3. Demensia
Syndrome of progressive, global decline in cognition
that is severe enough to degrade individual’s
well-being & sosial function.
(Cassel)
An acquired, persistent impairment of intellectual
function with compromise in at least three of the
following spheres of mental activity:
language, memory, and visuospatial skills
emotion or personality
cognition
(frontera)
4. Alzheimer’s Disease (AD)
• Is characterized by progressive cognitive &
behavioral deficits accompanied by diffuse
structural abnormalities in the brain. (Hazzard)
5. Genetics of AD
(Hazzard)
The common symptoms
memory loss, confusion, impaired
judgment, personality changes, disorientation,
& loss of language skills
Based on the onset of symptoms, AD is divided
into
– Early onset / familial AD (FAD)
– Late onset AD (LOAD)
6. Genetics of AD
FAD
• 3 % of all the case
• Linked to mutations in the genes for the
amyloid precursor protein (APP; gene name
APP) on chromosome 21, presenilin 1 PS1;
gene name PSEN1) on chromosome 14, &
preseniline 2 (PS2; gene name PSEN2) most
of the mutations in PSEN1
7. Genetics of AD
LOAD
= sporadic AD
• 97 % of all cases of AD
• Has not been linked w any mutations
• Aging is the most important risk factor
• Associated w many other environmental & genetic risk
factors hypercholesterolemia & other vascular risk
factors, history of head trauma, & low educational
attainment.
• Genetic risk factor Ɛ4 allele of the apolipoprotein E
(APOE) gene on chromosome 19
8. Neuropathology of AD
• Amyloid plaque
dominant componen is amyloid β peptide (A β)
The most characteristic form is “neuritic plaque
• Neurofibrillary tangles (NFT) appear as paired, helically twisted
protein filaments composed of highly stable polymers of
cytoplasmic protein called Tau
• Amyloid angiopathy diffuse loss of neurons & synapses in the
neocortex, hippocampus, & other subcortical region of the brain
Often observed in the classical LOAD, but seems to be more
prevalent in small subgroup of FAD (Dutch E693Q & Iowa
D694N mutations in the APP gene)
9. Pathobiology of AD
Amyloid precursor protein (APP) processing &
generation of Aβ
• Small Aβ aggregates (oligomeres) “preplaque”
neurotoxoc species of Aβ act as the proximate cause of
nueronal injury & synaptic loss associated w AD
Aβ : pivotal role in the pathogenesis of AD
• Px w Downs’ syndrome (DS) (trisomi 21) had higher
propensity of developing a cllinical & pathological
phenotype resmbling AD Aβ was the major component
in plaques from both px w AD & DS ; & that its genesis
was related to a gene (APP) located on chromosome 21,
close to obligate DS region.
10. • Alzheimer's dementia (70% to 90% of cases)
• multi-infarct dementia (15%)
• 1% to 5% are represented by Parkinson's
dementia, Creuztfeldt-Jacob disease, Huntington's
disease, Pick's disease, Lewy body dementia, &
progressive supranuclear palsy.
Dementia represents several disorders with
similar effects on mental activity.
Dementia can be divided into :
• cortical Alzheimer's dementia
• subcortical types Parkinson's disease
Frontera
12. Epidemiologi
(Cassel, Frontera)
• Alzheimer's disease is the most common
dementia for people age 65 years and older.
(8%-15% mengenai usia 65 tahun ke atas)
• It affects approximately 5% of the population
at age 65, with a prevalence reaching 35% at
age 85.
13. Etiology of Alzheimer's disease
(Frontera)
• Still not clearly known
• However, pathologic agent of this disease is
amyloid plaques in the brain.
• Age is the most important risk factor.
• Other risk factors include a positive family history,
estrogen deficiency in postmenopausal women,
severe head trauma, and the presence of a
genetic factor called the Apo-E-4 allele.
• Screening for this gene is still controversial since
there are no clear disease prevention therapies.
14. Risk factors for AD
• Aging teh most important
age associated increases the amount of amyloid plaques
& NFT in the brain
• APOE genotype Apolipoprotein E (APOE) gene is the major
determinant of risk factor in families w LOAD
• Gender women>men estrogen deficiency in
menopause
• Hypercholesterolemia & vascular risk factors APOE
allele is related to abN cholesterol metabolism
• Head trauma
• Depression education & ethnicity
15. • In Alzheimer's patients functional limitations slowly
progress with time-memory loss through a continuum to a
vegetative status.
