Skip to main content

Advertisement

SpringerLink
Log in

Olfactory Dysfunction in the Elderly: Basic Circuitry and Alterations with Normal Aging and Alzheimer’s Disease

  • Neurology of Aging (KS Marder, Section Editor)
  • Published:
Current Geriatrics Reports Aims and scope Submit manuscript

Abstract

Preclinical detection of Alzheimer’s disease is critical to determining at-risk individuals in order to improve patient and caregiver planning for their futures, and to identify individuals likely to benefit from treatment as advances in therapeutics develop over time. Identification of olfactory dysfunction at the preclinical and early stages of the disease is a potentially useful method to accomplish these goals. We first review basic olfactory circuitry. We then evaluate the evidence of pathophysiological change in the olfactory processing pathways during aging and Alzheimer’s disease in both human and animal models. We also review olfactory behavioral studies during these processes in both types of models. In doing so, we suggest hypotheses about the localization and mechanisms of olfactory dysfunction and identify important avenues for future work.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. Doty RL. Olfactory dysfunction in Parkinson disease. Nat Rev Neurol. 2012;8:329–39.

    PubMed  CAS  Google Scholar 

  2. Shepherd GM, et al. Olfactory Bulb. In: Shepherd GM, editors. Synaptic Organization of the Brain. Oxford, New York, 2004. pp. 165-216.

  3. Doty RL. Office procedures for quantitative assessment of olfactory function. Am J Rhinol. 2007;21:460–73.

    PubMed  Google Scholar 

  4. Paik SI, Lehman MN, Seiden AM, Duncan HJ, Smith DV. Human olfactory biopsy. The influence of age and receptor distribution. Arch Otolaryngol Head Neck Surg. 1992;118:731–8.

    PubMed  CAS  Google Scholar 

  5. Rawson NE, Gomez G, Cowart BJ, Kriete A, Pribitkin E, Restrepo D. Age-associated loss of selectivity in human olfactory sensory neurons. Neurobiol Aging. 2012;33:1913–9.

    PubMed Central  PubMed  Google Scholar 

  6. Maresh A, Rodriguez Gil D, Whitman MC, Greer CA. Principles of glomerular organization in the human olfactory bulb–implications for odor processing. PLoS One. 2008;3:e2640.

    PubMed Central  PubMed  Google Scholar 

  7. Meisami E, Mikhail L, Baim D, Bhatnagar KP. Human olfactory bulb: aging of glomeruli and mitral cells and a search for the accessory olfactory bulb. Ann N Y Acad Sci. 1998;855:708–15.

    PubMed  CAS  Google Scholar 

  8. Morgan CD, Geisler MW, Covington JW, Polich J, Murphy C. Olfactory P3 in young and older adults. Psychophysiology. 1999;36:281–7.

    PubMed  CAS  Google Scholar 

  9. Yousem DM, Maldjian JA, Hummel T, Alsop DC, Geckle RJ, Kraut MA, et al. The effect of age on odor-stimulated functional MR imaging. AJNR Am J Neuroradiol. 1999;20:600–8.

    PubMed  CAS  Google Scholar 

  10. Suzuki Y, Critchley HD, Suckling J, Fukuda R, Williams SC, Andrew C, et al. Functional magnetic resonance imaging of odor identification: the effect of aging. J Gerontol A Biol Sci Med Sci. 2001;56:M756–760.

    PubMed  CAS  Google Scholar 

  11. Kareken DA, Mosnik DM, Doty RL, Dzemidzic M, Hutchins GD. Functional anatomy of human odor sensation, discrimination, and identification in health and aging. Neuropsychology. 2003;17:482–95.

    PubMed  Google Scholar 

  12. Cerf-Ducastel B, Murphy C. FMRI brain activation in response to odors is reduced in primary olfactory areas of elderly subjects. Brain Res. 2003;986:39–53.

