Dementia Dan Alzheimer

8/13/2019 Dementia Dan Alzheimer

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Jan S. Purba MD, PhDDepartment of Neurology, Med School

of the University of IndonesiaJakarta

Demensia danPenyakit Alzheimer


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Seven week- old humanfetus is about an inch. Eyesand limbs are visible, andthe emerging brain isapparent.

Stimulation is needed tocompletedevelopment, a processthat formany neural systemscontinues

into neonatal life


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George Bernard Shaw, who died in1950 when he was 94, wrote several

plays in his nineties


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Proses degenerasi sebagai

penyebab demensia

Merupakan proses yang berjalan secara alami

berlangsung secara genetik

berperan terhadap kerusakan sel baik yang

bersumber dari dalam (endogen)

maupun yang diakibatkan oleh lingkungan

(eksogen)


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Perobahan yang terjadi

pada proses degenerasi berat otak yang menurun

perobahan fungsi otak perobahan status hormonal baik wanita

maupun pria

perobahan status hormonal ini akanmempengaruhi kinerja organ tubuhlainnya


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6Brain structures indicate in boldface are involved inlearnin and memor and reasonin


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Beberapa penyakit yang bisa

menyebabkan demensia depresi

intoksikasi / penyalahgunaan obat

penyakit metabolisme dan endokrin

pelagra

defisiensi vit. B12 imunodefisiensi (HIV)

penyakit Huntington


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Beberapa penyakit tertentu yang sering

berkorelasi dengan demensia

penyakit Parkinson,

penyakit Lewy body

gangguan serebrovaskuler

subdural hematom

tumor di otak

hidrosefalus dengan tekanan normal

sindroma Cushing

Prion disese (penyakit Creutzfeldt-Jacob,

Gerstmann-Streusler-Scheinker syndrome), dll


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Patologi degenerasi

menurunnya elastisitas jaringan

hilangnya kemampuan sel untuk

berproliferasi ditingkat khromosom bisa terjadi

pemendekan telomer

terjadi degenerasi pada organ tubuhlain perubahan membran mitokhondria

akibat peroksidasi lipid


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Peran zat-zat oksidan

pada proses degeneratifRadikal bebas dapat merusak

makromolekul yang fungsional didalam sel seperti:

karbohidrat

asam-asam nukleat protein membran

lipid membran terutama yang dialami oleh

PUFA


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Network of neurons in the brain provides peoplewith the ability to assimilate information. Will

stimulations of such networks reveal theunderlying mechanisms of learning?


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Demensia Alzheimer

penyakit demensia

sifatnya Progresiv

penderita pada umur 50an

wanita lebih banyak


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End stage of Alzheimers disease. Patient in fetalposition


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Alzheimers dementia

Neurodegenerative disorder of the CNS

Symptoms:

memory impairment, loss of function,behavioural symptoms

Incidence: 5% at 65 years of age

Cell biology:neuronal loss, synaptic damage, neurofibrillarytangles, neuritic plaques, granulovacuolardegeneration

D ti i th USA (F i h St d 1992)


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Dementia in the USA (Framingham Study, 1992)


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Perjalanan penyakit Alzheimer

1 2 3 4 5 6 7 8 9

0

5

10

15

20

25

30

waktu (tahun)

Simptom

Diagnosis

Mulai bergantung sama orang lain

Bermasalah dengan perilaku

Membutuhkan bantuan sehari-

hariKematian

Mini-MentalStateExam

ination(MMSE) Diagnose dini M il dsampai

moderatBerat


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Etiologi dan faktor Resiko

penyakit AlzheimerEtiologi yang pasti belum diketahui

Aluminium

Autoimun dan inflamasi

Radikal bebas

Neurotransmiter eksitatorik yang

berlebihan


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Risk Factors for AD

Known

Risk Factors

AgingGenetics

Down syndrome

Possible

Risk Factors

Head traumaFemale gender

Vascular disease

Possible

ProtectiveFactors

EducationNSAID

Estrogen


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PET scan of brains from a healthy aged adult (A)and a patient with AD (B) differ markedly. The

excess of dark shading in the second image shows

that brain activity is impaired

A B


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Brain of Alzheimers disease (top) and control (bottom)

N t k f i th b i id l


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Network of neurons in the brain provides peoplewith the ability to assimilate information. Will

stimulations of such networks reveal theunderlying mechanisms of learning?


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The classical neuropathologic

feature of AD

extra cellular amyloid plaque deposition

intra cellular neurofibrillary tangel formation,

associated with neuronal and synaptic loss

reactive gliosis

G b l l


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Gambaran normal sel neuronpada kontrol


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Neurofibrillary tangles


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Senile plaques


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PVN

PVN : paraventricular nucleus

nbM : nucleus basalis Meynert

nbM


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Two main approaches for

the treatment of AD: prevention of neurodegenerative changes

that result in irreversible loss of cognitive

function

slowing the progression of the disease

and /or alleviating the symptoms of thedisease

Communication of Neurons


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Communication of Neurons


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Terapi

Terapi Farmaka

Terapi inhibitorik kholinesterase

(Rivastigmin, Donepezil, Galantamine) Terapi hormonal

Anti inflamasi/ NSAID

Anti oksidan Neurotropin

Terapi non-farmaka

TENS, Cahaya


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General cholinergic enhancement by

reducing, in efficacy and time,

inactivation of ACh by hydrolysis

Results:

Therapeutic action

Side-effects, largely muscarinic (?)

Problems with AChE inhibition: If too strong: Receptor desensitisation

If too long: AChE upregulation

Inhibition of AChE

Slide courtesy of Professor Alfred Maelicke

ACh = acetylcholine

nAChRs = nicotinic acetylcholine receptors

mAChRs = muscarinic acetylcholine receptors


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Galantamine

esterase

Galantamine

Reseptor

nikotinik

ACh

Ca++

Gambar 7.Mekanisme kerja dari galantamine dengan reseptor nikotinik

a. Asetilkholine sterase inhibitor

b. Efek potensiasi alosterik galantamine

terhadap reseptor nikotinik

a b

Dementia Dan Alzheimer

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