Dementia and

Mild Cognitive Impairment

Abdul Gofir
Neurology Department
Medical Faculty
Gadjah Mada University
 Mild Cognitive Impairment
Transitional state between the cognitive changes of
normal aging and the fully developed features of
dementia
Peterson, RC. Seminars in Neurology 2001;27(1):22-31

Original Criteria
Memory complaint, preferably qualified by an informant
Memory impairment for age and education
Preserved general cognitive function
Intact activities of daily living
Not demented
Adapted from Reisberg B et al. Am J Psychiatry 1982;139:1136-1139
 Mild Cognitive Impairment
Petersen RC

 Memory complaint corroborated by

an informant
 Normal general cognitive function
 Normal activities of daily living
 Memory impairment in relation to
age and education
 Not demented
 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)
 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)
 Pre-dementia syndrome
Perbandingan AAMI-MCI-Alzheimer
 DISTRIBUTED COGNITIVE FUNCTION

Cognitive function Neural basis

1. Attention/concentration Reticular activating system (brain stem

and thalamic nuclei), and multimodal
association areas (prefrontal, posterior
parietal and temporal lobes)
2. Memory
Limbic system (especially
hippocampus and diencephalon)

3. Higher-order intellectual function, Frontal lobes

social behaviour, and personality
 Other Causes of “Cognitive
Impairment”

• PSP & related disorders • Infections

• Huntington’s – HIV
• Post-anoxic – Syphilis
• NPH – Lyme’s
• B12 – CJD
• Hypothyroidism • Encephelopathy
• Hypercalcemia – Uremic
• Alcohol/thiamine – Hepatic
 Alzheimer’s Disease
versus Dementia
– 50 - 70% of dementias are due to AD
– Probable AD - 30% of cases, 90% neuropath - correct
– 20% have other contributing diagnoses
– Possible AD - 40% of cases, 70% are AD at neuropath
– 40% have other contributing diagnoses
– Unlikely AD - 30% of cases, 30% are AD at neuropath
– 80% have other contributing diagnoses

– Alzheimer’s disease is a pathological condition

– Dementia is a clinical condition frequently caused by AD
• The AD dementia has some characteristics and some heterogeneity
CONVERSION FROM MCI
TO
ALZHEIMER’S DISEASE
Persentase konversi
Prediktor konversi
Mild cognitive
impairment Alzheimer’s disease
Amnestic

Mild cognitive
impairment Alzheimer’s disease
Multiple domains ? normal aging
slightly impaired

Mild cognitive Frontotemporal dementia

impairment Lewy body dementia
Primary progress. aphasia
Single non-
Parkinson’s disease
memory domain
Alzheimer’s disease
 MCI: Conversion to AD

Longitudinal studies Year Conversion rate

follow-up to AD (%)

MCI Normal

Petersen et al 1999* 4 12 1-2

Kluger et al 1999 6-7 67.2 11.9
Rubin et al 1989 3-7 69
Flicker 1991 2 71.9
Wolf et al 1998 2.7 19.8
Petersen et al 1995 4.5 55
Grundman et al 1996 3 44

* Rate per year

MCI prediction of conversion to AD

• Low score on MMSE delayed recall

subtest
• Selective reminding test : long term
retrieval
• Low scores on category naming for
animals
(Yustiani Dikot, 2004)
 PREDICTORS OF CONVERSION

• Clinical features
– presence of any quantifiable
abnormalities beyond memory
– Test of delayed verbal recall and
executive functions
• Apolipoprotein E4 genotype
• Neuroimaging (hippocampal volumes)
• PET (alterations in entorhinal cortex and/or
posterior cingulate cortex)
• CSF levels of A-beta, Tau Protein
 Other predictors - SPECT

•  perfusion1
– hippocampal-amygdaloid
– posterior cingulate
– anterior thalamus
– anterior cingulate
• No predictors2
•  Ratio between CFS tau and blood flow in
the posterior cingulate3