    PubMed  CAS  Google Scholar 

  13. Wang J, Eslinger PJ, Smith MB, Yang QX. Functional magnetic resonance imaging study of human olfaction and normal aging. J Gerontol A Biol Sci Med Sci. 2005;60:510–4.

    PubMed  Google Scholar 

  14. Mann DM, Tucker CM, Yates PO. Alzheimer's disease: an olfactory connection? Mech Ageing Dev. 1988;42:1–15.

    PubMed  CAS  Google Scholar 

  15. Reyes PF, Deems DA, Suarez MG. Olfactory-related changes in Alzheimer's disease: a quantitative neuropathologic study. Brain Res Bull. 1993;32:1–5.

    PubMed  CAS  Google Scholar 

  16. ter Laak HJ, Renkawek K, van Workum FP. The olfactory bulb in Alzheimer disease: a morphologic study of neuron loss, tangles, and senile plaques in relation to olfaction. Alzheimer Dis Assoc Disord. 1994;8:38–48.

    PubMed  Google Scholar 

  17. Mundinano IC, Caballero MC, Ordonez C, Hernandez M, DiCaudo C, Marcilla I, et al. Increased dopaminergic cells and protein aggregates in the olfactory bulb of patients with neurodegenerative disorders. Acta Neuropathol. 2011;122:61–74.

    PubMed  CAS  Google Scholar 

  18. Cai Y, Xue ZQ, Zhang XM, Li MB, Wang H, Luo XG, et al. An age-related axon terminal pathology around the first olfactory relay that involves amyloidogenic protein overexpression without plaque formation. Neuroscience. 2012;215:160–73.

    PubMed  CAS  Google Scholar 

  19. Esiri MM, Wilcock GK. The olfactory bulbs in Alzheimer's disease. J Neurol Neurosurg Psychiatry. 1984;47:56–60.

    PubMed Central  PubMed  CAS  Google Scholar 

  20. Ohm TG, Braak H. Olfactory bulb changes in Alzheimer's disease. Acta Neuropathol. 1987;73:365–9.

    PubMed  CAS  Google Scholar 

  21. Loopuijt LD, Sebens JB. Loss of dopamine receptors in the olfactory bulb of patients with Alzheimer's disease. Brain Res. 1990;529:239–44.

    PubMed  CAS  Google Scholar 

  22. Hyman BT, Arriagada PV, Van Hoesen GW. Pathologic changes in the olfactory system in aging and Alzheimer's disease. Ann N Y Acad Sci. 1991;640:14–9.

    PubMed  CAS  Google Scholar 

  23. Struble RG, Clark HB. Olfactory bulb lesions in Alzheimer's disease. Neurobiol Aging. 1992;13:469–73.

    PubMed  CAS  Google Scholar 

  24. Attems J, Lintner F, Jellinger KA. Olfactory involvement in aging and Alzheimer's disease: an autopsy study. J Alzheimers Dis. 2005;7:149–57. discussion 173-180.

    PubMed  CAS  Google Scholar 

  25. Kovacs T, Cairns NJ, Lantos PL. Olfactory centres in Alzheimer's disease: olfactory bulb is involved in early Braak's stages. Neuroreport. 2001;12:285–8.

    PubMed  CAS  Google Scholar 

  26. Kovacs T, Cairns NJ, Lantos PL. beta-amyloid deposition and neurofibrillary tangle formation in the olfactory bulb in ageing and Alzheimer's disease. Neuropathol Appl Neurobiol. 1999;25:481–91.

    PubMed  CAS  Google Scholar 

  27. Li W, Howard JD, Gottfried JA. Disruption of odour quality coding in piriform cortex mediates olfactory deficits in Alzheimer's disease. Brain. 2010;133:2714–26.

    PubMed Central  PubMed  Google Scholar 

  28. Wang J, Eslinger PJ, Doty RL, Zimmerman EK, Grunfeld R, Sun X, et al. Olfactory deficit detected by fMRI in early Alzheimer's disease. Brain Res. 2010;1357:184–94.

