smell is a key to our relationship to food , approach / avoidance behavior , and alarm response to dangerous chemicals . quality of life in general is partly dependent on the ability to smell , as shown by the complaints of patients experiencing loss of olfactory sensitivity : mood swings or depression , and worries about personal hygiene , safety , social interaction , and so forth , ( see   for a review ) . although epidemiological surveys were conducted in sweden , the usa , germany , and australia , the frequency of olfactory dysfunction remains poorly documented in the french population . the prime aim of this study was therefore to provide a tool to measure this prevalence . in recent decades , several olfactory tests were designed in various countries ( see ) . some measured identification only     [ 810 ] , some sensitivity only , others combined both     [ 7 , 1215 ] , and one added a discrimination measurement . thus , the different commercially available tests do not specifically measure the same olfactory competencies , but all are designed to detect hyposmia or anosmia . with hyposmia being operationally described as an impairment of both sensitivity and quality perception , we wanted a clinical test that would measure both . each addresses different competencies : whereas sensitivity reflects perceptual processes that do not strongly depend on language abilities , identification relies on language and culture . cultural variation conditions odor identification , which is based on learning of odors that have become familiar and  ecologically valid  ; such familiarity varies from country to country     [ 1719 ] , as does stimulus typicality for a given target odor . these considerations led doty et al . , for example , to modify the american upsit test for use in asia and europe . in the european test of olfactory capabilities ( etoc ) , odorants were selected so as to reduce cultural differences in familiarity across countries     [ 7 , 22 ] . the importance of language in odor perception is well known , and a requisite of identification tests is to help identification by providing participants with several names in a forced - choice paradigm . closer examination of these semantic cues shows that the choice of appropriate labels is a decisive factor in successful identification     . thus , a second prerequisite for our clinical test was the ecological validity of the odorants and of their names for a french population . one of the prominent causes of impaired smell ability is aging : this decrease in olfactory function during normal aging is called presbyosmia     [ 25 , 26 ] . it was therefore important to collect data from healthy subjects in all age groups from 15 to 90 years in order to establish normative lifespan data for both sexes . such control data were required in order to be able to compare patient groups to the general population . because clinicians need a short self - administered test of olfactory function , the lyon clinical olfactory test was designed with 3 main purposes : to describe the sensitivity and identification abilities of the french population by combining subtests based on perceptual and cognitive abilities so as to help orient clinicians towards a central or peripheral hypothesis in case of olfactory loss ; the test , therefore , crossed 3 types of measurement : threshold , supraliminal detection , and identification . this approach was intended to allow differentiation between problems of sensitivity and of naming and to be useful in patients with cognitive deficits ; to categorize the population into 3 classes ( normosmic , hyposmic , and anosmic ) by establishing cutoff values ; to validate the test and the derived norms by test - retest measurement and application to patient populations : one sample of patients with alzheimer 's disease and another of patients from our smell clinic . the lyon clinical olfactory test ( lcot ) is composed of blocks of four 15  ml vials     [ 22 , 27 , 28 ] . only 1 of the 4 contains an odorant , dissolved in odorless mineral oil ( sigma - aldrich ) soaked up on oil - absorbent to avoid any leakage during vial opening and to increase the area of exchange with the air . the other vials are blanks containing only the mineral oil solvent soaked up on the oil - absorbent . threshold measurements used 2 different odorants : r-(+)-carvone ( minty odor , sigma - aldrich ) and tetrahydrothiophene ( tht , gas odor and euracli ) . these familiar and thus  ecological  odorants were used instead of the classical l - butanol because the latter also stimulates the trigeminal nerve .   