Demensia dan Penyakit Alzheimer

Jan S. Purba MD, PhD Department of Neurology, Med School of the University of Indonesia Jakarta

Seven week- old human fetus is about an inch. Eyes and limbs are visible, and the emerging brain is apparent. Stimulation is needed to complete development, a process that for many neural systems continues into neonatal life

George Bernard Shaw, who died in 1950 when he was 94, wrote several plays in his nineties

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)

Perobahan yang terjadi pada proses degenerasi

berat otak yang menurun perobahan fungsi otak perobahan status hormonal baik wanita maupun pria perobahan status hormonal ini akan mempengaruhi kinerja organ tubuh lainnya

Brain structures indicate in boldface are involved in learning and memory and reasoning

Beberapa penyakit yang bisa menyebabkan demensia

depresi intoksikasi / penyalahgunaan obat penyakit metabolisme dan endokrin pelagra defisiensi vit. B12 imunodefisiensi (HIV) penyakit Huntington

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

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

Peran zat-zat oksidan pada proses degeneratif

Radikal bebas dapat merusak makromolekul yang fungsional di dalam 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 people with the ability to assimilate information. Will stimulations of such networks reveal the underlying mechanisms of learning?

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Demensia Alzheimer
penyakit demensia sifatnya Progresiv penderita pada umur 50an wanita lebih banyak

End stage of Alzheimers disease. Patient in fetal position

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, neurofibrillary tangles, neuritic plaques, granulovacuolar degeneration

Dementia in the USA (Framingham Study, 1992)

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Perjalanan penyakit Alzheimer

Mini-Mental State Examination (MMSE)

Diagnose dini
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Simptom 25
Diagnosis 20

Mild sampai moderat

Berat

Mulai bergantung sama orang lain 15 Bermasalah dengan perilaku 10 5 Membutuhkan bantuan seharihari Kematian

0
1 2 3 4 5 6 7 8
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waktu (tahun)

Etiologi dan faktor Resiko penyakit Alzheimer

Etiologi yang pasti belum diketahui Aluminium Autoimun dan inflamasi Radikal bebas Neurotransmiter eksitatorik yang berlebihan

Risk Factors for AD

Known Risk Factors Possible Risk Factors Possible Protective Factors Education NSAID Estrogen

Aging Genetics Down syndrome

Head trauma Female gender Vascular disease

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

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

Network of neurons in the brain provides people with the ability to assimilate information. Will stimulations of such networks reveal the underlying mechanisms of learning?

The classical neuropathologic feature of AD

extra cellular amyloid plaque deposition intra cellular neurofibrillary tangel formation, associated with neuronal and synaptic loss reactive gliosis

Gambaran normal sel neuron pada kontrol

Neurofibrillary tangles

Senile plaques

PVN

nbM

PVN : paraventricular nucleus 29 nbM : nucleus basalis Meynert

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 the disease
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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

Inhibition of AChE
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
ACh = acetylcholine nAChRs = nicotinic acetylcholine receptors mAChRs = muscarinic acetylcholine receptors

33 Slide courtesy of Professor Alfred Maelicke

Gambar 7. Mekanisme kerja dari galantamine dengan reseptor nikotinik

Galantamine Galantamine

ACh

a
esterase

Reseptor nikotinik

Ca++

a. b.

Asetilkholine sterase inhibitor Efek potensiasi alosterik galantamine terhadap reseptor nikotinik
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