    PubMed Central  PubMed  CAS  Google Scholar 

  29. Kareken DA, Doty RL, Moberg PJ, Mosnik D, Chen SH, Farlow MR, et al. Olfactory-evoked regional cerebral blood flow in Alzheimer's disease. Neuropsychology. 2001;15:18–29.

    PubMed  CAS  Google Scholar 

  30. Buchsbaum MS, Kesslak JP, Lynch G, Chui H, Wu J, Sicotte N, et al. Temporal and hippocampal metabolic rate during an olfactory memory task assessed by positron emission tomography in patients with dementia of the Alzheimer type and controls. Preliminary studies. Arch Gen Psychiatry. 1991;48:840–7.

    PubMed  CAS  Google Scholar 

  31. Forster S, Vaitl A, Teipel SJ, Yakushev I, Mustafa M, la Fougere C, et al. Functional representation of olfactory impairment in early Alzheimer's disease. J Alzheimers Dis. 2010;22:581–91.

    PubMed  Google Scholar 

  32. Meisami E. A proposed relationship between increases in the number of olfactory receptor neurons, convergence ratio and sensitivity in the developing rat. Brain Res Dev Brain Res. 1989;46:9–19.

    PubMed  CAS  Google Scholar 

  33. Hinds JW, McNelly NA. Aging in the rat olfactory system: correlation of changes in the olfactory epithelium and olfactory bulb. J Comp Neurol. 1981;203:441–53.

    PubMed  CAS  Google Scholar 

  34. Lee AC, Tian H, Grosmaitre X, Ma M. Expression patterns of odorant receptors and response properties of olfactory sensory neurons in aged mice. Chem Senses. 2009;34:695–703.

    PubMed Central  PubMed  Google Scholar 

  35. Richard MB, Taylor SR, Greer CA. Age-induced disruption of selective olfactory bulb synaptic circuits. Proc Natl Acad Sci U S A. 2010;107:15613–8.

    PubMed Central  PubMed  CAS  Google Scholar 

  36. Mirich JM, Williams NC, Berlau DJ, Brunjes PC. Comparative study of aging in the mouse olfactory bulb. J Comp Neurol. 2002;454:361–72.

    PubMed  Google Scholar 

  37. Tropepe V, Craig CG, Morshead CM, van der Kooy D. Transforming growth factor-alpha null and senescent mice show decreased neural progenitor cell proliferation in the forebrain subependyma. J Neurosci. 1997;17:7850–9.

    PubMed  CAS  Google Scholar 

  38. Enwere E, Shingo T, Gregg C, Fujikawa H, Ohta S, Weiss S. Aging results in reduced epidermal growth factor receptor signaling, diminished olfactory neurogenesis, and deficits in fine olfactory discrimination. J Neurosci. 2004;24:8354–65.

    PubMed  CAS  Google Scholar 

  39. Mobley AS, Bryant AK, Richard MB, Brann JH, Firestein SJ, Greer CA. Age-dependent regional changes in the rostral migratory stream. Neurobiol Aging. 2013;34:1873–81.

    PubMed  Google Scholar 

  40. Hinds JW, McNelly NA. Aging in the rat olfactory bulb: quantitative changes in mitral cell organelles and somato-dendritic synapses. J Comp Neurol. 1979;184:811–20.

    PubMed  CAS  Google Scholar 

  41. Forbes WB. Aging-related morphological changes in the main olfactory bulb of the Fischer 344 rat. Neurobiol Aging. 1984;5:93–9.

    PubMed  CAS  Google Scholar 

  42. Gocel J, Larson J. Evidence for loss of synaptic AMPA receptors in anterior piriform cortex of aged mice. Front Aging Neurosci. 2013;5:39.

