Dr.

Rimawati Tedjasukmana, SpS, RPSGT 1

Bag. Ilmu Penyakit Saraf
FK UKRIDA
 Ditemukan oleh Alois Alzheimer (1906)
 Penyebab demensia tersering.
 Jarang dibawah usia 45 tahun.
 Insidens meningkat dgn pertambahan usia.
 30% familial

AD, MCI 2009 2

 Definisi: Hilangnya kemampuan intektual yang
sangat berat sehingga mengganggu fungsi sosial atau
pekerjaan.
 Kriteria diagnosis:
 Gangguan atensi, orientasi, daya ingat, judgement,
bahasa, visuo-spasial.
 Tidak disebabkan depresi atau schizophrenia.

AD, MCI 2009 3

 Degeneratif:
 Alzheimer’s disease, Frontotemporal dementia, Dementia with Lewy
Bodies, Parkinson’s disease with dementia, Corticobasal degeneration,
Progressive supranuclear palsy, Huntington’s disease
 Serebrovaskuler:
 Multi infarct dementia, subcortical ischemic vascular dementia, chronic
subdural hematomas, cerebral amyloid angiopathy, CADASIL

AD, MCI 2009 5

 Gangguan struktural: Normal pressure
hydrocephalus
 Infeksi: Creutzfeld-Jakob disease, HIV, sifilis,
Progressive multifocal leukoencephalopathy
 Nutrisi ( Wernicke Korsakoff, defisiensi B12),
metabolik (hepar, tiroid), inflamasi (multiple
sclerosis, vasculitis), trauma, tumor
 Tauopathies:  Synucleopathies:
 Alzheimer’s Disease  Parkinson Disease
 Progressive Supranuclear Palsy  Multiple System Atrophy
 Corticobasal Degeneration  Dementia with Lewy Bodies
 Frontotemporal Dementia
 Non degenerative:
 Vascular Dementia
A. Timbulnya defisit kognitif multipel yang bermanifestasi
sebagai:
1. Gangguan daya ingat (terganggunya kemampuan utk
belajar informasi baru atau mengingat informasi yg telah
dipelajari).
2. Ditambah satu atau lebih gangguan:
a. Afasia (gangguan bahasa)
b. apraxia (ketidakmampuan melakukan aktivitas motorik
walaupun fungsi motorik normal)
c. agnosia (tdk dpt mengenal benda walaupun fungsi sensorik
normal)
d. Gangguan fungsi eksekutif (merencanakan, mengatur,
merunut, abstraksi)
AD, MCI 2009 8
B. Defisit kognitif tersebut di atas:
1. Menyebabkan gangguan fungsi sosial dan pekerjaan.
2. Menampakan perburukan dari keadaan sebelumnya.

C. Defisit tsb tdk hanya terjadi pada delirium.

D. Gangguan tsb tdk disebabkan gangguan depresi atau

schizophrenia.

AD, MCI 2009 9

AD, MCI 2009 10
OVERLAPS BETWEEN CLINICAL
SYNDROMES
Asymptomatic
AAMI/ARCD
cognitive performance

MCI AD or
dementia

AAMI= Age Associated Memory

Impairment
MCI= Mild Cognitive Impairment
Low
AD, MCI 2009 11
AD, MCI 2009 12
  Pd Alzheimer jumlah
neuron dan sinaps
berkurang.
 Plaques: kumpulan fragmen
protein abnormal, terdapat
di antara sel neuron.
 Sel saraf yang mati
mengandung “tangles”,
terbuat dari protein lain.
 Plaques dan tangles
kemungkinan merpk
penyebab kematian sel.

AD, MCI 2009 13

  Plaques berasal dari
protein beta-amyloid
 Tangles adalah
serabut2 yg terpuntir
karena protein tau.
 Plaques and tangles
menghambat aliran
listrik antar neuron.

AD, MCI 2009 14

AD, MCI 2009 15
  Plaques and tangles menyebar di
korteks serebri dengan pola tertentu.
 Kecepatan penyebaran sangat
bervariasi.
 Rata-rata pasien Alzheimer hidup 8
thn setelah diagnosis. Tapi bbrp
pasien bisa sampai 20 thn.
 Perkembangan penyakit tergantung
umur dan penyakit penyerta.
 Alzheimer's dini– perubahan mulai
20 thn sebelum diagnosis.
 Alzheimer’s ringan-sedang –
umumnya berlangsung 2 - 10 thn.
 Alzheimer’s lanjut– bisa bertahan 1-5
thn.