moreover , using the familiar main gas odor was relevant for the clinicians , who could warn people when they did not detect it . the same threshold determination procedure was used for both compounds : 5 concentration levels were presented , from weakest to strongest ( dilution factor : 10 ) , with a forced choice paradigm ( ascending staircase 4-afc procedure ) . for each block , subjects were told to smell the 4 vials consecutively and to indicate on a response sheet which one smelled strongest or else , if they did not smell any difference between the vials , to guess ( 4-afc ) . the blocks were presented in increasing order of concentration : 10 , 10 , 10 , 10and 10 ( vol./vol . ) for r-(+)-carvone and 10 , 10 , 10 , 10 and 10 ( vol./vol . ) for tht . supraliminal detection and identification measurements used a series of 16 odorants , diluted at an easily detectable concentration level ( around 10 ) ( table 1 ) . following the same 4afc procedure , subjects were to smell a block of 4 vials , detect which vial contained an odor , and then identify the odor by selecting a label among 4 proposed alternatives . for instance , the 4 alternative labels associated with the lavender stimulus were  leather  ,  paint ,   lavender ,  and  almond  . subjects were given the 26 test blocks ( 5 for carvone threshold , 5 for tht threshold , and 16 for suprathreshold detection and identification ) , an instruction sheet , and a response sheet ; they recorded their answers by circling their choice ( vial code or label ) on the response sheet , with their age , gender , smoking habits , and possible nasal diseases . the time required to open and close the 4 vials and to mark the response on the sheet ensured that there was an interval of at least 45  sec between stimulations , reducing the risk of adaptation . the threshold score was defined as the lowest odor concentration detected and followed by correct detections . scores ranged from 5 ( when the odor was detected correctly from the weakest concentration ) to 1 ( when the odor was detected correctly only at the strongest ) ; subjects who failed to detect the strongest concentration were scored 0 . two threshold scores were recorded for each subject : r-(+)-carvone threshold ( ct ) and tht ( gas odor ) threshold ( gt ) , both from 0 to 5 . for each subject , supraliminal detection performance ( dp ) was the number of correct detections ( from 0 to 16 ) , identification performance ( ip ) , and the number of correct responses ( from 0 to16 ) . the rationale of this supraliminal detection level is that odor identification was scored as correct only when the corresponding odor vial was detected correctly : as the risk of correct detection by chance and of correct identification by chance was for both 1/4 , the scoring procedure reduced the probability of identifying an odor by chance to 1/16 . moreover , because dp measured a perceptual ability and ip measured a more verbal one , it was hypothesized that the difference between these scores ( dpip ) could reveal some cognitive components of olfactory deficit ; a differential score ( dd = dp  ip ) was therefore calculated ( from 0 to 16 ) . the aromas were kindly provided by euracli ( chasse - sur rhne , france ) . these smelling compounds were selected for their high level of familiarity for a french population   ( table 1 ) . they were diluted in mineral oil ( sigma - aldrich , 1% ) , except for -pentadecalactone which was diluted in diethyl phthalate ( sigma - aldrich , 10% ) . the purpose of study 1 was to determine normative scores for normosmic , hyposmic , and anosmic subjects , and to assess test - retest reliability . thus , 407 participants between 15 and 91 years of age were included ( table 2 ) ; 92 ( 23% ) were smokers , 221 ( 54% ) had never smoked , and 94 ( 23% ) were exsmokers . they were diagnosed as anosmic according to their medical history , following rhinitis , head trauma , or kallmann syndrome , or without known etiology . twenty participants ( 12 women ) from 18 to 59 years of age were retested within a 2-month interval . regressions and anovas were performed using sas release 9.1.3 ( sas institute inc . , cary , nc ) and the reg and glm procedures . the hypothesis tests on the mean of the normal distribution were carried out with the t - test function of r release 2.12.0 ( the r foundation for statistical computing ) . standardization was based on the results of the 407 healthy participants ; table 3 presents their mean scores for each subtest . to test whether sex and smoking habits influenced scores on the 5 subtests , 2-way analysis of variance was performed ( yij =  + sexi + tobaccoj+ ( sex    tobacco)ij + ij , ijn(0 , 2 ) ) . for all 5 subtests ( ct , gt , dp , ip , and dd ) , the models showed no significance at the 5% level , indicating no influence of sex or smoking habits on test performance . to assess the influence of age on the scores of healthy participants , regression analysis was performed ( yi = a + b  agei + i , one regression was carried out for each subtest ( ct , gt , dp , ip , and dd ) . the effect of age