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Olfactory deficits and Alzheimer's disease
116
BIOL PSYCHIATRY 1986:21:11~-118
BRIEF REPORT
Olfactory Deficits and Alzheimer’s Disease M. Dhyanne Warner, Cecilia A. Peabody, Jennifer J. Flattery, and Jared R. Tinklenberg
Introduction Several preliminary reports have suggested the possibility of an olfactory deficit in Alzheimer’s disease. Averback (1983) and Esiri and Wilcock (1984) both reported signi~cant cell loss, senile plaques, and neurotibriliary tangles in the anterior olfactory nucleus in autopsy cases of Alzheimer’s disease. Additionally, Simpson et al. (1984) found the cholinergic system to be deficient in the olfactory tubercles. Two other studies indicated impa~ent of olfactory functioning in Alzheimer subjects (Peabody and Tinklenberg 1985; Serby et al. 1985). Neither study, however, used a standardized test, The present study employed a standardized smell identification test. An olfactory deficit was predicted in the Alzheiier group as compared with the control group.
Methods Seventeen subjects (12 men, 5 women) had a DSM-III diagnosis of primary degenerative dementia (Alzheimer’s disease) and an average age of 66.7 years (range 55-82). An additional 17 subjects (12 men, 5 women) served as the
From the Gem-Psychiatric Rehabilitation Unit, Veterans Administration Medical Center, Palo Alto, and the Department of Psychiatry and Behavioral Sciences, Department of Medicine, Stanford University School of Medicine, Stanford, CA. Supported by the Medical Research Service of the Veterans Administration and NJMH Grant MH40041. Address reprint requests to Dr. Cecilia A. Peabody, VA Medical Center, Psychiatry Sewice (116A3), 3801 Miranda Avenue, Palo Alto, CA 94304. Received June 22, 1985; revised July 23. 1985.
8 1986 Society of Biological Psychiatry
normal controls and had an average age of 67.9 years (range 60-80). The Alzheimer subjects had normal SMA20, complete blood count (CBC), UA, Bi2, folate, free T4, thyroid-stimulating hormone (TSH), and PTA-ABS tests. No significant abnormalities were noted on electrocardiogram (EKG) and chest x-ray, and a computerized tomography (CT) scan was consistent with Alzheimer’s disease. Global Deterioration Scores (GDS) (Reisberg et al. 1982) were either 3 or 4 on a 7point scale. These Alzheimer subjects were living at home, and none were able to work because of intellectual decline. Exclusion criteria for all subjects included: (1) any acute medical problems or chronic neurological problems; (2) viral infections or allergies in the past 2 weeks; (3) any history of head injury with resultant loss of consciousness; and (4) any use of medication in the past month or the presence of any disease that has been associated with olfactory deficits (Schiffman 1983), with the exception of hypoth~oidism, Hy~thyroidism has been associated with smell deficits, which appear to be largely reversed by thyroid treatment (MCCOMell et al. 1975). Three of the Alzheimer subjects and none of the controls were on thyroid medication. All subjects understood the testing procedure and gave informed written consent. The study was approved by the Stanford Human Subjects Committee. The University of Pennsylvania Smell Identification Test (SIT) (Doty et al ‘ 1984) was used to assess subjects’ olfactory function. This “scratch and sniff” test consists of a series of OCNX-3223/86/$03.50
BIOL PSYCHIATRY
Brief Reports
117
1986;21:116-118
Table 1. Smell IdentificationScores in Alzheimer (n = 17) and Control Subjects (n = 17)
40 chemically impregnated tapes that, when scratched with sandpaper, release an odor. It has a test-retest reliability of 0.92. The SIT was administered in the standardized way used by the University of Pennsylvania group, with one exception: the odor tapes were divided in half so that each booklet could be used for two subjects. Before choosing an answer, each subject read aloud the four choices. Regardless of whether or not a subject could smell the odor, he had to choose among the four alternative responses to identify it. Some people can correctly identify an odor even though they are not conscious of smelling it (R.L. Doty, personal communication, 1984). An examiner assisted all subjects with the test and allowed them unlimited time. The Alzheimer subjects needed approximately 35 min to complete the test, whereas the controls needed about 20 min.
40Item total 20.5 2 7.4e.b 30.2 k 6.9
Alzheimer Control
20-Item subtotal 10.5 2 3.4’ 14.0 rt 3.9
“Mean f SD. “p i 0.001.
