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DEMENTIA

Dr.Yotin ChinvarunM.D.Ph.D.

Neurology,Pramongkutklao hospital

Introduction

• In1901AugusteDeter, awomaninherearly50s, became1stpersondiagnosed withAlzheimer's disease, aformofdementia.Thedisease isnamedafterthedoctorwho firstdescribed it,Alois Alzheimer

• Thedisease is characterizedby– Oddbehavior– Memoryproblems– Paranoia– Disorientation,agitation,and

hallucinations

Introduction

• Dementia refers toagroupofsymptomscausedbyseveraldifferent braindisorders

• Dementia ischaracterized byimpairedintellectualfunctioningthat interferes withdailyactivities orpersonalrelationships.

• Thisimpairmentcanincludememoryloss,language difficulty,decreased perception, andimpairedreasoning

SignsandSymptom

• Mostcommonaffectedareas include– memory,– Visual-spatial– Language– Attention– Executivefunction (problem

solving)

– Most typesofdementiaareslow andprogressive

• Additional psychologicalandbehavioralproblems include:– Balance problems– Tremor– Speechandlanguage dif f iculty– Troubleeatingorswallowing– Memorydistortions– Wanderingorrestlessness– Behavioralandpsychological

symptomsof dementia(BPSD)almostalwaysoccurinalltypesof dementia.BPSDsmaymanifestas

– Agitation,Depression,Anxiety,Abnormalmotorbehavior,Elatedmood,Irritability,Apathy,Disinhibitionandimpulsivity,Delusionsorhallucinations

– Changesinsleeporappetite

Epidemiology

• As longevity increases, diseases ofagingbecomemoreprominent

• In2000,approximately4.5million individuals withAD inUnitedStatesandwill be increaseup to14million by2050

• TheprevalenceofADalso doubles everyfiveyears,agreaterprevalenceofAD inwomenthaninmenreflects thegreaterlongevityofwomen

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Dementia

• InindividualswhoultimatelydevelopAD,presumes• Agradualprogression of thepathologicprocesswhichbegins with

normalagingandevolvestoclinically probableADandultimately toneuropathologically provenAD

• Itislikelytheseindividualspassthroughatransitionalstagebetween normalagingandclinicallyprobableAD

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Mildcognitive impairment

• Inrecent years, mildcognitiveimpairmenthasbeendocumented inindividualswhotypicallyhave• Memory impairment• Butare onlymildlyfunctionallyimpaired.

• These personsdonotmeet criteria for clinicallyprobableADyet are worthy ofidentificationandmonitoring

Mildcognitive impairment

• Inthefirststages ofdementia, signsandsymptomssubtle

• The earliest stage ofdementia calledmildcognitiveimpairment (MCI)

• 70%ofMCIprogresstodementia atsomepoint

• PersonwithMCIscores27- 30ontheMini-MentalStateExamination(MMSE), whichisanormalscore– Theymayhavesomememory troubleand trouble finding words– But theysolve everydayproblemsandhandleown lifeaffairswell

Dementia

• The mostcommonformofisAlzheimer’stype(orAD),accounts65%ofdementiasinlatelife

• Prevalence ofADincreases withage, afflictingapproximately13%ofage65years oldandolderandupto50%ofthoseover 85years

Dementia

• Other commonformsofdementiae.g.– Vascular dementia(VAD), estimated 15–20%ofdementiasinU.S.AandEurope;andupto50%ofdementiasinJapan

– Dementiawith Lewybodies(DLB) 30%ofdementias

– Frontotemporal dementia(FTD), particularly affectspersonsunder65yrs,accounts5%ofdementias,althoughsomeestimates are higher

Dementia

• Othercommonformsofdementiae.g.– Lessfrequentdementiasyndromesinclude

– Creutzfeldt-Jakobdisease,– HIV-associateddementia, neurosyphilis,– Parkinson’s dementia PDD,– Normalpressure hydrocephalus,– Dementias resulting fromexposure totoxicsubstances (e.g.,alcohol, heavymetals, illicit substances), metabolicabnormalities,andpsychiatricdisorders

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Dementia

• Importance ofmakingaspecificdiagnosis– Clinical featuresanddiagnosticcriteria for

• Alzheimer'sdisease• Frontotemporaldementia• DiffuseLewyBodydisease

• Preclinicaldementia syndromes,characterized bymilderformsofmemorylossandnofunctionalimpairment,areprevalent ingeneral population

• Identificationisimportant because early pharmacologicinterventions indementiamay delayonset andslowprogressionofAD

AD,DLBorFTDDoesitMakeaDifference?