    PubMed Central  PubMed  Google Scholar 

  43. Samson RD, Barnes CA. Impact of aging brain circuits on cognition. Eur J Neurosci. 2013;37:1903–15.

    PubMed  Google Scholar 

  44. Terranova JP, Perio A, Worms P, Le Fur G, Soubrie P. Social olfactory recognition in rodents: deterioration with age, cerebral ischaemia and septal lesion. Behav Pharmacol. 1994;5:90–8.

    PubMed  Google Scholar 

  45. Schoenbaum G, Setlow B, Saddoris MP, Gallagher M. Encoding changes in orbitofrontal cortex in reversal-impaired aged rats. J Neurophysiol. 2006;95:1509–17.

    PubMed Central  PubMed  Google Scholar 

  46. Guerin D, Sacquet J, Mandairon N, Jourdan F, Didier A. Early locus coeruleus degeneration and olfactory dysfunctions in Tg2576 mice. Neurobiol Aging. 2009;30:272–83.

    PubMed  CAS  Google Scholar 

  47. Kameshima N, Nanjou T, Fukuhara T, Yanagisawa D, Tooyama I. Correlation of Abeta deposition in the nasal cavity with the formation of senile plaques in the brain of a transgenic mouse model of Alzheimer's disease. Neurosci Lett. 2012;513:166–9.

    PubMed  CAS  Google Scholar 

  48. Wu N, Rao X, Gao Y, Wang J, Xu F. Amyloid-beta deposition and olfactory dysfunction in an Alzheimer's disease model. J Alzheimers Dis. 2013;37:699–712.

    PubMed  CAS  Google Scholar 

  49. Cheng N, Cai H, Belluscio L. In vivo olfactory model of APP-induced neurodegeneration reveals a reversible cell-autonomous function. J Neurosci. 2011;31:13699–704.

    PubMed Central  PubMed  CAS  Google Scholar 

  50. Cao L, Schrank BR, Rodriguez S, Benz EG, Moulia TW, Rickenbacher GT, et al. Abeta alters the connectivity of olfactory neurons in the absence of amyloid plaques in vivo. Nat Commun. 2012;3:1009. By using a mouse model in which human APP is expressed only in olfactory receptor neurons, the authors demonstrate disruption of the peripheral olfactory circuits in the absence of Aβ plaque.

    PubMed Central  PubMed  Google Scholar 

  51. Cheng N, Bai L, Steuer E, Belluscio L. Olfactory functions scale with circuit restoration in a rapidly reversible Alzheimer's disease model. J Neurosci. 2013;33:12208–17.

    PubMed Central  PubMed  CAS  Google Scholar 

  52. Rockenstein E, Mallory M, Mante M, Sisk A, Masliaha E. Early formation of mature amyloid-beta protein deposits in a mutant APP transgenic model depends on levels of Abeta (1-42). J Neurosci Res. 2001;66:573–82.

    PubMed  CAS  Google Scholar 

  53. Lehman EJ, Kulnane LS, Lamb BT. Alterations in beta-amyloid production and deposition in brain regions of two transgenic models. Neurobiol Aging. 2003;24:645–53.

    PubMed  CAS  Google Scholar 

  54. Cassano T, Romano A, Macheda T, Colangeli R, Cimmino CS, Petrella A, et al. Olfactory memory is impaired in a triple transgenic model of Alzheimer disease. Behav Brain Res. 2011;224:408–12. Most animal models of Alzheimer’s disease utilize amyloidogenic genes. Here, odor-based memory testing was performed in a transgenic mouse expressing both Aβ and tau pathology. Severe deficits were found, but pathology was limited to higher order olfactory centers and not the olfactory bulb.

    PubMed  Google Scholar 

  55. Wesson DW, Levy E, Nixon RA, Wilson DA. Olfactory dysfunction correlates with amyloid-beta burden in an Alzheimer's disease mouse model. J Neurosci. 2010;30:505–14.

