0
August 1997, Vol 54, No. 8 >
Article | August 1997

Olfactory Dysfunction for Pyridine and Dementia Progression in Alzheimer Disease

Steven Nordin, PhD; Ove Almkvist, PhD; Birgitta Berglund, PhD; Lars-Olof Wahlund, MD
Arch Neurol. 1997;54(8):993-998. doi:10.1001/archneur.1997.00550200051010
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Comments

Objective:  To investigate whether odor detection sensitivity for pyridine, suggested by previous research not to be affected, is impaired in Alzheimer disease (AD) and whether an association exists between odor threshold and both degree of dementia and rate of dementia progression in AD.

Method:  The method of constant stimuli was used to determine odor thresholds for pyridine in 18 patients with AD (Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised and National Institute of Neurological and Communicative Disorders and Stroke—Alzheimer's Disease and Related Disorders Association criteria) and 16 healthy elderly control subjects. All participants were carefully examined with medical and neuropsychological tests.

Results:  Six patients with AD but none of the controls were anosmic (total olfactory loss) to pyridine, and the 12 nonanosmic patients had significantly higher detection thresholds (50% probability for detection, 323 parts per billion [ppb]) than did the controls (50% probability for detection, 105 ppb). In addition, an association was found between odor threshold and both degree of dementia and rate of dementia progression in AD.

Conclusions:  In contrast to previous findings, our results provide evidence that odor sensitivity in AD is impaired for pyridine. Odor sensitivity, in addition to other suggested predictors of progression rate, may be of interest for defining subgroups of AD or for clinical prognostic judgments of single patients.