• In Parkinson's dementia functional limitation of the
motor disease progresses more rapidly.
• In multi-infarct dementia the tendency is for step-wise
progression, with cognitive and motor functioning losses
worsening after new brain injury, followed by periods of
stability.
Functional limitations depend on the stage of
diagnosis and the underlying cause of the dementia.
The cortical dementias are
mostly characterized, in early
stages, by memory problems.
The subcortical dementias
show motor findings early in
the clinical course.
Frontera
16. Symptoms
Often insidious, with memory loss the most common early
sign.
Px & families often allow these losses to continue for
extended periods before having problem assessed.
Memory symptoms inability to remember names,
appointments, or recent important family gatherings.
More important symptoms are wandering, especially
getting lost in familiar areas.
Occasionally, px will present w behavioral problems, such
as aggression & sexual disinhibition.
Frontera
17. Diagnosis
• D/of Alzheimer's dementia is one of exclusion.
• History taking is extremely important especially onset
of symptoms, disease progression, & to rule out focal
neurologic symptoms.
• Impairment of both short-& long-term memory in addition
to abN in at least one of areas of mental function
abstract thinking, judgment, language, praxis, visual
recognition, constructional abilities, or personality.
• These disturbances must be sufficiently severe to interfere
with work, social activities, or relationships with others.
These symptoms
present by definition for at least 6 months & w a clear
sensorium
Frontera
18. Physical Examination
• Usually no physical or neurologic findings
• Disorder is D/ by history & findings on MMSE.
• Occasionally px structured neuropsychologic tests including geriatric
depression scale, are necessary to rule out depression and ischemic disease.
• The following should be evaluated during the mental status examination
state of consciousness, orientation, memory (long & short term),
language, visuospatial functions, calculations, insight, judgment, mood, &
affect.
Frontera
Exam for all dementias similar to that of the workup of Alzheimer's dementia.
Significant findings between various dementing disorders will be based on neurologic
exam. Example :
- in Lewy body dementia tremor & rigidity are often present.
- In supranuclear palsy ocular findings with abN gaze may be present.
On neurologic examination focal findings such as unilateral weakness of a cranial
or peripheral nerve group, painful neuropathic changes, or paresthesias are especially
important to rule out cerebrovascular disease or tumors.
20. Algoritma sederhana DD/ demensia
Insidious onset w
smooth decline &
motor function
minimally impaired ?
YES
Alzheimer’
s dementia
NO
Abrupt onset or
fluctuating course, little
is any psychosis ?
History of stroke or
ischemic brain
injury on CAT scan or
MRI ?
Vascular
dementia
YES
NO
Marked fluctuation in
cognitive impairment ,
hallucinations
prominent, signs of
Parkinsons’s syndrome
evident, falls
YES
Lewy body disease
Cassel
21. Algoritma for the clinical diagnosis of Alzheimer’s disease
Suspect AD & develop treatment &
management plan w px & family
Are there other systemic or CNS conditions,
substance avuse problems, medication side
effects, delirium or depression that could
explain cognitive decline?
had a gradual & progressive decline in cognition?
show impairement in social or occupatioanl function that
represents a declline from his or her previous
deficit s in other cognitive areas, such as language,
executive functioning, etc?
memory impairement by history & supported by
impaired recall on MMSE or other cognitive tests?
Perform clinical evaluation
Px presents w memory concern
Conciser D/ of N aging,
nonanamnestic MCI, or depression
If isolated memory deficit, consider
D/ of single-domain amnetic MCI
If no functional impairement,
consider D/ of multidomain amnestic
MCI
Consider D/ of non-Alzheimer
dementia, depression, or delirium
Reevaluate cognition after
confounding treated
NO
NO
NO
NO
YES
YES
YES
YES
YES
NO
Hazzard
22. Original Criteria for Mild Cognitive
Impairement
Memory complaint, qualified by an informant
Memory impairment for age and education
Preserved general cognitive function
Intact social and occupational function
No demented
Hazzard
