KNOWLEDGE AND ATTITUDES OF PARKINSON DISEASE RISK IN … · “Patients with GD and GBA...
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KNOWLEDGE AND ATTITUDES OF PARKINSON DISEASE RISK IN THE GAUCHER POPULATION* Leah Zaretsky Natasha Zeid, Dr. Manisha Balwani, Dr. Roy Alcalay *Property of Leah Zaretsky. No portion of this presentation should be used without permission
Transcript of KNOWLEDGE AND ATTITUDES OF PARKINSON DISEASE RISK IN … · “Patients with GD and GBA...
KNOWLEDGEANDATTITUDESOFPARKINSONDISEASERISKINTHEGAUCHERPOPULATION*
LeahZaretskyNatashaZeid,Dr.ManishaBalwani,Dr.RoyAlcalay
*PropertyofLeahZaretsky.Noportionofthispresentationshouldbeusedwithoutpermission
IndividualswithGBAmutationsareatanincreasedriskofdevelopingParkinsondisease
Gaucherdisease ARconditioncausedbydefectinglucocerebrosidase Type1ismostcommon,considerednon-neuronopathic Symptomscanincludebonedisease,hepatosplenomegaly,anemia
Parkinsondisease Second-most-commonneurodegenerativedisorder Lossofdopaminergicneuronsinsubstantianigra,accumulationofα-synuclein Symptomscanincludetremor,rigidity,sleepdisturbances
WhatistheconnectionbetweenGDandPD?
“AlthoughthespecificcontributionofmutantGBAtothepathogenesisofparkinsonismremainsunknown,evidencesuggestsbothlossoffunctionandtoxicgain-of-functionbyabnormalß-glucocerebrosidasemaybeimportant,andacloserelationshipbetweenß-glucocerebrosidaseandα-synuclein.”–SwanandSaunders-Pullman2013
“PatientswithGDandGBAheterozygoteshaveanincreasedage-specificriskforPDcomparedwithcontrolindividuals,withasimilarmagnitudeofPDriskby80yearsofage…”–Alcalayetal.2014
“…mildandsevereheterozygousGBAmutationsdifferentiallyaffecttheriskandtheAAOofPD.”–Gan-Oretal.2015
Whathavepaststudiesshown?
“PatientswithPDhaveahighlevelofinterestingeneticsandgenetictesting,butasanoverallgroup,demonstratealowlevelofgeneticsknowledge.–Falconeetal.2010
“BasedonexperienceinalargeParkinsondiseaseresearchprojectinwhichhundredsofcarriersofGBAmutationshavebeenidentifiedandcounseled,thereisindicationthattheremaybeinsufficientknowledgeandawarenessabouttheassociationofGaucherandParkinsondiseaseamongpatients.”–CookandSchulze2017
“…asurveywasadministeredtoindividualswhoscreenednegativeforGBAmutations….86.7%believedthatpatientsshouldbeinformedabouttheincreasedriskofPDpriortohavingGDcarrierscreening…”–Mulhernetal.2017
IRB-exempt24questionsurveyonSurveyMonkey Demographics Gaucherdetails AssessmentofknowledgeregardingGaucherdisease
Gaucherdiseasepatients18+-ISMMSviaemailsandinclinic,NationalGaucherFoundationviamonthlyelectronicnewsletter ISMMStotaln=76 NGFtotaln=49
StatisticalanalysisusingExcelandSPSS Analysisoftworecruitmentgroupsseparatelyandtogether
DEMOGRAPHICS
MountSinaiparticipantswereequallysplitbetweenmaleandfemale,whileNGFparticipants
weremostlyfemale
49%51%
Gender
MALE FEMALE
31%
67%
2%
Gender
MALE FEMALE NORESPONSE
ISMMSn=76 NGFn=49
TheaverageMountSinaiparticipantwas50yearsofage,whiletheaverageNGFparticipantwas62.5
yearsofage
50.0
62.5
55.0
ISMMS NGF COMBINED