1Johnson et al, 1998; 2McKelvey et al, 1999; 3Okamura et al, 2002

 Other predictors - Biomarkers

•  beta-amyloid
• ↑ protein Tau
•  APP Ratio in platelets

Andreasen et al., 2000; Riemenschneider et al., 2003; Rosenberg et al, 2000; Di

Luca et al, 2003; Borroni et al, 2004)
….combining platelet APP ratio along
with SPECT scans………
• platelet APP ratio by WB analysis (130
kDa/110-106 kDa)
• SPECT ROIs (Regions of Interest, spheres,
1mm, n=32) in posterior cingulate
cortex/cerebellum, temporo-parietal
regions/cerebellum*

* SPECT ROIs results are shown as mean between ROIs obtained in the
posterior cingualate cortex and temporo-parietal areas/cerebellum.
Data obtained by either posterior cingulate cortex or temporo-
parietal regions are comparable to mean value of combination of
both.
 APPr and SPECT scores
in stable MCI and pre-clinical AD patients

Variable MCI stable Pre-clinical AD p

n 12 21

APPr 0.76±0.33 0.39±0.21 0.0001

SPECT ROIs 0.89±0.18 0.78±0.05 0.02

APP*SPECT index 0.65±0.27 0.30±0.15 0.0001

Follow-up,years 2.2±0.8 2.7±0.5 0.01

^The two subgroups did not differ in term of age, gender and MMSE scores at
baseline. APP*SPECT index: APP values X SPECT ROIs scores.
Moleculer biology of
Alzheimer Disease Gamma-secretase
Cell membrane
Beta- secretase
Environment

Increased Ab42
formation and
Mutation genes : deposition
Amyloid Precursor Protein
Presenile 1 APOE4
Presenile 2

Diffuse Tau phosphoryla

Diffuse plaque tion and aggregation
plaque

Neuritic plaque Inflammatory Oxidative

response injury

Neurofibrillaryta
ngles
Cell dysfunction and death

Multiple neurotransmitter deficits, CI, dementia (Jeffrey, 2003; Sofia

Mubarika, 2004)
 Genes involved in MCI
• ApoE e4 allele increases risk of
progression to dementia
• ApoE genotype may be used to enrich
samples with AD
• Not a predictive test in an individual

(Sofia Mubarika, 2004)

APP – amyloid precursor protein
Cell surface protein – highly conserved in
evolution
Abundantly expressed in neurons
Several of the mutations in the bAPP gene
selectively increase the production of Ab42

Overproduction of the Ab peptide appears to

be the central pathogenic event on the
disease

(Sofia Mubarika, 2004)

bAPP

The Ab42 : the most neurotoxic because it is fibrillogenic.

The C-terminal APP intracellular fragment binds to transcription factors
and is translocated to the nucleus, where it influences transcription.
(Sofia Mubarika, 2004)
Amyloid hypothesis for AD development
1. Accumulation and aggregation of Ab
fragments in brain
2. Deposition of aggregates of Ab (diffuse
plaques)
3. Ab fragments injure surrounding cells
4. Initiation of inflammatory process
5. Progressive neuritic injury

(Sofia Mubarika, 2004)

Neuritic plaques & neurofibrillary tangles

tangles

plaques

(Sofia Mubarika, 2004)

Do you prefer to avoid social gatherings?
Yes (1 points)
No (0 points)
Do you often feel downhearted and blue?
Yes (1 points)
No (0 points)
Do you feel happy most of the time?
Yes (0 points)
No (1 points)
Do you often feel helpless?
Yes (1 points)
No (0 points)
Do you feel worthless and ashamed about yourself?
Yes (1 points)
No (0 points)
Do you often wish you were dead?
Yes (1 points)
No (0 points)
 CLINICAL DEMENTIA RATING (CDR)

Impairment levels are determined in six cognitive-functional categories:

1- Memory
2- Orientation
3- Judgment
4- Community Affairs
5- Home & Hobbies
6- Personal Care

A five-point scale is used to rate function in each category:

0 = Normal (no significant problem)
0.5 = Questionable Impairment (more than just normal aging)
1 = Mild Impairment (mildly impaired relative to peers)
2 = Moderate Impairment
3 = Severe Impairment
 CLINICAL DEMENTIA RATING (CDR)

