Hostname: page-component-8448b6f56d-c47g7 Total loading time: 0 Render date: 2024-04-20T01:47:29.862Z Has data issue: false hasContentIssue false
  • English
  • Français

Olfactory disturbances in ageing with and without dementia: towards new diagnostic tools

Published online by Cambridge University Press:  20 April 2017

A Gros ,
V Manera ,
C A De March ,
N Guevara ,
A König ,
L Friedman ,
P Robert ,
J Golebiowski  and
R David
A Gros*
Affiliation:
Ressource and Research Memory Center, France CoBTek (Cognition – Behaviour – Technology), France Dijon Stroke Registry, EA4184, University Hospital and Medical School of Dijon, University of Burgundy, France
V Manera
Affiliation:
CoBTek (Cognition – Behaviour – Technology), France
C A De March
Affiliation:
Institute of Chemistry, University of Nice Sophia Antipolis, France Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, USA
N Guevara
Affiliation:
Department of Ear Nose Throat Surgery, Institut Universitaire de la Face et du Cou, Nice University Hospital, France
A König
Affiliation:
CoBTek (Cognition – Behaviour – Technology), France
L Friedman
Affiliation:
Veterans Affairs Palo Alto Health Care System, Palo Alto, USA Department of Psychiatry and Behavioral Sciences, Stanford School of Medicine, Stanford University, Stanford, USA
P Robert
Affiliation:
Ressource and Research Memory Center, France CoBTek (Cognition – Behaviour – Technology), France
J Golebiowski
Affiliation:
Institute of Chemistry, University of Nice Sophia Antipolis, France Department of Brain & Cognitive Sciences, DGIST, Daegu Metropolitan City, Republic of Korea
R David
Affiliation:
Ressource and Research Memory Center, France CoBTek (Cognition – Behaviour – Technology), France
*
Address for correspondence: Dr A Gros, Centre Mémoire de Ressources et de Recherche, Institut Claude Pompidou, 10 rue Molière 06100, Nice, France Fax: +33 61437170 E-mail: gros.a2@chu-nice.fr
Get access Rights & Permissions [Opens in a new window]

Abstract

Background:

Olfactory disorders increase with age and often affect elderly people who have pre-dementia or dementia. Despite the frequent occurrence of olfactory changes at the early stages of neurodegenerative disorders such as Alzheimer's disease, olfactory disorders are rarely assessed in daily clinical practice, mainly due to a lack of standardised assessment tools. The aims of this review were to (1) summarise the existing literature on olfactory disorders in ageing populations and patients with neurodegenerative disorders; (2) present the strengths and weaknesses of current olfactory disorder assessment tools; and (3) discuss the benefits of developing specific olfactory tests for neurodegenerative diseases.

Methods:

A systematic review was performed of literature published between 2000 and 2015 addressing olfactory disorders in elderly people with or without Alzheimer's disease or other related disorders to identify the main tools currently used for olfactory disorder assessment.

Results:

Olfactory disorder assessment is a promising method for improving both the early and differential diagnosis of Alzheimer's disease. However, the current lack of consensus on which tests should be used does not permit the consistent integration of olfactory disorder assessment into clinical settings.

Conclusion:

Otolaryngologists are encouraged to use olfactory tests in older adults to help predict the development of neurodegenerative diseases. Olfactory tests should be specifically adapted to assess olfactory disorders in Alzheimer's disease patients.

