DEMENTIA

dr. Fidha Rahmayani, M.Sc, Sp.S

Bagian Ilmu Penyakit Saraf Fakultas Kedokteran
Unila/RS Abdul Muluk
 Contoh kasus
Seorang laki-laki 72 tahun datang ditemani anak
perempuannya. Pasien rutin mengkonsumsi
obat antihipertensi selama ini. Pasien dikatakan
menjadi pelupa yang terus memburuk sejak 2
tahun belakangan. Pasien masih mampu
mengingat kejadian masa kecilnya, tapi tidak
mampu mengingat kejadian kejadian yang baru
terjadi. Sering bertanya yang diulang-ulang.
Pasien juga sering tersesat.
 Definisi Demensia:

Suatu sindrom penurunan kemampuan

intelektual progresif yang menyebabkan
deteorisasi kognisi dan fungsional,
sehingga mengakibatkan gangguan fungsi
sosial, pekerjaan dan aktivitas sehari-hari

(AAzI, 2003)
 Demensia
Demensia merupakan penyakit akibat gangguan pada otak.
Gejala Demensia :
1. Mudah lupa
2. Tidak mampu melakukan aktivitas sehari-hari
3. Tidak mampu menghadapi situasi sosial

“Tidak semua orang yg mudah lupa menderita demensia”

• Gejala demensia akan memburuk seiring waktu

• Demensia tidak dapat disembuhkan, namun terapi akan
memperlambat perkembangan penyakit pengenalan jenis
demensia penting utk menentukan terapi yg tepat

Dementia booklet for patients, Scottish Intercollegiate Guidelines Network (2011)

 DSM IV Criteria
1. Memory impairment
2. At least one of the following:
Aphasia
Apraxia (movement)
Agnosia (Identified object)
Disturbance in executive functioning
3. Disturbance in 1 and 2 interferes with
daily function
4. Does not occur exclusively during delirium
 NINCDS/ADRDA
Definition of Dementia
1. Acquired intellectual deterioration in an
adult
2. At least 6 month’s duration
3. At least two spheres of mental activity (eg.
orientation,attention,memory,language, etc)
compromised
4. Impairs the ability to function
5. Optimally in the community
 Dementia
B = Behaviour
A = ADL’s  Anger
 Finances
 Shopping  Irritability
 Driving  Apathy
 Cooking
 Travel
 Depression
 Laundry  Agitation

C = Cognition
 Forgetfulness
 Repetitive questions/stories
 Word finding problems
 Planning meals/shopping
 Misplacing objects/getting lost
The Greatest Risk Factor for Dementia is Age

Risk of Risk doubles every 5

Age Developing years.
Dementia
< 65 1%
65 2% But each additional risk
factor approximately
70 4% doubles the risk
75 8%
80 16%
85 32%
+have family history
doubles the risk.
Back
 PATHOPHYSIOLOGY OF DEMENTIA
(MEYER-RAGE., 1992)

Metabolic aetiology
Primary degeneration aetioloy Ischaemic aetiology (intoxication, hipoxia,
(alzheimers, Pick,s disease) (stroke, multi-infarkdementia) Circulatory colapse)

Disturbed regulation of Qualitative exhaution of Disturbed energy supply

DNA Trancription neuronal reserve capacity through decreased
recupertaive capacity of
(disturbed template activity) for CNS performance
CNS metebolisme

Decreased glcolytic turnover

Decreased Ac-CoA synthetics

Decreased CAT activity

Decreased acetylcholine synthesis

Decrased cholinergic activity

DEMENT IA
 Tipe Dementia
1. Demensia Alzheimer
2. Demensia Vaskular
3. Demensia Lewy-Bodies
4. Demensia Fronto-Temporal
5. Mixed Dementia
 Demensia Alzheimer
• Penyakit neurodegeneratif tersering ditemukan
(60-80%)
• Terutama mengenai lansia (>65 tahun) namun
dapat juga ditemukan pada usia lebih muda
• Diagnosis akurat membutuhkan biopsi otak 
ditemukan adanya plak neuritik serta
neurofibrilary tangle (hypertphosphorylated
protein tau)
• Dapat juga digunakan MRI kepala untuk diagnosis
 Alzheimer’s Disease
Plaques of the protein, amyloid beta, develop around neurons and
cause the degeneration of axons and dendrites, thus destroying the
routes of signal transmissions in the brain.
 Penyakit Alzheimer
• Gejala Penyakit Alzheimer
1. Mudah lupa
2. Kesulitan dalam melakukan aktivitas
sehari-hari seperti berbelanja,
mengelola keuangan, minum obat
Symptoms

