Skip to main content

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

  • A Gros (a1) (a2) (a3), V Manera (a2), C A De March (a4) (a5), N Guevara (a6), A König (a2), L Friedman (a7) (a8), P Robert (a1) (a2), J Golebiowski (a4) (a9) and R David (a1) (a2)...
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.


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.


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.


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.

Corresponding author
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:
Hide All
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;340:170–3
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;11:465–9
3 Doty RL, Shaman P, Applebaum SL, Giberson R, Siksorski L, Rosenberg L. Smell identification ability: changes with age. Science 1984;226:1441–3
4 Choudhury ES, Moberg P, Doty RL. Influences of age and sex on a microencapsulated odor memory test. Chem Senses 2003;28:799805
5 Lafreniere D, Mann N. Anosmia: loss of smell in the elderly. Otolaryngol Clin North Am 2009;42:123–31
6 Enwere E. Aging results in reduced epidermal growth factor receptor signaling, diminished olfactory neurogenesis, and deficits in fine olfactory discrimination. J Neurosci 2004;24:8354–65
7 Attems J, Walker L, Jellinger KA. Olfaction and aging: a mini-review. Gerontology 2015;61:485–90
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
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;78:30–5
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;127:339–49
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;31:567–77
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;24:663–73
13 Nordin S, Murphy C. Impaired sensory and cognitive olfactory function in questionable Alzheimer's disease. Neuropsychology 1996;10:113–19
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;855:723–31
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;11:465–9
16 Stamps JJ, Bartoshuk LM, Heilman KM. A brief olfactory test for Alzheimer's disease. J Neurol Sci 2013;333:1924
17 Landis BN, Burkhard PR. Phantosmias and Parkinson disease. Arch Neurol 2008;65:1237–9
18 Hirsch AR. Parkinsonism: the hyposmia and phantosmia connection. Arch Neurol 2009;66:538–9
19 Landis BN, Reden J, Haehner A. Idiopathic phantosmia: outcome and clinical significance. ORL J Otorhinolaryngol Relat Spec 2010;72:252–5
20 Moller P, Wulff C, Koster EP. Do age differences in odour memory depend on differences in verbal memory? Neuroreport 2004;15:915–17
21 Moller P, Mojet J, Koster EP. Incidental and intentional flavor memory in young and older subjects. Chem Senses 2007;32:557–67
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;29:693706
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
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;220:861–6
25 Pentzek M, Grass-Kapanke B, Ihl R. Odor identification in Alzheimer's disease and depression. Aging Clin Exp Res 2007;19:255–8
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;84:2153–60
27 Petersen RC. Mild cognitive impairment as a diagnostic entity. J Intern Med 2004:256:183–94
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;349:179–84
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;84:182–9
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;157:1399–405
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;26:270–9
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;64:871–9
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;257:238–46
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
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;349:179–84
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
37 Solomon GS, Petrie WM, Hart JR, Brackin HB. Olfactory dysfunction discriminates Alzheimer's dementia from major depression. J Neuropsychiatry Clin Neurosci 1998;10:64–7
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;122:1455–62
39 Doty RL, Marcus A, William Lee W. Development of the 12-Item Cross-Cultural Smell Identification Test (CC-SIT). Laryngoscope 1996;106:353–6
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;127:130–6
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
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;162:5761
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;161:156–62
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;2014:5764–7
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;30:859–62
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
47 Whiting AC, Marmura MJ, Hegarty SE, Keith SW. Olfactory acuity in chronic migraine: a cross-sectional study. Headache 2015;55(1):71–5
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;25:1157–66
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
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;39:175–81
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;22:581–91
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;17:564–70
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:E259–66
54 Kim BG, Oh J-H, Choi HN, Park SY. Simple assessment of olfaction in patients with chronic rhinosinusitis. Acta Otolaryngol 2015;135:258–63
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;5:399407
56 Jones DE, Rowland M, Bracewell RM. Olfactory examination in Korsakoff's syndrome: implications for early diagnosis. ISRN Otolaryngology 2011;2011:14
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;18:616–21
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;210:208–14
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;17:2428–32
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;14:2531
61 Cramer CK, Friedman JH, Amick MM. Olfaction and apathy in Parkinson's disease. Parkinsonism Relat Disord 2010;16:124–6
62 Johansen KK, Warø BJ, Aasly JO. Olfactory dysfunction in sporadic Parkinson's disease and LRRK2 carriers. Acta Neurol Scand 2014;129:300–6
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;26:173–6
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;5:2835
65 Sorokowska A, Hummel T. Polish version of the Sniffin’ Sticks Test – adaptation and normalization [in Polish]. Otolaryngol Pol 2014;68:308–14
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;40:545–50
67 Lecanu JB, Faulcon P, Werner A, Bonfils P. Normative data of the Biolfa(®) olfactory test [in French]. Ann Otolaryngol Chir Cervicofac 2002;119:164–9
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;20:1260–2
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;30:381–7
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;31:1408–13
71 Doty RL, Frye RE, Agrawal U. Internal consistency reliability of the fractionated and whole University of Pennsylvania Smell Identification Test. Percept Psychophys 1989;45:381–4
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
73 Doty RL. Office procedures for quantitative assessment of olfactory function. Am J Rhinol 2007;21:460–73
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;273:381–90
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;28:715–17
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;112:8750–5
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;36:917
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;36:257–62
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;123:424–58
80 Buck L, Axel R. A novel multigene family may encode odorant receptors: a molecular basis for odor recognition. Cell 1991;65:175–87
81 Niimura Y. Olfactory receptor multigene family in vertebrates: from the viewpoint of evolutionary genomics. Current Genomics 2012;13:103–14
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;30:342–61
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

The Journal of Laryngology & Otology
  • ISSN: 0022-2151
  • EISSN: 1748-5460
  • URL: /core/journals/journal-of-laryngology-and-otology
Please enter your name
Please enter a valid email address
Who would you like to send this to? *



Altmetric attention score

Full text views

Total number of HTML views: 19
Total number of PDF views: 135 *
Loading metrics...

Abstract views

Total abstract views: 494 *
Loading metrics...

* Views captured on Cambridge Core between 20th April 2017 - 14th December 2017. This data will be updated every 24 hours.