Keywords

SmellAgingDementiaAlzheimer DiseaseEarly Diagnosis
Type
Review Articles
Information
The Journal of Laryngology & Otology , Volume 131 , Issue 7 , July 2017 , pp. 572 - 579
Copyright
Copyright © JLO (1984) Limited 2017 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1 Doty, RL, Bayona, EA, Leon-Ariza, DS, Cuadros, J, Chung, I, Vazquez, B, et al. The lateralized smell test for detecting Alzheimer's disease: failure to replicate. J Neurol Sci 2014;340:170–3Google Scholar
2 Murphy, C, Gilmore, M, Seery, C, Salmon, D, Lasker, B. Olfactory thresholds are associated with degree of dementia in Alzheimer's disease. Neurobiol Aging 1990;11:465–9CrossRefGoogle ScholarPubMed
3 Doty, RL, Shaman, P, Applebaum, SL, Giberson, R, Siksorski, L, Rosenberg, L. Smell identification ability: changes with age. Science 1984;226:1441–3CrossRefGoogle ScholarPubMed
4 Choudhury, ES, Moberg, P, Doty, RL. Influences of age and sex on a microencapsulated odor memory test. Chem Senses 2003;28:799–805 Google Scholar
5 Lafreniere, D, Mann, N. Anosmia: loss of smell in the elderly. Otolaryngol Clin North Am 2009;42:123–31Google Scholar
6 Enwere, E. Aging results in reduced epidermal growth factor receptor signaling, diminished olfactory neurogenesis, and deficits in fine olfactory discrimination. J Neurosci 2004;24:8354–65CrossRefGoogle ScholarPubMed
7 Attems, J, Walker, L, Jellinger, KA. Olfaction and aging: a mini-review. Gerontology 2015;61:485–90Google Scholar
8 Frasnelli, J, Lundström, JN, Schöpf, V, Negoias, S, Hummel, T, Lepore, F. Dual processing streams in chemosensory perception. Front Hum Neurosci 2012;6:288 Google Scholar
9 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;78:30–5CrossRefGoogle ScholarPubMed
10 Green, AJ, Cervantez, M, Graves, LV, Morgan, CD, Murphy, C. Age and apolipoprotein E ε4 effects on neural correlates of odor memory. Behav Neurosci 2013;127:339–49Google Scholar
11 Olofsson, JK, Nordin, S, Wiens, S, Hedner, M, Nilsson, L-G, Larsson, M. Odor identification impairment in carriers of ApoE-ε4 is independent of clinical dementia. Neurobiol Aging 2010;31:567–77CrossRefGoogle Scholar
12 Getchell, ML, Shah, DS, Buch, SK, Davis, DG, Getchell, TV. 3-Nitrotyrosine immunoreactivity in olfactory receptor neurons of patients with Alzheimer's disease: implications for impaired odor sensitivity. Neurobiol Aging 2003;24:663–73CrossRefGoogle ScholarPubMed
13 Nordin, S, Murphy, C. Impaired sensory and cognitive olfactory function in questionable Alzheimer's disease. Neuropsychology 1996;10:113–19Google Scholar
14 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;855:723–31Google Scholar
15 Murphy, C, Gilmore, M, Seery, C, Salmon, D, Lasker, B. Olfactory thresholds are associated with degree of dementia in Alzheimer's disease. Neurobiol Aging 1990;11:465–9Google Scholar
16 Stamps, JJ, Bartoshuk, LM, Heilman, KM. A brief olfactory test for Alzheimer's disease. J Neurol Sci 2013;333:19–24 Google Scholar
17 Landis, BN, Burkhard, PR. Phantosmias and Parkinson disease. Arch Neurol 2008;65:1237–9Google Scholar
18 Hirsch, AR. Parkinsonism: the hyposmia and phantosmia connection. Arch Neurol 2009;66:538–9Google Scholar
19 Landis, BN, Reden, J, Haehner, A. Idiopathic phantosmia: outcome and clinical significance. ORL J Otorhinolaryngol Relat Spec 2010;72:252–5Google Scholar
20 Moller, P, Wulff, C, Koster, EP. Do age differences in odour memory depend on differences in verbal memory? Neuroreport 2004;15:915–17Google Scholar
21 Moller, P, Mojet, J, Koster, EP. Incidental and intentional flavor memory in young and older subjects. Chem Senses 2007;32:557–67CrossRefGoogle Scholar
22 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 Google Scholar
23 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 Google Scholar
24 Naudin, M, Mondon, K, El-Hage, W, Desmidt, T, Jaafari, N, Belzung, C et al. Long-term odor recognition memory in unipolar major depression and Alzheimer׳s disease. Psychiatry Res 2014;220:861–6Google Scholar