was tested using the fisher statistic ( ( h0 ) : b = 0 against ( h1 ) : b  0 ) . age had no significant effect on ct and gt threshold scores , but significantly influenced ip , dp , and dd scores (  < 0.0001 ) . ct score distribution was not normal : 34 subjects scored 0 or 1 ; this represented 8.4% of the tested population , in agreement with the percentage of specific hyposmia to r-(+)-carvone in the general population ; the ct score was therefore discarded for normative data calculation . as age did not influence gt score , we looked for the lower limit of this subtest score for healthy participants . given the mean gt score of 3.97 , a student 's t - test was used to determine whether healthy participants could score lower than 3 ( h0 : gt  3 against h1 : gt > 3 ) ; results indicated that healthy participants statistically scored at least 4 ( df = 406 , t = 5.9 , p  0.0001 ) . as age influenced dp and ip scores , we looked for the lower limit of each subtest score according to age . for dp , a student 's t - test was used to determine whether healthy participants between 15 and 71 years of age could score lower than 14 ( age  [ 15  :  71 ] , h0 : dp  14 against h1 : dp < 14 ) ; results showed that they detected at least 14 odors ( df = 338 , t = 44.3 , and p = 1 ) , whereas healthy participants older than 72 years detected at least 13 odors ( age  [ 72  :  91 ] , h0 : dp  13 against h1 : dp < 13 ; df = 62 , t = 11.7 , p = 1 ) . the same procedure applied to ip scores showed that healthy participants between 15 and 64 years of age identified at least 13 odors ( age  [ 15  :  64 ] , h0 : ip  13 against h1 : ip < 13 ; t - value = 65.9 , df = 304 , p = 1 ) , compared to at least 12 odors between 65 and 74 years of age ( age [65 : 74 ] , h0 : ip  12 against h1 : ip < 12 ; t - value   = 36.6 , df = 52 , p = 1 ) and at least 9 odors between 75 and 91 years of age ( age  [ 75  :  91 ] , h0 : ip  9 against h1 : ip < 9 ; t - value   = 29.97 , df = 48 , p = 1 ) . for dd scores , the same procedure indicated that healthy participants between 15 and 61 years of age obtained a dd score 2 ( age  [ 15  :  61 ] , h0 :  dd  2 against h1 : dd > 2 ; t - value   = 14.4 , df = 292 , p = 1 ) , those between 62 and 71 years 4 ( age  [ 62  :  71 ] , h0 : dd  4 against h1 : dd > 4 ; t - value   = 6.9 , df = 45 , p = 1 ) and those between 72 and 91 years 7 ( age  [ 72  :  91 ] , h0 : dd  7 against h1 : dd > 7 ; t - value   = 13.97 , df = 67 , p = 1 ) . mean scores in the anosmic patients group were : gt = 0.88  1.05 , dp = 4.71  2.28 , ip = 1.42  1.80 , and dd = 3.5  1.63 . the mean dd score was higher than in the healthy participants sample : that is , most of the items detected were not identified . due to the small number of patients in anosmic group , the influence of smoking habits and sex was not tested . to assess the influence of age , simple regression analysis was performed ( yi = a + b  agei + i , i ~ n(0 , 2 ) ) for each subtest ( gt , dp , ip , and dd ) and tested on the fisher statistic ( ( h0 ) : b = 0 against ( h1 ) : b  0 ) : age was found not to influence scores , as none of the 4 regressions were significant (  = 0.05 ) . the lower limit of each subtest score was determined , regardless of age : anosmics never scored better than 3 for gt ( h0 : gt  3 against h1 : gt > 3 ; df = 16 , t - value   = 8.28 , p = 1 ) and did not detect more than 7 odors ( h0 : dp  7 against h1 : dp > 7 ; df = 16 , t - value   = 4.13 , p > 0.99 ) ; on ip , they did not identify more than 5 odors ( h0 : ip  5 against h1 : ip > 5 ; df = 16 , t - value   = 8.2 , p = 1 ) . these scores were higher than chance , as will be discussed later . dd ( i.e. , the difference between dp and ip ) did not exceed 5 ( h0 : dd  5 against h1 : dd > 5 ; df = 16 , t - value   = 3.92 , p > 0.99 ) . as shown in table 5 , for this sample of subjects , the condition , dp  7 , was sufficient to detect anosmics . to detect normosmics , the conditions dp  14 for ages [ 15  :  71 ] and dp  13 for ages > 71 were sufficient . by definition , hyposmics were in between . gt score was not included in the definition of normosmia because , according to the confidence limits of the mean , the scores of the healthy sample ranged from 3.10 to 4.84 ; thus requiring a gt score of 4 for normosmia would have categorized as hyposmic many participants who were within the normal range for the other criteria .   