REFERENCES

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Terry RD, Davies P.  Dementia of the Alzheimer type . Annu Rev Neurosci . 1980;; 3:77-95.
2 +
Katzman R.  Alzheimer's disease . N Engl J Med . 1986;;314:964-973
3 +
Averback P.  Two new lesions in Alzheimer's disease . Lancet . 1983;;2:1203.
4 +
Esiri MM, Wilcock GK.  The olfactory bulbs in Alzheimer's disease . J Neurol Neurosurg Psychiatry . 1984;;47:56-60.
5 +
Ohm TG, Braak H.  Olfactory bulb changes in Alzheimer's disease . Acta Neuropathol (Berl) . 1987;;73:365-369.
6 +
Reyes PF, Golden GT, Fagel PL, Fariello RG, Katz L, Carner E.  The prepiriform cortex in dementia of the Alzheimer's type . Arch Neurol . 1987;;44:644-645.
7 +
Hooper MW, Vogel FS.  The limbic system in Alzheimer's disease . Am J Pathol . 1976;;85:1-20.
8 +
Hyman BT, Van Hoesen GW, Damasio AR, Barnes CL.  Alzheimer's disease: cell-specific pathology isolates the hippocampal formation . Science . 1984;;225:1168-1170.
9 +
Herzog AG, Kemper TL.  Amygdaloid changes in aging and dementia . Arch Neurol . 1980;;37:625-629.
10 +
Ball MJ.  Neuronal loss, neurofibrillary tangles and granulovacuolar degeneration in the hippocampus with ageing and dementia: a quantitative study . Acta Neuropathol (Berl) . 1977;;37:111-118.
11 +
Simpson J, Yates CM, Gordon A, St Clair DM.  Olfactory tubercle choline acetyltransferase activity in Alzheimer-type dementia, Down's syndrome and Huntington's disease . J Neurol Neurosurg Psychiatry . 1984;;47:1138-1140.
12 +
Yates CM, Simpson J, Gordon A, et al.  Catecholamines and cholinergic enzymes in pre-senile and senile Alzheimer-type dementia and Down's syndrome . Brain Res . 1983;;280:119-126.
13 +
Davies P.  Neurotransmitter-related enzymes in senile dementia of the Alzheimer type . Brain Res . 1979;;171:319-327.
14 +
Perry EK, Gibson PH, Blessed G, Perry RH, Tomlinson BE.  Neuro-transmitter enzyme abnormalities in senile dementia: choline acetyltransferase and glutamic decarboxylase activities in necropsy brain tissue . J Neurol Sci . 1977;;34:247-265.
15 +
Rossor MN, Iversen LL, Mountjoy CQ, et al.  Arginine vasopressin and choline acetyltransferase in brains of patients with Alzheimer type senile dementia . Lancet . 1980;;2:1367-1368.
16 +
Pearson RCA, Esiri MM, Hiorns RW, Wilcock GK, Powell TPS.  Anatomical correlates of the distribution of the pathological changes in the neocortex in Alzheimer's disease . Proc Natl Acad Sci U S A . 1985;;82:4531-4534.
17 +
Talamo BR, Rudel RA, Kosik KS, et al.  Pathological changes in olfactory neurons in patients with Alzheimer's disease . Nature . 1989;;337:736-739.
18 +
Struble RG, Hughes L, Clark HB.  Olfactory bulb degeneration in aging and Alzheimer's disease . In: Pearl J, ed. Development, Growth and Senescence in the Chemical Senses . Washington, DC: National Institutes of Health; 1993;:161-166.
19 +
ter Laak HJ, Renkawek K, van Workum FPA.  The olfactory bulb in Alzheimer's disease: a morphological study of neuron loss, tangles, and senile plaques in relation to olfaction . Alzheimer Dis Assoc Disord . 1994;;8:38-48.
20 +
Price JL, Davis PB, Morris JC, White DL.  The distribution of tangles, plaques and related immunohistological markers in healthy aging and Alzheimer's disease . Neurobiol Aging . 1991;;12:295-312.
21 +
Knupfer L, Spiegel R.  Differences in olfactory test performance between normal aged, Alzheimer and vascular type dementia individuals . Int J Geriatr Psychiatry . 1986;;1:3-14.
22 +
Moberg PJ, Pearlson GD, Speedie LJ, Lipsey JR, Strauss ME, Folstein SE. J Clin Exp Neuropsychol . 1987;;9:650-664.
23 +
Nordin S, Murphy C.  Impaired sensory and cognitive olfactory function in questionable Alzheimer's disease . Neuropsychology . 1996;;10:113-119.
24 +
Serby M, Corwin J, Conrad P, Rotrosen J.  Olfactory dysfunction in Alzheimer's disease and Parkinson's disease . Am J Psychiatry . 1985;;142:781-782.
25 +
Doty RL, Reyes PF, Gregor T.  Presence of both odor identification and detection deficits in Alzheimer's disease . Brain Res Bull . 1987;;18:597-600.
26 +
Kesslak JP, Cotman CW, Chui HC, et al.  Olfactory tests as possible probes for detecting and monitoring Alzheimer's disease . Neurobiol Aging . 1988;;9:399-403.
27 +
Koss E, Weiffenbach JM, Haxby JV, Friedland RP.  Olfactory detection and identification performance are dissociated in early Alzheimer's disease . Neurology . 1988;;38:1228-1232.
28 +
Morgan CD, Nordin S, Murphy C.  Odor identification as an early marker for Alzheimer's disease: impact of lexical functioning and detection sensitivity . J Clin Exp Neuropsychol . 1995;;17:793-803.
29 +
