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mother'sbreastandrecallthemintestsmorethanayearlater.
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Olfactionis thusina positiontotrace
“continuity cues”todealadaptively withthe ever-changingenvironment,especiallyduring episodes of
instabilityinself-regulation(separation,stress)orperiodsofsocialorfoodtransitions(birth,weaning,
puberty, social networking). When such “odor bridges” are provided to the infant or child, adaptive
responsesgenerallyensueatindividualorinteractionallevels.Incontrast,whensucholfactorycontinuity
isignoredbycaretakingroutines,ordisruptedby
*Alliesthesiadefines the changein thelevel of pleasure associatedwith sensory stimulation. Negative alimentaryalliesthesiadenotes the
decreaseinpleasureoffood-relatedstimuliafterameal.pathologicalcausesoriatrogenicinterventions,maladaptiveconsequencescanoccur.
Forexample,applyingnovelodorantstothebreaststriggersdistressinnewborns,whilesmearingthebreastswiththeiramnioticfluidfacilitates
initiallatchingresponses.Inolderinfantsundergoingtransitiontopostlactealfood,thesimpletechniqueofintroducingmaternalmilkinanovel
foodfacilitatesitsacceptance.
Chemosensation also appears to promote early perceptual unitization with inputs from other sense
modalities. Thus, olfaction and taste become part of the developmental springboard that engages the
multisensoryprocessingofpersons,theestablishmentofattachments,andthelearningoftheenvironment
atlarge.Inconclusion,itappearsthatodor,taste,andflavorcuesareattended,processed,andrecalled
fromearliestinfancy,andthatsuchearlymemoriescontributetocurrentandsubsequentadaptivesocial
andfeedingresponses.Thefollowingsectionspresentdifferentwaystocharacterizetheperformanceof
earlynasalandoralchemosensations.
Infantilechemosensoryabilities are fine-tunedbysensoryexperience received inthewomb or in
contactwiththemother,andbyanever-expandingvarietyinfoodandintheenvironment.
EvaluationofChemosensoryFunctionsinNewbornsandInfants
Althougholfaction andtastehavebeenabundantly studied forfunctionality inearlydevelopment,they
have rarely been a topic of systematic psychophysical screening before the age of 3 years. Such
investigationsaredependentontheaccessibilityofpediatricpopulations,andmoredataareavailablefor
easilyreachable newbornsthanforinfants agedbetween2weeksand3 years. Thus, effortsshouldbe
madetodeveloppsychophysicaltestingadaptedoverthisearlyagerange.
Fewsuchstudieshavebeenattemptedinnewbornolfaction.Three
4,20,21
usedpeppermintandindicated
that nearlyall term-borninfants(cumulatedn =278) responded by oral, facial, segmental, or general
motions. However, infants born prematurely or with birth complications (asphyxia) or malformations
responded at lower rates or not at all. In another assessment of neonatal olfaction,
22
 the odorants
phenylethylalcohol,cyclotene,isovalericacid,undecalactone,andskatoleweredelivered orthonasally
to infants while their heart rate, respiration, and motor activity was recorded. Term-born neonates
respondedataratesimilartoadults;prematureinfantshadlowerdetectionperformance.Finally,afew
studieshavemeasuredbrainresponsestoodors,withmixedsuccess.Althoughtheodorsofcoffee,citral,
vanillin,andpyridinedid notcausesignificantalterationsintheelectroencephalography(EEG)before
postnatal day 6, reliable variations were seenafter day 6.
23
 EEGin 3- to 4-month-olds also reveals
inconsistentresults.
24,25
Suchvariabilityincerebralresponsemightbeattributedtorecordingconditions
(awakeversussleepingstates)andchoiceofodorants.
Anobjectiveclinicaltestoftastedysfunctioninneonatesandchildrenagedupto4yearshasnotbeen
carriedout.However,measuresofingestionofwaterversusatastant(volumeconsumed,suckingrates,
facial expressions) can provide a qualitative indicationof taste function and have the potential to be
developedintoapracticalmeasureoftaste.
Olfactionandtastehaverarelybeenatopicofsystematicpsychophysicalscreeningbeforetheageof
3years.