Confusion
Memory loss
Mood swings
Speech problems
Hallucinations
Delusions
Disturbed sleep
Incontinence
Difficulty swallowing
Difficulty moving without assistance
Loss of appetite
Vulnerability to infection
 NINCDS/ADRDA –Probable AD
• Dementia established by clinical examination and
documented by mental status questionnaire
• Dementia confirmed by neuropsychologic testing
• Deficits in two or more areas cognition
• Progressive worsening of memory and other
cognitive functions
• No disturbance of consciousness
• Onset between ages 40 and 90
• Absence of systemic disorders or other brain
diseases capable of producing a dementia
syndrome
NINCDS/ADRDA – Possible AD

• Presence of a systemic disorders or

other brain disease capable of
producing dementia but not thought
to be the cause of the dementia
• Gradually progressive decline in a
single intelectual function in the
absence of any other identifiable
cause (e.g. Memory loss or aphasia)
 NINCDS/ADRDA –
Definite AD
• Clinical criteria for probable AD
• Histopatological evidence of AD
(autopsy or biopsy)
 Tampilan Klinis
• Awitan penyakit perlahan-lahan
• Perburukan progresif memori disertai gangguan
bahasa, keterampilan motorik dan perubahan perilaku
yang mengakibatkan gangguan aktivitas fisik sehari-
hari
• Adanya riwayat keluarga dengan penyakit serupa
• Defisit neurologis bisa muncul pada tahap lanjut
seperti kejang, gangguan jalan, mioklonus
• Adanya gangguan lain seperti depresi, insomnia,
inkontinensi, delusi, halusinasi, dll
 Pemeriksaan Penunjang
• Radioimaging : Ct sken kepala, MRI
• Laboratorium : Urinalisis, elektrolit, Ureum,
Fungsi hati, kadar asam folat, Vit B12, LCS
• EEG : normal, spesifik
• Baku emas : ditemukan neurofibrilary tangles
dan plak senilis
 Diagnosis Banding
1. Demensia Vaskular
2. Demensia Lewy-Bodies
3. Demensia Fronto-Temporal
4. Pseudodementia
 Treatment Algorithm

Stage of AD Mild Moderate Severe

Treatment
Options ChEI ChEI/
Memantine Memantine
(alone or in (alone or in
combination) combination)
Neurotransmitter disturbances in dementia

70% Glutamatergic system

Cholinergic system

Less than
30% Noradrenergic system

Dopaminergic system
 Neurotransmiter

• Acetylcholine - voluntary movement of the muscles

• Norepinephrine - wakefulness or arousal
• Dopamine - voluntary movement and emotional arousal
• Serotonin - memory, emotions, wakefulness, sleep and
temperature regulation
• GABA (gamma aminobutyric acid) - motor behaviour
• Glycine - spinal reflexes and motor behaviour
• Neuromodulators - sensory transmission-especially pain
Acetylcholine (ACh)

• Neuromuscular
junction (movement)
• Central nervous
system (learning and
memory)

Back
 Anticholinesterase Drugs
Cholinesterase (ChE)
inhibitors comprise
another group drugs
mimicing ACh by
inhibiting the hydrolysis
of endogenous ACh.

Cholinoceptor
agonists bind to
and activate
cholinoceptors 32
西安交大医学院药理学系 曹永孝 yxy@xjtu.edu.cn; 029-82655140
 Cholinesterase Inhibitors (CI)
Type of Dementia CI
Mild-Moderate AD All
Moderate – Severe AD Donepezil,
Memantine
Lewy-body Dementia Rivastigmine
Parkinson’s-related Dementia Rivastigmine
VaD Donepezil
Mixed AD/ VaD Galantamine
Fronto - temporal Dementia Not indicated
Mild Cognitive Impairment Not indicated
Dementia Penatalaksanaan Farmakologik

• ChE-Inhibitor :
– Physostigmin
• Obat lama (1970)
• Efek samping banyak , ditinggalkan
– Tacrine
• Lebih baik dari tacrine
• Efek samping hepatotoksik
 Dementia Penatalaksanaan Farmakologik