AD, MCI 2009 16

  Stadium dini, gejala
belum bisa dideteksi
 Plaques and tangles
mulai timbul pd area
otak yg mengatur:
 Daya ingat dan belajar
 Berpikir dan berencana

AD, MCI 2009 17

  Plaques dan tangles makin
banyak.
 Mulai timbul gejala: memori,
berpikir, mengganggu fungsi
sosial.
 Plaques dan tangles juga
menyebar ke area lain:
 Gangguan wicara.
 gangguan visuospasial
(hubungan antara badan dan
lingkungan)
 Lama-lama pasien
mengalami perubahan
kepribadian dan perilaku.

AD, MCI 2009 18

  Hampir semua korteks
rusak.
 Atrofi otak krn banyak
sel mati.
 Pasien tak bisa
berkomunikasi,
mengenali keluarga
dan tak bisa mengurus
diri sendiri.

AD, MCI 2009 19

 Gangguan memori yang mengacaukan kehidupan sehari-hari.
 Lupa hal2 baru, lupa peristiwa penting, menanyakan sesuatu berulang-
ulang, memakai alat bantu (catatan, org lain).
 Sulit melakukan perencanaan atau menyelesaikan masalah.
 Kesulitan dlam membayar rekening bulanan, buat anggaran belanja
bulanan, mengikuti resep masakan. Sulit konsentrasi, kerja lebih lambat.
 Kesulitan dlm melaksanakan tugas sehari-hari di rumah atau pekerjaan.
 Kesulitan menggunakan suatu mesin, memahami aturan suatu permainan.

AD, MCI 2009 20

 Disorientasi tempat dan waktu.
 Sering lupa hari, tanggal. Tidak ingat sedang berada di mana
dan bagaimana sampai di sana, tersesat.
 Kesulitan memahami gambaran visual dan hubungan
spatial.
 Sulit membaca, memperkirakan jarak, kesulitan dgn warna dan
kontras. Gangguan persepsi, melihat cermin dan mengira
ada orang lain di ruangan.
 Kesulitan bicara dan menulis.
 Sulit mengikuti pembicaraan, sering mengulang kalimat, sulit
menemukan kata yang tepat.

AD, MCI 2009 21

 Sering lupa menaruh barang dan tak bisa
mengingatnya.
 Meletakan barang di tempat tdk lazim. Sering kehilangan
barang & tdk bisa menemukan kembali, kadang menuduh
orang mencuri barangnya.
 Berkurang atau hilangnya judgement (kebijakan).
 Misalnya memberikan uang banyak pd pengemis, tidak
memperhatikan kebersihan diri dan kerapihan berpakaian.

AD, MCI 2009 22

 Menarik diri dari pekerjaan atau kegiatan sosial.
 Tidak lagi melakukan hobby, olah raga favorit, aktivitas sosial, pekerjaan.

 Perubahan suasana hati dan kepribadian.

 Sering bingung, curiga, depresi, takut, cemas. Mudah marah.

AD, MCI 2009 23

Signs of Alzheimer's Typical age-related
changes
Poor judgment and decision making Making a bad decision once in a
while

Inability to manage a budget Missing a monthly payment

Losing track of the date or the season Forgetting which day it is and
remembering later
Difficulty having a conversation Sometimes forgetting which word to use

Misplacing things and being unable to Losing things from time to time
retrace steps to find them

AD, MCI 2009 24

 Umur: usia >65 thn. Risiko meningkat 2 kali setiap
kelipatan 5 thn pd >65 thn, >85 thn risiko 50%.
 Riwayat keluarga: risiko meningkat bila >1 anggota
keluarga dgn Alzheimer.
 Genetik: APOE-e4. APOE-e2, APOE-e3
 Faktor risiko yg dpt diubah:
 Cedera kepala
 Penyakit kardiovaskuler
 Hidup sehat

