Implied from these studies is the suggestion that olfactory sensation loss is associated with the early stages of Alzheimer’s disease and that the areas of the brain involved in this process may be involved with not only olfactory information but also memory consolidation. This does not seem true of the gustatory system as shown by Koss et al (3) in a study reported in the journal Neurology in 1988.

The take home message from all this research seems to be that olfactory tasks could become part of the armentarium used to clinically determine diagnosis of Alzheimer’s disease. It should not stand alone as a specific test for Alzheimer’s disease.

References:

Feldman JL., Murphy C., Davidson TM., Jalowayski AA., de Jaime GG. The rhinologic evaluation of Alzheimer’s disease. Laryngoscope 1991; 101:1198-1202.
Hyman BT., Arriagala PV., Van Hoesen GW. Pathological changes in the olfactory system in aging and Alzheimer’s disease. Ann NY Acad Sci. 1991; 640:14-19.
Koss E., Weiffenbach JM., Huxby JV., Friedland RP. Olfactory detection and identification performance are dissociated in early Alzheimer’s disease. Neurology 1988; 38:1228-1232.
Lehrner JP., Brucke T., Dal-Bianco P., Gatterer G., Kryspin-Exner I. Olfactory function in Parkinson’s disease and Alzheimer’s disease. Chem Senses 1997; 22:105-110.
Mesholam RI., Moberg PJ., Mahr RN., Doty RL. Olfaction in neurodegenerative disease: a meta-analysis of olfactory functioning in Alzheimer and Parkinson’s diseases. Arch Neurol 1998; 55:84-90.
Nordin S., Murphy C. Impaired sensory and cognitive olfactory function in questionable Alzheimer’s disease. Neuropsychology 1996; 10:113-199.
Rezek DL. Olfactory deficits as a neurological sign in dementia of the Alzheimer type. Arch Neurol 1987; 44:1030-1032.
Schiffman SS., Graham BG., Sattely-Miller EA., Zervakis J., Welsh-Buhmer K. Taste, smell and neuropsychological performance at familial risk for Alzheimer’s disease. Neurobiology of Aging 2002; 23:397-404.
Talamo BR., Rudel R., Kosik KS., Lee VM., Neff S., Adelman L., Kauer JS. Pathological changes in olfactory neurons in patients with Alzheimer’s disease. Nature 1989; 337:736-738.

For our other articles on Alzheimer's Disease-

FOR AN INFORMATIVE AND PERSONAL ARTICLE ON PRACTICAL SUGGESTIONS WHEN SELECTING A NURSING HOME SEE OUR ARTICLE "HOW TO SELECT A NURSING HOME"

Harold Rubin, MS, ABD, CRC and Guest Lecturer
updated October 12, 2017

http://www.therubins.com

email: hrubin12@nyc.rr.com or allanrubin4@gmail.com

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