Skip to main content
NCBI home page
Journal of Neurology, Neurosurgery, and Psychiatry logoLink to Journal of Neurology, Neurosurgery, and Psychiatry
. 2005 Oct;76(10):1342–1347. doi: 10.1136/jnnp.2003.032003

Anosmia is very common in the Lewy body variant of Alzheimer's disease

J Olichney 1, C Murphy 1, C Hofstetter 1, K Foster 1, L Hansen 1, L Thal 1, R Katzman 1
PMCID: PMC1739380  PMID: 16170073

Abstract

Background: Olfactory abnormalities are reported in Alzheimer's disease and Parkinson's disease. Anosmia appears to be common in dementia with Lewy bodies but not in pure Alzheimer's disease.

Objective: To determine whether anosmia improves discrimination between the Lewy body variant (LBV) of Alzheimer's disease and "pure" Alzheimer's disease.

Methods: 106 cases of necropsy confirmed pure Alzheimer's disease (n = 89) or LBV (n = 17) were reviewed. All had received butanol odour threshold testing. Anosmia was defined as a score ⩽1.0 on a 0–9 point scale. Logistic regression analysis was used to model potential predictors (for example, parkinsonism, smoking, hallucinations) of neuropathological diagnosis and anosmia.

Results: LBV cases had an increased prevalence of anosmia (65%) compared with Alzheimer's disease (23%; odds ratio (OR) = 6.3, p = 0.00045), or normal elderly people (6.7%). Within the dementia cases, the negative predictive value (92%) and specificity (78%) of anosmia were both good; sensitivity for detecting LBV was 65%, but the positive predictive value (PPV) was only 35%. Logistic regression models showed anosmia (OR = 5.4, p = 0.005) and visual hallucinations (OR = 7.3, p = 0.007) were strong independent predictors of Lewy body pathology. When anosmia was added as a core feature to consensus diagnostic criteria for probable Lewy body dementia, five additional cases of LBV were detected (29% increased sensitivity), but with four additional false positives (1% increased discrimination, 4% decreased specificity, 33% decreased PPV).

Conclusions: Anosmia is very common in LBV. Adding anosmia as a core feature improved sensitivity for detecting LBV, but did not improve discrimination between Alzheimer's disease and LBV owing to a concomitant increase in false positives.