Impairment Level and CDR Score (0, 0.5, 1, 2, 3)

None Questionable Mild Moderate Severe

0 0.5 1 2 3

No memory loss or Consistent slight Moderate memory Severe memory loss; Severe memory loss;
Memory slight inconsistent forgetfulness; loss; more marked only highly learned only fragments
forgetfulness partial recollection for recent events; material retained; remain
of events; "benign" defect interferes new material rapidly
forgetfulness with everyday lost
activities

Fully oriented Fully oriented Moderate difficulty Severe difficulty Oriented to person
Orientat except for slight with time with time only
ion difficulty with time relationships; relationships;
relationships oriented for place at usually disoriented
examination; may to time, often to
have geographic place
disorientation
elsewhere
 Impairment Level and CDR Score (0, 0.5, 1, 2, 3)

None Questionable Mild Moderate Severe

0 0.5 1 2 3

Judgmen Solves everyday Slight impairment Moderate Severely impaired Unable to make
t& problems & in solving difficulty in in handling judgments or
handles business problems, handling problems, solve problems
Problem
& financial affairs similarities, and problems, similarities, and
Solving well; judgment differences similarities, and differences;
good in relation differences; social judgment
to past social judgment usually impaired
performance usually
maintained
Communi Independent Slight impairment Unable to No pretense of No pretense of
ty Affairs function at usual in these activities function independent independent
level in job, independently at function outside function outside
shopping, these activities home home
volunteer and although may still Appears well Appears too ill to
social groups be engaged in enough to taken be be taken to
some; appears to functions functions outside
normal to casual outside a family a family home
inspection home
 Impairment Level and CDR Score
(0, 0.5, 1, 2, 3)

None Questionabl Mild Moderate Severe

0 e 1 2 3
0.5
Home Life at home, Life at home, Mild but definite Only simple No significant
and hobbies, and hobbies, and impairment of chores function in
Hobbie intellectual intellectual function at preserved; very home
interests well interests slightly home; more restricted
s maintained impaired difficult chores interests, poorly
abandoned; maintained
more
complicated
hobbies and
interests
abandoned

Person Fully capable of self-care Needs Requires Requires much

al Care prompting assistance in help with
dressing, personal care;
hygiene, frequent
keeping of incontinence
personal effects
 Level Clinical Characteristics

1 No subjective complaints of memory deficit. No memory deficit evident on

No cognitive clinical interview.
decline

2 Subjective complaints of memory deficit, most frequently in following areas: (a)

Very mild forgetting where one has placed familiar objects; (b) forgetting names one
cognitive decline formerly knew well. No objective evidence of memory deficit on clinical
(Age Associated interview. No objective deficits in employment or social situations. Appropriate
Memory concern with respect to symptomatology.
Impairment)

3 Earliest clear-cut deficits. Manifestations in more than one of the following

Mild areas: (a) patient may have gotten lost when traveling to an unfamiliar location;
Cognitive decline (b) co-workers become aware of patient's relatively poor performance; (c) word
(Mild Cognitive and name finding deficit becomes evident to intimates; (d) patient may read a
Impairment) passage or a book and retain relatively little material; (e) patient may
demonstrate decreased facility in remembering names upon introduction to
new people; (f) patient may have lost or misplaced an object of value; (g)
concentration deficit may be evident on clinical testing. Objective evidence of
memory deficit obtained only with an intensive interview. Decreased
performance in demanding employment and social settings. Denial begins to
become manifest in patient. Mild to moderate anxiety accompanies symptoms.
 Level Clinical Characteristics

4 Clear-cut deficit on careful clinical interview. Deficit manifest in following

Moderate areas: (a) decreased knowledge of current and recent events; (b) may
cognitive decline exhibit some deficit in memory of ones personal history; (c)
(Mild Dementia) concentration deficit elicited on serial subtractions; (d) decreased ability
to travel, handle finances, etc. Frequently no deficit in following areas: (a)
orientation to time and place; (b) recognition of familiar persons and
faces; (c) ability to travel to familiar locations. Inability to perform
complex tasks. Denial is dominant defense mechanism. Flattening of
affect and withdrawal from challenging situations frequently occur.