‘p < 0.01.
nificantly lower subtotal score of the first 20 items @ < 0.01) (Table 1). The control group did better on 38 of the 40 individual items (Figure 1). Of these 38, 14 were significant (p < 0.05), and 9 of these 14 occurred in the last 12 items of the test. Overall, the 5 items that maximally differentiated @ < 0.005) the Alzheimer and control groups were bubble gum (No. 2), root beer (No. 24), watermelon (No. 30), grass (No. 32), and rose (No. 39). Our control group had a mean total score of 30. The University of Pennsylvania aged-matched controls also had a mean scorn of 30 (Doty 1983), taking into account the ratio of male to females used in our sample.
Results A two-sample t-test (two-tail) was used to determine differences between the groups on each of the 40 items as well as the total of the first 20 items and the overall total of the 40 items. The Alzheimer group had a significantly lower SIT total score (p < 0.001) as well as a sig-
Figure 1. Smell IdentificationTest scores for Alzheimer patients and controls.
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Brief Reports
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Discussion Our data suggest that olfactory deficits may be one of the earlier symptoms of Alzheimer’s disease. Our subjects were deliberately chosen to be in the early stages of the disease, so that there would be little question as to their ability to understand and perform the smell test. This fact, plus the pathological changes in the olfactory system, suggest that the etiology of the deficit is olfactory and not cognitive. It is interesting to note that the Alzheimer subjects seemed to have more difficulty at the end of the test. Possible explanations are that (1) they physically tired more easily than the controls, (2) their sense of smell adapted rapidly, or (3) the odors at the end of the test were more sensitive in detecting their deficits. Doty (personal communication, 1985) states that he is unaware of any unique characteristics of the last 12 items of the smell test as compared to earlier items. This difficulty at the end of the test is not solely responsible for the olfactory deficit, as the first 20 items also indicated impairment (p < 0.01). A disordered sense of smell is not unique to Alzheimer’s disease. It can occur with many diseases and medications. The diseases include Parkinson’s disease, multiple sclerosis, and many endocrine disorders (Schiffman 1983). However, the most common causes are probably viral infections, head injuries, normal aging, and local obstructions (Schiffman 1983). A diminished sense of smell in Alzheimer’s disease is more than an intellectual interest; it is a practical one. It can present major problems, such as a decreased appetite, with resultant weight loss and poor nutritional status. Another problem may be the inability to detect noxious odors such as gas and smoke. Both the patient and
family should be made aware of this deficit and the potential problems it may cause.
References Averback P (1983): Two new lesions in Alzheimer’s disease. Lancet ii: 1203. Doty RL (1983): The Smell Identification Test Administration Manual. Philadelphia: University of Pennsylvania. Doty RL, Shaman P, Dann M (1984): Development of the University of Pennsylvania Smell Identification Test. A standard micro-encapsulated test of olfactory function. Physiol Behav 321489-502. Esiri MM, Wilcock GK (1984): The olfactory bulbs in Alzhiemer’s disease. J Neural, Neurosurg, Psychiatry 4756-60.
Folstein MF, Folstein SE, McHugh, PR (1975): Mimmental state. J Psychiatr Res 12: 189-I 98, McConnell RJ, Menendez CE, Smith FR, Henk Rl, Bivlin RS (1975): Defects of taste and smell in patients with hypothyroidism. Am J Med 59:354-364.
Peabody CA, Tinkle&erg JR (1985): Olfactory deficits and primary degenerative dementia. Am J Psychiatry 1421524-525. Reisberg B, Ferris SH, de Leon MJ, Crook T (1982): The Global Deterioration Scale (GDS): An instrument for the assessment of primary degenerative dementia. Am J Psychiatry 139: 1136-I 139. Schiffman S (1983): Taste and smell in disease. N Engl J Med 308:1275-1279.
Serby M, Corwin J, Novatt A, Conrad P, Rotrosen J (1985): Olfaction in Dementia. J Neural, Neurosurg Psychiatry (in press). Simpson J, Yates CM, Gordon A, St. Clair DM (1984): Olfactory tubercle choline acetyltransferase activity in Alzheimer-type dementia, Down’s syndrome and Huntington’s disease. J Neurol Neurosurg Psych&y 47:1138-l 139.