Full Text

The Full Text of this article is available as a PDF (91.7 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Braak H., Braak E. Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol. 1991;82(4):239–259. doi: 10.1007/BF00308809. [DOI] [PubMed] [Google Scholar]
  2. Braak Heiko, Del Tredici Kelly, Rüb Udo, de Vos Rob A. I., Jansen Steur Ernst N. H., Braak Eva. Staging of brain pathology related to sporadic Parkinson's disease. Neurobiol Aging. 2003 Mar-Apr;24(2):197–211. doi: 10.1016/s0197-4580(02)00065-9. [DOI] [PubMed] [Google Scholar]
  3. Cain W. S., Gent J., Catalanotto F. A., Goodspeed R. B. Clinical evaluation of olfaction. Am J Otolaryngol. 1983 Jul-Aug;4(4):252–256. doi: 10.1016/s0196-0709(83)80068-4. [DOI] [PubMed] [Google Scholar]
  4. Doty R. L., Deems D. A., Stellar S. Olfactory dysfunction in parkinsonism: a general deficit unrelated to neurologic signs, disease stage, or disease duration. Neurology. 1988 Aug;38(8):1237–1244. doi: 10.1212/wnl.38.8.1237. [DOI] [PubMed] [Google Scholar]
  5. Doty R. L., Riklan M., Deems D. A., Reynolds C., Stellar S. The olfactory and cognitive deficits of Parkinson's disease: evidence for independence. Ann Neurol. 1989 Feb;25(2):166–171. doi: 10.1002/ana.410250210. [DOI] [PubMed] [Google Scholar]
  6. Frye R. E., Schwartz B. S., Doty R. L. Dose-related effects of cigarette smoking on olfactory function. JAMA. 1990 Mar 2;263(9):1233–1236. [PubMed] [Google Scholar]
  7. Galasko D., Hansen L. A., Katzman R., Wiederholt W., Masliah E., Terry R., Hill L. R., Lessin P., Thal L. J. Clinical-neuropathological correlations in Alzheimer's disease and related dementias. Arch Neurol. 1994 Sep;51(9):888–895. doi: 10.1001/archneur.1994.00540210060013. [DOI] [PubMed] [Google Scholar]
  8. Gearing M., Mirra S. S., Hedreen J. C., Sumi S. M., Hansen L. A., Heyman A. The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part X. Neuropathology confirmation of the clinical diagnosis of Alzheimer's disease. Neurology. 1995 Mar;45(3 Pt 1):461–466. doi: 10.1212/wnl.45.3.461. [DOI] [PubMed] [Google Scholar]
  9. Hansen L. A., Galasko D., Samuel W., Xia Y., Chen X., Saitoh T. Apolipoprotein-E epsilon-4 is associated with increased neurofibrillary pathology in the Lewy body variant of Alzheimer's disease. Neurosci Lett. 1994 Nov 21;182(1):63–65. doi: 10.1016/0304-3940(94)90206-2. [DOI] [PubMed] [Google Scholar]
  10. Hansen L. A., Masliah E., Galasko D., Terry R. D. Plaque-only Alzheimer disease is usually the lewy body variant, and vice versa. J Neuropathol Exp Neurol. 1993 Nov;52(6):648–654. doi: 10.1097/00005072-199311000-00012. [DOI] [PubMed] [Google Scholar]
  11. Hansen L. A., Samuel W. Criteria for Alzheimer's disease and the nosology of dementia with Lewy bodies. Neurology. 1997 Jan;48(1):126–132. doi: 10.1212/wnl.48.1.126. [DOI] [PubMed] [Google Scholar]
  12. Hansen L., Salmon D., Galasko D., Masliah E., Katzman R., DeTeresa R., Thal L., Pay M. M., Hofstetter R., Klauber M. The Lewy body variant of Alzheimer's disease: a clinical and pathologic entity. Neurology. 1990 Jan;40(1):1–8. doi: 10.1212/wnl.40.1.1. [DOI] [PubMed] [Google Scholar]
  13. Hendriks A. P. Olfactory dysfunction. Rhinology. 1988 Dec;26(4):229–251. [PubMed] [Google Scholar]
  14. Lopez O. L., Hamilton R. L., Becker J. T., Wisniewski S., Kaufer D. I., DeKosky S. T. Severity of cognitive impairment and the clinical diagnosis of AD with Lewy bodies. Neurology. 2000 May 9;54(9):1780–1787. doi: 10.1212/wnl.54.9.1780. [DOI] [PubMed] [Google Scholar]
  15. McKeith I. G., Ballard C. G., Perry R. H., Ince P. G., O'Brien J. T., Neill D., Lowery K., Jaros E., Barber R., Thompson P. Prospective validation of consensus criteria for the diagnosis of dementia with Lewy bodies. Neurology. 2000 Mar 14;54(5):1050–1058. doi: 10.1212/wnl.54.5.1050. [DOI] [PubMed] [Google Scholar]
  16. McKeith I. G., Galasko D., Kosaka K., Perry E. K., Dickson D. W., Hansen L. A., Salmon D. P., Lowe J., Mirra S. S., Byrne E. J. Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB): report of the consortium on DLB international workshop. Neurology. 1996 Nov;47(5):1113–1124. doi: 10.1212/wnl.47.5.1113. [DOI] [PubMed] [Google Scholar]
