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The Role of Olfactory Challenge Tests in Incipient Dementia and Clinical Trial Design

  • Dementia (KS Marder, Section Editor)
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Abstract

The brain changes associated with Alzheimer’s disease (AD) develop slowly over many years before the onset of dementia. Biomarkers for AD that allow its detection during this clinically silent phase will be hugely important when disease-modifying treatments that halt or slow its progression become available. Early detection, leading to early treatment, may in some cases avert dementia. Biomarkers aid our understanding of the presymptomatic stages of the disease and enable the identification of individuals with early disease who, by participating in clinical trials of investigational treatments with disease-modifying potential, contribute unique and vital information necessary to evaluate novel therapies. Most currently available AD biomarkers are expensive and not widely available and there are major efforts underway to find cheaper, simpler options. The olfactory system is affected by AD and the results from simple and inexpensive tests of the sense of smell, especially when paired with other information, can help identify individuals early in the disease. We review recent literature relevant to the use of simple olfactory tests, including some novel approaches, as aids to the early detection of AD. We consider their possible role in the design and conduct of clinical trials and suggest how in the future, when more effective treatments become available, they might be integrated into screening programs for early AD detection.

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References

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

  1. Wesson DW, Wilson DA, Nixon RA. Should olfactory dysfunction be used as a biomarker of Alzheimer’s disease? Expert Rev Neurother. 2010;10:633–5. doi:10.1586/ern.10.33. A concise account of the issues relating to olfactory testing in the early detection of AD.

    Article  PubMed Central  PubMed  Google Scholar 

  2. Albersa MW, Kayec J, Murphyd C, Wingfielde A, Boxerg AL, Buchmanf AS, et al. At the interface of sensory and motor dysfunctions and Alzheimer’s disease. Alzheimer Dement. 2014; An important, broad systematic summary, examining sensory and motor changes in AD.

  3. Amieva H, Jacqmin-Gadda H, Orgogozo JM, Le Carret N, Helmer C, Letenneur L, et al. The 9 year cognitive decline before dementia of the Alzheimer type: a prospective population-based study. Brain. 2005;128(Pt 5):1093–101. doi:10.1093/brain/awh451.

  4. Jack CR, Knopman DS, Jagust WJ, Shaw LM, Aisen PS, Weiner MW, et al. Hypothetical model of dynamic biomarkers of the Alzheimer's pathological cascade. Lancet Neurol. 2010;9(1):119–28.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  5. Jack CR, Knopman DS, Jagust WJ, Petersen RC, Weiner MW, Aisen PS, et al. Tracking pathophysiological processes in Alzheimer's disease: an updated hypothetical model of dynamic biomarkers. Lancet Neurol. 2013;12(2):207–16. doi:10.1016/s1474-4422(12)70291-0.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  6. Rahayel S, Frasnelli J, Joubert S. The effect of Alzheimer's disease and Parkinson's disease on olfaction: a meta-analysis. Behav Brain Res. 2012;231(1):60–74. doi:10.1016/j.bbr.2012.02.047.

    Article  PubMed  Google Scholar 

  7. Sun GH, Raji CA, Maceachern MP, Burke JF. Olfactory identification testing as a predictor of the development of Alzheimer's dementia: a systematic review. Laryngoscope. 2012;122(7):1455–62. doi:10.1002/lary.23365.

    Article  PubMed  Google Scholar 

  8. 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(7):1157–66. doi:10.1017/S1041610213000446.

    Article  PubMed  Google Scholar 

  9. Schubert CR, Cruickshanks KJ, Fischer ME, Huang GH, Klein R, Pankratz N, et al. Odor identification and cognitive function in the Beaver Dam Offspring Study. J Clin Exp Neuropsychol. 2013;35(7):669–76. doi:10.1080/13803395.2013.809701.

    Article  PubMed Central  PubMed  Google Scholar 

  10. Schubert CR, Carmichael LL, Murphy C, Klein BE, Klein R, Cruickshanks KJ. Olfaction and the 5-year incidence of cognitive impairment in an epidemiologic study of older adults. J Am Geriatr Soc. 2008;56(8):1517–21. doi:10.1111/j.1532-5415.2008.01826.x.