as an internal validation of the normative data is obtained , the criteria for dp , ip , and dd were applied to both populations ( 407 healthy participants and 17 anosmic patients ) , with the following results ( table 6 ) . twenty three healthy participants were found to differ from the healthy and anosmic groups and were classified as hyposmic ( 5.6% ) . in the anosmic sample , figure 1 presents the mean scores of this hyposmic group , which was composed of 14 women ( 61% ) and 9 men ( 39% ) , with a mean age of 62  19 years . the smell problems of these 23 subjects did not concern supraliminal detection : they detected only 1 odor less than the whole healthy sample . their mean thresholds were moderately lower than those of the 407 healthy subjects : ct = 3.09 versus 3.36 ; gt = 3.52 versus 3.97 . therefore , these 23 subjects seemed to experience mild hyposmia with moderate reduction in sensitivity . their main smell problem resided in identification performance , which was 5 points less than the sample as a whole ( 9 versus 14.1 ) , entailing a higher dd score ( 5.56 versus 1.47 ) . first , the difference between the test and retest scores was calculated for each participant : 0 if the subject obtained the same score twice ( good repeatability ) or different from 0 if the scores differed . if participants responded randomly on test and retest , the number of 0 differences should follow a binomial distribution with n = 20  p = 0.2 ( in the case of threshold tests , where scores ranged from 0 to 5 ) and p = 0.0625 ( in the case of dp and ip , where scores ranged from 0 to 16 ) . with a p = 0.05 risk level , where p = 0.2 , the limit to reject the null hypothesis is 9 and , where p = 0.06 , 5 . the null hypothesis could thus in the present case be rejected : that is , test and retest showed significant repeatability ( subjects ' scores were not random ) at risk level < 0.05 for gt and much less than 0.001 for dp and ip . other studies define hyposmia in terms of the 10th percentile 's global score on the olfactory test ( combining threshold , discrimination , and identification scores )     [ 5 , 31 ] of the performance of patients identified a priori as anosmic   or by comparison ( 2 standard deviations ) with the performance of healthy subjects under 40 years of age . a statistical approach was used to obtain cut - off values so that participants whose scores fell in between could be considered hyposmic . thus , 5.6% of the healthy participants without any declared smell problem could be considered hyposmic . this may have been due to the small number of concentrations used and the absence of a staircase procedure such as recommended for precise measurement of thresholds . another issue was the high threshold found for l - carvone in 34 subjects , which may be explained by a specific hyposmia , resulting in a bimodal distribution of thresholds . it would then follow that the carvone threshold is not suitable for screening sensitivity in the population as a whole . on the other hand , the threshold for tht ( gas odor ) alone seemed to be sufficient to identify anosmics , who scored less than 3 . in detecting hyposmia , a difficulty arose regarding the cut - off value for gt : a score of 3 would correspond to hyposmia and a score under 3 to anosmia ; but requiring a score of 4 or 5 as a condition for normosmia would result in a large proportion of hyposmics because the scores of the healthy sample actually ranged from 3 to 5 . the gt score was therefore discarded from the definition of normosmia and used only in defining anosmia . the results showed that supraliminal detection ( dp ) alone could distinguish normosmics from hyposmics and anosmics : even the oldest normosmics , over 76 years of age , scored higher than 13 ; anosmic subjects did not obtain scores higher than 7 . the one subject who detected 10 odors was therefore classified as hyposmic according to this cut - off score . the mean performance of anosmics did not differ from chance ; some odorants , however ( eucalyptol , carvone , and possibly others ) included a trigeminal component that could help some anosmics to detect them above chance level ( i.e. , 4/16 ) . on the basis of our sample of subjects , detection performance could be considered as sufficient to categorize subjects as normosmic or hyposmic . this is an important finding because this measure is nonverbal , with the advantages of quick diagnosis and of being independent of culture and linguistic knowledge . this allows smell deficits to be diagnosed on a perceptual basis , whatever the language the subject speaks . the identification task ( ip score ) was more sensitive to age than detection ( dp score ) , indicating a stronger decrease in cognitive than in perceptual aspects of smell . it is acknowledged that odor identification is cognitively demanding   and that age impairs both memory and lexical access to odor names     [ 34 , 35 ] . overall , the results suggest that some subtests were more relevant to detecting smell impairment ; this is important for clinicians , who may thus use rapid screening with dp only when they are short of time . the gt score is relevant to confirming anosmia and the ip score to assessing distortions of odor quality . this score also increased with normal aging : from 2 to 7 between 61 