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ALZHEIMER'S DISEASE
Inside the Human
Brain
Slide 12
Inside the Human Brain
The Brain in Action
Slide 13
Inside the
Human Brain
Neurons
Slide 14
AD and the Brain
Plaques and Tangles: The Hallmarks of AD
Mild Cognitive
Impairment
Dementia
“Man fools himself.
He prays for a long life,
yet he fears an old age.”
Chinese Proverb
Dementia cases
double every 20 years
Mild cognitive impairment
Probable AD
Function
Definite AD
Age
Mild cognitive
impairment Alzheimer’s disease
Amnestic
Mild cognitive
impairment Alzheimer’s disease
Multiple domains ? normal aging
slightly impaired
Frontotemporal dementia
Mild cognitive
Lewy body dementia
impairment
Primary progressive aphasia
Single non-
memory domain Parkinson’s disease
Alzheimer’s disease
Mild Cognitive Impairment(MCI)
Criteria:
• Memory complaint
• Normal general cognitive function
• Normal activities of daily living
• Memory impaired for age
• Not demented
VIDEO
Definition Dementia
•A decline of intellectual function in comparison
with patient’s previous level of function.
•Severe enough to cause impairment of social
and professional activities
•Reflected on decline on ADL and IADL
•Usually associates with behavior changes.
Area involves in dementia
ADL
BEHAVIOR
FUNCTION
COGNITION
1) To be earlier: potential benefits
• Get greater access to help within the healthcare system and within communities
Psychosocial (interview)
•Disinhibition, hoarding, cursing and shadowing
•Anxiety, depression, hallucination and
delusions.
Physical Examination
• General physical examination
• Neurological Examination:
– Increased ICP
– Focal Neurological deficit:
• Gait, motor & sensory deficit
• Abnormal muscle tone & movement and
primitive reflexes
Cognitive Screening Test
• Considering of practicality
• A brief screening test for cognitive
impairment that can be performed in 10
minutes or less is easier incorporated into
daily practice than a comprehensive but time
consuming
Brief & Objective Screening Tests
Patient examination
• Structural MRI
– Hippocampus
– Entorhinal cortex
• Functional Imaging
– MRS
– fMRI
– PET/SPECT
Diagnosis of AD
DSM-IV; APA, 1994:
•Gradual onset & progressive decline in:
– Memory + at least one of the:
– 3 A (Aphasia, Apraxia, Agnosia )
– Dysexecutive functioning
•Impairment in social and professional activities, can’t
be explained by any other neurological, psychiatric,
systemic or substance-induced or only occur in
delirium.
Triggers of Non-AD Diagnosis
• Onset < 60 y.o; sudden onset, cognition
fluctuation, rapid progression
• Neurologic abnormalities early in course e.g.
involuntary movement, focal deficits, gait
disturbance, ataxia, seizures
• BPSD early in course: visual hallucination,
disinhibition, marked apathy, social conduct
• Neuropsychological profile early in course:
prominent aphasia, marked deficit in
attention, executive function, visual agnosia
Common Differential Diagnosis
• DLB (Dementia Lewy Body)
• PDD (Parkinson Disease Dementia)
• FTLD (Fronto-Temporal Lobe Dementia)
• VaD (Vascular Dementia)
• Others
DLB Clinical Diagnosis
(Revised criteria III 2005)
• Dementia with prominent deficits in attention,
executive function, and visuospatial ability.