AD, MCI 2009 25

 Anamnesis:
 Derajat penurunan intelektual, gangguan fungsi sosial
 Riwayat keluarga
 Riwayat nutrisi, alkohol, obat-obatan, infeksi, diabetes,
hipertensi, penyakit jantung, ginjal, hati, thyroid.
 Pemeriksaan fisik umum.
 Pemeriksaan neurologis (termasuk fungsi kognitif), Tes
Mini mental (MMSE)
 Laboratorium
 Radiologis: struktur (CT, MRI), fungsi (PET, fMRI)

AD, MCI 2009 26

 Status Mini Mental (Mini mental State Examination/MMSE)
 Skor maksimum 30
 Screening test fungsi kognitif (orientasi waktu dan tempat, perhatian, daya
ingat, bahasa, visuospatial)
 Dipengaruhi tingkat pendidikan
 Pendidikan tinggi >28, pendidikan rendah >24.

AD, MCI 2009 27

AD, MCI 2009 28
AD, MCI 2009 29
Tanpa gejala extrapiramidal:
 AD: ggn memori menonjol, ggn bahasa, visuospatial, depresi, ansietas,
waham
 FTD: ggn perilaku, bahasa
 CJD: myoclonus, ataxia, perodic EEG complexes
 NPH: inkontinensia, ggn gait

AD, MCI 2009 30

Dengan gejala extrapiramidal:
 Demensia with Lewy Bodies: ggn kognitif
berfluktusasi, halusinasi visual, parkinsonism
 Huntington: chorea, psikosis
 Progressive supranuclear palsy: oftalmoplegia
supranuklear, apraxia, ggn sensibilitas kortikal
Depresi (pseudo dementia)

AD, MCI 2009 31

 Terapi gejala kognitif

 Terapi gejala psikiatrik

AD, MCI 2009 32

 Cholinesterase inhibitor

 Menghambat pemecahan acetylcholine

 Menghambat perburukan gejala 6-12 bulan.

AD, MCI 2009 33

AD, MCI 2009 34
 Gejala: mengamuk, cemas, gelisah, halusinasi,
waham,dll.
 Merupakan masalah yang berat bagi pasien dan
keluarga.
 Terapi:
 Non farmakologis: dicoba lebih dulu.
 Farmakologis

AD, MCI 2009 35

 Memahami bahwa gejala psikiatrik merpk bagian dr penyakitnya.
 Mencari penyebab.
 Mengubah lingkungan sehingga pasien merasa nyaman.
 Mencari kelainan fisik:
 Efek samping obat, nyeri, gangguan penglihatan/pendengaran.

AD, MCI 2009 36

 Anti depresan
 Anxyolitic
 Anti psikotik

AD, MCI 2009 37

38
 Definisi: penurunan fungsi kognitif dari > 1 ranah
(domain) kognitif sebanyak 1-1,5 SD di bawah usianya
tanpa adanya gangguan pada aktivitas sehari-hari.
 Merupakan transisi antara kondisi normal dan patologis
(stadium simtomatik prademensia)
 Prevalensi 3- 22% pada usia >65 tahun.
 Lebih dari separuh menjadi demensia dlm 5 tahun.

AD, MCI 2009 39

stable age-appropriate
memory impairment

Normative
Aging Dementia
Aging MCI Dementia

incipient dementia
reversible cognitive
impairment (i.e. confusion) • prodromal AD
• prodromal VaD
• prodromal mixed
physical illness • AD/VaD
depression
• prodromal DLBD
• prodromal FLD
AD, MCI 2009 40
 Revised MCI diagnostic criteria (MCI-R)
 Subjects report cognitive problems, and/or informant reports that subject has
cognitive problems
 Subject and/or informant reports a history of declining in cognitive and/or
functional performances, in relation to that individual’s previous abilities
 Demonstration of a mild cognitive impairment by cognitive testing : memory
impairment and/or impairment in other cognitive domains
 This cognitive impairment does not induce functional impairment in activities of
daily living. Mild difficulties in complex daily living activities could be present
 Absence of clinically defined dementia.