BIOL PSYCHIATRY 1986:21:11~-118
BRIEF REPORT
Olfactory Deficits and Alzheimer’s Disease M. Dhyanne Warner, Cecilia A. Peabody, Jennifer J. Flattery, and Jared R. Tinklenberg
Introduction Several preliminary reports have suggested the possibility of an olfactory deficit in Alzheimer’s disease. Averback (1983) and Esiri and Wilcock (1984) both reported signi~cant cell loss, senile plaques, and neurotibriliary tangles in the anterior olfactory nucleus in autopsy cases of Alzheimer’s disease. Additionally, Simpson et al. (1984) found the cholinergic system to be deficient in the olfactory tubercles. Two other studies indicated impa~ent of olfactory functioning in Alzheimer subjects (Peabody and Tinklenberg 1985; Serby et al. 1985). Neither study, however, used a standardized test, The present study employed a standardized smell identification test. An olfactory deficit was predicted in the Alzheiier group as compared with the control group.
Methods Seventeen subjects (12 men, 5 women) had a DSM-III diagnosis of primary degenerative dementia (Alzheimer’s disease) and an average age of 66.7 years (range 55-82). An additional 17 subjects (12 men, 5 women) served as the
From the Gem-Psychiatric Rehabilitation Unit, Veterans Administration Medical Center, Palo Alto, and the Department of Psychiatry and Behavioral Sciences, Department of Medicine, Stanford University School of Medicine, Stanford, CA. Supported by the Medical Research Service of the Veterans Administration and NJMH Grant MH40041. Address reprint requests to Dr. Cecilia A. Peabody, VA Medical Center, Psychiatry Sewice (116A3), 3801 Miranda Avenue, Palo Alto, CA 94304. Received June 22, 1985; revised July 23. 1985.
8 1986 Society of Biological Psychiatry
normal controls and had an average age of 67.9 years (range 60-80). The Alzheimer subjects had normal SMA20, complete blood count (CBC), UA, Bi2, folate, free T4, thyroid-stimulating hormone (TSH), and PTA-ABS tests. No significant abnormalities were noted on electrocardiogram (EKG) and chest x-ray, and a computerized tomography (CT) scan was consistent with Alzheimer’s disease. Global Deterioration Scores (GDS) (Reisberg et al. 1982) were either 3 or 4 on a 7point scale. These Alzheimer subjects were living at home, and none were able to work because of intellectual decline. Exclusion criteria for all subjects included: (1) any acute medical problems or chronic neurological problems; (2) viral infections or allergies in the past 2 weeks; (3) any history of head injury with resultant loss of consciousness; and (4) any use of medication in the past month or the presence of any disease that has been associated with olfactory deficits (Schiffman 1983), with the exception of hypoth~oidism, Hy~thyroidism has been associated with smell deficits, which appear to be largely reversed by thyroid treatment (MCCOMell et al. 1975). Three of the Alzheimer subjects and none of the controls were on thyroid medication. All subjects understood the testing procedure and gave informed written consent. The study was approved by the Stanford Human Subjects Committee. The University of Pennsylvania Smell Identification Test (SIT) (Doty et al ‘ 1984) was used to assess subjects’ olfactory function. This “scratch and sniff” test consists of a series of OCNX-3223/86/$03.50
BIOL PSYCHIATRY
Brief Reports
117
1986;21:116-118
Table 1. Smell IdentificationScores in Alzheimer (n = 17) and Control Subjects (n = 17)
40 chemically impregnated tapes that, when scratched with sandpaper, release an odor. It has a test-retest reliability of 0.92. The SIT was administered in the standardized way used by the University of Pennsylvania group, with one exception: the odor tapes were divided in half so that each booklet could be used for two subjects. Before choosing an answer, each subject read aloud the four choices. Regardless of whether or not a subject could smell the odor, he had to choose among the four alternative responses to identify it. Some people can correctly identify an odor even though they are not conscious of smelling it (R.L. Doty, personal communication, 1984). An examiner assisted all subjects with the test and allowed them unlimited time. The Alzheimer subjects needed approximately 35 min to complete the test, whereas the controls needed about 20 min.
40Item total 20.5 2 7.4e.b 30.2 k 6.9
Alzheimer Control
20-Item subtotal 10.5 2 3.4’ 14.0 rt 3.9
“Mean f SD. “p i 0.001.