    Article  PubMed Central  PubMed  Google Scholar 

  11. Devanand DP, Michaels-Marston KS, Liu XH, 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(9):1399–405. doi:10.1176/appi.ajp.157.9.1399.

  12. Devanand DP, Liu XH, 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(10):871–9. doi:10.1016/j.biopsych.2008.06.020. Remains a key work, showing how combining measures enhances predictive yield.

    Article  PubMed Central  PubMed  Google Scholar 

  13. Wilson RS, Schneider JA, Arnold SE, Tang YX, Boyle PA, Bennett DA. Olfactory identification and incidence of mild cognitive impairment in older age. Arch Gen Psychiatry. 2007;64(7):802–8. doi:10.1001/archpsyc.64.7.802.

    Article  PubMed  Google Scholar 

  14. Wilson RS, Arnold SE, Schneider JA, Boyle PA, Buchman AS, Bennett DA. Olfactory impairment in presymptomatic Alzheimer's disease. Ann N Y Acad Sci. 2009;1170:730–5. doi:10.1111/j.1749-6632.2009.04013.x.

    Article  PubMed Central  PubMed  Google Scholar 

  15. Lee WH, Wee JH, Kim DK, Rhee CS, Lee CH, Ahn S, et al. Prevalence of Subjective olfactory dysfunction and its risk factors: Korean National Health and Nutrition Examination Survey. Plos One. 2013;8(5). doi:10.1371/journal.pone.0062725.

  16. Murphy C, Schubert CR, Cruickshanks KJ, Klein BEK, Klein R, Nondahl DM. Prevalence of olfactory impairment in older adults. J Am Med Assoc. 2002;288(18):2307–12. doi:10.1001/jama.288.18.2307.

    Article  Google Scholar 

  17. Nordin S, Bramerson A, Bende M. Prevalence of self-reported poor odor detection sensitivity: the Skovde population-based study. Acta Otolaryngol. 2004;124(10):1171–3. doi:10.1080/00016480410017468.

  18. Schubert CR, Cruickshanks KJ, Murphy C, Huang GH, Klein BEK, Klein R, et al. Olfactory Impairment in Adults The Beaver Dam Experience. In: Finger TE, editor. International Symposium on Olfaction and Taste. Ann N Y Acad Sci. 2009. p. 531–6.

  19. Galvin JE, Fagan AM, Holtzman DM, Mintun MA, Morris JC. Relationship of dementia screening tests with biomarkers of Alzheimer's disease. Brain. 2010;133(11):3290–300. doi:10.1093/brain/awq204.

    Article  PubMed Central  PubMed  Google Scholar 

  20. Lim YY, Ellis KA, Harrington K, Pietrzak RH, Gale J, Ames D, et al. Cognitive decline in adults with amnestic mild cognitive impairment and high amyloid-beta: prodromal Alzheimer's disease? J Alzheimers Dis. 2013;33(4):1167–76. doi:10.3233/JAD-121771.

    CAS  PubMed  Google Scholar 

  21. Stewart R. Mild cognitive impairment—the continuing challenge of its “real-world” detection and diagnosis. Arch Med Res. 2012;43(8):609–14. doi:10.1016/j.arcmed.2012.10.011.

    Article  PubMed  Google Scholar 

  22. Brown J, Pengas G, Dawson K, Brown LA, Clatworthy P. Self administered cognitive screening test (TYM) for detection of Alzheimer's disease: cross sectional study. Br Med J. 2009;338. doi:10.1136/bmj.b2030.

  23. Scharre DW, Chang S-I, Murden RA, Lamb J, Beversdorf DQ, Kataki M. Self-administered Gerocognitive Examination (SAGE): a brief cognitive assessment Instrument for mild cognitive impairment (MCI) and early dementia. Alzheimer Dis Assoc Disord. 2010;24(1):64–71. doi:10.1097/WAD.0b013e3181b03277.

  24. McEvoy M, Smith W, D'Este C, Duke J, Peel R, Schofield P, et al. Cohort profile: the hunter community study. Int J Epidemiol. 2010;39(6):1452–63. doi:10.1093/ije/dyp343.

