ALZHEIMER’s DISEASE: CAUSES &

TREATMENT – A REVIEW
M. Chairil Riskyta Akbar / Siti Khadidjah / Rezky Ramadhani Syarif
Introduction
• Dr. Alois Alzheimer (German physiatrist and
neuropathologist)
• Alzheimer’s Disease (AD)  aggressive form of
dementia, memory, langguange and behavioral deficit
• 46.8 million (2010)  74.7 million (2030)  114
million dementia’s patient in 2050
• Risk Factor > gene (APOE4 allele, homozygote
situation)
• There are no known cure for AD
• Preventive  decreasing cardiovascular disease,
mantain mental funtion
Clinical Features
PRE DEMENTIA
01 • Unreliably distinguished from normal aging/stress related
• Deterioration of episodik memory
• Impaired of executive, verbal and visuospatial

MILD DEMENTIA
02 Memory lost, >short term

MODERATE DEMENTIA
• Continue short memory lost
• Inability to create new memories (seems like live in the past)
03 • Still able to manage basic ADL
• Help is required in such as grooming/dressing
• Cognitive decline, aggression, depression
• delusional

SEVERE DEMENTIA
04 • Early memory loss
• Basic ADL are affected
• deterioration of Communication
• Behavioral disturbance
Risk Factor

AGE EDUCATION COEXISTING GENETIC

• 65 years or above Higher years of • Hearh disease APOE 4
• ↑ 5% in 65-74 yo education  ↑ • Hypertension allele, >homozygote.
• ↑50% in 85 yo sinaptic connection • Dislipidemia
in the brain • Type II DM
 PSEN 1 /Presenilin-1

EOAD-
PSEN 2 /Presenilin-2
Early
< Symptomp /Amyloid
APP Precursor
Protein
AD 1:8
APOE /Apolypoprotein E
7th Death US
LOAD- /Sortilin-
SORL1 Related
Late
receptor
1 : 8 >65
1 : 2 >85 GAB2
 EOAD-Early E2 <<
>> ᵝ-Amyloid
(A ᵝ)
APOE e3

E4 >>
Research
1. NCRAD (National Cell Repository)
• Data Bank  sample
2. NIA (National Institute of Aging)
• Multicenter Study  research
3. AlzGene Database
• Rank
• SORL1 & GAB2
Other Genes DAPK1
Chromosome
Apoptosis Enzyme
9

Protein Degradation UBQLN1

Chromosome
10

Chromosome AD Neuropathology
11 Insulin-degrading enzyme
GAB2
IDE-Gen
Genetic Counseling
1. Information about family history
>> than age
2,5 times
2. Risk factor
3. Testing options
Symptomatic and family history (1 degree), or research
4. DNA Banking
Future clinical genetic testing
Clinical PSEN 1 Common

Testing EOAD-
PSEN 2 Rare
Early

APP Symptomatic
AD
Family history
APOE (1st degree)

LOAD- Exp. Research

SORL1
Late REVEAL

GAB2
Gene/ Protein/ Chr Age of Onset No. Mutation Availability of
osomal Loc / No. Families Clinical Testing
APP/ Amyloid Precu 40-60 28/ 76 Yes (Limited)
rsor Protein/
21q21.3
PSEN1/ Presenilin1 30-60 165/ 354 Yes
/ 14q24.3
PSEN2/ Presenlin2/ Late Onset 10/ 18 Yes (Limited)
19q.13.32
APOE/ apolipoprote Late Onset Increased risk Yes (Recommende
inE/ 19q13.32 d, for symptomatic
only)
SORL1/ Sortilin-rela Late Onset n/a No
ted receptor/ 1q23
GAB2/11q14 Late Onset n/a No
Diagnosis Criteria

1 2 3
History Mental State Physical
Taking Assassment Exam

History should Include avalidated Focus on vascular

include information cognitive function and neurological
from the person test sign suplementted
related to the by investigation
patient CLOCK TEST and patient history
(Populer)
2-step process of dementia assassment:

#1 #2
Distinguish dementia Subtype diagnosis
syndrome from: Determine the kind of
• Depression treatmen possible
• Delirium
• Mild cognitive impairment
DETECTION
METHODE
PET #1
DETECTION
METHODE
MRI #2
DETECTION
METHODE
CT SCAN #3
3 Hypothesis: Penyebab Alzheimer

1 2 3

Cholinergic Amyloid Tau Hypothesis

Hypothesis Hypothesis
 Drug
Therapy

1. CHOLINESTERASE INHIBITOR
• Donepezil (Aicept)
• Alantamin (reminyl)
• Rivastigmin and Tachrine (cognex)

2. NMDA Receptor Antagonist

• Memantine (Namenda).

3. Antidepressant & Antipsykotic

• SSRI (Citalopram, fluoxetine, Paroxetine, sertraline, trazodone)
• Olanzapine, quetiapine, risperidon
Thank you
#FASTABIQUL KHAERAT