• Core features (two core features: probable
DLB; one for possible DLB):
– Fluctuating cognition with pronounced variations
in attention and alertness
– Recurrent of well formed and detailed visual
hallucinations
– Spontaneous features of parkinsonism
Clinical Diagnosis
(Revised criteria III 2005)
•Suggestive features
– REM sleep behavior disorder
– Severe neuroleptic sensitivity
– Low dopamine transporter uptake in basal ganglia
demonstrated by SPECT or PET imaging
2. Stereotypy of speech
3. Echolalia
4. Perseveration
5. Mutism
Fronto-temporal dementia
C. Physical signs
•1. Primitive reflexes
•2. Incontinence
•3. Akinesia, rigidity, and tremor
•4. Low and labile blood pressure
Fronto-temporal dementia
Dementia with:
•Behavioral disturbances & affective symptoms
•Speech disorders
•Physical signs of primitive reflexes
•Incontinence
•Akinesia and rigidity
Vascular dementia
Dementia with:
•Evident of cerebrovascular disease
•A clear temporal relationship between
dementia and cerebrovascular disease
VaD
Hachinski Ischaemic Score
• A brief clinical tool helpful in the “bedside”
differentiation of the commonest dementia
types, Dementia of Alzheimer’s Type (AD) and
Vascular Dementia (VaD)
• A cut-off score ≤ 4 for AD and ≥ 7 for VaD has
a sensitivity of 89% and a specificity of 89%
(Moroney 1997)
6/27/2019
Hachinski Ischaemic Score
Item No. Description Value
1 Abrupt onset 2
2 Stepwise deterioration 1
3 Fluctuating course 2
4 Nocturnal confusion 1
5 Preservation of personality 1
6 Depression 1
7 Somatic complaints 1
8 Emotional incontinence 1
9 History of hypertension 1
10 History of stroke 2
11 Associated atherosclerosis 1
12 Focal neurological symptoms 2
13 Focal neurological signs 2
6/27/2019
AD Vs VaD
AD VaD
Neuro transmitter defect Hemodynamic defect
Female predominance Male predominance
Gradual onset Abrupt onset
Steady deterioration Stepwise deterioration,
fluctuating course
BP normal Hypertension
No history of stroke History of stroke
Global decline in cognitive Focal neurological symptoms
function and signs
Unlikely to respond to May respond to a drug which
treatment modifies microcirculation and
enhance cerebral tissue
perfusion
• Delirium
– Acute onset
– Fluctuating course
– Autonomic disturbances
– Precipitating factors like infection, metabolic and
drugs
MMSE
• Screening test to provide brief, objective
measure of cognitive function
• Administered in 10-15 minutes, scores range
from 0 to 30
Total 30 points
MMSE
Cut-off Score
• cholinesterase inhibitors:
– donepezil
– rivastigmine
– galantamine
• memantine
Cholinesterase inhibitors
• these drugs stop the breakdown of
acetylcholine which is an important
neurotransmitter in memory and cognition
• all show modest improvement in cognition
and function, and behavioural symptoms
• response: 1/3 improve, 1/3 stabilise, 1/3
have no response
• do not prevent progression of underlying
disease
Cholinesterase inhibitors
• donepezil (Aricept)
– given once daily, dosage of 5mg to 10mg
• rivastigmine (Exelon)
– given twice daily, dosages of 3mg to 12mg
• galantamine (Reminyl)
– given once daily, dosages of 8mg to 24mg (can
also be given twice daily)
Use of cholinesterase inhibitors
• need specialist diagnosis of Alzheimers
Disease, and a MMSE score of 10 to 24.
• need to show an improvement on MMSE of
2 points to continue medication on PBS
• side effects - nausea, vomiting, diarrhoea,
dizziness, headache, muscle cramps
• use carefully if gastric ulcer, heart disease,
chronic lung disease present
Use of cholinesterase inhibitors
• warn against unrealistic expectations
• watch for return of insight leading to
depression or anxiety
• stopping of medication:
– unacceptable side effects
– lack of response to medication
– late stages of the disease
Memantine (Ebixa)
• glutamate is a transmitter in the brain that
is affected by Alzheimers Disease
• memantine blocks the pathological effects
of abnormal glutamate release, and allows
better function of the impaired brain
• indicated for moderate to severe AD
• trials show slowing in cognitive and
functional decline and decrease in agitation
in treated group compared to placebo
Memantine
• can use with other AD medications
• side effects - headaches, dizziness
• do not use in kidney disease or seizure
disorders
• dosage: start with 5mg daily and increase
to10mg twice daily
• private script - not on the PBS
• costs approx $160/month
Medications to treat secondary
symptoms
• many people with dementia develop
symptoms such as agitation, aggression,
depression, delusions, hallucinations, sleep
disturbance and wandering
VIDEO
• antidepressants:
– specific serotonin reuptake inhibitors
(citalopram, sertraline)
Medications to treat secondary
symptoms
• antipsychotics:
– typical antipsychotics (haloperidol)
– atypical antipsychotics (risperidone)
– modest effect on symptoms
– watch for side-effects
• mood stabilisers:
– anticonvulsants (carbemazepine)
Causes?
Several competing hypotheses:
Cholinergic hypothesis
-Caused by reduced synthesis of acetylcholine
-Destruction of these neurons causes disruptions in
distant neuronal networks (perception, memory,
judgment)
Amyloid hypothesis
-Abnormal breakdown; buildup of amyloid beta
deposits
-Damaged amyloid proteins build to toxic levels,
causing call damage and death
Tau hypothesis
-Caused by tau protein abnormalities
-Formation of neurofibrillary tangles
Risk Factors
• Obesity
• High blood pressure
• Head trauma
• High cholesterol
• Being American!