    Article  PubMed  Google Scholar 

  25. Schofield PW, Stephen L. Home-based testing of cognition with the tape-administered cognitive screen. Neurobiol Aging. 2004;25:S129–30. doi:10.1016/s0197-4580(04)80435-4.

  26. Noyce AJ, Bestwick JP, Silveira-Moriyama L, Hawkes CH, Knowles CH, Hardy J, et al. PREDICT-PD: identifying risk of Parkinson's disease in the community: methods and baseline results. J Neurol Neurosurg Psychiatry. 2014;85(1):31–7. doi:10.1136/jnnp-2013-305420.

  27. Oremus M, Tarride J-E, Pullenayegum E, Clayton N. Canadian Willingness-to-Pay Study G, Raina P. Patients’ willingness-to-pay for an Alzheimer’s disease medication in Canada. Patient. 2013;6(3):161–8. doi:10.1007/s40271-013-0014-3.

    Article  PubMed  Google Scholar 

  28. Mansouri D, McMillan DC, Grant Y, Crighton EM, Horgan PG. The impact of age, sex and socioeconomic deprivation on outcomes in a colorectal cancer screening programme. PLoS One [Elec]. 2013;8(6)):e66063. doi:10.1371/journal.pone.0066063.

    Article  CAS  Google Scholar 

  29. Doty RL, Kamath V. The influences of age on olfaction: a review. Front Psychol. 2014;5:20. doi:10.3389/fpsyg.2014.00020.

    Article  PubMed Central  PubMed  Google Scholar 

  30. Gaines A. Chapter 13: olfactory disorders. Am J Rhinol Allergy. 2013;27 Suppl 1:S45–7. doi:10.2500/ajra.2013.27.3898.

    Article  PubMed  Google Scholar 

  31. Albers MW, Tabert MH, Devanand DP. Olfactory dysfunction as a predictor of neuro-degenerative disease. Curr Neurol Neurosci Rep. 2006;6(5):379–86. doi:10.1007/s11910-996-0018-7.

  32. Ross GW, Petrovitch H, Abbott RD, Tanner CM, Popper J, Masaki K, et al. Association of olfactory dysfunction with risk for future Parkinson's disease. Ann Neurol. 2008;63(2):167–73. doi:10.1002/ana.21291.

    Article  PubMed  Google Scholar 

  33. Kovacs T. The olfactory system in Alzheimer's disease: pathology, pathophysiology and pathway for therapy. Transl Neurosci. 2013;4(1):34–45. doi:10.2478/s13380-013-0108-3. A valuable and comprehensive summary by an important contributor.

    Article  Google Scholar 

  34. Arnold SE, Lee EB, Moberg PJ, Stutzbach L, Kazi H, Han LY, et al. Olfactory epithelium amyloid-beta and paired helical filament-tau pathology in Alzheimer disease. Ann Neurol. 2010;67(4):462–9. doi:10.1002/ana.21910.

  35. Attems J, Walker L, Jellinger KA. Olfactory bulb involvement in neurodegenerative diseases. Acta Neuropathol. 2014;127(4):459–75. doi:10.1007/s00401-014-1261-7. Review with new data, very comprehensive.

    Article  CAS  PubMed  Google Scholar 

  36. Velayudhan L, Lovestone S. Smell identification test as a treatment response marker in patients with Alzheimer disease receiving donepezil. J Clin Psychopharmacol. 2009;29(4):387–90. doi:10.1097/JCP.0b013e3181aba5a5.

    Article  CAS  PubMed  Google Scholar 

  37. de Almeida L, Idiart M, Linster C. A model of cholinergic modulation in olfactory bulb and piriform cortex. J Neurophysiol. 2013;109(5):1360–77. doi:10.1152/jn.00577.2012.

    Article  PubMed Central  PubMed  Google Scholar 

  38. Mundinano IC, Hernandez M, Dicaudo C, Ordonez C, Marcilla I, Tunon MT, et al. Reduced cholinergic olfactory centrifugal inputs in patients with neurodegenerative disorders and MPTP-treated monkeys. Acta Neuropathol. 2013;126(3):411–25. doi:10.1007/s00401-013-1144-3.