Peabody CA, Tinklenberg JR.  Olfactory deficits and primary degenerative dementia . Am J Psychiatry . 1985;;142:524-525.
30 +
Rezek DL.  Olfactory deficits as a neurologic sign in dementia of the Alzheimer type . Arch Neurol . 1987;;44:1030-1032.
31 +
Warner MD, Peabody CA, Flattery JJ, Tinklenberg JR.  Olfactory deficits and Alzheimer's disease . Biol Psychiatry . 1986;;21:116-118.
32 +
Richard J, Bizzini L.  Olfaction et démences: premiers résultats d'une étude clinique et expérimentale avec le N-propanol . Acta Neurol (Belg) . 1981;;81:333-351.
33 +
Murphy C, Gilmore MM, Seery CS, Salmon DP, Lasker BR.  Olfactory thresholds are associated with degree of dementia in Alzheimer's disease . Neurobiol Aging . 1990;;11:465-469.
34 +
Nordin S, Monsch AU, Murphy C.  Unawareness of smell loss in normal aging and Alzheimer's disease: discrepancy between self-reported and diagnosed smell sensitivity . J Gerontol B Psychol Sci Soc Sci . 1995;;50B:P187-P192.
35 +
Feldman JI, Murphy C, Davidson TM, Jalowayski AA, Galindo de Jaime G.  The rhinologic evaluation of Alzheimer's disease . Laryngoscope . 1991;;101:1198-1202.
36 +
Sherman AH, Amoore JE, Weigel V.  The pyridine scale for clinical measurement of olfactory threshold: a quantitative reevaluation . Otolaryngol Head Neck Surg . 1979;;87:717-733.
37 +
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders , Third Edition, Revised. Washington, DC: American Psychiatric Press; 1987;.
38 +
McKhann G, Drachmann D, Folstein M, Katzman R, Price D, Stadlan EM.  Clinical diagnosis of Alzheimer's disease: report from the NINCDS-ARDRA Work Group under the auspices of the Department of Health and Human Service Task Force on Alzheimer's disease . Neurology . 1984;;34:939-944.
39 +
Wahlund L-O, Agartz I, Almkvist O, et al.  The brain in healthy aged individuals: MR imaging . Radiology . 1990;;174:675-679.
40 +
Murphy C.  Taste and smell in the elderly . In: Meiselman HL, Rivlin RS, eds. Clinical Measurement of Taste and Smell . New York, NY: Macmillan Publishing Co Inc; 1986;:343-371.
41 +
Folstein MF, Folstein SE, McHugh PR.  'Mini-Mental State': a practical method for grading the cognitive state of patients for the clinician . J Psychiatr Res . 1975;; 12:189-198.
42 +
Wechsler D. WAIS-R: Manual . New York, NY: Psychological Corporation; 1981;.
43 +
Kaplan E, Goodglass H, Weintraub S. The Boston Naming Test . Philadelphia, Pa: Lea & Febiger; 1978;.
44 +
Benton A, Hamsher KS. Multilingua Aphasis Examination . Iowa City: Department of Neurology, University Hospital of Iowa; 1978;.
45 +
Wechsler D. Wechsler Intelligence Scale for Children: Manual . New York, NY: Psychological Corporation; 1949;.
46 +
Wechsler D.  A standardized memory scale for clinical use . J Psychol . 1945;;19:87-95.
47 +
Smith PJ, Langolf GD, Goldberg J.  Effects of occupational exposure to elemental mercury on short-term memory . Br J Ind Med . 1983;;40:413-419.
48 +
Milner B.  Interhemispheric differences in the location of psychological processes in man . Br Med Bull . 1971;;27:272-277.
49 +
Gamberale F, Iregren A, Kjellberg A. SPES: The Computerized Swedish Performance Evaluation System: Background, Critical Issues Empirical Data: A User's Manual . Stockholm, Sweden: Arbete och Hälsa (Work and Health); 1989;:6.
50 +
Berglund B, Berglund U, Johansson I, Lindvall T.  Research equipment for air quality studies of nonindustrial environments . Environ Int . 1986;;8:189-194.
51 +
Engen T. Psychophysics,  I: discrimination and detection . In: Kling JW, Riggs LA, eds. Woodworth & Schlosberg's Experimental Psychology . New York, NY: Holt Rinehart & Winston Inc; 1971;:11-46.
52 +
Nordin S, Murphy C, Nijjar R, Quiñonez C.  Odor detection and recognition memory in Alzheimer's disease . Chem Sens . 1993;;18:607-608.
53 +
Mortimer JA, Ebbitt B, Jun S-P, Finch MD.  Predictors of cognitive and functional progression in patients with probable Alzheimer's disease . Neurology . 1992;; 42:1689-1696.
54 +
Ortof E, Crystal HA.  Rate of progression of Alzheimer's disease . J Am Geriatr Soc . 1989;;37:511-514.
55 +
Glasko D, Corey-Bloom J, Thai LJ.  Monitoring progression in Alzheimer's disease . J Am Geriatr Soc . 1991;;39:932-941.
56 +
Devos M, Patte F, Rouault J, Laffort P, Van Gemert LJ. Standardized Human Olfactory Thresholds . New York, NY: Oxford University Press Inc; 1992;.
57 +
Amoore JE.  Specific anosmias . In: Getchell TV, Doty RL, Bartoshuk LM, Snow JB, eds. Smell and Taste in Health and Disease . New York, NY: Raven Press; 1991;:655-664.
58 +
Engen T. The Perception of Odors . Orlando, Fla: Academic Press Inc; 1982;.
59 +
Berglund B, Berglund U, Lindvall T.  Theory and methods for odor evaluation . Experientia . 1986;;42:280-287.

