AGING

SURYADI
 Definisi Aging

hilangnya kemampuan jaringan tubuh

kita secara perlahan-lahan untuk
melakukan pembaharuan terhadap
jaringan itu sendiri, mempertahankan
struktur normal dan fungsinya serta
ketahanan terhadap lesi dan
perbaikan kerusakan yang dialaminya.
 Cause of Aging
1. The genetic clock theory
Aging merupakan suatu proses yang
sudah di program secara genetik,
dimana jam genetik ini akan bekerja
sebagai penghitung jumlah mitosis
dan menyetop replikasi sel.
 Aging neuron
1. Loss of neuron
Jumlah neuron otak manusia /mamalia
pada proses penuaan berhubungan
nyata dengan hilangnya neuron.
Dari usia 1 - 60 th 25-40% neuron 
ditandai dengan semakin menipisnya
girus dan melebarnya sulcus
2. Loss of neuron part

Penuaan mengarah pada pe jumlah

utas DNA yang terputuspada tikus.
Dan akan mengurangi sintesis rRNA
oleh DNA pada neuron anjing.
3. Development of abnormal fibrillar
proteins in neuron

Didalam sitoplasma neuron yg menua

terjadi degenerasi neurofibril
( Neurofibrillary tangle = NFT)
 dementia

mild cognitive impairment

forgetfulnes

normal
Etiology of
Demensia
• Alzheimer disease 50 - 60
• Vascular dementia 10 - 30
• Alcoholics 1 - 10
• Metabolic disorders 1 - 10
• Intoxications 1 - 10
• Hydrocephalus 1 - 5
• Cerebral anoxia 1 - 2
• Cerebral infections 1 - 2
• Cerebral injuries 1 - 2
• Subdural hematome 1 - 2
• Others 10 - 20

(persen)
ALZHEIMER DISEASE

K O N T I N U U M
Forgetfulness -
Mild Cognitive Impairment -
Dementia Alzheimer
 DEMENSIA ALZHEIMER

DEMENSIA :
GANGGUAN PROGRESIF INTELEKTUAL DAN
KEMAMPUAN KOGNITIF, MENGGANGGU
PERFORMANS, SOSIAL DAN PEKERJAAN

NEURITIC PLAQUES & NEUROFIBRILLARY

TANGLES, KLINIS BARU TAMPAK
30 TAHUN SEJAK AWAL PROSES
 DEMENSIA ALZHEIMER
(MAYO CLINIC, 1999) - 1

• SHORT-TERM MEMORY LOSS-

KEMUNDURAN MEMORI SEBAGAI TANDA AWAL

• LEARNING AND RETAINING NEW INFORMATION

KESULITAN BELAJAR HAL BARU, MENGULANG -
ULANG, LUPA PEMBICARAAN & JANJI

• REASONING AND ABSTRACTIVE THOUGHT-

KESULITAN BACA KALENDER, MEMAHAMI LELUCON,
MENENTUKAN WAKTU, BALANS CEK, MASAK, TUGAS
YANG BUTUH LANGKAH URUTAN.
 (MAYO CLINIC, 1999) - 2
• JUDGMENT AND PLANNING-
KESULITAN ANTISIPASI / PERTIMBANGAN PERISTIWA / TINDAKAN
TIDAK MAMPU MEMECAHKAN MASALAH SEHARI-HARI
KESULITAN ARAH DAN TERSESAT

• LANGUAGE SKILLS--
SULIT MENEMUKAN KATA UNTUK UNGKAPAN PIKIRAN DAN
KONVERSASI

• INHIBITION AND IMPULSIVE CONTROL--

LEBIH IMPULSIF, AGRESIF, BERPERILAKU WAJAR, IRITABLE,
PARANOID.
Diagnosis demensia memerlukan 3 syarat :

1. Gangguan fungsi intelektual setelah lahir

dan berdasarkan atas suatu penyakit
organik di otak.
2. Kemunduran fungsi kognitif bersifat global.
3. Perubahan kognitif sampai pada tingkat
mengganggu fungsi personal-sosial dan
pekerjaan.
 PENYAKIT ALZHEIMER
 Semakin bertambahnya kehilangan memori.
 Sulit mencari kata saat berbicara.
 Sulit berhitung sederhana.
 Disorientasi waktu dan ruang.
 Sulit mengenal teman lama /anggota
keluarga.
 Stupor vegetatif.
 Meninggal.
 Penyakit
Alzheimer
Ditemukan oleh Dr. Alois Alzheimer, seorang
dokter Jerman, pada tahun 1906.
Sel-sel otak dirusak dan mati secara
perlahan sehingga menimbulkan:
Daya ingat mundur secara bertahap
Turunnya kemampuan melakukan
tugas rutin
Disorientasi
Kesulitan dalam “belajar”
Hilangnya kemampuan berbahasa
Terganggunya pengambilan keputusan
Perubahan kepribadian
 STADIUM-STADIUM PENYAKIT ALZHEIMER