  39. 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(2):505–14. doi:10.1523/JNEUROSCI.4622-09.2010. Important findings in a mouse model of AD.

  40. Wesson DW, Morales-Corraliza J, Mazzella MJ, Wilson DA, Mathews PM. Chronic anti-murine Abeta immunization preserves odor guided behaviors in an Alzheimer's beta-amyloidosis model. Behav Brain Res. 2013;237:96–102. doi:10.1016/j.bbr.2012.09.019.

  41. Bales KR, Tzavara ET, Wu S, Wade MR, Bymaster FP, Paul SM, et al. Cholinergic dysfunction in a mouse model of Alzheimer disease is reversed by an anti-A beta antibody. J Clin Invest. 2006;116(3):825–32. doi:10.1172/JCI27120.

  42. Krosnowski K, Ashby S, Sathyanesan A, Luo W, Ogura T, Lin W. Diverse populations of intrinsic cholinergic interneurons in the mouse olfactory bulb. Neuroscience. 2012;213:161–78. doi:10.1016/j.neuroscience.2012.04.024.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  43. Doty RL. Olfactory dysfunction and its measurement in the clinic and workplace. Int Arch Occup Environ Health. 2006;79(4):268–82. doi:10.1007/s00420-005-0055-6.

    Article  PubMed  Google Scholar 

  44. Eibenstein A, Fioretti AB, Lena C, Rosati N, Amabile G, Fusetti M. Modern psychophysical tests to assess olfactory function. Neurol Sci. 2005;26(3):147–55.

    Article  CAS  PubMed  Google Scholar 

  45. Hummel T, Kobal G, Gudziol H, Mackay-Sim A. Normative data for the “Sniffin’ Sticks” including tests of odor identification, odor discrimination, and olfactory thresholds: an upgrade based on a group of more than 3,000 subjects. Eur Arch Otorhinolaryngol. 2007;264(3):237–43. doi:10.1007/s00405-006-0173-0.

  46. Yucepur C, Ozucer B, Degirmenci N, Yildirim Y, Veyseller B, Ozturan O. University of Pennsylvania smell identification test: application to Turkish population. Kulak Burun Bogaz Ihtis Derg. 2012;22(2):77–80. doi:10.5606/kbbihtisas.2012.014.

    Article  PubMed  Google Scholar 

  47. Bahar-Fuchs A, Moss S, Rowe C, Savage G. Olfactory performance in AD, aMCI, and healthy ageing: a unirhinal approach. Chem Senses. 2010;35(9):855–62. doi:10.1093/chemse/bjq094.

    Article  PubMed  Google Scholar 

  48. Schubert CR, Cruickshanks KJ, Klein BEK, Klein R, Nondahl DM. Olfactory impairment in older adults: five-year incidence and risk factors. Laryngoscope. 2011;121(4):873–8. doi:10.1002/lary.21416.

  49. Bahar-Fuchs A, Moss S, Rowe C, Savage G. Awareness of olfactory deficits in healthy aging, amnestic mild cognitive impairment and Alzheimer's disease. Int Psychogeriatr. 2011;23(7):1097–106. doi:10.1017/S1041610210002371.

    Article  PubMed  Google Scholar 

  50. Reid LM, Maclullich AMJ. Subjective memory complaints and cognitive impairment in older people. Dement Geriatr Cogn Disord. 2006;22(5–6):471–85.

    Article  PubMed  Google Scholar 

  51. Amariglio RE, Becker JA, Carmasin J, Wadsworth LP, Lorius N, Sullivan C, et al. Subjective cognitive complaints and amyloid burden in cognitively normal older individuals. Neuropsychologia. 2012;50(12):2880–6. doi:10.1016/j.neuropsychologia.2012.08.011.

    Article  PubMed Central  PubMed  Google Scholar 

  52. Sohrabi HR, Bates KA, Rodrigues M, Taddei K, Laws SM, Lautenschlager NT, et al. Olfactory dysfunction is associated with subjective memory complaints in community-dwelling elderly individuals. J Alzheimers Dis. 2009;17(1):135–42. doi:10.3233/JAD-2009-1020.