  17. McKhann G., Drachman D., Folstein M., Katzman R., Price D., Stadlan E. M. Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology. 1984 Jul;34(7):939–944. doi: 10.1212/wnl.34.7.939. [DOI] [PubMed] [Google Scholar]
  18. McShane R. H., Nagy Z., Esiri M. M., King E., Joachim C., Sullivan N., Smith A. D. Anosmia in dementia is associated with Lewy bodies rather than Alzheimer's pathology. J Neurol Neurosurg Psychiatry. 2001 Jun;70(6):739–743. doi: 10.1136/jnnp.70.6.739. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Merdes A. R., Hansen L. A., Jeste D. V., Galasko D., Hofstetter C. R., Ho G. J., Thal L. J., Corey-Bloom J. Influence of Alzheimer pathology on clinical diagnostic accuracy in dementia with Lewy bodies. Neurology. 2003 May 27;60(10):1586–1590. doi: 10.1212/01.wnl.0000065889.42856.f2. [DOI] [PubMed] [Google Scholar]
  20. Mirra S. S., Heyman A., McKeel D., Sumi S. M., Crain B. J., Brownlee L. M., Vogel F. S., Hughes J. P., van Belle G., Berg L. The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part II. Standardization of the neuropathologic assessment of Alzheimer's disease. Neurology. 1991 Apr;41(4):479–486. doi: 10.1212/wnl.41.4.479. [DOI] [PubMed] [Google Scholar]
  21. Morgan C. D., 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 Oct;17(5):793–803. doi: 10.1080/01688639508405168. [DOI] [PubMed] [Google Scholar]
  22. Murphy C., Bacon A. W., Bondi M. W., Salmon D. P. Apolipoprotein E status is associated with odor identification deficits in nondemented older persons. Ann N Y Acad Sci. 1998 Nov 30;855:744–750. doi: 10.1111/j.1749-6632.1998.tb10654.x. [DOI] [PubMed] [Google Scholar]
  23. Murphy C., Gilmore M. M., Seery C. S., Salmon D. P., Lasker B. R. Olfactory thresholds are associated with degree of dementia in Alzheimer's disease. Neurobiol Aging. 1990 Jul-Aug;11(4):465–469. doi: 10.1016/0197-4580(90)90014-q. [DOI] [PubMed] [Google Scholar]
  24. Murphy Claire, Schubert Carla R., Cruickshanks Karen J., Klein Barbara E. K., Klein Ronald, Nondahl David M. Prevalence of olfactory impairment in older adults. JAMA. 2002 Nov 13;288(18):2307–2312. doi: 10.1001/jama.288.18.2307. [DOI] [PubMed] [Google Scholar]
  25. Nordin S., Almkvist O., Berglund B., Wahlund L. O. Olfactory dysfunction for pyridine and dementia progression in Alzheimer disease. Arch Neurol. 1997 Aug;54(8):993–998. doi: 10.1001/archneur.1997.00550200051010. [DOI] [PubMed] [Google Scholar]
  26. Petersen R. C., Smith G. E., Waring S. C., Ivnik R. J., Tangalos E. G., Kokmen E. Mild cognitive impairment: clinical characterization and outcome. Arch Neurol. 1999 Mar;56(3):303–308. doi: 10.1001/archneur.56.3.303. [DOI] [PubMed] [Google Scholar]
  27. Robins L. N., Helzer J. E., Croughan J., Ratcliff K. S. National Institute of Mental Health Diagnostic Interview Schedule. Its history, characteristics, and validity. Arch Gen Psychiatry. 1981 Apr;38(4):381–389. doi: 10.1001/archpsyc.1981.01780290015001. [DOI] [PubMed] [Google Scholar]
  28. Serby M. Olfaction and Alzheimer's disease. Prog Neuropsychopharmacol Biol Psychiatry. 1986;10(3-5):579–586. doi: 10.1016/0278-5846(86)90027-8. [DOI] [PubMed] [Google Scholar]
  29. Stern Y., Alexander G. E., Prohovnik I., Mayeux R. Inverse relationship between education and parietotemporal perfusion deficit in Alzheimer's disease. Ann Neurol. 1992 Sep;32(3):371–375. doi: 10.1002/ana.410320311. [DOI] [PubMed] [Google Scholar]
  30. Verghese J., Crystal H. A., Dickson D. W., Lipton R. B. Validity of clinical criteria for the diagnosis of dementia with Lewy bodies. Neurology. 1999 Dec 10;53(9):1974–1982. doi: 10.1212/wnl.53.9.1974. [DOI] [PubMed] [Google Scholar]
  31. Westervelt Holly James, Stern Robert A., Tremont Geoffrey. Odor identification deficits in diffuse lewy body disease. Cogn Behav Neurol. 2003 Jun;16(2):93–99. doi: 10.1097/00146965-200306000-00002. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Neurology, Neurosurgery, and Psychiatry are provided here courtesy of BMJ Publishing Group

RESOURCES