    PubMed Central  PubMed  CAS  Google Scholar 

  56. Saiz-Sanchez D, De La Rosa-Prieto C, Ubeda-Banon I, Martinez-Marcos A. Interneurons and beta-amyloid in the olfactory bulb, anterior olfactory nucleus and olfactory tubercle in APPxPS1 transgenic mice model of Alzheimer's disease. Anat Rec (Hoboken). 2013;296:1413–23.

    CAS  Google Scholar 

  57. Haughey NJ, Liu D, Nath A, Borchard AC, Mattson MP. Disruption of neurogenesis in the subventricular zone of adult mice, and in human cortical neuronal precursor cells in culture, by amyloid beta-peptide: implications for the pathogenesis of Alzheimer's disease. Neuromol Med. 2002;1:125–35.

    CAS  Google Scholar 

  58. Demars M, Hu YS, Gadadhar A, Lazarov O. Impaired neurogenesis is an early event in the etiology of familial Alzheimer's disease in transgenic mice. J Neurosci Res. 2010;88:2103–17.

    PubMed Central  PubMed  CAS  Google Scholar 

  59. Sotthibundhu A, Li QX, Thangnipon W, Coulson EJ. Abeta(1-42) stimulates adult SVZ neurogenesis through the p75 neurotrophin receptor. Neurobiol Aging. 2009;30:1975–85.

    PubMed  CAS  Google Scholar 

  60. Zhang C, McNeil E, Dressler L, Siman R. Long-lasting impairment in hippocampal neurogenesis associated with amyloid deposition in a knock-in mouse model of familial Alzheimer's disease. Exp Neurol. 2007;204:77–87.

    PubMed Central  PubMed  CAS  Google Scholar 

  61. Lewis J, Dickson DW, Lin WL, Chisholm L, Corral A, Jones G, et al. Enhanced neurofibrillary degeneration in transgenic mice expressing mutant tau and APP. Science. 2001;293:1487–91.

    PubMed  CAS  Google Scholar 

  62. Kim TK, Lee JE, Park SK, Lee KW, Seo JS, Im JY, et al. Analysis of differential plaque depositions in the brains of Tg2576 and Tg-APPswe/PS1dE9 transgenic mouse models of Alzheimer disease. Exp Mol Med. 2012;44:492–502.

    PubMed Central  PubMed  CAS  Google Scholar 

  63. Saiz-Sanchez D, Ubeda-Banon I, De la Rosa-Prieto C, Martinez-Marcos A. Differential expression of interneuron populations and correlation with amyloid-beta deposition in the olfactory cortex of an AbetaPP/PS1 transgenic mouse model of Alzheimer's disease. J Alzheimers Dis. 2012;31:113–29.

    PubMed  CAS  Google Scholar 

  64. Wesson DW, Borkowski AH, Landreth GE, Nixon RA, Levy E, Wilson DA. Sensory network dysfunction, behavioral impairments, and their reversibility in an Alzheimer's beta-amyloidosis mouse model. J Neurosci. 2011;31:15962–71. The investigators used the Tg2576 Alzheimer mouse to demonstrate that aberrant electrical activity in the OB coincides with amyloid in that region, but prior to the behavioral deficits that coincide with piriform cortex dysfunction.

    PubMed Central  PubMed  CAS  Google Scholar 

  65. Girard SD, Baranger K, Gauthier C, Jacquet M, Bernard A, Escoffier G, et al. Evidence for early cognitive impairment related to frontal cortex in the 5XFAD mouse model of Alzheimer's disease. J Alzheimers Dis. 2013;33:781–96.

    PubMed  CAS  Google Scholar 

  66. Eibenstein A, Fioretti AB, Simaskou MN, Sucapane P, Mearelli S, Mina C, et al. Olfactory screening test in mild cognitive impairment. Neurol Sci. 2005;26:156–60.