25 Pentzek, M, Grass-Kapanke, B, Ihl, R. Odor identification in Alzheimer's disease and depression. Aging Clin Exp Res 2007;19:255–8CrossRefGoogle Scholar
26 Growdon, ME, Schultz, AP, Dagley, AS, Amariglio, RE, Hedden, T, Rentz, DM et al. Odor identification and Alzheimer disease biomarkers in clinically normal elderly. Neurology 2015;84:2153–60Google Scholar
27 Petersen, RC. Mild cognitive impairment as a diagnostic entity. J Intern Med 2004:256:183–94CrossRefGoogle ScholarPubMed
28 Vyhnalek, M, Magerova, H, Andel, R, Nikolai, T, Kadlecova, A, Laczo, J et al. Olfactory identification in amnestic and non-amnestic mild cognitive impairment and its neuropsychological correlates. J Neurol Sci 2015;349:179–84Google Scholar
29 Devanand, DP, Lee, S, Manly, J, Andrews, H, Schupf, N, Doty, RL et al. Olfactory deficits predict cognitive decline and Alzheimer dementia in an urban community. Neurology 2015;84:182–9Google Scholar
30 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;157:1399–405Google Scholar
31 Makowska, I, Kloszewska, I, Grabowska, A, Szatkowska, I, Rymarczyk, K. Olfactory deficits in normal aging and Alzheimer's disease in the Polish elderly population. Arch Clin Neuropsychol 2011;26:270–9CrossRefGoogle ScholarPubMed
32 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;64:871–9CrossRefGoogle ScholarPubMed
33 Steinbach, S, Hundt, W, Vaitl, A, Heinrich, P, Förster, S, Bürger, K et al. Taste in mild cognitive impairment and Alzheimer's disease. J Neurol 2010;257:238–46Google Scholar
34 Kjelvik, G, Saltvedt, I, White, LR, Stenumgård, P, Sletvold, O, Engedal, K et al. The brain structural and cognitive basis of odor identification deficits in mild cognitive impairment and Alzheimer's disease. BMC Neurol 2014;14:168 CrossRefGoogle ScholarPubMed
35 Vyhnalek, M, Magerova, H, Andel, R, Nikolai, T, Kadlecova, A, Laczo, J et al. Olfactory identification in amnestic and non-amnestic mild cognitive impairment and its neuropsychological correlates. J Neurol Sci 2015;349:179–84Google Scholar
36 Li, Y, Wang, Y, Wu, G, Shi, F, Zhou, L, Lin, W et al. Discriminant analysis of longitudinal cortical thickness changes in Alzheimer's disease using dynamic and network features. Neurobiol Aging 2012;33:427 Google Scholar
37 Solomon, GS, Petrie, WM, Hart, JR, Brackin, HB. Olfactory dysfunction discriminates Alzheimer's dementia from major depression. J Neuropsychiatry Clin Neurosci 1998;10:64–7Google Scholar
38 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;122:1455–62Google Scholar
39 Doty, RL, Marcus, A, William Lee, W. Development of the 12-Item Cross-Cultural Smell Identification Test (CC-SIT). Laryngoscope 1996;106:353–6Google Scholar
40 Delahaye, L, Le Gac, MS, Martins-Carvalho, C, Vazel, L, Potard, G, Marianowski, R. Gap between odor perception threshold and identification threshold: calculation based on a graph of the Biolfa(®) olfactory test. Eur Ann Otorhinolaryngol Head Neck Dis 2010;127:130–6Google Scholar
41 Cenedese, V, Mezzavilla, M, Morgan, A, Marino, R, Ettorre, CP, Margaglione, M et al. Assessment of the olfactory function in Italian patients with type 3 von Willebrand disease caused by a homozygous 253 Kb deletion involving VWF and TMEM16B/ANO2. PLoS One 2015;10:e0116483 Google Scholar
42 Strauss, GP, Keller, WR, Koenig, JI, Gold, JM, Ossenfort, KL, Buchanan, RW. Plasma oxytocin levels predict olfactory identification and negative symptoms in individuals with schizophrenia. Schizophr Res 2015;162:57–61 Google Scholar
43 Lin, A, Brewer, WJ, Yung, AR, Nelson, B, Pantelis, C, Wood, SJ. Olfactory identification deficits at identification as ultra-high risk for psychosis are associated with poor functional outcome. Schizophr Res 2015;161:156–62Google Scholar