Mudah lupa, seperti meletakkan barang

Lupa peristiwa/kejadian yang baru
Sulit menemukan kata-kata waktu bicara
Enggan melakukan kegiatan sosial
Tahun pertama

Memori jangka panjang mulai terganggu

Sulit melakukan kegiatan kompleks, seperti
belanja, membuat neraca keuangan
sehari-hari
Apatis, lebih suka menyendiri
Tahun ke 5
Sering tersesat

Semua aspek fungsi kognitif terganggu

Hilangnya kemampuan bicara, hanya
mengulang kata-kata atau kalimat
Lupa orang-orang disekitarnya, termasuk
dirinya sendiri
Tahun ke 10-15 Tak mampu berjalan, hanya berbaring
Gejala dan Tanda

Kemunduran fungsi kognitif

 Daya ingat (memori) baru

 Kesulitan dalam bekerja akibat kemampuan
berfikir abstrak
 Sering tersesat
 Apraksia
 Kemampuan berbahasa lisan dan tulis
Contoh
Apraksia waktu berjalan
Prevalensi Jenis-jenis Demensia
di Negara-negara Barat
50

45

40

35

30
Alzheimer
25
Demensia Vaskuler
20
Lainnya
15

10

5
0
DEMENSIA
Prevalensi Jenis-jenis Demensia
di Negara-negara Timur
40
35
30
25
Alzheimer
20 Demensia Vaskuler
15 Lainnya
10
5
0
DEMENSIA
 Alzheimer disease

• Loss of cholinergic neuron

• Neurofibrillary tanggles

• Neuritic plaque

• Amiloidosis
Hallmarks of Alzheimer's disease include neuritic plaques (outside
neurons) and neurofibrillary tangles (inside neurons) neurons.
 Neurofibrillary tanggle
• Gen amyloid  precusor protein (APP) pada kromosom
21, pemecahan APP  amyliod  komponen utama
NFT maupun NP.
• Neurofibril pengacau tersebut dibuat dari protein Tau
• Akumulasi neurofibril dalam neuron akan menyebabkan
kematian sel pada PA.
 BRAIN ATROPHY

Alzheimer's disease is characterized grossly by widening of the sulci and

narrowing of the gyri (atrophy) of cerebral cortices and enlarged ventricles
A single senile plaque in an Alzheimer's brain. The arrows point to dead
synaptic terminals within the plaque.
AMYLOID-BETA ALZHEIMER PLAQUES
Melihat kata (tulisan)
Mendengar kata-kata
Berfikir tentang kata-kata
Mengucapkan kata-kata
plaque

tangles
Plague amyloid in Alzheimer disease
Neurofibrillatory tangles
in CA1 region of
hippocampus
Neurofibrillary
tangle
CTscan of Alzheimer’s patient
 PETscan of PETscan of
the normal brain Alzheimer’s patient
Kesulitan menjalankan aktivitas pokok
harian
MRIscan of Alzheimer’s patient
Validation by means of indirect objective markers
Of neuropathology

• Neuroimaging markers

• Biological markers

• Genetic markers
 THE CHOLINERGIC HYPOTHESIS

AChE degrade ACh

ACh
Presynaptic Receptors Postsynaptic
Terminal Terminal

Action Potential Summated Potential

ACh ACh receptors

AChE or BuChE
ACh
ChE inhibitors block AChE
ChE inhibitor
( ARICEPT )
McNeil. Alzheimer’s Disease: Unraveling the Mystery. 1995:1–48.
Pengelolaan AAzI
DEMENSIA
MEDIS/PROFESIONAL KELUARGA MASYARAKAT

Diagnosis Asuhan keperawatan “Support group”

Riwayat lengkap dalam keluarga
Pemeriksaan medik
Informasi
Tes neuropsikologik Peran serta anggota Media massa
Scan-otak keluarga Internet
Terapi
Obat-obat Peran “Caregiver” Pendanaan
Perawatan medik (pendamping)
Pada stadium lanjut/ “Networking”
komplikasi
Konsultasi
 Kesimpulan
1. Penuaan dan kematian  banyak faktor dan
berhubungan
2. Teori penuaan yang dianut saat ini :
- adanya genetic clock
- metabolic disorder terus-menerus
- berkembangnya penyakit degeneratif
- heteroimun  ok Ag asing
- Ag tubuh   autoimun
TERIMAKASIH
Vascular
Vascular Dementia
Dementia