– Donepezil
• Dipasarkan th 1996
• Efek samping lebih menimal
• Dipergunakan luas
• Signifikan memperbaiki f. kognisi, memori
• @ Aricepts, Fordesia
– Rivastigmin
• Lebih baru, dipergunakan luas, signifikan
• Minimalisasi efek samping
• @ Exelon
– Galantamin
• Paling baru
• Belum dipergunakan luas
 Antidementia drugs and nootropics –
Mode of action

Piracetam Effect on neuronal metabolism

Nootropics Gingko biloba Cerebral blood flow, radical scavenger

Nicergoline Vascular dilatation

Donepezil
Rivastigmine Cholinesterase inhibitors (AChEIs)
Anti-dementia Galantamine Cholinergic neurotransmitter system
drugs
NMDA antagonism
Memantine Glutamatergic neurotransmitter system
 Vitamins
• Antioxidant - Vitamin E

• Vitamins B6, B12, and folate

 Ginkgo Biloba
• Studies do not show benefit in
improving age-related memory loss in
cognitively intact adults
• A review of 33 trials of ginkgo for
cognitive impairment and dementia
concluded that ginkgo is safe and
shows promise Most of the studies
had poor methods
• Large US and French trials are
underway to determine if ginkgo
prevents dementia or Alzheimer's
disease
• Results are expected around 2010

Birks J et al. Cochrane Database Syst Rev 2002

 Lifestyle & Activity
• Maintain cognitive function during ageing
– Higher levels of physical activity
– Mental activity
– Social interaction
– Cognitive training intervention
Exercise & Dementia Risk
Exercise associated with a delay in the
onset of dementia

Larson, E. B. et. al. Ann Intern Med 2006;144:73-81

 Dementia Vaskuler
Dementia yang
disebabkan gangguan
serebrovaskuler dengan
adanya penurunan fungsi
kognitif ringan sampai
berat dapat/tidak disertai
gangguan perilaku
sehingga menimbulkan
gangguan aktivitas harian
yang bukan disebabkan
oleh gangguan fisik akibat
stroke
 Demensia Vaskuler
• Demensia vaskular disebabkan berkurangnya
suplai darah ke otak
• Dapat terjadi setelah stroke, atau berkembang
lambat seiring waktu
• Gejala demensia vaskuler:
1. Mudah lupa
2. Kesulitan membuat rencana
3. Gangguan keseimbangan
4. Gangguan berkemih; pasien kesulitan
mengontrol kandung kemih untuk menahan BAK
Symptoms

• Difficulty with tasks requiring planning and concentration.

• Memory loss
• Personality and mood changes
• Periods of Confusion
• Stroke-like symptoms e.g. muscle weakness and
paralysis down one side of the body
• Hallucinations
• Wandering at night
• Slow, unsteady gait
 Vascular Damage
Healthy cell with
oxygen and
nourishment

No
message

Dead nerve cell - no blood

supply
 Patologi vaskuler
• Infark tunggal
• Multi infark dementia
• Lesi kortikal iskemik
• Stroke perdarahan
• Gangguan hipoperfusi
• Dementia campuran (Alzheimer dan stroke)
 Penunjang
• Brain imaging : Ct sken kepala, MRI
• Laboratorium : Hematologi faktor risiko stroke
 Terapi
• Medikamentosa terhadap faktor risiko stroke
• Terapi simptomatik terhadap gangguan
kognitif : Asetilkolinesterase inhibitor, anti
depresan, neuroleptik
 Dementia Lewy Bodies
Lewy Bodies are small circular lumps of protein inside the brain,
but how they are caused and their effects are not fully
understood. One theory is that the neurotransmitters, dopamine
and acetylcholine, are blocked. This affects brain functions such
as memory, learning, mood and attention.
Demensia Lewy Bodies
• Gejala Demensia Lewy bodies:
1. Mudah lupa
2. Halusinasi visual
3. Gerakan melambat dan mudah
terjatuh
Symptoms

Memory loss
Low attention span
Hallucinations
Periods of confusion
Delusions
Difficulty planning ahead
Stiff and slow movements
Trembling of the limbs
Shuffling whilst walking
Problems sleeping
Loss of facial expressions
 Fronto-temporal Dementia
Shrinking occurs to the temporal and frontal lobes of the brain. 40%-
50% of cases are patients who have inherited a genetic mutation that
affects the tau protein. Tau proteins keep brain cells stable, but if they
stop working, brain cells are damaged.
Motor neurone disease can also cause fronto-temporal dementia.
Demensia Frontotemporal
Gejala demensia frontotemporal :
1. Perubahan mood dan perilaku
2. Kesulitan menilai situasi dan
rencana
3. Gangguan bicara
Symptoms

Aggression
Compulsive Behaviour
Easily distracted
Increasing lack of interest
in washing self
Personality changes
 Mixed Dementia
• Beberapa pasien mengalami
gejala campuran dari beberapa
jenis demensia
• Dapat disebabkan karena pada
satu pasien terdapat ≥ 1 jenis
demensia. Misalnya: demensia
vaskuler dan penyakit Alzheimer
Reversible causes ? Dementia ? MCI ? CIND ?