MeanAge(+/-1S.D.) ISMMSn=76 Averageage=50years Standarddeviation=16.4years
NGFn=49 Averageage=62.5years Standarddeviation=14.5years
Combinedn=125 Averageage=55.0years Standarddeviation=16.8years
AlargemajorityofparticipantsidentifiedasWhite,includingEasternEuropeanandAshkenaziJewish
99%
1%
Ethnicity
White(includingEasternEuropeanandAshkenaziJewish)
Asian/PacificIslander
ISMMSn=76 NGFn=49
92%
2%
4% 2%
Ethinicity
White(includingEasternEuropeanandAshkenaziJewish)
White/HispanicorLatino
White/BlackorAfricanAmerican/NativeAmericanorAmericanIndian
NativeAmericanorAmericanIndian
Overall,around74%ofparticipantshadatleastabachelor’sdegree
1%
8%11%
3%
33%26%
18%
Education
Lessthanahighschooldiploma
Highschooldiplomaorequivalent
Somecollege,nodegree
Associatedegree
Bachelor'sdegree
Master'sdegree
Professionalordoctoraldegree
2%
10%
17%
2%
35%
16%
16%2%
Education
Lessthanahighschooldiploma
Highschooldiplomaorequivalent
Somecollege,nodegree
Associatedegree
Bachelor'sdegree
Master'sdegree
Professionalordoctoraldegree
ISMMSn=76 NGFn=49
Overall,participantshailedfrom18states,withamajoritylivinginNewYorkandNewJersey
43%
2%37%
18%
Residence
Northeast
Midwest
South
West
91%
4%
5%
Residence
Northeast
West
Noresponse
ISMMSn=76 NGFn=49
HaveyoubeendiagnosedwithType1Gaucher
disease?
GAUCHERDETAILS
TheaverageMountSinaiparticipantwasdiagnosedat31.8yearsofage,whiletheaverageNGFparticipantwasdiagnosedat31.2yearsofage
31.8 31.2 31.5
ISMMS NGF COMBINED
Ageatdiagnosis(+/-1S.D.) ISMMSn=76 Averageageatdiagnosis=31.8years Standarddeviation=17.2years
NGFn=49 Averageageatdiagnosis=31.2years Standarddeviation=15.9years
Combinedn=125 Averageageatdiagnosis=31.5years Standarddeviation=16.6years
Overall,approximately80%ofparticipantsreceivetreatmentforGaucherdisease
86%
14%
TreatedforGD
YES
NO
75%
25%
TreatedforGD
YES
NO
ISMMSn=76 NGFn=49
Mostparticipants(approximately85%)arefollowedforGaucherdiseaseinalargehospital
setting
63%23%
4%10%
Inwhattypeofmedicalpracticeareyoufollowedfor
Gaucherdisease?
Largehospitalsetting
Privatepractice
Smallcommunityhospital
Unsure99%
1%
Inwhattypeofmedicalpracticeareyoufollowedfor
Gaucherdisease?
Largehospitalsetting
Privatepractice
ISMMSn=76 NGFn=49
Approximately41%wereunsurehowmanyGDpatientstheirdoctorfollows,and45%answered
thattheirdoctorfollows20+patients
18%
14%
23%
45%
HowmanypatientswithGaucherdiseasedoesyour
doctorfollow?
Fewerthan5
5-20
20+
Unsure
3%
59%
38%
HowmanypatientswithGaucherdiseasedoesyour
doctorfollow?
Fewerthan5
20+
Unsure
ISMMSn=76 NGFn=49
Overall,54%ofparticipantsreportedthatnooneintheirfamilyhasPD,and66%reportedthatno
oneintheirfamilyhasLBD
2.6 13.2 17.1
61.8
5.30
1.3
0
69.7
28.9
SELF FIRSTDEGREERELATIVE
SECONDDEGREERELATIVE
NOONEINMYFAMILY
UNSURE
Asfarasyouareaware,doyouoranyoneinyourfamilyhave
PDorLBD?
Parkinsondisease Lewybodydementia
10.2 12.2
24.5
42.9
12.2
08.2
4.1
61.2
28.6
SELF FIRSTDEGREERELATIVE
SECONDDEGREERELATIVE
NOONEINMYFAMILY
UNSURE
Asfarasyouareaware,doyouoranyoneinyourfamilyhave
PDorLBD?