and 91 years . this measure of cognitive smell impairment was useful in study 2 , in comparison with pathological aging . the repeatability of the lcot was good : at a 0.05 risk level for the gt score and considerably less than 0.001 for the ct , dp , and ip scores . classification of anosmic participants was good , with 5% misclassification , which was the accepted error risk . the classification of healthy participants suggested a hyposmia prevalence of 5.6% in a sample that excluded subjects with smell problems . this is in the same range as in studies using the tenth percentile of the population to define hyposmia ; nevertheless , the question remains as to whether this resulted from misclassification by the statistical model ( with an error risk of 5% ) or from correct classification of participants with true smell deficits . these  healthy hyposmic participants may have been unaware of their deficit , or may have suspected it and volunteered precisely in order to test their sense of smell . alternatively , it could be argued that around 10% of the general population is hyposmic and that a figure of 5.6% represents a recruitment bias in study 1 , which was based on volunteers . the validation study provided norms for the healthy sample and for anosmics , categorizing individuals scoring between the cut - off values as hyposmic . study 2 sought to test the model and cut - off values on 2 pathological samples : patients with alzheimer 's disease ( alz group ) and volunteer smell - clinic patients complaining of smell troubles ( pat group ) . these patient groups were compared with a group of healthy controls matched for age with the alz patients ( cont group ) .   the 36 smell - clinic patients ( 22 women ) consulted at the olfaction outpatients department of edouard herriot hospital ( lyon university ) , france . the alzheimer 's study was carried out on patients during day hospital care ( saint jean de dieu hospital , lyon ) ( alz group ) and on age - matched control volunteers ( cont group ) without known olfactory disorder ( often alz - group members ' spouses or main caretakers ) . thirty - three alzheimer 's patients ( 28 women ; mean age , 77  8 years ) and 32 age - matched control volunteers ( 26 women ; mean age , 76  7 years ) participated . cognitive impairment was measured in patients and control participants using the mini - mental state examination ( mmse , ) . a ct scan was performed in the alzheimer 's patients to control vascular dementia , which was an exclusion criterion . when demented patients had praxis difficulties , the physician presented the open vials to the patient and asked :  does this bottle smell or not ?  in the identification test , a second set of questions was : what does it smell of ? does it smell of leather ? does it smell of paint ? does it smell of lavender ? does it smell of almond ?  , to which patients could answer yes / no ; when patients refused to make any choice between the 4 items , the investigator randomly attributed one of the four answers . as regards cognitive impairment , the mmse scores of the control ( cont ) group were normal ( mean  sd = 29.2  1.2 ) ; the alz group obtained lower scores with a larger standard deviation ( mean  sd = 13.0  4.0 ; range , 5/30 to 21/30 ) . two - way analysis of variance ( age , group ) indicated a significant difference between alz and cont ( f = 11.2 ; p < 0.001 ) and no significant effect of age on mmse score ( f = 0.027 , p = 0.97 ) . statistical analyses were conducted using sas release 9.1.3 ( sas institute inc . , analysis of variance was performed with the glm procedure followed by multiple comparison between means ( tukey 's hsd correction for multiple comparisons ) . according to the cut - off scores , 14 pat group participants were classified as anosmic ( 39% ) , 18 as hyposmic ( 50% ) , and 4 as normosmic ( 11% ) . according to the same rules , the alz group comprised 1 anosmic ( 3% ) , 21 hyposmics ( 64% ) , and 11 normosmics ( 33% ) , and the cont group 5 hyposmics ( 16% ) and 27 normosmics ( 84% ) . analysis of variance including age as covariate was carried out for each type of score to assess differences between the 3 groups ( cont , pat , and alz ) . results consistently showed a significant group effect ( gt : f(2,97 ) = 6.4 , p = 0.003 ; dp : f(2,97 ) = 7.2 , p = 0.001 ; ip : f(2,97 ) = 27.3 , p < 0.0001 ; and dd : f(2,97 ) = 31.1 , p < 0.0001 ) . age had only a barely significant effect on gt score ( f(1,97 ) = 4.1 , p = 0.046 ) . tht threshold ( gt ) discriminated between groups : the cont group scored significantly higher than the pat and alz groups ( see figure 2 ) . as regards dp , it is noteworthy that alz patients did not score lower than the age - matched controls . only the pat group detected significantly fewer odorants , which is a confirmation of lower sensitivity . identification