SURYADI
Vascular Dementia
Dementia
Dementia due
due to
to cerebrovascular
cerebrovascular disease
disease in
in
general
general

Multiinfarct dementia
Single infarct in eloquent areas,
episodes of hypotension
Leukoaraiosis, incomplete infarction
Cerebral hemorrhage
VCI
Vascular Cognitive Impairment

All cases of cognitive impairment of

cerebrovascular origin without a
requirement for dementia and not
requiring prominent memory loss
Hachinski,
Hachinski, Dementia,
Dementia, 1994;
1994; 5:130-2
5:130-2
VCI
Vascular Cognitive Impairment
This new term is aimed at emphasizing the
importance for treatment and prevention
by including the entire range of the
dementia process, from the very early
stage (i.e. brain-at-risk) through a whole
spectrum of cognitive impairment
Hachinski,
Hachinski, Dementia,
Dementia, 1994;
1994; 5:130-2
5:130-2
 Clinically-Relevant
Symptoms of Dementia
Alzheimer’s Vascular
pathology pathology
Visuo- Attentional
constructional deficits
disabilities Memory
impairments Executive
dysfunction
Language
problems Constructional
problems

Behavioural Fluctuating
problems consciousness
 Organization of the
three frontal-subcortical circuits
Dorsolateral Lateral orbital Anterior cingulate
Prefrontal cortex cortex cortex

Caudate Caudate Nucleus

(dorsolateral) ventromedial accumbens

Globus pallidus Globus pallidus Globus pallidus

(Lateral dorsomedial) (Medial dorsomedial) (Rostrolateral)

Thalamus Thalamus Thalamus

(VA and MD) (VA and MD) (MD)
VA: ventral anterior; MD: medial dorsal
Inzitari et al 2002
BambangHartono
 LARGE VESSEL PATHOLOGY

ATHEROSCLEROSIS OTHER ARTERIOPATHIES

Arterial dissection
Fibromuscular dysplasia
Moyamoya
Non-infectious arteritis of large vessels
Temporal arteritis
Takayasu’s disease
Infectious arteritis of large vessels

INFARCTS
 SMALL VESSEL PATHOLOGY

ARTERIOLOSCLEROSIS
FIBRINOID NECROSIS
ATHEROSCLEROSIS
CEREBRAL AMYLOID ANGIOPATHY
BASAL GANGLIA CALCIFICATION
CADASIL

DEEP LACUNAR INFARCTS

WHITE MATTER CHANGES (WMC)
 Major risk factor candidates or markers
for dementia after stroke

Neuroimaging factors
Mean volume of infarcts
Demographic Number of infarcts
Age Location of infarcts
Men Increase in third ventricular size
Race/ethnicity Silent cerebral infarcts of deep
Education structures and white matter

Atherogenic Genetic
Hypertension Autosomal dominant hereditary
Cigarette smoking cerebral hemorrhage with
Myocardial infarction amyloidosis – Dutch type
Atrial fibrilation
Diabetes mellitus
Hypercholesterolemia
Heavy alcohol consumption

BambangHartono
 Mixed Dementia
Cerebral infarcts
White matter pathology
AD Cerebral amyloid angiopathy VaD
Amyloid deposits
Tangles
Transmitter specific
changes

Overlap of Alzheimer’s Disease and Vascular Dementia

ACh LEVELS ARE DIMINISHED
IN THE BRAINS OF VaD PATIENTS

35
30
ACh levels (nM)

25
20
15
10
5
0
VaD patients Healthy controls
(n = 18) (n = 12)
Tohgi. J Neural Transm 1996;103:1211–20
Differential characteristic of AAMI/ARCD, MCI and
Alzheimer Dementia

Classification AAMI/ARCD MCI Alzheimer’s

Dementia

Cognition Memory Mild impair- Impairment in

decline ment in memory and other
relative to memory and domains, sufficient
when young and usually to impair common
other domains ADL
relative to
normal ageing
Source Self-report Self-report Patient and caregiver
and informant
ADL Normal Some decline Loss of complex, and
in very eventually basic
complex activities
activities
Behavioral None Mild Apathy, agitation,
depression sleep dysfunction,
psychotic symptoms
Hypothetical sequence of clinico-pathological findings
in ageing and AD