    PubMed  Google Scholar 

  53. 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(7):1480–7.

    Article  CAS  PubMed  Google Scholar 

  54. Albers MW, Marder KS. A tale of two etiologies: loss and recovery of olfactory function. Ann Neurol. 2008;63(2):132–4. doi:10.1002/ana.21330.

    Article  PubMed  Google Scholar 

  55. Schofield PW, Lee SJ, Lewin TJ, Lyall G, Moyle J, Attia J, et al. The Audio Recorded Cognitive Screen (ARCS): a flexible hybrid cognitive test instrument. J Neurol Neurosurg Psychiatry. 2010;81(6):602–7. doi:10.1136/jnnp.2009.188003.

    Article  PubMed  Google Scholar 

  56. Audio Recorded Cognitive Screen webpage. www.cognitionhealth.com.

  57. Cullen B, O'Neill B, Evans JJ, Coen RF, Lawlor BA. A review of screening tests for cognitive impairment. J Neurol Neurosurg Psychiatry. 2007;78(8):790–9. doi:10.1136/jnnp.2006.095414.

    Article  PubMed Central  PubMed  Google Scholar 

  58. Sohrabi HR, Bates KA, Weinborn MG, Johnston ANB, Bahramian A, Taddei K, et al. Olfactory discrimination predicts cognitive decline among community-dwelling older adults. Transl Psychiatry. 2012;2:e118. doi:10.1038/tp.2012.43.

  59. Schofield PW, Ebrahimi H, Jones AL, Bateman GA, Murray SR. An olfactory ‘stress test’ may detect preclinical Alzheimer's disease. BMC Neurol. 2012;12. doi:10.1186/1471-2377-12-24. A novel preliminary study requiring replication.

  60. Sunderland T, Tariot PN, Cohen RM, Weingartner H, Mueller III EA, Murphy DL. Anticholinergic sensitivity in patients with dementia of the Alzheimer type and age-matched controls. A dose-response study. Arch Gen Psychiatry. 1987;44(5):418–26.

  61. Uusvaara J, Pitkala KH, Tienari PJ, Kautiainen H, Tilvis RS, Strandberg TE. Association between anticholinergic drugs and apolipoprotein E epsilon4 allele and poorer cognitive function in older cardiovascular patients: a cross-sectional study. J Am Geriatr Soc. 2009;57(3):427–31. doi:10.1111/j.1532-5415.2008.02129.x.

  62. Pressler RT, Inoue T, Strowbridge BW. Muscarinic receptor activation modulates granule cell excitability and potentiates inhibition onto mitral cells in the rat olfactory bulb. J Neurosci. 2007;27(41):10969–81. doi:10.1523/JNEUROSCI.2961-07.2007.

    Article  CAS  PubMed  Google Scholar 

  63. Kovacs T, Cairns NJ, Lantos PL. Olfactory centres in Alzheimer's disease: olfactory bulb is involved in early Braak's stages. Neuroreport. 2001;12(2):285–8.

    Article  CAS  PubMed  Google Scholar 

  64. Schofield P, Moore T, Finnie S, Ebrahimi H. Olfactory stress test (OST) performance in cognitively normal elders is associated with apolipoprotein E (APOE) genotype. Alzheimers Dement. 2013;9(4):202.

  65. Albers A, Kelly K, Asafu-Adjei J, Betensky R, Hastings L, Albers M. Perception of Odor Episodic Memory (POEM) test as a candidate biomarker for early Alzheimer's disease. Alzheimers Dement. 2013;9(4):199. A preliminary report on an intriguing approach that seems to have considerable promise.

  66. 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(4):1081–7. doi:10.3233/JAD-2010-100696. Comparison of olfactory measures with PiB imaging results. More studies like this are needed.

  67. Vos SJ, Xiong C, Visser PJ, Jasielec MS, Hassenstab J, Grant EA, et al. Preclinical Alzheimer's disease and its outcome: a longitudinal cohort study. Lancet Neurol. 2013;12(10):957–65. doi:10.1016/S1474-4422(13)70194-7.