• Drug treatment differs• InFTDnoevidenceofacholinergic deficiency• InFTDbehavior less likely torespond tousualdrug treatmentsand

appear tobemorespontaneous rather than responsive toenvironment

• Understanding behaviorcanhelp caregivers• InDLBhallucinations mayrespond toChEls

• InFTDandDLB impairedinitiativeiseasilyconfusedwithdepression

• InFTD andDLB amyloidstrategies are inappropriate• Prognosisandgeneticsdiffer

Alzheimer'sDisease

• Insidiousonsetofgradualprogressive dementia, account60%ofalldementia

• Memory lossusuallyinitialandmostprominentsymptom,eventually affects language, visuospatialabilityandbehavior

• Nofocalweakness orsensoryloss

• Gait normalandcontinentuntillateillness

• NINCDS-ADRDA criteria validated

NINCDS/ADRDA

• CriteriaforDiagnosisofProbableAD:a. Dementiaestablished byclinicalexamination, anddocumentedbya

standard testofcognitivefunction ,andconfirmedbyneuropsychological tests.

b. Significantdeficiencies in twoormoreareasofcognition, forexample,wordcomprehension and taskcompletion ability.

c. Progressive deterioration ofmemoryandother cognitivefunctions.d. No lossof consciousness.e. Onset fromage40to90, typicallyafter65.f. Nootherdiseases ordisorders thatcouldaccount forthe loss of

memoryandcognition.

TheContinuum ofAD

SperlingRA2011

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Current approach toClinicalassessmentofEarlyAD

• Current diagnosisisbasedonamultimensionalclinicalpicture: cognition,,function,behavior,QoL– Hx,caregiver reports, symptompattern, duration– PE,briefneurological exam– Mental status tests

• Ideallyneed toaccurately identificationADeven earlier andmonitorprogressionandRxresponse

ClinicalevaluationofAD

• Currently AD isaclinicaldiagnosisbasedonHxandneurologicalandcognitive exams

• Neuropsychologicaltesting – mayhelpdistinguishADfromage-related decline

• Depression (maybe comorbid)

• Imagingmaybe helpfulinrulingoutotherCNScausesofcognitive decline– Tumor,stroke

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Diagnosis:AD

• Newcriteria forearly diagnosis

• Whyearly diagnosisisimportant

• MRIinAD• ADDx andDDX

– F18-FDG-PET– Dopaminetransporter imaging(DaT)– AmyloidandTauimaging

Newcriteria forearlydiagnosisofAD

• 2Setofcriteria have evolved– IWG/Dubois criteria– National institute onAging/Alzheimer’s Association criteria– Thesehavemanysimilarities

• Newcriteria– Identifybiology ofADbeforeanysymptomappear– IdentifyaprodromalorMCIformofADwhensymptomsarepresent,

butcriteria fordementia arenotmet

Newcriteria forearlydiagnosisofAD

• Biomakers innewcriteria identifypre-dementia formsofAD

– Neurodegeneration inMRIatrophy

– Reducedmetabolism inFDG-PET

– Fibrillar amyloiddeposition inamyloidPET

– ADCSFsignatureofhigh tauandlow amyloid (AB42)

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DDxofDementia

• AD• Mixeddementia (AD plusvasculardementia)• Diffuse Lewy disease• Fronto-temporal dementia• Purevascular dementia• Other Parkinson-plussyndrome• Reversible causes

– Metabolic,infectious,toxic,alcoholetc.

Neuroimaging inAD:PreviouslyDxofexclusion

• CT:reveals changes characteristic ofADinlaterstages– Diffusecorticalatrophy– Enlargecorticalsulci– Ventricleenlargement

• Drawbacks– Ionizing radiation– Atrophymaybepresent inhealthy individuals– Somepatient havedementia,butnoatrophy– Normalvariations in skull size– Serial scansnotclinicallyuseful– Specificitynotwell established

Neuroimaging inAD:Volumetric MRI

• MRI– Measures hippocampalatrophyandcorticalthinning– Tissue contrast– Absenceof ionizing radiation