Parkinsondisease Lewybodydementia
ISMMSn=76 NGFn=49
THEMONEYSHOT
Priortotakingthissurvey,wereyouawarethatpeoplewithGaucherdiseasehaveahigherriskofdeveloping
Parkinsondiseasethanthegeneralpopulation?
79%
21%
Didyouknow?
YES
NO
82%
18%
Didyouknow?
YES
NO
ISMMSn=76 NGFn=49
Participantswereloyaltotheirrecruitmentsiteandoneparticipantansweredthattheyfirst
learnedfromageneticcounselor
40%
2%
1%
17%6%
14%
20%
Howdidyoufirstlearnabouttheincreasedriskof
developingParkinsondisease?MyGaucherdoctor
AnotherdoctorormedicalproviderGeneticcounselor
NGF
Otherwebsite
Other
Noresponse
Other “Doingresearchovertheyearssincemydiagnosisin1968”
“Gaucherpatientmeetings” “Research,internet,NIHstudy” “Symptoms” “Myownreading” “Idonotremember”
Combinedn=125
Mostparticipantsreportedfirstlearningoftheincreasedrisksometimeafterdiagnosis,rather
thanatthetimeofdiagnosis
2%
8%
70%
20%
Whenwereyoufirstinformedoftheincreasedriskof
developingParkinsondisease?
BeforeGaucherdiseasediagnosis
AttimeofGaucherdiseasediagnosis
AfterGaucherdiseasediagnosis
Noresponse
WhofirstlearnoftheincreasedriskatthetimeofGaucherdiseasediagnosis? ISMMSparticipants:~13% NGFparticipants:0%
Combinedn=125
Mostparticipantsansweredthattheyhavenotmadechangesbasedonknowledgeoftherisk,
indicatingthatitisnotasourceofsignificantstress
8%
72%
20%
Haveyouevermadeanymedicalorlifestylechangesbasedonknowledgeofthis
risk?
YES
NO
Noresponse
Ifyes,whatchangesareyoumaking? “Exercisemore” “TakevitaminD” “Yearlyexams”
Combinedn=125
Amajorityofparticipantsbelievethebestwaytofindoutabouttheincreasedriskisfromahealth
careprovider
83%
11%2%2%2%
TheidealwaytofindoutabouttheincreasedParkinson
diseaseriskisfrom:
Healthcareprovider
NGF
Educationalbrochureorfactsheet
Other
Noresponse
Ifother,whatdoyouthinkistheidealwaytofindout? “Parkinsonfoundation” “Allofaboveandreadeverythingyoucanfind”
Combinedn=125
MostparticipantsbelievethebesttimetofindoutabouttheincreasedriskisatthetimeofGaucher
diseasediagnosis
70%
6%
13%
4%
6%1%
TheidealtimetofindoutabouttheincreasedParkinson
diseaseriskis:
AtGaucherdiseasediagnosis
Atage18
Afterage50
Never
Other
Noresponse
Ifother,whendoyouthinktheidealtimeistofindout? “Nogoodtime,butshouldbetoldnolaterthanwhensymptomsofParkinson'smaybeevident”
“Whensomethingcanbedoneorwhenitmanifests”
“Assoonaspossible” “Rightnow”
Combinedn=125
Only15%ofparticipantsindicatedtheywouldnotbeinterestedinanonlineexamtoevaluatefor
symptomsofParkinsondisease
64%15%
21%
IftherewereastudyofferinganonlinephysicalexaminationperformedbyaneurologisttoevaluateforsymptomsofParkinson,wouldyoube
interestedinparticipating?
Yes
No
Unsure
Futuredirectionforastudy?