AD, MCI
Gauthier & Touchon, 2009
2004 41
Normal Brain aging
cognition
R
E
V
E
Mild cognitive Stable or
Prodromal R
S
Impairment reversible
dementia
I

impairment
B
L
E

Dementia
Other Alzheimer’s Vascular
dementia Disease Dementia
AD, MCI 2009 42
1. Faktor risiko demografis:
 Usia, jenis kelamin, pendidikan

2. Faktor risiko biologis:

 Penyakit kardiovaskuler
 Cedera kepala
 Penyakit endokrin dan metabolic
 Genetik: ApoE4
 Faktor neuropsikiatrik
 Proses autoimun dan inflamasi
 Radikal bebas

AD, MCI 2009 43

 MCI pertama kali diperkenalkan oleh Petersen (1999).
 Transisi antara stadium normal dan stadium ringan DA (demensia
Alzheimer)
 Gangguan kognitif awal berupa gangguan fungsi memori, namun
aktivitas sehari-hari dalam batas normal.
 Dapat memiliki gangguan pada satu atau lebih ranah lain selain memori.

AD, MCI 2009 44

 Klinis Degeneratif Vaskuler Psikiatrik
MCI amnestik:
• Ranah tunggal DA - Depresi
• Ranah jamak DA DVa Depresi
MCI non amnestik:
• Ranah tunggal FTD -
• Ranah jamak DLB DVa

DA=demensia Alzheimer, Dva= demendia vaskuler, FTD=

frontotemporal demensia, DLB= demensia with Lewy bodies

AD, MCI 2009 45

1. Keluhan penurunan fungsi memori dari pasien dan informan
2. Gangguan memori sesuai usia dan Pendidikan
3. Fungsi kognitif secara umum masih baik
4. Fungsi aktivitas sehari-hari (ADL) masih baik
5. Tidak demensia

Pemeriksaan laboratorium dan imaging

AD, MCI 2009 46

 Memory complaints by the patient and/or by the family

 Progressive onset

 Normal or mildly impaired complex activities of daily living

 Amnestic syndrome of the hippocampic type

 Persistence or worsening at subsequent evaluations

 Absence of the fully developed syndrome of dementia

 Exclusion of other conditions potentially causing the MCI

AD, MCI
Dubois & Albert, 2004
2009 48
 Increase in CSF tau (Sunderland et al., 1999; Galasko et al., 1999;
Maruyama et al., 2001)
 Decrease (Andreassen et al., 1999) or no change (Maruyama et al.,
2001) in CSF Aβ42
 Combination of tau and Aβ42 measurments in CSF
(Andreassen et al., 1999)
 Increase in CSF phosphorylated-tau protein
(Arai et al., 2000)

AD, MCI 2009 49

 Hippocampal atrophy (De Leon et al., 1997; Jack et al 1999)
 Annual rate of hippocampal atrophy (Jack et al., 2000)
 Entorhinal cortex atrophy (Xu et al., 2000; Du et al., 2002)
 Medial temporal atrophy (Visser et al., 2002)
In itself the presence of atrophy adds little

AD, MCI 2009 50

 SPECT / PET + +
 Metabolic and / or perfusional deficits in :
 temporo-parietal regions
 Amygdalo-hippocampal regions
 Posterior cingulate cortex

(Kennedy et al., 1995; Jonhson et al., 1998; Kogure et al., 2000)

 Amyloid imaging by PET: possible reference

(Pittsburg group, 2004)

AD, MCI 2009 51

 MMSE (Folstein MF et al. J Psychiatric Res 1975; 12: 189198) & Clock
Drawing test (Thalmann et al 1996)

 The Mental Status Examination ( Mark D’Esposito MD 1999, American

Academy of Neurology)

AD, MCI 2009 52

1. Mini-Mental State Examination
 Evaluates global mental status
 orientation to time and place
 registration of three words
 attention and calculation
 recall of three words
 language and
 visual construction tasks
 It is made up of 30 questions (items)
 Each correct answer receives 1 point
 An overall MMSE score (ranging from 0 to 30)
 Dementia, cut off point < 24

Folstein MF et al. J Psychiatric Res 1975; 12: 189198.