44 Prashanth, R, Roy, SD, Mandal, PK, Ghosh, S. Parkinson's disease detection using olfactory loss and REM sleep disorder features. Conf Proc IEEE Eng Med Biol Soc 2014;2014:5764–7Google Scholar
45 Sharer, JD, Leon-Sarmiento, FE, Morley, JF, Weintraub, D, Doty, RL. Olfactory dysfunction in Parkinson's disease: positive effect of cigarette smoking. Mov Disord 2015;30:859–62Google Scholar
46 Gaig, C, Vilas, D, Infante, J, Sierra, M, García-Gorostiaga, I, Buongiorno, M et al. Nonmotor symptoms in LRRK2 G2019S associated Parkinson's disease. PLoS One 2014;9:e108982 CrossRefGoogle ScholarPubMed
47 Whiting, AC, Marmura, MJ, Hegarty, SE, Keith, SW. Olfactory acuity in chronic migraine: a cross-sectional study. Headache 2015;55(1):71–5Google Scholar
48 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;25:1157–66Google Scholar
49 Tonacci, A, Borghini, A, Mercuri, A, Pioggia, G, Andreassi, MG. Brain-derived neurotrophic factor (Val66 Met) polymorphism and olfactory ability in young adults. J Biomed Sci 2013;20:57 Google Scholar
50 Fusetti, M, Fioretti, AB, Silvagni, F, Simaskou, M, Sucapane, P, Necozione, S et al. Smell and preclinical Alzheimer disease: study of 29 patients with amnesic mild cognitive impairment. J Otolaryngol Head Neck Surg 2010;39:175–81Google Scholar
51 Förster, S, Vaitl, A, Teipel, SJ, Yakushev, I, Mustafa, M, la Fougère, C et al. Functional representation of olfactory impairment in early Alzheimer's disease. J Alzheimers Dis 2010;22:581–91Google Scholar
52 Seligman, SC, Kamath, V, Giovannetti, T, Arnold, SE, Moberg, PJ. Olfaction and apathy in Alzheimer's disease, mild cognitive impairment, and healthy older adults. Aging Ment Health 2013;17:564–70CrossRefGoogle ScholarPubMed
53 Alt, JA, Mace, JC, Buniel, MCF, Soler, ZM, Smith, TL. Predictors of olfactory dysfunction in rhinosinusitis using the brief smell identification test. Laryngoscope 2014;124:E259–66Google Scholar
54 Kim, BG, Oh, J-H, Choi, HN, Park, SY. Simple assessment of olfaction in patients with chronic rhinosinusitis. Acta Otolaryngol 2015;135:258–63Google Scholar
55 Soler, ZM, Hyer, JM, Ramakrishnan, V, Smith, TL, Mace, J, Rudmik, L et al. Identification of chronic rhinosinusitis phenotypes using cluster analysis. Int Forum Allergy Rhinol 2015;5:399–407 Google Scholar
56 Jones, DE, Rowland, M, Bracewell, RM. Olfactory examination in Korsakoff's syndrome: implications for early diagnosis. ISRN Otolaryngology 2011;2011:1–4 Google Scholar
57 Silva, AM, Santos, E, Moreira, I, Bettencourt, A, Coutinho, E, Gonçalves, A et al. Olfactory dysfunction in multiple sclerosis: association with secondary progression. Mult Scler 2012;18:616–21Google Scholar
58 Bersani, G, Quartini, A, Ratti, F, Pagliuca, G, Gallo, A. Olfactory identification deficits and associated response inhibition in obsessive-compulsive disorder: on the scent of the orbitofronto-striatal model. Psychiatry Res 2013;210:208–14Google Scholar
59 Demirhan, A, Erdem, K, Akkaya, A, Tekelioglu, UY, Bilgi, M, Isik, C et al. Evaluation of the olfactory memory after spinal anaesthesia: a pilot study. Eur Rev Med Pharmacol Sci 2013;17:2428–32Google Scholar
60 Ådén, E, Carlsson, M, Poortvliet, E, Stenlund, H, Linder, J, Edström, M et al. Dietary intake and olfactory function in patients with newly diagnosed Parkinson's disease: a case–control study. Nutr Neurosci 2011;14:25–31 Google Scholar
61 Cramer, CK, Friedman, JH, Amick, MM. Olfaction and apathy in Parkinson's disease. Parkinsonism Relat Disord 2010;16:124–6Google Scholar
62 Johansen, KK, Warø, BJ, Aasly, JO. Olfactory dysfunction in sporadic Parkinson's disease and LRRK2 carriers. Acta Neurol Scand 2014;129:300–6Google Scholar
63 Rodríguez-Violante, M, Lees, AJ, Cervantes-Arriaga, A, Corona, T, Silveira-Moriyama, L. Use of smell test identification in Parkinson's disease in Mexico: a matched case–control study. Mov Disord 2011;26:173–6CrossRefGoogle ScholarPubMed