5 Patient can no longer survive without some assistance. Patient is unable

Moderately severe during interview to recall a major relevant aspect of their current lives,
cognitive decline e.g., an address or telephone number of many years, the names of close
(Moderate family members (such as grandchildren), the name of the high school or
Dementia) college from which they graduated. Frequently some disorientation to
time (date, day of week, season, etc.) or to place. An educated person
may have difficulty counting back from 40 by 4s or from 20 by 2s.
Persons at this stage retain knowledge of many major facts regarding
themselves and others. They invariably know their own names and
generally know their spouse’s and children’s names. They require no
assistance with toileting and eating, but may have some difficulty
choosing the proper clothing to wear.
 Level Clinical Characteristics

6 May occasionally forget the name of the spouse upon whom they are entirely
Severe dependent for survival. Will be largely unaware of all recent events and experiences
in their lives. Retain some knowledge of their past lives but this is very sketchy.
cognitive decline
Generally unaware of their surroundings, the year, the season, etc. May have
(Moderately Severe difficulty counting from 10, both backward and, sometimes, forward. Will require
Dementia) some assistance with activities of daily living, e.g., may become incontinent, will
require travel assistance but occasionally will be able to travel to familiar locations.
Diurnal rhythm frequently disturbed. Almost always recall their own name. Frequently
continue to be able to distinguish familiar from unfamiliar persons in their
environment. Personality and emotional changes occur. These are quite variable and
include: (a) delusional behavior, e.g., patients may accuse their spouse of being an
impostor, may talk to imaginary figures in the environment, or to their own reflection
in the mirror; (b) obsessive symptoms, e.g., person may continually repeat simple
cleaning activities; (c) anxiety symptoms, agitation, and even previously nonexistent
violent behavior may occur; (d) cognitive abulla, i.e., loss of willpower because an
individual cannot carry a thought long enough to determine a purposeful course of
action.

7 All verbal abilities are lost over the course of this stage. Frequently there is no
Very severe speech at all -only unintelligible utterances and rare emergence of seemingly
forgotten words and phrases. Incontinent of urine, requires assistance toileting and
cognitive decline
feeding. Basic psychomotor skills, e.g., ability to walk, are lost with the progression
(Severe Dementia) of this stage. The brain appears to no longer be able to tell the body what to do.
Generalized rigidity and developmental neurologic reflexes are frequently present.
 Geriatric depression scale
Do you often get bored?
Yes (1 points)
No (0 points)
Do you often get restless or fidgety?
Yes (1 points)
No (0 points
Do you feel in good spirits?
Yes (0 points)
No (1 points)
Do you feel you have more problems with memory than most
people?
Yes (1 points)
No (0 points)
Can you concentrate easily when reading the papers?
Yes (0 points)
No (1 points)
Do you prefer to avoid social gatherings?
Yes (1 points)
No (0 points)
Do you often feel downhearted and blue?
Yes (1 points)
No (0 points)
Do you feel happy most of the time?
Yes (0 points)
No (1 points)
Do you often feel helpless?
Yes (1 points)
No (0 points)
Do you feel worthless and ashamed about yourself?
Yes (1 points)
No (0 points)
Do you often wish you were dead?
Yes (1 points)
No (0 points)
 MINI MENTAL STATE EXAMINATION (MMSE)
No Tes Penilaian Total
Nilai