• Drawbacks– Expense– Claustrophobia– Presenceofmetal implants ordevices– Lackofstandardized acquisition parametersorquantitativeanalytic

protocols

Rationale forEarlydiagnosis

• 10Phase3trialfailureatthe stage ofADove rthe pastdecade

• Intervention before dementia (stage ofirreversible braincellloss)mayhavebetter chance ofchangingclinicalcourseofthedisease

• Delaying dementia by5years, reduce projected medicare costbynearly 50%

• Appropiate useofimagingmodalitieshasclinicalutility

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Alzheimerdisease

• Estimate the mean age ofonset(typicallyinthe40s)

• 20yearsbefore dementia onset,beta-amyloid levelsincerebrospinal fluidbegantodrop

• 15yearsbefore dementia onset,– beta-amyloiddeposits canbedetectedbyamyloid imagingscans,– Taulevelsbegin rising incerebrospinal fluid,– Atrophyof thebrainbegins tobecomedetectablebyMRI

Alzheimerdisease

• 10yearsbefore dementia onset,brainmetabolicchanges arepresent onFDG-PET andthe firsthintsofepisodicmemorydeficitsbegin

• 5years before dementia onset,patients developmildcognitive impairment.

Importance ofEarlydiagnosis

• Identify peopleatriskfor progressiontoAD

• Begintherapy asearly asindicated

• Lifeplanning

• Relationshippreservation

• Clinicaltrialparticipation

BrainimagingcanassistinEarlyDxandDDX

• MRIatrophy• FDG-PET inAD• FDG-PET inDDxofADandFTD• I-123PETinADandDLB• AmyloidPET• Tau PET

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FluidbiomakersandGenetics inADdiagnosis

• CSF– Amyloid b-1-42– TotalTau;phosphorylated tau– Combination/ratios

• Plasmameasures are notyetuseful

• Genetic– APOEe4– Autosomal dominant mutation (rare)

Beta-amyloidPET• F18agents

– Flobetapir– Flutemetamol– Flobetaben

• C-11– PIBcompound

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DiffuseLewyBodyDisease

• lnsidiousonsetofgradualprogressive dementia

• Memory lossusuallyinitialandmostprominentsymptom

• Hallucinations/misperceptions

• Often Gait andmotorsymptoms'within1year’ofonsetofdementia

• Attention andsleepabnormalities

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DiffuseLewyBodyDisease

• UnlikeAD,mostDLBpatients morelikely tobemen,and the illness hasashorter course(<10years)thanAD

• MostcasesofDLBoccur>65yrs

• Characterizedby frontal-subcortical cognitivedeficitpattern(earlyandprominent impairment inattentionandexecutivedysfunction, comparedwith less prominent andlatermemory impairment), fluctuating levelofcognition andalertness, parkinsonism, andvisualhallucinations

• DLBmaybedifficult todistinguish fromParkinson’s disease,– ParkinsonisminDLBdiffersfromParkinson’sdiseasebybeingmoreoften

symmetric,withlesspronouncedtremor– HallucinationsmoreprominentinParkinson’sdiseasethaninDLB

Revisedconsensus criteria

• CentralFeatures:– Progressivecognitivedeclinethatinterfereswithnormalfunction.– Prominentdeficitsontestinginoneormoreareasofattention,executive

function,andvisuo-spatialability.– Memoryimpairmentwhichmayoccurlaterinthedisease.

• CoreFeatures:– Pronouncedvariationsinattention,alertness,andcognition.– Visualhallucinationswhicharetypicallywell-formed– Parkinsonism

• Suggestive features– REMsleepbehaviordisorder– Severeneuroleplic sensitivity– LowdopaminetransporteruptakeinbasalgangliademonstratedbySPECTor

PETimaging

Fronto-temporal Dementia(FTD)

• lnsidiousonsetofprogressivedementia• Disturbingbehavior andspeech problemsmostprominent,

lessevident memory loss• Perseveration, decreased verbal fluency

• Typicalbehavioral changes includingapathyunrestrained andinappropriate socialconduct

• Memory lossoftennotprominent;ADscreening tests maybeinsensitive

• May beassociated withmotorneurondisease

FTD:ThreeClinicalprofiles

• Frontotemporal dementia behavioral variant (FTDbv):Personalitychange,disordered social conduct.lnstrumental functions relativelywellpreserved.

• Progressive nonfluent aphasia (PA):Expressivelanguagedeficit is thedominant feature initially and throughout theillness. Otherwise cognitionrelativelywell preserved.