    PubMed  CAS  Google Scholar 

  67. Djordjevic J, Jones-Gotman M, De Sousa K, Chertkow H. Olfaction in patients with mild cognitive impairment and Alzheimer's disease. Neurobiol Aging. 2008;29:693–706.

    PubMed  Google Scholar 

  68. Laakso MP, Tervo S, Hanninen T, Vanhanen M, Hallikainen M, Soininen H. Olfactory identification in non-demented elderly population and in mild cognitive impairment: a comparison of performance in clinical odor identification versus Boston Naming Test. J Neural Transm. 2009;116:891–5.

    PubMed  Google Scholar 

  69. Bahar-Fuchs A, Chetelat G, Villemagne VL, Moss S, Pike K, Masters CL, et al. Olfactory deficits and amyloid-beta burden in Alzheimer's disease, mild cognitive impairment, and healthy aging: a PiB PET study. J Alzheimers Dis. 2010;22:1081–7.

    PubMed  Google Scholar 

  70. Velayudhan L, Pritchard M, Powell JF, Proitsi P, Lovestone S. Smell identification function as a severity and progression marker in Alzheimer's disease. Int Psychogeriatr. 2013;25:1157–66. This group investigated whether olfactory decline correlated with cognitive progression and illness severity in AD patients. AD patients with recent rapid cognitive progression were found to be associated with rapid olfactory decline at 3 months follow-up, whereas non-rapid cognitive progression was associated with slow olfactory decline. Rapid olfactory decline with higher olfactory dysfunction correlated with high illness severity.

    PubMed  Google Scholar 

  71. Westervelt HJ, Bruce JM, Coon WG, Tremont G. Odor identification in mild cognitive impairment subtypes. J Clin Exp Neuropsychol. 2008;30:151–6.

    PubMed  Google Scholar 

  72. Lehrner J, Pusswald G, Gleiss A, Auff E, Dal-Bianco P. Odor identification and self-reported olfactory functioning in patients with subtypes of mild cognitive impairment. Clin Neuropsychol. 2009;23:818–30.

    PubMed  Google Scholar 

  73. Devanand DP, Tabert MH, Cuasay K, Manly JJ, Schupf N, Brickman AM, et al. Olfactory identification deficits and MCI in a multi-ethnic elderly community sample. Neurobiol Aging. 2010;31:1593–600.

    PubMed Central  PubMed  CAS  Google Scholar 

  74. Bacon AW, Bondi MW, Salmon DP, Murphy C. Very early changes in olfactory functioning due to Alzheimer's disease and the role of apolipoprotein E in olfaction. Ann N Y Acad Sci. 1998;855:723–31.

    PubMed  CAS  Google Scholar 

  75. Graves AB, Bowen JD, Rajaram L, McCormick WC, McCurry SM, Schellenberg GD, et al. Impaired olfaction as a marker for cognitive decline: interaction with apolipoprotein E epsilon4 status. Neurology. 1999;53:1480–7.

    PubMed  CAS  Google Scholar 

  76. Devanand DP, Michaels-Marston KS, Liu X, Pelton GH, Padilla M, Marder K, et al. Olfactory deficits in patients with mild cognitive impairment predict Alzheimer's disease at follow-up. Am J Psychiatry. 2000;157:1399–405.

    PubMed  CAS  Google Scholar 

  77. Royall DR, Chiodo LK, Polk MS, Jaramillo CJ. Severe dysosmia is specifically associated with Alzheimer-like memory deficits in nondemented elderly retirees. Neuroepidemiology. 2002;21:68–73.

    PubMed  CAS  Google Scholar 

  78. Tabert MH, Liu X, Doty RL, Serby M, Zamora D, Pelton GH, et al. A 10-item smell identification scale related to risk for Alzheimer's disease. Ann Neurol. 2005;58:155–60.

    PubMed  Google Scholar 

  79. Wilson RS, Arnold SE, Schneider JA, Tang Y, Bennett DA. The relationship between cerebral Alzheimer's disease pathology and odour identification in old age. J Neurol Neurosurg Psychiatry. 2007;78:30–5.