performance ( ip ) discriminated elderly controls from both pat and alz groups . as hypothesized , the dd difference between detection and identification scores was relevant to comparison between different causes of olfactory impairment : dd was maximum in cognitively impaired persons , the alz group scoring highest , and the cont group lowest ; the pat group differed from both alz and cont . the following cut - off scores may thus be suggested for dd : with a 95% confidence interval around the mean , the dd score may be [ 14 [ for cont , [ 46 [ for pat and [ 68 [ for alz . screening 101 new subjects allowed various degrees of olfactory impairment to be examined . normosmia was present in 84% of cont group participants , 33% of the alz group , and 11% of the pat group . the incidence of 16% hyposmia in the cont group is in agreement with other studies in older adults . more surprisingly , dp , which discriminated strongly between healthy and anosmic participants in study 1 , only separated the pat group from the others in study 2 . one reason may be that this subtest was too easy to be able to separate different degrees of hyposmia . identification performance ( ip ) uses a more difficult task to match a verbal description with perceived odor quality , resulting in larger differences between groups . the dd difference was lowest in the cont group , although this group included 16% hyposmics . thus , the addition of this differential score improved description of qualitative change in smell perception with normal aging and various pathologies : dd was highest in alzheimer 's patients , which can be interpreted as a feature of their dementia affecting perceptual less than cognitive processes . as underlined , alzheimer patients did not score lower in detection performance than age - matched controls , but their identification scores were in the same range as for the smell - clinic patients . dd also discriminated these patients from healthy elderly controls , despite the greater age of the latter . comparison of the pat group with the group of 23  healthy  hyposmics of study 1 shows that the latter score is higher on dp and ip , which confirms that they experience a mild hyposmia . the difference between the pat group and the anosmic group of study 1 relies mainly on dp : these patients detect more odorants than anosmic participants , which explains why their dd score is also higher . the incidence of smell deficit was estimated at 5.6% in the healthy population of study 1 and at 16% in the elderly control group of study 2 . because the samples were made up of volunteers , it is difficult to generalize these figures to the french population as a whole , but they were in the same range as in other studies . that 16% of subjects over 60 years of age were found to be hyposmic is , however , questionable : a number of illnesses and medications are known to impair olfaction     [ 38 , 39 ] . a norm for healthy aging should consider only participants in very good health and without medication ; such a procedure strongly reduces the incidence of smell deficit accompanying normal aging ( presbyosmia ) . no effect of smoking was found in the present as in other studies ; sex , however , is frequently found to influence performance     [ 5 , 6 ] . because sex differences mainly concern the verbal performance of women , the present absence of sex effect may be due to the identification task of the lcot being rather easy , inducing a ceiling effect . the present study sought to segregate one olfactory loss from another , whereas most olfactory tests cumulate subtask scores . in agreement with cain et al . , the present results show that detection and identification , when dissociated , provide different cues for screening the severity of smell deficit . supraliminal detection in particular emerged as a simple tool to classify subjects as anosmic , hyposmic or normosmic .
the lcot is a self - administered test designed to assess olfactory deficits . 
 altogether , 525 subjects contributed to the validation . 
 elderly participants were well represented in this sample . in a validation study ( 
 study 1 ) , 407 healthy and 17 anosmic volunteers between 15 and 91 years of age underwent threshold , supraliminal detection , and identification testing . 
 cutoff values for normosmia and hyposmia were calculated and applied in a second study in a group of patients with smell complaints and in a group of alzheimer patients with age - matched controls . 
 incidence of smell deficit was estimated at 5.6% in the healthy population of study 1 , and at 16% in the elderly control group of study 2 . 
 assessment of the ability of each subtest to discriminate between groups showed that lcot is relevant to differentiating between perception and identification deficits and between alzheimer 's and hyposmic patients .