AD, MCI 2009 53
AD, MCI 2009 54
AD, MCI 2009 55
AD, MCI 2009 56
 The Clock Draw Test

Time: 5.00 Time: .10.30

Score: 7 (normal) Score: 3 (demented)

Time: 'no real time' Time: 1/4 past 25

Score: 2 (demented) Score: 3 (demented)
Cognitive
AD, MCI Assessment Thalmann et al 1996.
2009 57
 Functional Activities Questionnaire (FAQ)
 Instrumental Activities Daily Living scale (IADL) &
Activities Daily Living scale (ADL)
 Blessed Dementia Scale (BDS) 0-17.
 Global Deterioration Scale (GDS) score 1-7.
 Clinical Dementia Rating Scale (CDRS)- gold
standards in global ratings in AD. Score 0;
0.5;1;2;3.
 Clinician’s Interview-Based Impression of Change-
plus (CIBIC-plus) rating 1-7.

AD, MCI 2009 63

 Alzheimer’s Disease Functional
Assessment and Change Scale (ADFACS)
INSTRUMENTAL ACTIVITIES OF DAILY LIVING :

Each IADL was assessed on a 4-point scale from 0 (no impairment) to 3 (severe
impairment)
• Ability to use the telephone • Performance of household tasks
• Use of household appliances • Handling money
• Shopping • Food preparation
• Ability to get around inside and outside the home • Hobbies and leisure activities
• Handling personal mail • Grasping situations or explanations

BASIC ACTIVITIES OF DAILY LIVING :

Each ADL was assessed on a 5-point scale from 0 (no impairment) to 4 (very severe
impairment)
• Toileting • Feeding
• Dressing • Personal hygiene and grooming
• Physical ambulation
• Bathing

AD, MCI Lawton MP et. al., Gerontol, 179

2009 (1969)
64
 Donepezil memberi sedikit perbaikan dalam 1-2 tahun.
 Pencegahan dengan kontrol faktor risiko (misalnya: hipertensi).

AD, MCI 2009 67

68
 Cognitive impairment that is caused by or associated with
vascular factors has been termed “vascular cognitive
impairment”
 VCI can occur either alone or in association with Alzheimer
disease (AD).
 A strong interaction between cerebrovascular and AD
pathologies, such that individuals having both frequently
show greater cognitive impairment than those having either
pathology alone.
 Because vascular risk factors are treatable, it should
bepossible to prevent, postpone, or mitigate VCI, as well as
the vascular exacerbation of AD

AD, MCI 2009 69

  History
 Stroke/vascular risk factors
 Acute onset/Onset after stroke or TIA
 Fluctuations or stabilisation

 Neurological examination
 Focal symptoms and signs

MRI/CT: vascular lesions

AD, MCI 2009 70

 Neuropsychological assessment
 Frontal dysfunction
 With or without memory impairment (encoding, effect of cueing)
 Dysexecutive syndrome
 Attention deficit

AD, MCI 2009 71

AD, MCI 2009 72
 The NINDS-AIREN criteria define probable vascular
dementia as cognitive decline from a previously higher level
of functioning in memory and two or more cognitive
domains, the decline being severe enough to interfere with
activities of daily living.
 Evidence of cerebrovascular disease on both clinical
examination and neuroimaging is required, as is evidence of
a relationship between the stroke and cognitive decline,
which can be provided by two of the following:
 (a) onset of dementia within 3 months after a recognized stroke,
 (b) abrupt deterioration in cognition and
 (c) stepwise deterioration.

AD, MCI 2009 73

 Manajemen faktor risiko vaskuler
 Asetilkolin esterase inhibitor (donepezil, galantamine)  hasil kurang
baik

AD, MCI 2009 74

75
 Pick’s Disease.
 Atrofi lobus frontal dan temporal.
 Histologi: tau or ubiquitin inclusions.
 Etiologi: kebanyakan tak diketahui, genetik.
 Onset usia <60 thn.

AD, MCI 2009 76

 Frontal lobe dementia:
 Perubahan perilaku, emosi tumpul, insight terganggu
 Progressive nonfluent aphasia:
 Lobus frontalis dominan
 Semantic dementia:
 Fluent aphasia, lobus temporalis dominan
 Prosopagnosia:
 Tak bisa mengenal wajah, lobus temporalis nondominan
 FTD + Parkinsonism/Motor Neuron Disease

AD, MCI 2009 77

 Gejala klinis:
 Onset usia < 60 thn
 Keluhan daya ingat tidak dominan
 Gangguan perilaku atau afasia

 CT/MRI: atrofi lobus frontal dan temporal asimetris

 Belum ada terapi yang efektif

AD, MCI 2009 78