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Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature

Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal

1 +
Terry RD, Davies P.  Dementia of the Alzheimer type . Annu Rev Neurosci . 1980;; 3:77-95.
2 +
Katzman R.  Alzheimer's disease . N Engl J Med . 1986;;314:964-973
3 +
Averback P.  Two new lesions in Alzheimer's disease . Lancet . 1983;;2:1203.
4 +
Esiri MM, Wilcock GK.  The olfactory bulbs in Alzheimer's disease . J Neurol Neurosurg Psychiatry . 1984;;47:56-60.
5 +
Ohm TG, Braak H.  Olfactory bulb changes in Alzheimer's disease . Acta Neuropathol (Berl) . 1987;;73:365-369.
6 +
Reyes PF, Golden GT, Fagel PL, Fariello RG, Katz L, Carner E.  The prepiriform cortex in dementia of the Alzheimer's type . Arch Neurol . 1987;;44:644-645.
7 +
Hooper MW, Vogel FS.  The limbic system in Alzheimer's disease . Am J Pathol . 1976;;85:1-20.
8 +
Hyman BT, Van Hoesen GW, Damasio AR, Barnes CL.  Alzheimer's disease: cell-specific pathology isolates the hippocampal formation . Science . 1984;;225:1168-1170.
9 +
Herzog AG, Kemper TL.  Amygdaloid changes in aging and dementia . Arch Neurol . 1980;;37:625-629.
10 +
Ball MJ.  Neuronal loss, neurofibrillary tangles and granulovacuolar degeneration in the hippocampus with ageing and dementia: a quantitative study . Acta Neuropathol (Berl) . 1977;;37:111-118.
11 +
Simpson J, Yates CM, Gordon A, St Clair DM.  Olfactory tubercle choline acetyltransferase activity in Alzheimer-type dementia, Down's syndrome and Huntington's disease . J Neurol Neurosurg Psychiatry . 1984;;47:1138-1140.
12 +
Yates CM, Simpson J, Gordon A, et al.  Catecholamines and cholinergic enzymes in pre-senile and senile Alzheimer-type dementia and Down's syndrome . Brain Res . 1983;;280:119-126.
13 +
Davies P.  Neurotransmitter-related enzymes in senile dementia of the Alzheimer type . Brain Res . 1979;;171:319-327.
14 +
Perry EK, Gibson PH, Blessed G, Perry RH, Tomlinson BE.  Neuro-transmitter enzyme abnormalities in senile dementia: choline acetyltransferase and glutamic decarboxylase activities in necropsy brain tissue . J Neurol Sci . 1977;;34:247-265.
15 +
Rossor MN, Iversen LL, Mountjoy CQ, et al.  Arginine vasopressin and choline acetyltransferase in brains of patients with Alzheimer type senile dementia . Lancet . 1980;;2:1367-1368.
16 +
Pearson RCA, Esiri MM, Hiorns RW, Wilcock GK, Powell TPS.  Anatomical correlates of the distribution of the pathological changes in the neocortex in Alzheimer's disease . Proc Natl Acad Sci U S A . 1985;;82:4531-4534.
17 +
Talamo BR, Rudel RA, Kosik KS, et al.  Pathological changes in olfactory neurons in patients with Alzheimer's disease . Nature . 1989;;337:736-739.
18 +
Struble RG, Hughes L, Clark HB.  Olfactory bulb degeneration in aging and Alzheimer's disease . In: Pearl J, ed. Development, Growth and Senescence in the Chemical Senses . Washington, DC: National Institutes of Health; 1993;:161-166.
19 +
ter Laak HJ, Renkawek K, van Workum FPA.  The olfactory bulb in Alzheimer's disease: a morphological study of neuron loss, tangles, and senile plaques in relation to olfaction . Alzheimer Dis Assoc Disord . 1994;;8:38-48.