– Higher rates in
• Japanese-Americans than Japanese
• African-Americans than Africans
• Depression
• Lower rates in highly educated
– Beneficial consequences of learning and
memory
Possible Protective Factors
• Education
The ability of the brain to change suggests to some that
staying mentally active as you age may help to maintain
healthy brain synapses. A 2002 study reported an
association between frequent participation in cognitively
stimulating activities (such as reading, doing crossword
puzzles, visiting museums) and a reduced risk for
Alzheimer's.
• Exercise
Lowers risk of high blood pressure and other risk factors
associated with Alzheimer’s
• Alcohol Consumption
Men who consume one to three drinks of alcohol per day cut
their risk of developing the disease by nearly half. Among
women, however, the risk was reduced by only 4%. The type
of alcohol had no effect on the results. But further study is
needed. In the meantime, experts do not recommend
drinking alcohol to fend off Alzheimer's disease.
AD Research: Managing Symptoms
Between 70 to 90% of people with AD eventually develop
behavioral symptoms, including sleeplessness, wandering
and pacing, aggression, agitation, anger, depression, and
hallucinations and delusions. Experts suggest these general
coping strategies for managing difficult behaviors:
• Stay calm and be understanding.
• Be patient and flexible. Don’t argue or try to convince.
• Acknowledge requests and respond to them.
• Try not to take behaviors personally. Remember: it’s
the disease talking, not your loved one.
Manage
cognitive
symptoms
Increased
Manage BPSD quality of
life for
patient and
family
Support
patient/family
Pharmacologic Options for AD
• Cognitive enhancers
─ 2 classes
• Cholinesterase inhibitors (ChEIs)
• NMDA-receptor antagonist
─ Do not cure the disease or reverse cognitive
impairment
─ Can improve cognition and functional ability
─ Reduce the rate of decline 9-12 months (ChEIs)
─ Delay in nursing home placement was 17-21
months (ChEIs)
Behavioral and Psychological
Symptoms of Dementia (BPSD)
• Apathy • Disinhibition
• Depressive symptoms • Euphoria
• Anxiety • Loss of appetite
• Agitation/irritability/ • Sleep disturbances
aggression
• Stereotyped
• Psychotic symptoms behaviors (eg,
─ Delusions pacing, wandering,
─ Hallucinations rummaging, picking
• Identify triggers
─ Observe symptom timing and frequency
─ Look for environmental triggers, eg noise, lighting
─ Investigate potentially treatable causes, eg pain
• Make adjustments
─ Address medical causes
─ Adapt environment
─ Adapt caregiving
• Modify as needed
Managing BPSD
Nonpharmacological Interventions
• Use the “3 Rs”—repeat, reassure, redirect
• Simplify the environment, task, routine
• Anticipate unmet needs
• Allow adequate rest between stimulating
events
• Use cues
• Encourage physical activity
• Other interventions
• PROVIDE A CALM,QUIET ENVIRONMENT
TO MUCH STIMULATION CAN CAUSE A CATASTROPHIC
REACTION
• PROVIDE A CONSISTENT ROUTINE
PERFORM ADLs AT SAME TIME EACH DAY
AVOID CHANGES IN ROUTINE OR ENVIRONMENT
• REASSURE AND EXPLAIN FREQUENTLY
DO NOT ARGUE WITH THE PATIENT
• PROTECT SAFETY
PATIENT AT INCREASED RISK OF ACCIDENTS
• ELIMINATE CAFFEINE FROM THE DIET
• PROVIDE ACTIVITIES TO DISTRACT THE PATIENT FROM INAPPROPRIATE
BEHAVIOR
• MAINTAIN A REGULAR ROUTINE
• USE PATIENCE AND UNDERSTANDING
• MAINTAIN A CALM, QUIET ENVIRONMENT
• USE SIMPLE, CLEAR WORDS AND SENTENCES
• GIVE FREQUENT PRAISE AND REASSURANCE
• USE TOUCH AND OTHER FORMS OF NONVERBAL COMMUNICATION
• USE REALITY ORIENTATION
Conclusion
• Early diagnosis enables prompt and
effective management, yields better quality
of life for patients and caregiver
• Neuroimaging especially MRI scan is
widely used in clinical setting now.
• Biomarker especially CSF study has been
included in research diagnostic criteria, but
not yet recommended for general clinical
use, further validation is eagerly awaited
Conclusion
• The core of all assessment in dementia care
is careful enquiry and attentive listening,
and
• There is no substitute for a clinical
interview by a trained clinician
• By doing appropriate work-up and
recognizing the clinical pattern, most of the
cause of dementia especially Alzheimer’s
disease dementia can be determined on
enough certainty