Ira Lott: Down Syndrome and Dementia
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Transcript of Ira Lott: Down Syndrome and Dementia
7/14/2019 Ira Lott: Down Syndrome and Dementia
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DownSyndromeandDemen-a
IraT.Lo2,MD
ChildNeurologist
ProfessorEmeritus
UniversityofCalifornia,Irvine
7/14/2019 Ira Lott: Down Syndrome and Dementia
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PrevalenceofDemen-ainDown
Syndrome
• Byage40years,allindividualswithDShavethepathologicalchangesofAlzheimerdisease
• However,demen-aisnotinvariableevenatolderages
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Defini-onofdemen-a
• Demen-aisageneraltermthatreferstoa
progressivelossofmemory,judgment,
language,complexmotorskills,andother
intellectualfunc-ons
• Alzheimerdiseaseisthemostfrequentcause
ofdemen-a
7/14/2019 Ira Lott: Down Syndrome and Dementia
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PlaquesandtanglesinDS(CourtesyE.Head)
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Deposi-onofbrainamyloidinDS
• Depositedfirstininfancyandaccumulates
acrossthelifespan
• Earlyamyloidplaquesareconsidered
“benign”butthereisalreadyevidenceofapoptosisorneuronal“cellsuicide”.
7/14/2019 Ira Lott: Down Syndrome and Dementia
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EarlyOnsetAβ in Down syndrome
4monthsold–an-Aβ1-16 immunostaining in free-floatingformic acid pretreated 50 µm thick formalin-fixed sections.
Intact
Neurons
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Caspaseproductsin“benign”plaques
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Findingsinamanwithpar-altrisomy
1
• Hasnot3copiesofamyloidprecursor
proteingene
• Notdementedatage70years
• Hasveryli2leamyloidbindinginhisbrain
comparedtocontrols
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Manwithpar-altrisomy1
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47XY+del(1)(q11.q.1)
7/14/2019 Ira Lott: Down Syndrome and Dementia
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0
0.5
1
1.5
.5
pDS_009 pDS_01 DS_avg AD_avg MCI_avg NC_avg
S U V r ( C B )
PIBSUVrbyRegionofInterest
Temporal_Lobe
Frontal_Lobe
Parietal_Lobe
Lowamyloidbindinginpa-entwith
par-altrisomy009,01
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Thereappearstobea“compensatoryresponse”in
thehippocampusbeforetheageofdemen-aonset
thisprovidesapoten-altargetfortherapeu-ctrials
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FDG uptake in hippocampus, increased in young adults withDS, decreased in AD patients general population
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Conclusions
• Amyloidaccumula-oninDSrequiredfordemen-a
• Treatmentinterven-onsthataresuccessfulatolderagesmaybetargetedtoyoungerage
groupsandimprovecogni-vefunc-oning
• ClinicaltrailsforyoungadultswithDSare
underway
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CollaboratorsandSupport
• ElizabethHeadUnivKyneurobiology• RichardHaierimaging
• DavidKeatorimaging
• GarySmallandcolleagues,UCLAimaging
• EricDoranprogrammanager
• SupportedinpartbyHD591,HD065160,AG1657;AlzheimerAssocia-on;Stateof
California,UCIMINDIns-tute