Marsel Mesulam, MD Center Director

Northwestern Alzheimer’s Disease Center Northwestern University Feinberg School of Medicine Funded by the National Institute On Aging (NIA)

Website: http://www.brain.northwestern.edu

Alzheimer’sdisease(AD)isthemostwidelyrecognizedformofdemen9a.Itismostfrequentlyseenintheelderlyandtypicallycausesprofoundmemoryimpairments.

ManyofusthereforedeveloptheimpressionthatADanddemen9aarethesamething,thatdemen9acanonlyoccurintheelderlyandthatadiagnosisofdemen9acannotbemadeintheabsenceofmemoryloss.

ThemajormessagethatmycolleaguesandIwouldliketobringtothishearingistheneedtocri9callyre‐examinetheseassump9ons.

1.

2.

3.

ADCANARISEINTHEYOUNG.THEYOUNGESTPATIENTISAWWAS24. 

DEMENTIACANBECAUSEDBYDISEASESOTHERTHANAD.THEMOSTFREQUENTYOUNG‐ONSET,NON‐ADDEMENTIAISKNOWNASFRONTOTEMPORALLOBARDEGENERATION(FTLD).

 

FTLDANDUNUSUALFORMSOFADCANCAUSEDISABILITYBYIMPAIRINGLANGUAGE,SPATIALORIENTATIONORBEHAVIORRATHERTHANMEMORY.INSOMEOFTHESEPATIENTSADIAGNOSISOFDEMENTIAISMADEALTHOUGHMEMORYISNORMAL.

 

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ALZHEIMER’SDISEASEHASAMYLOIDINTHEBRAIN,FTLDDOESNOT.HEREDITARYADISLINKEDTOCHR1,14,21.FTLDISLINKEDTOCHR3,9,17.TYPICALALZHEIMER’SLEADSTOANAMNESTICDEMENTIA,FTLDUSUALLYSPARESMEMORY.FTLDCANCAUSETWODIFFERENTCLINICALSYNDROMESOFDEMENTIA‐bvFTDANDPPA.

AMYLOID

TANGLE

ALZHEIMER

PICKBODY

TDP‐43

FRONTOTEMPORAL

bvFTD(akaFTD)causesagraduallossofjudgment,insightandcomportmenttothepointwherethepersoncannotmakesounddecisionsandengagesin

inappropriateimpulsivebehaviors.

PPAresultsinagraduallossofwordusageandcomprehensiontothepointwherethepersonlosestheabilitytocommunicate

thoughtsorunderstandwhatothersaresaying.Theproblemisnotinar9cula9ngorhearingspeechbutinthebrain’sabilitytouseandinterpretwords.

BOTHbvFTDANDPPAUSUALLYSTARTBEFORETHEAGEOF60ANDCANSPAREMEMORYFORMANYYEARS

bvFTDHASBEENINCLUDEDINTHECOMPASSIONATEALLOWANCESLISTBUTPPAHASNOT

SURGICALLYCAUSEDMEMORYLOSSNORMALBRAIN

TOP

LEFT RIGHT

TYPICALAMNESTICAD

atrophy NORMAL

bvFTD

FRONT

BACK

PPA

RIGHT

LEFT

1. DOCUMENTEDHISTORYOFDISABLINGANDPROGRESSIVEIMPAIRMENTIN‐• word‐finding• wordusage• orderingwordsintomeaningfulsentences• wordcomprehensionandreading• wriOngandspelling

2.OBJECTIVENEUROPSYCHOLOGICALEVIDENCEOFLANGUAGEIMPAIRMENTANDRELATIVESPARINGOFOTHERCOGNITIVEABILITIES.

3.IMAGINGEVIDENCEOFPROGRESSIVEBRAINDAMAGEINLANGUAGEAREAS

LEFT RIGHTPPACOMPUTERIZEDMAPPINGOFATROPHY

LEFT

SPECT

LEFT RIGHT

LOWBRAINFUNCTION