MeasurementofChemosensoryFunctionsinSchool-ageChildren
The greatest limitation to determining chemosensory function in children is their cognitive ability to
understandtherequirementsofthetestandtheirabilitytomaintainattentionduringthetask.Clinicaltests
for children should (1) require minimal or no training for a child to be able to complete the test
successfully; (2) have a low withdrawal rate;(3) be reliable; (4) be suitable for use at the bedside,
outpatientclinic,school,orhome;and(5)producedatathatallowclassificationofchildrenofdifferent
agesasnormative,hyposmic/hypogeusic,oranosmic/ageusic.
OlfactoryFunction
By 5 years ofage, children are familiar withmany smells, and this provides the basis ofhighly
reliablesmelltests.
SydneyChildren'sHospitalOdorIdentificationTest
The Sydney Children's HospitalOdorIdentificationTest(SCHOT)was specificallydeveloped for the
clinicalmeasurementofolfactoryfunctioninschool-agechildren.SCHOTinvolvestheidentificationof
16odorsthatarehighlyfamiliartoAustralianchildrenandhasatest–retestreliabilityofr=0.98.
26
The
testrequiresachildtosniffanodorantcontainedinawhiteopaqueflip-topsqueezebottlemarkedwitha
three-digitcodenumber,andindicatewhichofthreelabeledphotographsbestrepresentstheodor.The16
sets of photographs (one setforeachodor) are contained in a booklet.Theodorantsrepresent floral,
orange, strawberry, fish, chocolate, baby powder,paint,cutgrass, sour, minty, onion,VicksVapoRub,
spicy,Dettol,cheese,andpetrol(Fig.10.2).
Thetesthasnotbeenusedwithotherculturesandafewoftheodorantsmayneedtobereplacedby
odors that are more familiar to a particular culture. Advantages of this test are as follows: onlyone
practicetrialisrequiredtofamiliarizeachildwiththetest;itisrareforachildtorefuseornotcomplete
thetest;itiscompletedwithin5minutes;andtherearesufficientodorstoprovidearangeofscoresto
enablereadyclassificationofnormosmics,hyposmics,andanosmics.Todate,normativedatahavebeen
obtainedfor642childrenandindicatethattheprevalenceofolfactorydysfunctioninchildrenaged5to
12yearsislowat0.38%.Thetesthasbeenusedatthebedsideofpatients,inoutpatientclinics,andat
schools.Regardingthedefinitionofnormalityinthistest,thefollowingtwocriteriahavebeenfoundto
produce similar outcomes: (1) The first commonly applied clinical criterion defines normality as the
score obtained by90% of a population group; and (2) the second defines normality as two standard
deviationsbelow themeanscoreofapopulation group. Thesecriteriaindicatethatachildhasnormal
olfactoryfunctioniftheycorrectlyidentify13outof16oftheodorants,hyposmiaifthescoreis8to12
outof16, and anosmiaifthescoreis<8 outof16. Scores of11 outof16 and12outof16indicate
normal function for 5- and 6-year-olds, respectively. Two of the odorants, namely, Vicks VapoRub
(methylsalicylate)andsour(aceticacid),arealsotrigeminalnervestimulantsandprovideanindication
of function in this nerve. The test has been used to assess olfactory function in children with otitis
Данная книга находится в списке для перевода на русский язык сайта https://meduniver.com/
media,
26
 chronic renal disease,
27
 cystic fibrosis,
28
 nasopharyngeal carcinomas, and bone marrow
transplants(unpublishedstudiesatSydneyChildren'sHospital).
Fig.10.2Childsniffing1of16odorcontainers.Abookletof16setsofthreephotographsrepresentingeachodorandtwodistractionodorsis
provided.Thechildchoosesthephotographthatbestrepresentstheodorthechildhasperceived.
“Sniffin’Sticks”(Threshold,Discrimination,andIdentificationTest)
ThistestisdescribedinChapter6.Recently,itwasusedwith230childrenaged4to15yearsandwas
foundtobesuitableforusewithchildrenaged7yearsandabove.