• Semanticaphasia andassociative agnosia dementia (Semanticdementia,SD):impairedunderstanding ofwordmeaningand/orobject identity.

Diagnostic featuresoffrontotemporaldementiabehavioral variant

• Core diagnosticfeatures ofFTD– lnsidious onset andgradualprogression– Earlydecline in social interpersonal conduct– Earlyimpairment ofpersonal conduct– Earlyemotional blunting– Earlyloss of insight

• Supportive diagnosticfeatures ofFTD– Behavioral disorder– Speechand language– Physical signs

Diagnostic featuresofProgressivenon-fluent aphasia

• CorediagnosticfeaturesofPA– lnsidious onsetandgradualprogression– Nonfluent spontaneousspeechwith:agrammatism,phonemicparaphasias,anomia

• SupportivediagnosticfeaturesofPA– Speechandlanguage. 1.Stutteringororalapraxia2.Impairedrepetition

3.Alexia,agraphia 4.Earlypreservationofwordmeaning,5.Latemutism

– Behavior. 1.Earlypreservationofsocialskills 2.LatebehavioralchangessimilartoFTD

– Physicalsigns:latecontralateralprimitivereflexes,akinesia.rigidity.andtremor

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Diagnostic featuresofSemanticaphasiaandAssociativeagnosia

• CorediagnosticfeaturesofSD– lnsidious onsetandgradualprogression– LanguageDisorderand/or– Perceptualdisorder– Preservedperceptualmatchinganddrawingreproduction– Preservedsingle-word repetition– Preservedability toreadaloudandwritetodictationorthographically

regularwords

• Supportivediagnosticfeaturesofsemanticdementia– Speechandlanguage– Behavior– Physicalsigns

FTDMayMimicAD

• Criteriaaresubjectiveandmustbeinterpretated

• ADmoreprevalentthanFTD,especiallyage>65

• BehaviordisturbancealsocommoninAD

• ADissometimesasymmetriccausingprominentaphasia

• MostpatientswithFTDeventuallydevelopasignificantmemorydisturbance

• MostpatientswithFTDalsomeetNINCDS-ADRDAcriteriaforAD(Varmaetal. JNNP1999;66:184-188)

• Cliniciansdependuponrelativeseverityofsymptoms;nonearepathognomonic

NACCAccuracystudy• 88(16.7%)ofNACCpersonwithclinicaldiagnosisADdidnotmetneuropathofAD

• MedianreportsensitivityforclinicaldiagnosisofAD87%,butmedianspecificity58%

Primaryfindingin8cases N

NeuropathoAD(belowcriteria) 17

TanglepredominanceAD 15

Fronto-temporaldementia 15

Cerebrovasculardisease 10

Lewy bodydisease 10

Hippocampalsclerosis(withorwithoutAD) 9

BeachTGet.al.,2012

Preclinicaldementia• Twocommonpreclinicalsyndromesinclude

A.Age-associated memory impairment (AAMI)B.Mild cognitive impairment (MCI)

• A.Age-associated memory impairment(AAMI) – Mildest formofage-relatedmemoryloss– Occursinpersons >50years– Characterizedbyself-reported memorycomplaints, decreased

memoryperformancescomparedwithyoungeradults (1SDbelowyoungadultsonmemorytests), butnormalmemorycomparedwithagepeers.

– Prevalence40%inpeople 65yearsofageorolder– Approximately 1%develop dementiaeachyear.

Preclinicaldementia

• B.Mildcognitiveimpairment(MCI)– Typically involvesamoresevereloss ofmemorythat is still not

associatedwith functionaldecline

– Reductions inmemoryorothercognitivedomains comparedwithagepeers

– Manypersons with MCIshow similar cerebralpathology topersonswithAD

– Approximately 15%ofpersons withMCIdevelopdementiaannuallyandmostoftenAD.

Obstacles toAccurateDiagnosisofDementia

• Previous studies indicate thatfalse-negativediagnoses occur50–90%ofcases,mistakenlyattribute earlycognitivedecline tonormalaging

• Evaluationand treatmentmaybedelayeduntil diseaseseverityandneuronal damageprogressed

• Overrelianceonandoverinterpretation ofCTandMRIresults

• Similarly, overrelianceon typicalcutoffscores onmental statusorcognitivescreening tests, orusingsuch tests for solepurpose ofdiagnosis– Highly educated individuals whosufferedcognitivedecline may shownormal

functiononcognitivescreening testssuchasMini Mental State Exam (MMSE)

– Whereas personswithloweducationmayappear tohave cognitive impairment ordementia whenthey actually have notdeclined

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WhyPET lmaging?

• Recognition ofdementia is oftendelayedanddiagnoses areoftennon-specific

• Physicians lackdiagnosticconfidence

• Clinical MRIandCTdon'tprovide information aboutbiochemicalandphysiological changes thatarecharacteristicofthemostcommondementingdisorders

• Currentclinical diagnosticcriteriaare imperfecte.g.,patients withFTDoftenmeetscriteria forAD

PETlmagingisNotAPanaceaforMemoryEvaluations

• lmaging(radiologists)willnever beabletodetermine whethersomeonehasdementia -symptomsdetermine that

• Imagingwilladdsanotherpiece ofinformationthathastobeinterpreted (clinicalcorrelationrecommended) andincorporated intodecision-making

• Benefit shouldbetoincreaseaccuracy anddiagnosticconfidenceindementia andpatient withmemoryimpairment

18-FFlurodeoxyglucosePositronEmissionTomography(FDG-PET)

• FDG-PETprovidesunique information, complementary tostructuralimaging

• Short-livedpositron-labeled formofsugar that follows theearlysteps ofglucose, butgets trapped in thecell

• Fluorine -18:120min

• PETscanneruses physicalproperties ofpositrons to localize relevantradioactiveemissions anddiscards others (improving resolution comparedtoSPECT)

WhatGlucoseMetabolismMeasures

• Undernormalconditionsthebrainusesglucoseasitssolesourceofenergy

• Glucosemetabolismprimarilyreflectssynapticactivity

• Hypometabolismmaynotcorrespondtoareaswithgreatestchangesinroutineneuropathology

• Routineneuropathologyisbetteratdetectinglossofneuronalcellbodiesthansynapses

• Itisnotdirectlyaffectedbyintracellularorextracellularinclusions

FDG-PET lnterpretation

• EvaluatethePATTERNofregional glucosehypometabolism, not justindividual region,hotorcoldspot,orglobal changesinmetabolism

• Evaluatewhether therearestructuralabnormalities thatmightaffectmetabolism– CasesdiscussedtonighthadnofocalstructuralbrainabnormalitiesonCTor

MRI

• Consider theclinical context– Whatistheclinicalquestion?– Medications,delirium,behaviorduringFDGuptakecanalleffectscanresults

UsefulnessofFDG-PETindementia

• Adding PETtoaclinical dementiaevaluationcanenhancediagnosticsensitivity

• Thesensitivity fordetectinghistopathologically confirmedADusingPETfalls in the rangeof91.5%± 3.5%,comparedwith 66%± 17%toidentifying probableAD inclinicalevaluations performedwithout PET

• Incaseswithpossible orprobablydementia, specificitywithout PETthenfalls toarange (55.5%± 5.5%)thatis substantially lower thanthatachievedwhenusingPET (70%± 3%).

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UsefulnessofFDG-PETindementia

• AutopsyconfirmedADor FTD– 31ADpatients– 14FTDpatients

• Sixdementia specialistsdecideondiagnosiswithdegree ofconfidencetwice:– After reviewofclinical history– ThenafterFDG-PET

• 98%specificityforFTD inautopsy-confirmedcases

UsefulnessofFDG-PETindementia

• Inpatientsalready diagnosedwithdementia PET scancanclarify thediagnosis,whichisrelevanttoappropriatetreatment, forexample

– DifferentiatingAD fromFTD,becauseunlike AD,FTDdoesnot respondwell toacetylcholinesterase inhibitor treatment

– Also, mightbeuseful toDDXfromothers typeofdementia• Lewisbodydementia• Corticalbasaldegeneration(CBD)• Parkinson’sdiseasedementia(PDD)

UsefulnessofFDG-PETindementia

• Amajorclinical challenge is earlyidentification ofpatients whowilldevelopADorotherdementias, which is relevant toearlier treatmentintervention andplanning forapatient’s futureneeds

– SeveralstudiesshowedPETsensitivetoAD-likehypometabolicbrainchangesinnon-dementedpersonswiththeapolipoproteinepsilon4(APOE-4)geneticriskforAD

– PETpredictscognitivedeclineinpersonswithAPOE-4,innormalelderlypersons,inpersonswithmildmemorycomplaints,inpersonswithquestionabledementia.

– RecentstudiesalsosupportuseofPETtopredict• Convers ion of MCI todementia for differentiating s tablefrom progress ive amnestic MCI,

particularly incombination withmemory test performance scores

UsefulnessofFDG-PETindementia

• Somepatients withanormalinitialevaluationrequest aPETstudybecause they are concerned abouttheir personal riskfordementia, suchas– Priorheadtrauma– Familyhistoryofdementia.– AnegativePETmayreassuretheseworriedwell– If,however,thescanresultsareconsistentwithaprogressive

neurodegenerativedementia,thenpatientscanconsiderearlytreatmentinterventionstrategiestoslowprogressionofcognitiveimpairment,althoughconsideredanoff-labeluseofmedication

Case• F65yrs old• Complainedwithpoorshort-termmemoryfor6months

– Usuallyforgetfulthings,poorconcentration

• Notdisturbednormalfunction,abletowork,havetotakecarehusbandwhohavestrokeforayear

• PE:normalgeneralandneurologicalexamination

• MRIbrainshowsmildgeneralizedcorticalatrophy

• HavebeentreatedwithAChEI

FDG-PETdiagnosis

• Alzheimer'sdisease– Temporoparietalcortexhypometabolism>frontalcortex– Posteriorcingulatecortexhypometabolic

• Frontotemporaldementia– Frontalcortexhypometabolism>temporoparietalcortex– Anteriortemporalandanteriorcingulatecortexhypometabolic

• When several areas affected, are ADor FTD regionsmosthypometabolic

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PETTauTracers

• Tau proteins result fromsinglemicrotubule-associated proteintaugene inhumans,discoveredin1975

• Healthy neuronscontainmicrotubules,supportstructure andguidenutritionalsupplies

• Chemicalchanges (namelyhyperphosphorylation) occurintauproteininAD–Causingdisintegrationofmicrotubules,collapseofneuron’stransport system, formationofextremely insolubleaggregates, disruptneuronalcommunicationandleadtocelldeath

PETTauTracers

• Development ofPETligandsfortau(detect neurofibrillarytangles)

• Seven tau pathologyPET tracers have beendeveloped andusedinclinicalstudies:C-11PBB3,F-18THK-523,F-18THK-5105,F-18THK-5117,F-18T808,F-18FDDNP,andF-18T807

• 18F-AV-1451 selectivelyboundtoPhosphorylatedhelicalfilaments(PHFs), andhasvery weak ornoaffinitytothe β-amyloidaccumulation

Case• M69yrs old• Progressivememorylossfortwoyears,

– poorshort termmemory,– Languageisnormalbutunable tospeakfull sentence,– deteriorationof selfcare,unabletodresshimselfandbuttoning,– Normalgait,impairedcalculation,recall,clockdrawing

• Unabletotravelbyhimself,moodisstable

• PEgeneralexaminationisnormal,neurologicalexaminationrevealedwelldressman,oriented,poorrecall0/3,calculationimpaired,namingpreserved

• MRIbrainshowsmoderategeneralizedcorticalatrophy

Case:AD• M87yrsold• Hxofprogressive cognitiveimpairment for>5yrs• HxofHT, memorydecline withpoorshortterm memory,

repetitive speaking anddoingthesame thingrepetitively,poorrecall,goodmood,normalperception

• PE:oriented, language able tospeckinalongsentence,usuallyrepetitive wordwhilehavingaconversation, alsodoingtherepetitive task– Generalexaminationwasunremarkable

Case

• Diagnosis:Alzheimer'sdementia

Frontotemporaldementia

• M62yrsold

• Progressive cognitive impairment for6months, rapidlydecline in thelast4months

• Behavioral changewithaggressivebehavior, usually spitting salivaall over,walking isnormal, unable tonaming, less talkingand recentlymute,poorsleep-wakecycledisturbance, hyperphagia, agitation, urgencyincontinence

• Also, hadseveralepisodes ofblankstaring lasting forseveralminutes withconfusion afterward, frequency3-4permonth

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Frontotemporaldementia

• PE:well dressed gentleman,agitated, response toverbal command,ableto tellname,objects, echolalia

• Generalexaminationwasnormal

• Neurological examinationCN:WNL,motorallgrV, cerebellar systemwasnormal, normalgait