Ageing Early AD Late AD

Preclinical Very mild
Cognitive normality Severe dementia
First clinical detection of
dementia
No plaques, or only Marked increase in Many neuritic plaques
patchy diffuse plaques in neocortical amyloid throughout cortex
neocortex deposition, including
some neuritic plaques
Slow formation of tangles Increase in tangles, Many tangles in
in limbic regions, none in including some in neocortex and
neocortex neocortex hippocampus
None Detectable

Morris 1999
Ischemic Score (Hachinski et al, 1975)
Feature Score

Abrupt onset 2
Stepwise deterioration 1
Fluctuating course 2
Nocturnal confusion 1
Relative preservation of personality 1
Depression 1
Somatic complaints 1
Emotional incontinence 1
History of hypertension 1
History of strokes 2
Evidence of association atherosclerosis 1
Focal neurological symptoms 2
Focal neurological signs 2
Two magnetic resonance imaging proton-density transaxial cuts
from the brain of a hypertensive patient with vascular dementia.
Note extensive involvement of white matter, which appears as
hyperintense signals. The patient's computed tomography brain
scan showed minor periventricular hypodensity.
Mild hippocampal atrophy in a patient with MCI
 The advantages of
pharmacotherapeutic intervention

Prevention of neurodegeneration
Intellectual decline
Behavioral disorders
Sleep disorders
Common medical complications
Abrupt worsening of dementia
(Caselli
(Caselli et
et al
al 2001)
2001)
Prognosis of
Vascular Dementia
MID
MID shortens
shortens life
life expectancy
expectancy to to about
about 50%
50% of
of
normal
normal at
at 44 years
years from
from initial
initial evaluation
evaluation
(Barclay
(Barclay et
et al
al 1985;
1985; Hier
Hier et
et al
al 1989)
1989)

In
In the
the very
very elderly,
elderly, 3-year
3-year mortality
mortality may
may reach
reach
two
two thirds,
thirds, almost
almost 33 times
times that
that of
of control
control
(Skoog
(Skoog et
et al
al 1993)
1993)

Overall,
Overall, the
the effect
effect of
of VD
VD on
on mortality
mortality is
is similar
similar
to
to that
that of
of AD
AD
(Aevarsson
(Aevarsson et
et al
al 1998;
1998; Aguero
Aguero -Torres
-Torres et
et al
al 1998)
1998)
Prevention on
Vascular Dementia
Primary prevention
Treatment of hypertension
Statins
Secondary prevention
Treatment of hypertension
Statins
Antiplatelet
Anticoagulant
Surgery
Prevention on
Vascular Dementia
Controlling other risk factors
Smoking
Hyperfibrinogenemia
Orthostatic hypotension
Cardiac arrhythmias
Congestive heart failure
Obstructive sleep apnea
Blood glucose control in diabetes
Hyperhomocysteinemia
Instrumen Skrining & Diagnosis Demensia
Dementia Rating Scale (Mattis,1988)
Mini-mental State (Folstein, McHugh,1975)
Short Portable Mental Status Questionnaire (Pfeiffer, 1975).
Telephone Interview for Cognitive Status
(Brandt, Spencer, and Folstein, 1988).
Alzheimer Disease Assessment Scale (Rosen et al, 1986)
Blessed Dementia Scale (Blessed et al, 1968)
Brief Cognitive Rating Scale (Reisberg, 1983)
Geriatric Mental State Schedule (Gurland et al 1976)
Behavioral Pathology in Alzheimer Disease Rating Scale
(Reisberg et al, 1987)
Cognitive Behavior Rating Scales (William, 1991)
Diagnosis and Statistical Manual of Mental Disorders (DSM)
(American Psychiatric Ass, 1994)
Terima kasih ….
 ICD-10 CRITERIA FOR
PICK’S DISEASE
1. Progressive dementia
2. A predominance of frontal lobe features with
euphoria, emotional blunting, & coarsening
of social behaviour, disinhibition, and with
apathy or restlesness.
3. Behavioural manifestations, which
commonly precede frank memory
impairment.
4. Frontal lobe features are more marked than
temporal and parietal, unlike AD
CORONAL T1-W MRI:
FRONTAL TYPE FTD
CORONAL T1-W MRI: PICK’S DISEASE
(FTD TYPE): FRONTAL & L.TEMP. ATROPHY
CONSENSUS CRITERIA FOR PROBABLE DEMENTIA WITH
LEWY BODIES (DLB)
 LEWY BODY
(EOSINOPHILIC INCLUSION WITH A CLEAR HALO)
 Apa yg dimaksud dengan
SINDROMA GERSTMANN?
Terima Kasih