Combinedn=125
KNOWLEDGE
73%ofparticipantscorrectlyansweredtheriskofdevelopingParkinsondisease,while59%correctlyansweredtheaverageagethatsymptomspresent
13%
73%
10%1%
3%
TheriskforParkinsondiseaseinpatientswithGaucherdiseaseisapproximately:
2-4%
5-15%
40-50%
70-90%
Noresponse
1%
59%
37%
1%
2%
TheaverageagethatsymptomsofParkinsondiseasestartinGaucher
patientsis:
Under30
40-60
70-90
90+
Noresponse
Combinedn=125 Combinedn=125 Correctanswer
ApproximatelyhalfwereunsureifGauchertreatmentreducesParkinsonrisk,reflectingthe
uncertaintyinthescientificcommunity
15%
32%51%
2%
TreatmentforGaucherdiseasewillreducetheriskof
developingParkinsondisease
TRUE
FALSE
Unsure
Noresponse
“Todate,enzymereplacementtreatmentusedtotreatGaucherdiseasedoesnotappeartobenefitindividualswithGBAmutationswhodevelopParkinsondisease.”–CookandSchulze2017
“EvidencefromavarietyofinvitroandinvivomodelsindicatethatGCaseactivityandα-synucleinlevelshaveareciprocalrelationship,althoughthemolecularmechanismsunderlyingthisarenotfullyunderstood.”–BalestrinoandSchapira2018
Combinedn=125 Correctanswer
Avastmajorityofparticipantsknewoftheassociationwithosteoporosis,butonly37%knew
oftheassociationwithmultiplemyeloma
“DataemergingfromtheInternationalCollaborativeGaucherGroup(ICGG)GaucherRegistrytogetherwithothercontemporaryclinicalsurveyshaverevealedacloseassociationbetweenGaucherdiseaseandnon-Hodgkin'sB-celllymphomaandmyelomaandGaucherdiseaseandParkinson'sdisease.”–Coxetal.2015
Combinedn=125
92%
6%
37%
2%
8%
94%
63%
98%
OSTEOPOROSIS HIGHBLOODPRESSURE
MULTIPLEMYELOMA
HAIRLOSS
Gaucherdiseaseisalsoassociatedwith:
Yes No
Correctanswer
CONCLUSION
PatientswishtofindoutabouttheincreasedParkinsonriskfromtheirhealthcareproviderat
thetimeofGaucherdiagnosis HealthcareprovidersshouldcounselGaucherpatientsabouttheincreasedParkinsondiseaserisk Thisshouldincludetherisknumberaswellastheaverageageatonset
Informationabouttheriskshouldbereiteratedateveryvisit Thestudyparticipantswerewelleducatedandwellinformed,yet20%reportednotpreviouslyknowingabouttheincreasedriskofParkinsondisease
Informationaboutcomorbiditiesshouldbereiteratedateveryvisit Only37%ofparticipantsknewabouttheincreasedriskofmultiplemyeloma Butwhatabouttiming?Riskformultiplemyelomais50-60s
Studylimitationsincludesamplesizeandsamplecharacteristics
SamplemaynotberepresentativeofGaucherpatientselsewhereinthecountry
Surveytakenby“captiveaudience”(ISMMS)andthosewhoareinterestedinandfamiliarwithGaucherdisease(NGF)
Nostatisticallysignificantresults PriorknowledgeofParkinsondiseaseriskwasnotpredictiveofansweringtheknowledge-basedquestionscorrectly(CIspanned1)
Futuredirectionsincludeaddressingthelimitationsandcreatingnewstudies
Surveyalargercohorttoincludeotherdemographics,includingparticipantsfromareaswheretherearefewGaucherpatientsanddoctors
Assesshealthcareproviders’counselingpracticeswithregardtoincreasedParkinsondiseaserisk
CreateastudyassessingforsymptomsofParkinsondisease
WhataboutGaucherdiseasecarriers?
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References
THANKYOU!!
ManishaBalwani,MD
RoyAlcalay,MD
NatashaZeid,MS,CGC
ChananStauffer,MS,RN,NP-C
CarolFisher,BA,RN
AmyBlum,COOofNGF
SamanthaRubinstein,VPofEducation,AwarenessandPatientAdvocacyatNGF
Randi,Sabrina,Lisa,andHetanshi Supervisinggeneticcounselors Attendingphysicians Residentsandfellows