29
Normativedatawereobtainedfor
1027-to9-year-oldsand7310-to15-year-olds.Thefailureof4-to6-year-oldstoidentifytheodorants
was a result of issues of familiarity with the odorants used (identification task) and attending and
understandingthetestprocedures(discriminationandthresholdtasks),with33%failingtocompletethe
thresholdtest.Also,threeodors(turpentine,anise,andcloves)wereunfamiliartomanyofthechildren
andneedtobereplacedtoprovideamoreappropriatesetofodorantsintheidentificationtest.Themain
disadvantage ofthe testisthat itrequires30 minutestocomplete,making itlesssuitableforusewith
patientsexperiencingchronicpainornausea,orwhenlargegroupsofchildrenarescreenedforolfactory
dysfunctioninschoolswherelimitedtimeisallowedawayfromclassroomactivities.
Other olfactorytestsdescribed for usewith childrenincludetheSanDiego OdorIdentificationtest
(SDOIT),
30
 Sniff Magnitude test (SMT),
31
 Alcohol Sniff test (AST),
32
 and Match-to-Sample Odor
Identificationtest(MTST).
33
Exceptfor MTSTina studyof825healthychildren, nonehasbeenused
withsignificantnumbersofchildrenandtheASTand SMTtestshavebeen limitedtooneodorantata
singleconcentration.Accordingly,theycannotindicate,forexample,whetherachildwhoishyposmicis
also dysosmic. Themainlimitationof theSDOIT and the MTST is that the use ofonly eightandfive
odorants,respectively,providesaverynarrowrangeofscoresonwhichtoclassifyachildasnormosmic,
hyposmic,oranosmic.NoreportsontheuseoftheMTSThaveappearedsince1995.
RetronasalFunction
A simplebutreliabletestofretronasalfunction in childrenaged7yearsandabove, termedthe Candy
Smell Test (CST), was reported recently.
29
 The test was not suitable for the 4- to 6-year-olds who
participated.Inthistest,subjectsplacedcandyontheirtonguesandcheweduntiltheyhadselectedoneof
fourpossibleodorchoices,asinthe“Sniffin’Sticks”test.Aminormodificationwasthatchildrenwere
presentedwithpicturesoftheobjectodorsinadditiontotheusualwords.Reliabilityforchildrenaged4
to15yearswasr=0.71,whichcomparedfavorablywiththatforadultsofr=0.84.Comparisonwith
data from the “Sniffin’ Sticks” test allowed classification of participants. Thus, using a threshold,
discrimination,andidentificationtest(TDI)valueof30.3asthecut-offfornormosmicsgaveascoreof
16outof23fortheCST.ACSTscoreof16correctlyclassified83%subjectswithTDIscoresbelow
30.3, while a CST score of 17 correctly classified 88% of subjects with TDI scores > 30.3 (i.e.,
normosmics).However,asindicatedbytheauthors,thetestneedsrefiningregardingchoiceofodorants,
asadultshadlowidentificationscores(<80%)forsixodors,andchildren<16yearsoldhadlowscores
foreightodors.Thistestshouldnotbeusedinchildrenwithfructosemia.
Finally,datafromtheCSTand“Sniffin’Sticks”teststhatincludedallagegroupstested(otherthan4-
to6-year-olds)showedasignificantcorrelationofr=0.84.Importantly,theCSTcouldbeusedasatest
ofolfactionasitprovidedasimilarclassificationofadultstothe“Sniffin’Sticks”test.
QualitativeAssessmentofOlfactioninEverydayLife
TheChildren'sOlfactoryBehaviorsinEverydayLifequestionnairewasdevelopedtoassessattentionto,
andreliance on,odorsin real-life situations,andtoevaluateindividual variations.
34
 It consists of16
itemspromptingself-reportsofactiveseekingof,awarenessof,andaffectivereactivitytoodorsimagined
inconnectionwithfood,people,andtheenvironment(Table10.1).Thequestionnairehasbeenusedwith
215childrenaged6to10years.Itrevealedthatgirlsweresignificantlymoreolfaction-orientedthanboys
intheir everyday life.An increasingabilityofchildrentodescribe theodorfacetsoftheir perceptual
world was foundbetween6 and10years, partly duetotheir improving cognitiveskillsandolfactory
experiences.
Table 10.1 TheChildren'sOlfactory BehaviorinEverydayLifequestionnaire,aqualitative toolusedfrom6yearsofage.Itconsistsof16
itemsinagivenorderonfood,socialrelations,andthegeneralenvironment.Forfulldetailsandthescoringmethod,seeref.34
1.Odorinfood
dislikes
Aretheresomefoods/drinksthatyouhate(yes/no)?Whichones(uptosix)?Forwhichreasons(foreachcitedfood)?
2.Responseto
unknownfood
Imagineyourparentspresentyouwithadishyoudonotknow:willyoudosomethingbeforeputtingitinyourmouth
(yes/no)?Whatdoyoudo?Willyousmellit(yes/no)?
3.Sensesin
nature
Whenyouwalkinnature,whatdoyouprefer(rankfrom1to4:touching,smelling,watching,listening)?
4.Yesterday
odors(memory)
Doyourememberodorsyousmelledyesterday(foododorsnotacceptable)?Whichones?
5.Odorssought
whensad
Arethereodorsyoulikesmellingwhenyoufeelsad?Whichones?
6.Beloved
odorousobjects
Aretherethingsyoutreasurejustbecausetheysmellverygood?Whichones?
7.Outsideodors Imaginetherewerenoodorsoutsideanymore:wouldyounotcare/woulditbotheryou/woulditsuityou?
8.Smellingschool
tools
Doyouhappentosmellyourschoolthings(never/sometimes/often)?Whichones?
9.Odorincars Inyourparents’car,doesitsmellofsomethingornothing?Doyoulove/like/notcare/notlikethisodor/feelill?
10.Odorof
bathroomobjects
Pleaselistobjectsofyourbathroom(uptoeight).Whichonessmellofsomething?
11.Familyodors
Doyoufindthatyourparents/siblingssmellofsomething?Imaginetheywouldnotsmellofanythinganymore:would
younotcare/woulditbotheryou/woulditsuityou—alittle/alot?Why?
12.People's
naturalodor
Doyoufindthatpeoplesmellofsomething,evenwithoutperfumeordeodorant(no/yessomepeople/yeseveryone)?
13.Smelling
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clothes
Doyouhappentosmellyourclothes(never/sometimes/often)?Why?
14.Smellingself-
odor
Doyouhappentosmellpartsofyourbody(never/sometimes/often)?Whichparts?Why?
15.Tobacco
smell
Imaginesomeoneissmokingnexttoyou.Doyoulove/like/notcare/notlike/hatethisodor?
16.Guessingfood
odor
Whenyousmellafoododor,doyoutrytoguessforfunwhatitis(never/sometimes/often)?
NasalTrigeminalFunction
TrigeminalsensitivitycanbeassessedusingthelateralizationtaskdescribedinChapter12,whereachild
is requested to identify the side of the nose to which an odorous stimulus was presented. Only one
detailedmeasureofnasaltrigeminalfunctioninchildrenhasbeenreported.
35
Thisinvolved262children
and86adults,andindicatedthatthemethodcanbeusedby5-year-olds,withlittlechangeinperformance
from7yearsofage.Althoughthephenomenonoflateralizationappearstobeanexcellentworkingtool
fordeterminingnasaltrigeminalfunction,itsreliabilityhasyettobedemonstrated.
GustatoryFunction
Loss of one or more taste qualities is more common than not being able to perceive any taste.
Completelossofallqualitiesisrareandisduetothetongue,palate,andthroatbeinginnervatedby
severaltastenerves.
Whole-mouthTest
The Sydney Children's Hospital Gustatory Test (SCHGT) is the only clinical taste test that has been
specifically developed for use in children.
27,28,36
 The test is a three-choice task that requires the
identification of 25 samples of sweet (sucrose), sour (citric acid), salt (sodium chloride), and bitter
(quininehydrochloride)tastesandwater.Eachtastantispresentedatfiveconcentrationsthatrangefrom
weak but identifiable for a healthy 5-year-old, to very strong. Children are required to identify each
sampleusingasetofthreephotographslabeledwithappropriatewords,bychoosingthephotothatbest
represents the taste (Fig. 10.3). Different sets are used with each sample, and each set contains a
photographofaglassofwater.Water isalwaysgivenas oneofthe choices toprovide anappropriate
choice if a child cannot perceive a taste. Thus, a child who chooses water consistently instead of a
specifictastecanbeclassifiedashypogeusic.Onewhoconsistentlychoosesatasteotherthanthecorrect
oneisclassifiedasdysgeusic.Thestimuliarepresentedinarandomorderwithanintertrialintervalof
30 seconds, during whichtime children rinse their mouths withwater. Meanidentificationscores for
healthy children for each of the tastants and water have exceeded 90% inthree clinical studies with
children,
27,28,36
 and comparison of the overall identification scores over two test days indicated a
reliabilityofr=0.52.However,classificationofachildashavingatastedisorderisnotbasedonthe
overallidentificationscorebutontheidentificationofatleastthreeofthefiveconcentrationsofataste
quality. Loss of one or more taste qualities appears to be muchmore common than not being able to
perceiveanytaste.Indeed,completelossoftasteforallqualitiesisrare,andperceptionofatleastsome
tastesis owing,inpart, to thetongue, palate, and throatbeing innervatedbyseveral tastenerves. For
example,damagetothechordatympaniinthemiddleearbyotitismediapathogens
37
isnotaccompanied
by damage to the glossopharyngeal nerve, which is the other main nerve innervating the tongue.
Prevalence of taste dysfunction appears to be high, reported at 12 and 7.9% for 8- to 12-year-old
AustralianAboriginalandnon-Aboriginalchildren,respectively.
36
Othertestshavebeenusedtoassess
tastefunctioninchildpatients,butnonehavebeendevelopedspecificallyforuseinchildren,orhadtheir
reliabilityestablished.
Fig.10.3Childsippingatastantandpointingtothephotographthatbestrepresentsthetasteshehasperceived.
RegionalTasteFunction
Clinical measurement of disorders within taste-sensitive parts of the mouth, including the tongue and
palate, has rarely been reported in children. The only report concerning regional measurements in
children involved a taste identification task with5- to 7-year-olds, where moderate strength aqueous
solutionsweredeliveredtofourregionsofthetongue.
38
Thetestwasamodifiedversionoftheclinical
testused with adults
39
 and used the same tastants at the following concentrations: sweet, 1 M; sour,
0.0032M;salty,1M;andbitter,0.001M.Modificationofthetestwasnecessarybecausetheadulttest
requiresparticipantstousearatingscaletoestimatethestrengthoftastants,andchildrenunder~8years
of age cannot do this without substantial training. Accordingly, a much easier identification task was
adopted.Thefourregionsexaminedweretworegionsoneachsideofthedorsaltongue,namely,thetipof
thetongueandlaterallyjustforwardofthemostanteriorcircumvallatepapilla.Stimuliwere delivered
using cotton buds.Tobe consistent inthe size of thearea stimulated,the cotton bud was dipped ina
tastantsolutionandthenrolled~1cmtowardtheposteriortongueatthechosenregion.Toachievethis,
children were asked to protrude their tongues as far as was comfortable until they had identified the
tastantinaregion.Itwasexplainedthatwithdrawalofthetonguewouldspreadthesolutionovermuchof
thetongueandthetestwouldhavetoberepeated.Subjectsindicatedtheidentityofatastantbypointingto
oneofthreephotographs.Thesetsofphotographswerethesameasthoseusedinthewhole-mouthtest.
Theorderofpresentingthestimuliwasrandomizedacrosssubjectsandacrossthefourtongueregions,to
result in 20 presentations during the test. To familiarize a child with the tastants and the general
identificationprocedure,achildsampledeachtastantfromasmallcupandidentifieditfromsetsofthe
photographs. There was an intertrial interval of30 seconds, during whichthe child rinsed his or her
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mouthwithwater.Thedata,basedon212children,indicatethat90%of5-,6-,and7-year-oldscanbe
expected toidentifyatleastthreeofthefivetastesateachofthefour regions,which is similar tothe
resultsachievedby52adults.
38
Morerecently,thistestwasusedwith2189-to12-year-oldAustralian
Aboriginalstoassesstheeffectsofotitismediaonregionsofthetonguethatcoincidedwiththeside(s)
andearthathadbeenshowntoexhibithearingloss(ArmstrongandLaing,inpreparation).
Electrogustometry
Electrogustometric measurement (seeChapter14)ofdetectionthresholds hasbeenusedtoassess taste
functionin160 childrenaged4to18years whohadundergone otological surgery.
40
Tastedysfunction
was found in patients who had experienced tympanoplasty (27%), mastoidectomy(30%), or cochlear
implantation (26% unilateral; 5% bilateral). Interestingly, 9% of controls exhibited taste dysfunction,
which is similar to the prevalence in children reported recently using the SCHGT.
36
 A limitation of
electrogustometryisthatitdoesnotindicatethenatureofthetasteloss.Forexample,itcannotindicate
whethertastelossisconfinedtooneormorequalities,ortheextentofsuchaloss.
Summary
This chapter summarizes the functionaldevelopment of the human chemical senses anddescribes
methodsformeasuringfunctionatdifferentages.Cognitiveabilitieslimittheuseofpsychophysical
testsuntil~6to7yearsofage,andonlyqualitativetestshavebeenusedinnonclinicalassessments
ofolfactoryfunctioninnewbornsandinfants.Asyet,notestusedwithchildrenhasbecomea“gold
standard“forassessingthechemicalsenses,althoughreliableolfactoryandgustatorytestshavebeen
reportedforolderchildren.Themostglaringshortcomingistheabsenceofobjectiveclinicaltestsof
smellandtastefornewbornsandchildren<6yearsofage.
References
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22.ShimadaM,TakahashiS,ImuraS,BabaK.Olfactioninneonates.ChemSenses1987;12:518
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2010;25(8):1497–1504
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11NeurologicalDiseasesandOlfactoryDisorders
AntjeHaehner,JohnE.Duda
Impairment of olfaction is a characteristic feature of many neurological diseases. This chapter
summarizes the available information about olfactory function in neurodegenerative and other
neurological conditions, and describes the advantageous use of olfactory testing in the diagnosis of
severaldisorders,includingParkinsondisease(PD)andAlzheimerdementia.
OlfactoryLossinNeurodegenerativeDisorders
Neurodegenerativedisordersarecharacterizedbyaprogressivelossofstructureorfunctionofneurons.
Impaired olfaction has been associatedwith a variety of age-relatedneurodegenerative conditions that
impaircognitiveandmotorfunction,includingPD,
1–5
Alzheimerdisease(AD),
6
Huntingtondisease,
7
and
motorneurondisease.
8
Smelllossmaythereforebeconsideredanimportantcontributiontothediagnosis
ofthesediseases,andphysiciansshouldbefamiliarwiththisattendantsymptom.
ParkinsonianSyndromes
PrevalenceofOlfactoryLossinParkinsonDisease
TheassociationbetweenolfactorydysfunctionandPDwasnotedmorethan30yearsago.
9
Virtuallyall
studies performed since then have shown olfactory disturbances in patients with PD. The reported
prevalenceofolfactorydysfunctioninPD,however,rangesfrom45and49%inthepioneeringstudiesof
AnsariandJohnson
9
andWardetal,
2
respectively,upto74%intheworkofHawkesetal,
3
orashighas
90% inastudypublishedbyDotyetal.
1
Ina recent multicenterstudy
10
using a comprehensive testing
method in a large sample of patients with PD (n = 400) from three independent populations, the
prevalenceofolfactorydysfunctioninpeoplewithPDwasgreaterthanpreviouslyreported.Morethan
96% of patients with PD were found to presentwith significant olfactory dysfunction compared with
young,normosmicpatients.Whenusingage-dependentnormativecriteria,74.5%ofthisstudypopulation
wasdiagnosedwitholfactoryloss(Fig.11.1).Furthermore,ofthepatientswithPDwithsmellloss,more
than80%werefunctionallyanosmicorseverelyhyposmicregardlessoftheolfactorytestbeingusedfor
diagnosis.Thesedataalsoconfirmednumerouspreviousstudiesregardingalackofcorrelationbetween
olfactorylossandbothdurationofdisease
1,3,11
andtheclinicalseverityofPD,asmeasuredbymeansof
the Hoehn and Yahr scale and the Unified Parkinson Disease Rating Scale (compare with ref. 12)—
althoughsomestudiesfoundacorrelationbetweentheseverityofPDandcertainmeasuresofolfactory
function(namelylatenciesofolfactoryevent-relatedpotentials
13
orresultsfrom anodordiscrimination
task).