64 Jiang, R-S, Kuo, L-T, Wu, S-H, Su, M-C, Liang, K-L. Validation of the applicability of the traditional Chinese version of the University of Pennsylvania Smell Identification Test in patients with chronic rhinosinusitis. Allergy Rhinol (Providence) 2014;5:28–35 Google Scholar
65 Sorokowska, A, Hummel, T. Polish version of the Sniffin’ Sticks Test – adaptation and normalization [in Polish]. Otolaryngol Pol 2014;68:308–14CrossRefGoogle ScholarPubMed
66 Fjaeldstad, A, Kjaergaard, T, Van Hartevelt, TJ, Moeller, A, Kringelbach, ML, Ovesen, T. Olfactory screening: validation of Sniffin’ Sticks in Denmark. Clin Otolaryngol 2015;40:545–50Google Scholar
67 Lecanu, JB, Faulcon, P, Werner, A, Bonfils, P. Normative data of the Biolfa(®) olfactory test [in French]. Ann Otolaryngol Chir Cervicofac 2002;119:164–9Google ScholarPubMed
68 Driver-Dunckley, E, Adler, CH, Hentz, JG, Dugger, BN, Shill, HA, Caviness, JN et al. Olfactory dysfunction in incidental Lewy body disease and Parkinson's disease. Parkinsonism Relat Disord 2014;20:1260–2Google Scholar
69 Velayudhan, L, Gasper, A, Pritchard, M, Baillon, S, Messer, C, Proitsi, P. Pattern of smell identification impairment in Alzheimer's disease. J Alzheimers Dis 2015;30:381–7Google Scholar
70 Mahlknecht, P, Pechlaner, R, Boesveldt, S, Volc, D, Pinter, B, Reiter, E et al. Optimizing odor identification testing as quick and accurate diagnostic tool for Parkinson's disease: odor identification in PD. Mov Disord 2016;31:1408–13Google Scholar
71 Doty, RL, Frye, RE, Agrawal, U. Internal consistency reliability of the fractionated and whole University of Pennsylvania Smell Identification Test. Percept Psychophys 1989;45:381–4Google Scholar
72 Hugh, SC, Siu, J, Hummel, T, Forte, V, Campisi, P, Papsin, BC et al. Olfactory testing in children using objective tools: comparison of Sniffin’ Sticks and University of Pennsylvania Smell Identification Test (UPSIT). J Otolaryngol Head Neck Surg 2015;44:10 Google Scholar
73 Doty, RL. Office procedures for quantitative assessment of olfactory function. Am J Rhinol 2007;21:460–73Google Scholar
74 Joussain, P, Bessy, M, Faure, F, Bellil, D, Landis, BN, Hugentobler, M et al. Application of the European Test of Olfactory Capabilities in patients with olfactory impairment. Eur Arch Otorhinolaryngol 2016;273:381–90CrossRefGoogle ScholarPubMed
75 Gu, D, Li, P. Comparison of application of several psychophysical olfactory test methods in clinic [in Chinese]. Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 2014;28:715–17Google Scholar
76 Secundo, L, Snitz, K, Weissler, K, Pinchover, L, Shoenfeld, Y, Loewenthal, R et al. Individual olfactory perception reveals meaningful nonolfactory genetic information. Proc Natl Acad Sci U S A 2015;112:8750–5Google Scholar
77 Pelchat, ML, Bykowski, C, Duke, FF, Reed, DR. Excretion and perception of a characteristic odor in urine after asparagus ingestion: a psychophysical and genetic study. Chem Senses 2011;36:9–17 CrossRefGoogle ScholarPubMed
78 Štenc Bradvica, I, Bradvica, M, Matić, S, Reisz-Majić, P. Visual dysfunction in patients with Parkinson's disease and essential tremor. Neurol Sci 2015;36:257–62Google Scholar
79 Näätänen, R, Kujala, T, Escera, C, Baldeweg, T, Kreegipuu, K, Carlson, S et al. The mismatch negativity (MMN) – a unique window to disturbed central auditory processing in ageing and different clinical conditions. Clin Neurophysiol 2012;123:424–58Google Scholar
80 Buck, L, Axel, R. A novel multigene family may encode odorant receptors: a molecular basis for odor recognition. Cell 1991;65:175–87Google Scholar
81 Niimura, Y. Olfactory receptor multigene family in vertebrates: from the viewpoint of evolutionary genomics. Current Genomics 2012;13:103–14Google Scholar
82 De March, CA, Ryu, S, Sicard, G, Moon, C, Golebiowski, J. Structure–odour relationships reviewed in the postgenomic era: olfactory receptors and odourants. Flavour Fragr J 2015;30:342–61Google Scholar