DEMENTIA: Alzheimer’s Disease

and Vascular Dementia

Christian Kamallan
Neurologist
SKDI
“I am living with dementia,
not dying with dementia.”

ALZHEIMER'S DISEASE
 Inside the Human
Brain

Other Crucial Parts

• Hippocampus: where short-term memories are converted to long-term

memories
• Thalamus: receives sensory and limbic information and sends to
cerebral cortex
• Hypothalamus: monitors certain activities and controls body’s internal
clock
• Limbic system: controls emotions and instinctive behavior (includes the
hippocampus and parts of the cortex)

Slide 12
 Inside the Human Brain
The Brain in Action

Hearing Words Speaking Words Seeing Words Thinking about Words

Different mental activities take place in different parts of the

brain. Positron emission tomography (PET) scans can
measure this activity. Chemicals tagged with a tracer “light
up” activated regions shown in red and yellow.

Slide 13
 Inside the
Human Brain
Neurons

• The brain has billions of

neurons, each with an
axon and many
dendrites.
• To stay healthy, neurons
must communicate with
each other, carry out
metabolism, and repair
themselves.
• AD disrupts all three of
these essential jobs.

Slide 14
AD and the Brain
Plaques and Tangles: The Hallmarks of AD

The brains of people with AD have an abundance of two

abnormal structures:
• beta-amyloid plaques, which are dense deposits of
protein and cellular material that accumulate outside
and around nerve cells
• neurofibrillary tangles, which are twisted fibers that build
up inside the nerve cell

An actual AD plaque An actual AD tangle

Slide 16
 Cognitive Continuum
Normal

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

• Obtain appropriate treatment earlier

• Help the family to understand and accept

• Financial and legal plans while competent

• Enable the patient and family to make lifestyle choices

• Induce better adherence and management of other medical conditions

• Take appropriate steps to prevent injury (driving, weapons)

• Get greater access to help within the healthcare system and within communities

from Cummings, 2011

 Diagnosis
BASED ON CLINICAL JUDGMENT

Type of dementia can be defined enough

certainty through:
•Clinical patterns of dementing illness
•Doing appropriate dementia work-up
 Steps in Dementia Work-up
• History taking (Collateral source & patient)
• Physical examination
• Mental status examination
• Relevant laboratory and follow up
 Collateral Source
• Usually the spouse or an adult child.
• ...Observations by the collateral source
correlate better with dementia than self-
reported complaints which correlate more
with depression.
• Absence of collateral source seriously
compromises dementia diagnosis
 History Taking
Consists of
•Neurobehavioral history  dementia or not?
•General medical history
Possible underlying
•General neurological history etiology or
other condition
•Psychiatric history
associates
•Toxic, nutritional /drug history with dementia
•Familial history
 Neurobehavioral History Taking
Ask the collateral source

Specifically ask about changes : (ABC)

– Cognitive function: memory problems, orientation,
language, executive function, personality/apathy
– Change of behavior
– Degree of interference with ADL and IADL
Enquire about:
– first symptoms
– time of onset
– nature of illness
 Impairment in Memory
Symptoms:
•Repetitive questions or conversations,
•Misplacing personal belongings,
•Forgetting events or appointments,
•Getting lost on a familiar route
 Impairment in Language
• Involve speaking, reading, writing
• Difficulty thinking of common words while
speaking, hesitations; speech, spelling and
writing errors
 Impairment Visual spatial & abilities
Symptoms:
•Inability to recognize faces or common objects
or to find objects in direct view despite good
acuity
•Inability to operate simple implements or
orient clothing to the body.
 Dysexecutive function
Impaired reasoning and handling of complex
tasks, poor judgment – symptoms
•poor understanding of safety risks
•inability to manage finances
•poor decision-making ability
•inability to plan complex or sequential activities
Changes in personality / character
Impaired motivation, initiative
Symptoms:
•increasing apathy & loss of drive
•social withdrawal
•decreased interest in previous activities
 Behavioral and psychological
symptoms of dementia (BPSD)
Behavioural (observation)
•Physical aggression, screaming, restlessness,
agitation, wandering, culturally inappropriate or
sexual abberants behaviours

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

•Clock Drawing Test (CDT)..............................5 ‘

•Short Blessed Test (SBT)................................5-10’
•Abbreviated Mental Test ……………………..…… 5-10’
•Mini Mental State Examination (MMSE).......10-15’
•Montreal Cognitive Assessment (MoCA)...... 20-25’
 Psychometric Testing
• Are not by themselves diagnostic.
• Help in diagnosis by providing qualitative
assessment of mental function and the
pattern of involvement.
• Help in longitudinal assessment of
deterioration or improvement with treatment
 Laboratory Diagnostic Work-up
Basic: Ancillary:
•CBC • EEG
•FBS, liver and renal function • CSF analysis
tests • Serology for syphilis
• HIV testing
•Thyroid stimulating hormone
• Heavy metal screen
(TSH)
•Serum B12
 NEUROIMAGING

• 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

•Probable DLB: 1 or more core features +1 or

more suggestive features
•Possible : if 1 or more suggestive features
 Fronto-temporal dementia
Core diagnostic features
•A. Insidious onset and gradual progression
•B. