Topic 6

Front 1

• The financial costof AD in Australia is about

Back 1

6.8 bill/per anum

Front 2

Atleast 1 in every 40 in the Australian health system is spent on

Back 2

AD/Dementia

Front 3

dementia is the progressive decline in

Back 3

cognitive function (due to damage or disease in the brain beyond what might be expected from normal aging)

Front 4

manifestations of dementia include:

Back 4

– deficitsinlanguage

– memoryloss

– moodswings

Hint 4

DMM "puppet DuMMy with memory loss"

Front 5

defenition of cognitive function

Back 5

anintellectualprocessbywhichonebecomesawareof,perceives,orcomprehendsideas.ItinvolvesallaspectsofpercepHon,thinking,reasoning,andremembering.

Front 6

alzheimers is a common form of

Back 6

dementia (50-70% of all dementia cases)

Front 7

what are the different types of dementia?

Back 7

there are 7 types of dementia: AD, vascular dementia, HIV/AIDS related dementia, alcahold related dementia, fronto temporal lobar degeneration, Creutzfeild-Jacob dementia, dementia with lewy bodies

Front 8

AD is the most common type of dementia, its characterised by

Back 8

plaques and tangles

Front 9

Alzheimer’sdiseaseisthemostcommonform of

Back 9

dementia

Front 10

what is AD caused by?

Back 10

neuronallossoratrophytogetherwiththedepositionofamyloidplaquesandneurofibrillarytangles.

Front 11

when was AD first recognised?

Back 11

1907

Front 12

who discovered AD?

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AloisAlzheimer,aGermanpsychiatristandneuropathologist

Front 13

how did Aloiw Alzheimer disvoer AD?

Back 13

Performedanautopsyona51-­‐yearoldwomanwhohadbecomemoreandmoreconfusedintheyearsprecedingherdeath

Aloysius"Alois"AlzheimerwasaGermanpsychiatristandneuropathologistandacolleagueofEmilKraepelin.AlzheimeriscreditedwithidenHfyingthefirstpublishedcaseof"preseniledemenHa",whichKraepelinwouldlateridenHfyasAlzheimer'sdisease.

Front 14

WhatisAlzheimer’sDisease?

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AformofneurodegeneraHondisease

ThemostcommontypeofdemenHa-­‐theprogressivelossofintellectualabiliHesduetomalfuncHoningofpartsofthebrain

Front 15

what are the two kinds of AD?

Back 15

Familial(early onset) and Sporatic (late onset)

Front 16

describe Familial–earlyonset AD

Back 16

ADpaHenthasatleastoneotherfamilymemberwiththedisease

Front 17

describe Sporadic–lateonsetAD

Back 17

ADpaHenthasnootherfamilymemberswiththedisease

Front 18

what are the areas of the brain effected by AD?

Back 18

A) cerebral cortex

B) Basal Forebrain

C) Hippocampus

Front 19

what is the fucntion of thje cerebral cortex?

Back 19

▪ Thought
▪ Voluntary movement
▪ Language
▪ Reasoning
▪ PercepHon

Hint 19

TVLRP "Very Tall People Look Ready" in court

Front 20

what is the function of the basal forebrain?

Back 20

• Movement
• EmoHons
• Judgment
• Personality

Hint 20

MEJP "Many Escimos Judge people" as they sit at there base made of frozen ice

Front 21

in detail, talk about the basal forebrain

Back 21

consideredtobethemajorcholinergicoutputofthecentralnervoussystem(CNS).

Itincludesagroupofstructuresthatlienearthebo"omofthefrontofthebrain,includingthenucleusbasalis,diagonalbandofBroca,substanHainnominata,andmedialseptalnuclei.

ThesestructuresareimportantintheproducHonofacetylcholine,whichisthendistributedwidelythroughoutthebrain

Front 22

what is the function of the hippocampus?

Back 22

• Learning
• Memory

Front 23

how can AD be detected?

Back 23

Pi"sburghcompoundB(PiB PET SCANS)maybeusedininvesHgaHonalstudiesofAlzheimer'sdisease due to the following property:

Pi"sburghcompoundB(PiB)isafluorescentanalogofthioflavinT,whichcanbeusedinpositronemissiontomographyscanstoimagebeta-­‐amyloidplaquesinneuronalHssue.

Front 24

how many different stages of AD are there and what are they?

Back 24

early or mild stage

middle or moderate stage

late or severe stage

Front 25

what are the symptoms of early or milk stage AD?

Back 25

• memoryloss,especiallyofrecentevents
• difficultyinlearningnewinformaHon
• personalitychanges

Hint 25

a patient early in the morning with AD tries to get out of bed he looks at the sun but cant remember what it is as he has memopry loss,

he looks at his shoe but has difficulty in learning how to put it on

he then goes outside to a tree and has personality changes and talks to the tree

Front 26

what are the symptoms of Middle or moderate stage AD?

Back 26

• worseningmemoryloss,especiallyofcurrentevents

• depression,withdrawal,agitaion,confusion

• increasingrelianceonfamilyfordecisionmakingandmanagingpersonallife

Hint 26

the same patient with AD goes to his back door at the farm where he has worsening memopry loss especially current events as he wonders at the door,

he then walks to a nearby bee hive where he gets depressed with the sad beens, withdraws, gets aggidated and confused

he then goes to the outside fire place where his family is and has increased reliance on them for decisionm aking etc

Front 27

what are the symptoms of late or severe stage AD?

Back 27

• Lossoflong-­‐termmemories

• unawareofHomeandplace

• inabilitytoidentifyfamilymembers

• Unlearn’basicdailymotorskills-­‐brushingteeth,combinghair

• verydependentandrequiresconstantcare

• Death5–15yearsofdiagnosis

Hint 27

the same AD patient then goes to heaven in a dream and when he gets there he loses his long term memories from earth

he then comes back to life and goes to the farm gate and stands there unaware of his home and place

after he gets a glass of wine in the shed and has an inability to identify any of his family

he then goes to a hen in the back yard and unlearns all his basic motions of even how to pick up an egg and brush its teeth and comb its hair

he then comes back inside the kitchen where he meet tony beven who he becomes very de[endnt on and requires constant care from him

he then gets a letter from his doctor that he puts on a shelf which has a picture of a hive and someone shifting it

Front 28

how is AD diagnosed?

Back 28

there is no single way to identify AD, however a clinical diagnosis might include:

– Adetailedmedicalhistory– AthoroughphysicalandneurologicalexaminaHon

– AtestofintellectualfuncHon

– Psychiatricassessment

– Aneuropsychologicaltest

Front 29

ClinicaldiagnosisofADcanbemadewithabout

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80-90% accuracy

Front 30

when can diagnosis of AD be confimed?

Back 30

DiagnosiscanonlybeconfirmedaserdeathbyexaminaHonofthebrainHssue

Front 31

what is the treatment for AD?

Back 31

there is no cure,

cholinergic drugs may improve cognitive function for some with MILD to moderate AD (Acetylcoline)

secondary symptoms can be treated with drugs to help restessness or depression or help person sleep better

Community support is available (support makes positive difference)

Front 32

describe the pharmacology of AD

Back 32

acetylcholinesterase inhibitors and NMDA antagonists may slow the progression of increased acetylcholine levels

Front 33

describe the mechanism of AD

Back 33

Acetylcholinesteraseinhibitors

– ↓DestrucHonofacetylcholine

• NMDAantagonists

-↓OversHmulaHonofglutamate(∴↓excitotoxicity)

Front 34

what has microscopic views of AD brain reavealed?

Back 34

MicroscopicviewsofADbrainshaverevealedalossofneuronsincertainregionsofthebrain

Microscopicviewsalsorevealtwoformsofclustersofproteinsinthebrain:

1. Amyloidplaques

2. Neurofibrillarytangles

Front 35

some of the dying neurons in AD brain are

Back 35

cholinergic

Front 36

what kind of neurotransmitter is used in cholinergic neurons?

Back 36

Acetylcholine

Front 37

what is the main component of amyloid plaques?

Back 37

Maincomponentisaβ-­‐amyloidpepHdemadeupofeither40or42aa

Front 38

where does Beta-amyloid peptide originate from?

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β-­amyloidpepHdeoriginatesfromthelongeramyloidprecursorprotein(βAPP)madeupofeither695and770aa

Front 39

where is βAPP gene located?

Back 39

βAPPgeneislocatedonchromosome21

Front 40

people with down syndrome(threeratherthantwocopiesofchromosome21) therefore display

Back 40

atleastsomefeaturesofADbyageof40

Front 41

βAPPisproducedby

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manykindsofcellsandHssues

Front 42

how many ways is βAPPcleaved?

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two ways

Front 43

what is the first way βAPP is cleaved?

Back 43

1. βAPPisfirstcleavedbyaputaHveenzymecalledα-­‐secretasethencutbyanotherputaHveenzymecalledγ-­‐secretase,producingaharmlesspepHdefragmentcalledp3

Front 44

what is the second way βAPP is cleaved?

Back 44

2. βAPPisfirstclippedbyanenzymecalledβ-­‐secretaseresultsinaC99-­‐βAPPfragmentwhichisthensnippedbyγ-­‐secretasetoproduceanamyloidpepHdethatmaybe:

• NormalamyloidpepHdescontain40aaor

• HarmfulamyloidpepHdescontain42aa

Front 45

Several potential activities have been discovered for Aβthat are not associated with disease which include?