14
However,thisinabilitytodemonstratearelationshipbetweendiseasedurationandolfactoryloss
maybepartiallyowingtoa“basementeffect”ofolfactorydysfunctioninpatientswithPDwithmoderate-
to-severedisease,andifonlypatientswithearlyPDareassesseditmightbepossibletodemonstratea
worseningfunction withdiseaseduration.Withregardtoolfactoryfunction,nomajordifferenceswere
found among subtypes of PD (tremor-dominant PD, akinetic-rigid PD, or mixed-type PD). While this
confirmspreviousobservationsinsmallsamplesizes,
15,16
thepresentfindingsareincontrasttoreports
byStern andcolleagues,
11
 who reportedsignificantlybetter odor identification scores in patients with
tremor-predominantPD(n=40)thaninpatientswithposturalinstabilitygaitdisorder–predominantPD(n
= 23). While differences among studies may be due to the type of olfactory test used, sample size,
normativedata,andagedistribution(whichvariedamongtheseinvestigations),availabledataallowthe
conclusionthatolfactorydysfunctionisahighlyreliablesymptomofthe disease.Thisconcurswiththe
resultsofacase–controlstudyof90patientswithPDandhealthycontrolsbyBohnenetal,
17
whofound
that the accuracy of smell testing in PD diagnosis outweighs theaccuracy of motor testbatteries and
nonmotortestsofdepression,andanxiety.
Fig. 11.1 Olfactory function of 400 patients with PD. Results are shown as a composite TDI score (sum of odor threshold, odor
discrimination,andodoridentificationscore)adjustedtoage-relatednorms.(FromHaehneretal.
10
)
OlfactoryDysfunctioninEarlyParkisonDiseaseDiagnosis
PatientswithPDfrequentlyreportareductionintheirsenseofsmellthatoccursafewyearspriortothe
onset of motor symptoms. Support for the existence of a prodromal phase of PD, including a long
premotor phase,comes fromimaging, neuropathology, andvariousclinical or epidemiologicalsurveys.
The best evidence for a long premotor phase is derived from large prospective studies examining
olfaction, constipation, rapid eye movement (REM) sleep behavior disorder, and depression.
18–20
Estimatesforthedurationoftheprodromerangefrom2to50yearsdependingonthesymptom,duration
offollow-up,accuracyofdiagnosis,andindividualvariation.
However, patients’ lack of awareness of smell deficits may account for the inconsistent results
describedinretrospectivesurveys.Intwosmallstudies,
21,22
uponquestioningpriortoolfactorytesting,
24 and 39% of respondents indicated an awareness of decreased olfactory function which actually
preceded their diagnosis of PD. Several studies could show evidence of olfactory dysfunction in
untreated,newlydiagnosedpatients.
1
Aplethoraofevidencefrom recentstudiessupportstheviewthat
deficitsinthesenseofsmellmayprecedeclinicalmotorsymptomsbyyears.AstudybyPonsenetal
23
of
361 asymptomatic relatives of patients with PD selected 40 relatives with the lowest olfactory
performance.Within2yearsoffollow-up,10% ofthesefirst-degreerelativesofpatientswithPDwith
significantolfactorylossdevelopedclinicalPD.Inafollow-upstudy5yearsfrombaselinetesting,five
relativeshaddevelopedclinicalPDasdefinedbytheUnitedKingdomParkinson'sDiseaseSocietyBrain
Bank Diagnostic Criteria for Parkinson's Disease. Initial clinical (motor) symptoms appeared 9 to 52
months (median 15 months) after baseline testing. Poorer performance on each of three olfactory
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