• Currentmed– LVT,VPA,Exelonpatch,Ebixa

Case• M76yrsold

• Hxofchronic insomnia andhavingabaddreamfrequently,onClonazepam andzopidem foralong timeperiod, progressive memorydeclinewith poorshort termmemory,poorconcentration

• PHofHTandCAD, still drivinga sportcare, sometimedrivingupwith highspeed, sometimeup to200km/hr, nowable todriveeveryday

• PE– Sleepy,generalandneurologicalexaminationwasunremarkable– Regidity+ve,instability

– DiagnosispossiblydementiawithearlyParkinson’sdisease

REMBehaviorDisorder

• Oldermales• Injurious ordisruptive behaviourduring sleep• Easilyaroused;Dreamrecallprominent

• Two-thirds ofpatients developParkinsons– meanlatencyof13years;associatedwith synucleinopathies (PD,

Lewisbodydementia, MSA)

• Polysomnography diagnostically helpful

• Highly responsive toClonazepam

Lewisbody dementia

• There are very fewneuropathologically-confirmed imagingstudiesofLBD.

• More occipitalatrophyinLBDthaninADhasbeenreportedbyagroupwithagooddiagnosticrecord

• Inagreement isthefindingofdecreased metabolisminoccipitalassociationcortex

Case• F78yrs

• Hxofprogressive cognitiveimpairment withimpairmentofspeech forayear, hallucination

• PE:aphasia,bedridden,apraxia, regidity +ve

• CTbrainmildtomoderategeneralized cortical atrophy

Non-amyloiddementias

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Case• M55yrs• Hxofpulmonaryedema withpneumoniaafter cardiac arrest,

ARDS, ATNwithCRFanddialysisdependent,large umblilicalhernia andepilepsy

• Patient hasataxicgait, parkinsonismfeatures, mostlyapathy,speechless

Case

• Dx:Dementiawithprobablycorticalbasaldegeneration

MildCognitiveImpairment

• Transitionalstate between healthy aging anddementia,duringabletoperform usualactivities ofdailylivingbutsufferisolatedmemory difficultiesexceeding thoseexpected onthebasisofnormalaging,mightberiskfordevelopingfuture AD

• However, notallMCIpatientsdevelopAD

• Astheclinicaldiagnosisperseisoftenuncertain,PETevaluations are increasingly usedtosupporttheclinicaldiagnosisearly stages ofAD.

MildCognitiveImpairment

• MCIpatientsusuallypresent onPETwithmildglobalandregional hypometabolism

• FDG PET examinationsrevealed MCIpatients showapatternofbrainhypometabolismthatistopographicallyconsistentwiththat observed inclinicalAD

• However, somestudiesdidnotobservethesame distributionofcorticalmetabolicdeficitsinMCI,particularly inthecaseofvery mildlyaffected subjects

MildCognitiveImpairment

• Mesial temporal lobehypometabolism inMCIcanbeidentified

• Studies thatusedquantitative measureshaveshown significant absolutereductions ofglucosemetabolic rates inMCIpatients relative tocontrols.

• These reductions aremilder than inADandaffecttheMTL(7%–17%),lateral temporal (8%),andposterior cingulatecortices (23%).

MildCognitiveImpairment

• Agrowingbodyoflongitudinal FDGPETstudies hasbeencarriedout toexaminethepredictivevalueofcerebralmetabolicmeasures in thedecline fromMCItoAD– Demonstratingmetabolicchangessharethesametopographyofthe

characteristicADPETpattern,i.e.,reducedparietotemporalandposteriorcingulatecortexmetabolism,andaredetectableseveralyearsbeforeclinicaldiagnosis

– MetabolicreductionsinthedecliningMCIpatientsareprogressive,indicatingPETmeasuresarebothpredictorsandcorrelatesofdeclinetoAD

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Case• M77yrsold,a retired toparmyofficer

• Presenting withpoorshort termmemory forayear, oftenforgetful things,found itverydifficult to recall thenameofthe familial people

• Playinggolfeveryweekandable todonormal dailyactivities, still travelaboardoccasionally

• Languagefunction isnormal, recently reportedbypatient’s wifeashavinglabile mood, sometime agitated

• PE:normalgeneralandneurological examination

• MRIbrain shows mildgeneral corticalatrophy

case

• PatientwasdiagnosedasMCIwithprobablyanearlydevelopmentofAD