Acute onset Gradual onset Hallucinations Behavioural

Stepwise Memory loss Fluctuations Language
Risk factors Normal Visuospatial Family hx
Gait examination Parkinsonism Young onset
Neurological

Vascular Alzheimer’s Lewy Body Frontotemporal

Dementia Disease Dementia Dementia

Back
Back
 Pre-dementia syndromes
• Age Associated Memory Impairment (AAMI)
• Age Related Memory Decline (ARMD)
• Age Related Cognitive Decline (ARCD)
• Benign Senescent Forgetfulness (BSF)
• Cognitive Impairment No Dementia (CIND)
• Memory Impairment
• Mild Cognitive Disorder (MCD)
• Mild Cognitive Impairment (MCI)
• Mild Neurocognitive Disorder (MND)
• Questionable dementia (QD)
 Mild Cognitive Impairment
Cognitive Performance

Normal MCI Dementia

‘MCI refers to the state of cognition and

functional ability between normal aging and
very mild AD’
(Petersen, 2001)
 Mild Cognitive Impairment

• Prevalensi MCI 17 – 34 % pada usia tua

• Progresivitas MCI menjadi alzheimer
rata-rata 10 – 15 % per tahun,
dibanding dengan tanpa MCI 1 – 2 %
per tahun
• Perubahan MCI menjadi alzheimer
pada penelitian kohort 6 tahun adalah
80 % (Petersen, 1995)
 Mild Cognitive Impairment
• Memory complaint
• Objective memory impairment for age
• Normal general cognitive function
• Normal ADL
• No dementia
Neuropsychological examinations for MCI

• Mini Mental State Examination (MMSE)

> 24
• Clock Drowing Test (CDT)
• Clinical Dementia Rating Scale (CDR)
0.5
• Global Deterioration Scale (GDS) :
stage 2 – 3
(Yustiani Dikot, 2004)
 TERAPI FARMAKOLOGIS
DAN NONFARMAKOLOGIS MCI
 Therapeutic approach of MCI
Pharmacological approach
• Symtomatic treatment
Nootropics
Cognitive enhancers
Cholinesterase inhibitors
• Physiopathological treatment
Anti-oxidants
Anti-inflammatory drugs
Estrogen
(Troeboes Poerwadi, 2004)
 Therapeutic approach of MCI (con’t)

Non pharmacological approach

• Stress reduction
• Mental activity
• Healthy brain diet
• Reguler physical exercise
• Sport and activities with low risk for head trauma
• Avoidance of tobacco and exercise use of alcohol
• Activities that have personal meeting
(Troeboes Poerwadi, 2004)
 Tatalaksana
• Tujuan Umum :
– Mengurangi gejala - gejala
– Meningkatkan kemampuan optimal
pasien
– Memperbaiki harga diri ( esteem)
– Memperlambat terjadinya demensia

• Prinsip umum dapat dilakukan pada semua

golongan menua patologis / sehat
 Jenis Tatalaksana
Non-farmakologis Farmakologis
• Psikososial • ChE-I
• Program terapi • Nootropik
- Stimulasi kognitif • Neuroproktektiv
- Terapi rekreatif • NSAID
= Reminisens • Estrogen
= Orientasi nyata • Antieksitotoksik
• Latihan fisik & otak
 Program terapi
• Usia menua : kesulitan learning & memori
• Dapat diterapkan pada MCI tergantung kebutuhan
• Strategi dasar : Perhatian - Latihan - Assosiasi
• Aplikasi keseharian : LUPA (latih- Ulang- Perhatikan-
assosiasi)
• Kondisi yg berpengaruh : kelelahan umum , tidak ada
motivasi/usaha, materi memori tidak familiar, kondisi
emosial buruk
• Bila diperlukan obat-obatan simptomatik