ORIENTASI
Tahun berapa? 1
Bulan apa? 1
1 Sekarang ini Tanggal berapa? 1
Hari apa? 1
Musim apa? 1
Negara mana? 1
Propinsi mana? 1
2 Kita dimana Kota mana? 1
Rumah sakit mana? 1
Ruang apa/tingkat berapa? 1
No Tes Penilaia Total
n Nilai
PENCATATAN
3 Sebutkan 3 obyek dengan waktu 1 detik tiap
obyek. Kemudian minta pasien menyebutkan 3
ketiga obyek tersebut. Ulangi jawaban pasien
sampai dapat menyebut ketiganya
ATENSI DAN KALKULASI
4 Seri tujuh. Minta pasien untuk menghirung
mundur dengan selisish 7 dimulai dari angka 5
100. Berikan 1 nilai untuk tiap jawaban yang
benar. Hentikan setelah 5 jawaban.
Alternatif lain: eja secara mundur kata
MESRA
MENGINGAT KEMBALI
5 Minta pasien untuk menyebutkan 3 obyek
yang telah dipelajari pada pertanyaan no. 3. 3
Berikan 1 nilai untuk tiap jawaban yang benar
No Tes Penilaia Tota
n l
BAHASA Nilai

6 Tunjuk pada sebuah pensil dan sebuah arloji tangan. 2

Minta pasien untuk menyebutkan nama benda yang anda
tunjuk
7 Minta pasien mengulang: “tanpa, bila, dan, atau, tetapi” 1

8 Minta pasien untuk mengikuti 3 tahap tugas: 3

“ambil kertas dengan tangan kanan anda”
“lipat kertas menjadi dua”
“letakkan kertas diatas lantai”
9 Minta pasien membaca dan melakukan tugas yang 1
dibacanya “ Mohon pejamkan mata anda”
10 Minta pasien menulis kalimat pilihan sendiri pada 2 garis. 1
(Kalimat harus mengandung subyek dan obyek dan harus
mempunyai arti. Abaikan kesalahan eja saat menilai)
11 Minta pasien menyalin gambar di bawah ini (berikan nilai 1
1 bila semua sisi dan sudut tergambar utuh dan gambar
yang saling memotong merupakan sebuah segi empat)
Alat Bantu no. 9
Mohon Pejamkan Mata
Alat Bantu no. 10

Alat Bantu no. 11

 MINI MENTAL STATE EXAMINATION (MMSE)
No Tes Penilaian Total
Nilai

ORIENTASI
Tahun berapa? 1
Bulan apa? 1
1 Sekarang ini Tanggal berapa? 1
Hari apa? 1
Musim apa? 1
Negara mana? 1
Propinsi mana? 1
2 Kita dimana Kota mana? 1
Rumah sakit mana? 1
Ruang apa/tingkat berapa? 1
No Tes Penilaia Total
n Nilai
PENCATATAN
3 Sebutkan 3 obyek dengan waktu 1 detik tiap
obyek. Kemudian minta pasien menyebutkan 3
ketiga obyek tersebut. Ulangi jawaban pasien
sampai dapat menyebut ketiganya
ATENSI DAN KALKULASI
4 Seri tujuh. Minta pasien untuk menghirung
mundur dengan selisish 7 dimulai dari angka 5
100. Berikan 1 nilai untuk tiap jawaban yang
benar. Hentikan setelah 5 jawaban.
Alternatif lain: eja secara mundur kata
MESRA
MENGINGAT KEMBALI
5 Minta pasien untuk menyebutkan 3 obyek
yang telah dipelajari pada pertanyaan no. 3. 3
Berikan 1 nilai untuk tiap jawaban yang benar
No Tes Penilaia Tota
n l
BAHASA Nilai

6 Tunjuk pada sebuah pensil dan sebuah arloji tangan. 2

Minta pasien untuk menyebutkan nama benda yang anda
tunjuk
7 Minta pasien mengulang: “tanpa, bila, dan, atau, tetapi” 1