‘p < 0.01.
nificantly lower subtotal score of the first 20 items @ < 0.01) (Table 1). The control group did better on 38 of the 40 individual items (Figure 1). Of these 38, 14 were significant (p < 0.05), and 9 of these 14 occurred in the last 12 items of the test. Overall, the 5 items that maximally differentiated @ < 0.005) the Alzheimer and control groups were bubble gum (No. 2), root beer (No. 24), watermelon (No. 30), grass (No. 32), and rose (No. 39). Our control group had a mean total score of 30. The University of Pennsylvania aged-matched controls also had a mean scorn of 30 (Doty 1983), taking into account the ratio of male to females used in our sample.
Results A two-sample t-test (two-tail) was used to determine differences between the groups on each of the 40 items as well as the total of the first 20 items and the overall total of the 40 items. The Alzheimer group had a significantly lower SIT total score (p < 0.001) as well as a sig-
Figure 1. Smell IdentificationTest scores for Alzheimer patients and controls.
0 Alzheimers
I 5
I
I
1
I
1
I
10
15
I
20
25
30
35
40
Item Number
118
Brief Reports
BIOL PSYCHIATRY 1986:21:11~--11X
Discussion Our data suggest that olfactory deficits may be one of the earlier symptoms of Alzheimer’s disease. Our subjects were deliberately chosen to be in the early stages of the disease, so that there would be little question as to their ability to understand and perform the smell test. This fact, plus the pathological changes in the olfactory system, suggest that the etiology of the deficit is olfactory and not cognitive. It is interesting to note that the Alzheimer subjects seemed to have more difficulty at the end of the test. Possible explanations are that (1) they physically tired more easily than the controls, (2) their sense of smell adapted rapidly, or (3) the odors at the end of the test were more sensitive in detecting their deficits. Doty (personal communication, 1985) states that he is unaware of any unique characteristics of the last 12 items of the smell test as compared to earlier items. This difficulty at the end of the test is not solely responsible for the olfactory deficit, as the first 20 items also indicated impairment (p < 0.01). A disordered sense of smell is not unique to Alzheimer’s disease. It can occur with many diseases and medications. The diseases include Parkinson’s disease, multiple sclerosis, and many endocrine disorders (Schiffman 1983). However, the most common causes are probably viral infections, head injuries, normal aging, and local obstructions (Schiffman 1983). A diminished sense of smell in Alzheimer’s disease is more than an intellectual interest; it is a practical one. It can present major problems, such as a decreased appetite, with resultant weight loss and poor nutritional status. Another problem may be the inability to detect noxious odors such as gas and smoke. Both the patient and
family should be made aware of this deficit and the potential problems it may cause.
References Averback P (1983): Two new lesions in Alzheimer’s disease. Lancet ii: 1203. Doty RL (1983): The Smell Identification Test Administration Manual. Philadelphia: University of Pennsylvania. Doty RL, Shaman P, Dann M (1984): Development of the University of Pennsylvania Smell Identification Test. A standard micro-encapsulated test of olfactory function. Physiol Behav 321489-502. Esiri MM, Wilcock GK (1984): The olfactory bulbs in Alzhiemer’s disease. J Neural, Neurosurg, Psychiatry 4756-60.
Folstein MF, Folstein SE, McHugh, PR (1975): Mimmental state. J Psychiatr Res 12: 189-I 98, McConnell RJ, Menendez CE, Smith FR, Henk Rl, Bivlin RS (1975): Defects of taste and smell in patients with hypothyroidism. Am J Med 59:354-364.
Peabody CA, Tinkle&erg JR (1985): Olfactory deficits and primary degenerative dementia. Am J Psychiatry 1421524-525. Reisberg B, Ferris SH, de Leon MJ, Crook T (1982): The Global Deterioration Scale (GDS): An instrument for the assessment of primary degenerative dementia. Am J Psychiatry 139: 1136-I 139. Schiffman S (1983): Taste and smell in disease. N Engl J Med 308:1275-1279.
Serby M, Corwin J, Novatt A, Conrad P, Rotrosen J (1985): Olfaction in Dementia. J Neural, Neurosurg Psychiatry (in press). Simpson J, Yates CM, Gordon A, St. Clair DM (1984): Olfactory tubercle choline acetyltransferase activity in Alzheimer-type dementia, Down’s syndrome and Huntington’s disease. J Neurol Neurosurg Psych&y 47:1138-l 139.