    PubMed Central  PubMed  CAS  Google Scholar 

  80. Devanand DP, Liu X, Tabert MH, Pradhaban G, Cuasay K, Bell K, et al. Combining early markers strongly predicts conversion from mild cognitive impairment to Alzheimer's disease. Biol Psychiatry. 2008;64:871–9.

    PubMed Central  PubMed  Google Scholar 

  81. Schubert CR, Carmichael LL, Murphy C, Klein BE, Klein R, Cruickshanks KJ. Olfaction and the 5-year incidence of cognitive impairment in an epidemiological study of older adults. J Am Geriatr Soc. 2008;56:1517–21.

    PubMed Central  PubMed  Google Scholar 

  82. Conti MZ, Vicini-Chilovi B, Riva M, Zanetti M, Liberini P, Padovani A, et al. Odor identification deficit predicts clinical conversion from mild cognitive impairment to dementia due to Alzheimer's disease. Arch Clin Neuropsychol. 2013;28:391–9. This article assessed whether baseline olfactory deficit in MCI patients predicted conversion to dementia. At two years followup, 47 % of dysosmic MCI patients converted to dementia compared to 11 % of the normosmics, with an odds ratio for conversion of 5.1, independent of baseline MMSE.

    PubMed  Google Scholar 

  83. Murphy C, Jernigan TL, Fennema-Notestine C. Left hippocampal volume loss in Alzheimer's disease is reflected in performance on odor identification: a structural MRI study. J Int Neuropsychol Soc. 2003;9:459–71.

    PubMed  Google Scholar 

  84. Doty RL, Shaman P, Applebaum SL, Giberson R, Siksorski L, Rosenberg L. Smell identification ability: changes with age. Science. 1984;226:1441–3.

    PubMed  CAS  Google Scholar 

  85. Wilson RS, Schneider JA, Arnold SE, Tang Y, Boyle PA, Bennett DA. Olfactory identification and incidence of mild cognitive impairment in older age. Arch Gen Psychiatry. 2007;64:802–8.

    PubMed  Google Scholar 

  86. Bacon Moore AS, Paulsen JS, Murphy C. A test of odor fluency in patients with Alzheimer's and Huntington's disease. J Clin Exp Neuropsychol. 1999;21:341–51.

    PubMed  CAS  Google Scholar 

  87. Kraemer S, Apfelbach R. Olfactory sensitivity, learning and cognition in young adult and aged male Wistar rats. Physiol Behav. 2004;81:435–42.

    PubMed  CAS  Google Scholar 

  88. Patel RC, Larson J. Impaired olfactory discrimination learning and decreased olfactory sensitivity in aged C57Bl/6 mice. Neurobiol Aging. 2009;30:829–37.

    PubMed Central  PubMed  Google Scholar 

  89. LaSarge CL, Montgomery KS, Tucker C, Slaton GS, Griffith WH, Setlow B, et al. Deficits across multiple cognitive domains in a subset of aged Fischer 344 rats. Neurobiol Aging. 2007;28:928–36.

    PubMed  CAS  Google Scholar 

  90. Prediger RD, De-Mello N, Takahashi RN. Pilocarpine improves olfactory discrimination and social recognition memory deficits in 24 month-old rats. Eur J Pharmacol. 2006;531:176–82.

    PubMed  CAS  Google Scholar 

  91. Luu TT, Pirogovsky E, Gilbert PE. Age-related changes in contextual associative learning. Neurobiol Learn Mem. 2008;89:81–5.

    PubMed Central  PubMed  Google Scholar 

  92. Guan X, Dluzen DE. Age related changes of social memory/recognition in male Fischer 344 rats. Behav Brain Res. 1994;61:87–90.