8 Minta pasien untuk mengikuti 3 tahap tugas: 3

“ambil kertas dengan tangan kanan anda”
“lipat kertas menjadi dua”
“letakkan kertas diatas lantai”
9 Minta pasien membaca dan melakukan tugas yang 1
dibacanya “ Mohon pejamkan mata anda”
10 Minta pasien menulis kalimat pilihan sendiri pada 2 garis. 1
(Kalimat harus mengandung subyek dan obyek dan harus
mempunyai arti. Abaikan kesalahan eja saat menilai)
11 Minta pasien menyalin gambar di bawah ini (berikan nilai 1
1 bila semua sisi dan sudut tergambar utuh dan gambar
yang saling memotong merupakan sebuah segi empat)
 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
• Kondisi yg berpengaruh : kelelahan umum , tidak
ada motivasi/usaha, materi memori tidak familiar,
kondisi emosial buruk
• Bila diperlukan obat-obatan simptomatik
 KIE
• Komunikasi - Informasi - Edukasi
• Pemahaman penyakit / kondisi MCI
• Dasar kerjasama program terapi
 Stimulasi kognitif
• Memory training , cognitive rehabilitation
• Stimulasi eksternal reorganisasi otak
• Aspek atensi, konsentrasi, memori, reasoning ,
keterampilan visuomotor & visuospasial
• Aplikasi menggunakan model 8 ; memilih strategi,
pengukuran dasar, menyepakati tujuan,
mempelajari strategi, melaksanakan strategi,
evaluasi strategi, mengembangkan terapan
strategi dalam keseharian dan mempraktekan
 Terapi Rekreasi

• Aktifitas bernuansa rekreasi namun

berdampak terapi kognitif
• Pelatihan fisik, stimulasi kognitif &
kreatifitas
• Dapat kelompok maupun individual
• Acuan : ADL & problem yg dihadapi
• Aktifitas reminisens & orientasi nyata
 Aktifitas Reminisens
• Meningkatkan memori masa lalu
dengan cara imaginasi, ekpresi dan
komunikasi
• Bersama mengingatkan peristiwa lalu :
kapan , siapa pelaku, dimana ? Dan
dikomunikasikan kembali
• Stimulasi kognitif !
• Kelompok : Re-uni
• Individual : penulisan autobiografi
 Aktifitas Orientasi Nyata
• Usia lanjut : sering menurun daya
orientasinya
• Stimulasi orientasi tempat, waktu & orang
• Stimulasi memori, visuospasial
• Membaca foto bersama
 Aktifitas Fisik
• Untuk kebugaran fisik usila &
meningkatkan kemampuan kognitif.
• “Gerak dan Latih Otak” ( Brain movement
& exircise )
• Ringan, santai, aman, tidak lama
• Dasar : teori organisasi otak
 Beberapa strategi psikologis
memori keseharian
• Meletakkan alfabetik berkas- berkas
kantor
• Meletakkan disatu tempat khusus
barang2 sejenis / penting sehari-hari.
• “ Errorless learning “
 TATALAKSANA FARMAKOLOGIS

• Belum ada obat etiologi MCI

• Strategi pengobatan sama dengan DA
• Dasar patofisiologis yang sama
• Tergantung gejala yang menonjol
/penyerta
• Tujuan umum mengurangi gejala &
mencegah deteriorisasi
• Dalam penelitian
 Jenis obat-obatan
• Penguat sistim kolinergik
• Nootropik
• Neuroprotektif
• NSAID
• Neurotropik
 Penguat kolinergik

• ChE-Inhibitor :
– Physostigmin
• Obat lama (1970)
• Efek samping banyak , ditinggalkan
– Tacrine
• Lebih baik dari tacrine
• Efek samping hepatotoksik
• @ Cognex
 Penguat kolinergik
– 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
 Golongan Nootropik
• Sebagai penguat metabolik sel otak
• Meningkatkan fungsi learning & memori
• Bila digabung dgn stimulasi kognitif
hasilnya lebih baik.
• Banyak dipasaran (nootropil, neurotam
dsb)
 Anti - oksidan

• Anti radikal bebas di otak

• Dapat menghambat deteriorisasi
penyakit
• Tidak memberi efek pada kognitif
• Vitamin E, C, selegiline
 NSAID
• Pada otak DA dapat dijumpai proses
peradangan
• Deposit B amiloid peptide ada
hubungannya dgn proses peradangan
kronis
• Dasar dari penggunaan NSAID
 Neuroprotektif lain
• Ginko biloba ;
– Banyak dipublikasikan tetapi masih
kontroversial hasilnya.
• Estrogen ;
– Dapat memperbaiki performance penderita
Alzheimer