    Article  PubMed  Google Scholar 

  68. Macklin EA, Blacker D, Hyman BT, Betensky RA. Improved design of prodromal Alzheimer's disease trials through cohort enrichment and surrogate endpoints. J Alzheimers Dis. 2013;36(3):475–86. doi:10.3233/JAD-122212.

    CAS  PubMed Central  PubMed  Google Scholar 

  69. Cummings JL. Controversies in Alzheimer's disease drug development. Int Rev Psychiatry. 2008;20(4):389–95. doi:10.1080/09540260802094548.

    Article  PubMed Central  PubMed  Google Scholar 

  70. Kohannim O, Hua X, Hibar DP, Lee S, Chou YY, Toga AW, et al. Boosting power for clinical trials using classifiers based on multiple biomarkers. Neurobiol Aging. 2010;31(8):1429–42. doi:10.1016/j.neurobiolaging.2010.04.022.

    Article  PubMed Central  PubMed  Google Scholar 

  71. Lorenzi M, Donohue M, Paternico D, Scarpazza C, Ostrowitzki S, Blin O, et al. Enrichment through biomarkers in clinical trials of Alzheimer's drugs in patients with mild cognitive impairment. Neurobiol Aging. 2010;31(8):1443–51. doi:10.1016/j.neurobiolaging.2010.04.036. e1.

    Article  CAS  PubMed  Google Scholar 

  72. Mormino EC, Kluth JT, Madison CM, Rabinovici GD, Baker SL, Miller BL, et al. Episodic memory loss is related to hippocampal-mediated beta-amyloid deposition in elderly subjects. Brain. 2009;132(Pt 5):1310–23. doi:10.1093/brain/awn320.

  73. Rowe CC, Ng S, Ackermann U, Gong SJ, Pike K, Savage G, et al. Imaging beta-amyloid burden in aging and dementia. Neurology. 2007;68(20):1718–25. doi:10.1212/01.wnl.0000261919.22630.ea.

  74. Rowe CC, Ellis KA, Rimajova M, Bourgeat P, Pike KE, Jones G, et al. Amyloid imaging results from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging. Neurobiol Aging. 2010;31(8):1275–83. doi:10.1016/j.neurobiolaging.2010.04.007.

  75. Karlawish J. Addressing the ethical, policy, and social challenges of preclinical Alzheimer disease. Neurology. 2011;77(15):1487–93. doi:10.1212/WNL.0b013e318232ac1a.

    Article  PubMed  Google Scholar 

  76. Schubert CR, Cruickshanks KJ, Nondahl DM, Klein BEK, Klein R, Fischer ME. Association of exercise with lower long-term risk of olfactory impairment in older adults. JAMA Otolaryngol Head Neck Surg. 2013;139(10):1061–6. doi:10.1001/jamaoto.2013.4759.

  77. Perricone C, Shoenfeld N, Agmon-Levin N, de Carolis C, Perricone R, Shoenfeld Y. Smell and autoimmunity: a comprehensive review. Clin Rev Allergy Immunol. 2013;45(1):87–96. doi:10.1007/s12016-012-8343-x.

  78. Chen K, Zhou B, Chen S, He S, Zhou W. Olfaction spontaneously highlights visual saliency map. Proc R Soc London, Ser B: Biol Sci. 2013;280(1768):1729. doi:10.1098/rspb.2013.1729.

    Article  Google Scholar 

  79. 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(30):12208–17. doi:10.1523/JNEUROSCI.0291-13.2013.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  80. Feron F, Perry C, Girard SD, Mackay-Sim A. Isolation of adult stem cells from the human olfactory mucosa. Methods Mol Biol. 2013;1059:107–14. doi:10.1007/978-1-62703-574-3_10.

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Schofield, P.W., Finnie, S. & Yong, Y.M. The Role of Olfactory Challenge Tests in Incipient Dementia and Clinical Trial Design. Curr Neurol Neurosci Rep 14, 479 (2014). https://doi.org/10.1007/s11910-014-0479-z

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