20 +
Price JL, Davis PB, Morris JC, White DL.  The distribution of tangles, plaques and related immunohistological markers in healthy aging and Alzheimer's disease . Neurobiol Aging . 1991;;12:295-312.
21 +
Knupfer L, Spiegel R.  Differences in olfactory test performance between normal aged, Alzheimer and vascular type dementia individuals . Int J Geriatr Psychiatry . 1986;;1:3-14.
22 +
Moberg PJ, Pearlson GD, Speedie LJ, Lipsey JR, Strauss ME, Folstein SE. J Clin Exp Neuropsychol . 1987;;9:650-664.
23 +
Nordin S, Murphy C.  Impaired sensory and cognitive olfactory function in questionable Alzheimer's disease . Neuropsychology . 1996;;10:113-119.
24 +
Serby M, Corwin J, Conrad P, Rotrosen J.  Olfactory dysfunction in Alzheimer's disease and Parkinson's disease . Am J Psychiatry . 1985;;142:781-782.
25 +
Doty RL, Reyes PF, Gregor T.  Presence of both odor identification and detection deficits in Alzheimer's disease . Brain Res Bull . 1987;;18:597-600.
26 +
Kesslak JP, Cotman CW, Chui HC, et al.  Olfactory tests as possible probes for detecting and monitoring Alzheimer's disease . Neurobiol Aging . 1988;;9:399-403.
27 +
Koss E, Weiffenbach JM, Haxby JV, Friedland RP.  Olfactory detection and identification performance are dissociated in early Alzheimer's disease . Neurology . 1988;;38:1228-1232.
28 +
Morgan CD, Nordin S, Murphy C.  Odor identification as an early marker for Alzheimer's disease: impact of lexical functioning and detection sensitivity . J Clin Exp Neuropsychol . 1995;;17:793-803.
29 +
Peabody CA, Tinklenberg JR.  Olfactory deficits and primary degenerative dementia . Am J Psychiatry . 1985;;142:524-525.
30 +
Rezek DL.  Olfactory deficits as a neurologic sign in dementia of the Alzheimer type . Arch Neurol . 1987;;44:1030-1032.
31 +
Warner MD, Peabody CA, Flattery JJ, Tinklenberg JR.  Olfactory deficits and Alzheimer's disease . Biol Psychiatry . 1986;;21:116-118.
32 +
Richard J, Bizzini L.  Olfaction et démences: premiers résultats d'une étude clinique et expérimentale avec le N-propanol . Acta Neurol (Belg) . 1981;;81:333-351.
33 +
Murphy C, Gilmore MM, Seery CS, Salmon DP, Lasker BR.  Olfactory thresholds are associated with degree of dementia in Alzheimer's disease . Neurobiol Aging . 1990;;11:465-469.
34 +
Nordin S, Monsch AU, Murphy C.  Unawareness of smell loss in normal aging and Alzheimer's disease: discrepancy between self-reported and diagnosed smell sensitivity . J Gerontol B Psychol Sci Soc Sci . 1995;;50B:P187-P192.
35 +
Feldman JI, Murphy C, Davidson TM, Jalowayski AA, Galindo de Jaime G.  The rhinologic evaluation of Alzheimer's disease . Laryngoscope . 1991;;101:1198-1202.
36 +
Sherman AH, Amoore JE, Weigel V.  The pyridine scale for clinical measurement of olfactory threshold: a quantitative reevaluation . Otolaryngol Head Neck Surg . 1979;;87:717-733.
37 +
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders , Third Edition, Revised. Washington, DC: American Psychiatric Press; 1987;.
38 +
McKhann G, Drachmann D, Folstein M, Katzman R, Price D, Stadlan EM.  Clinical diagnosis of Alzheimer's disease: report from the NINCDS-ARDRA Work Group under the auspices of the Department of Health and Human Service Task Force on Alzheimer's disease . Neurology . 1984;;34:939-944.