    PubMed  CAS  Google Scholar 

  93. Roman FS, Alescio-Lautier B, Soumireu-Mourat B. Age-related learning and memory deficits in odor-reward association in rats. Neurobiol Aging. 1996;17:31–40.

    PubMed  CAS  Google Scholar 

  94. Phillips M, Boman E, Osterman H, Willhite D, Laska M. Olfactory and visuospatial learning and memory performance in two strains of Alzheimer's disease model mice–a longitudinal study. PLoS One. 2011;6:e19567.

    PubMed Central  PubMed  CAS  Google Scholar 

  95. Montgomery KS, Simmons RK, Edwards 3rd G, Nicolle MM, Gluck MA, Myers CE, et al. Novel age-dependent learning deficits in a mouse model of Alzheimer's disease: implications for translational research. Neurobiol Aging. 2011;32:1273–85.

    PubMed  CAS  Google Scholar 

  96. Young JW, Sharkey J, Finlayson K. Progressive impairment in olfactory working memory in a mouse model of Mild Cognitive Impairment. Neurobiol Aging. 2009;30:1430–43.

    PubMed  CAS  Google Scholar 

  97. Deacon RM, Koros E, Bornemann KD, Rawlins JN. Aged Tg2576 mice are impaired on social memory and open field habituation tests. Behav Brain Res. 2009;197:466–8.

    PubMed  CAS  Google Scholar 

  98. Rey NL, Jardanhazi-Kurutz D, Terwel D, Kummer MP, Jourdan F, Didier A, et al. Locus coeruleus degeneration exacerbates olfactory deficits in APP/PS1 transgenic mice. Neurobiol Aging. 2012;33(426):e421–411.

    Google Scholar 

  99. Murphy C, Bacon AW, Bondi MW, Salmon DP. Apolipoprotein E status is associated with odor identification deficits in nondemented older persons. Ann N Y Acad Sci. 1998;855:744–50.

    PubMed  CAS  Google Scholar 

  100. Olofsson JK, Nordin S, Wiens S, Hedner M, Nilsson LG, Larsson M. Odor identification impairment in carriers of ApoE-varepsilon4 is independent of clinical dementia. Neurobiol Aging. 2010;31:567–77.

    PubMed  CAS  Google Scholar 

  101. Doty RL, Petersen I, Mensah N, Christensen K. Genetic and environmental influences on odor identification ability in the very old. Psychol Aging. 2011;26:864–71.

    PubMed Central  PubMed  Google Scholar 

  102. Nee LE, Lippa CF. Inherited Alzheimer's disease PS-1 olfactory function: a 10-year follow-up study. Am J Alzheimers Dis Other Demen. 2001;16:83–4.

    PubMed  CAS  Google Scholar 

Download references

Compliance with Ethics Guidelines

Conflict of Interest

Arjun V. Masurkar has received financial support through grants from the National Institute of Mental Health (T32) and the Charles and Lee Brown Fellowship.

D. P. Devanand has received financial support through grants from the National Institute on Aging and Eli Lilly (investigator-initiated research grant), and has served as an advisory board member for AbbVie.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Author information

Authors and Affiliations

  1. Division of Geriatric Psychiatry, New York State Psychiatric Institute, NY, USA; Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, NY, USA

    D. P. Devanand

  2. Division of Aging and Dementia, Department of Neurology, Columbia University, New York, NY, USA

    Arjun V. Masurkar

  3. Neurological Institute of New York, 710 West 168th Street, New York, NY, 10032, USA

    Arjun V. Masurkar

Authors
  1. Arjun V. Masurkar
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. D. P. Devanand
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Arjun V. Masurkar.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Masurkar, A.V., Devanand, D.P. Olfactory Dysfunction in the Elderly: Basic Circuitry and Alterations with Normal Aging and Alzheimer’s Disease. Curr Geri Rep 3, 91–100 (2014). https://doi.org/10.1007/s13670-014-0080-y

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13670-014-0080-y

Keywords

Search

Navigation