Back 45

activation of kinase enzymes,

protection againstoxidative stress,

regulation of cholesterol transport,

functioning as a transcription factor,

and anti-microbialactivity (potentially associated with Aβ's proinflammatoryactivity).

Front 46

Neurotoxicityofafragmentoftheamyloidprecursoris associatedwith

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Alzheimer'sdisease

Front 47

Neurotrophicandneurotoxiceffectsof

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amyloidbetaprotein

reversalbytachykininneuropeptides.

Front 48

Aninvivomodel showedtheneurodegenerativeeffectsofbetaamyloidandprotectionby

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substanceP

Front 49

Therehasbeenconsiderablecontroversyconcerningwhetherfragmentsoftheamyloidprecursorproteinmaybe

Back 49

neurotoxic,neurotrophic,orwithouteffectonneurons

Somestudiesdemonstratetoxicortrophiceffects,whereasothersfailtofindeitheroftheseeffects.ThisissueofNeurobiologyofAgingisdevotedtosuchdifferingstudies,starHngwiththeassumpHonthatdifferingresultsareaconsequenceofdifferencesinmethods

Front 50

what are Neurofibrillarytangles?

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• ClustersofproteinaccumulaHonsfoundinsidetheneurons

• AppearslateinAD

• Consistoftauprotein

Front 51

what stabilize microtubules?

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Tau proteins are proteins that stabilize microtubules

Front 52

Microtubules are a component of?

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Microtubules are a component of the cytoskeleton

Front 53

what is the maincomponentofneurofibrillarytangles?

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Hyperphosphorylated tau

Front 54

ThenumberanddistribuHonofneurofibrillarytanglesare...

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correlatedwiththedegreeofdementiainAlzheimer'sdisease.

Front 55

Activationofproteinkinasecdk5mightcontributeto...

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tobothtauphosphorylaHonandneuronalapoptosis.

Front 56

Cdk5 enzyme activity is mainly detected in neurons of the

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central nervous system

Front 57

p35nck5a and p39nck5ai are

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Cdk5 specific activators and

primarily expresed in CNS neurons

Front 58

Cdk5/p35nck5a is a...

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key enzyme in many cellular activities of CNS neurons

-neuronal diferentiation

-neurocytoskeletal dynamics

-neuronal migration

-synaptic structure and plasticity

Front 59

describe Cdk5 and AD

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Conversion of p35 to p25 deregulates Cdk5 activityand

promotes neurodegeneration.

Front 60

describe Cdk5 and tau phosphoylation, what does neurotoxicity induce?

Back 60

Neurotoxicity induces cleavage of p35 to p25 by calpain.

Front 61

BrainlevelsofCDK5activatorp25are

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notincreasedinAlzheimer'sorotherneurodegenera1vediseaseswithneurofibrillarytangles.

Front 62

what is the role of cholesterol (ApoE gene )in AD?

Back 62

ApoEgeneis onchromosome19q13

it encodes apolipoprotein E (ApoE)

it has many variants but only three polymorphisms which are: ApoE2, ApoE3, ApoE4

Front 63

what does ApoE play a fundamental role in?

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inthemaintenanceandrepairofneurons,butitsthreeisoformsdifferintheirabiliHes

Front 64

what is the major genetic risk factor for AD?

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ApoE4

Front 65

40–80%ofpaHentswithADpossessatleastone

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ApoE4allele

Front 66

ThroughinteracHonswithbetaamyloid,ApoE4may...

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increasebetaamyloiddeposiHoninplaquesandimpairitsclearance

Front 67

Studysuggestsflavanolsincocoadrinkcouldimprove...

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cognitive function

Front 68

Acocoa-­‐basedmilkdrinkcouldimprove

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cognitivefunctioninolderpeople

Front 69

The cocoadrinkcontainedflavanols,whichhavebeenshownpreviouslyto

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protectnervecells.

Front 70

InasmallstudycarriedoutbytheUniversityofL'AquilainItaly,90elderlyparHcipantswithmildcogni1veimpairmentweregivenacocoadrinkcontainingeitherhigh,intermediateorlowlevelsofflavanols.Aserconsumingthedrinksoveraneightweekperiod,what did researchers find?

Back 70

there were improvementsinmotorresponses,workingmemory,task-­‐switchingandverbalmemoryforthosegiventhedrinkswithahigherflavanolcontent.

GreaterlevelsofflavanolsalsoledtohigheroverallcogniHvescoresthanthoseparHcipantsdrinkinglower-­‐levels.

Front 71

how is dark chocolate made?

Back 71

Dark chocolate is produced by adding fatand sugar to the cacao mixture

Front 72

Dark chocolate or cocoa powder daily can help reduce

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blood pressure

Front 73

Researchers from the National Institute of Integrative Medicine in Melbourne and University of Adelaideconducted short-term trials and found that participants who were given cocoa compounds showed a

Back 73

slight drop in blood pressure compared to a control group.