39 +
Wahlund L-O, Agartz I, Almkvist O, et al.  The brain in healthy aged individuals: MR imaging . Radiology . 1990;;174:675-679.
40 +
Murphy C.  Taste and smell in the elderly . In: Meiselman HL, Rivlin RS, eds. Clinical Measurement of Taste and Smell . New York, NY: Macmillan Publishing Co Inc; 1986;:343-371.
41 +
Folstein MF, Folstein SE, McHugh PR.  'Mini-Mental State': a practical method for grading the cognitive state of patients for the clinician . J Psychiatr Res . 1975;; 12:189-198.
42 +
Wechsler D. WAIS-R: Manual . New York, NY: Psychological Corporation; 1981;.
43 +
Kaplan E, Goodglass H, Weintraub S. The Boston Naming Test . Philadelphia, Pa: Lea & Febiger; 1978;.
44 +
Benton A, Hamsher KS. Multilingua Aphasis Examination . Iowa City: Department of Neurology, University Hospital of Iowa; 1978;.
45 +
Wechsler D. Wechsler Intelligence Scale for Children: Manual . New York, NY: Psychological Corporation; 1949;.
46 +
Wechsler D.  A standardized memory scale for clinical use . J Psychol . 1945;;19:87-95.
47 +
Smith PJ, Langolf GD, Goldberg J.  Effects of occupational exposure to elemental mercury on short-term memory . Br J Ind Med . 1983;;40:413-419.
48 +
Milner B.  Interhemispheric differences in the location of psychological processes in man . Br Med Bull . 1971;;27:272-277.
49 +
Gamberale F, Iregren A, Kjellberg A. SPES: The Computerized Swedish Performance Evaluation System: Background, Critical Issues Empirical Data: A User's Manual . Stockholm, Sweden: Arbete och Hälsa (Work and Health); 1989;:6.
50 +
Berglund B, Berglund U, Johansson I, Lindvall T.  Research equipment for air quality studies of nonindustrial environments . Environ Int . 1986;;8:189-194.
51 +
Engen T. Psychophysics,  I: discrimination and detection . In: Kling JW, Riggs LA, eds. Woodworth & Schlosberg's Experimental Psychology . New York, NY: Holt Rinehart & Winston Inc; 1971;:11-46.
52 +
Nordin S, Murphy C, Nijjar R, Quiñonez C.  Odor detection and recognition memory in Alzheimer's disease . Chem Sens . 1993;;18:607-608.
53 +
Mortimer JA, Ebbitt B, Jun S-P, Finch MD.  Predictors of cognitive and functional progression in patients with probable Alzheimer's disease . Neurology . 1992;; 42:1689-1696.
54 +
Ortof E, Crystal HA.  Rate of progression of Alzheimer's disease . J Am Geriatr Soc . 1989;;37:511-514.
55 +
Glasko D, Corey-Bloom J, Thai LJ.  Monitoring progression in Alzheimer's disease . J Am Geriatr Soc . 1991;;39:932-941.
56 +
Devos M, Patte F, Rouault J, Laffort P, Van Gemert LJ. Standardized Human Olfactory Thresholds . New York, NY: Oxford University Press Inc; 1992;.
57 +
Amoore JE.  Specific anosmias . In: Getchell TV, Doty RL, Bartoshuk LM, Snow JB, eds. Smell and Taste in Health and Disease . New York, NY: Raven Press; 1991;:655-664.
58 +
Engen T. The Perception of Odors . Orlando, Fla: Academic Press Inc; 1982;.
59 +
Berglund B, Berglund U, Lindvall T.  Theory and methods for odor evaluation . Experientia . 1986;;42:280-287.

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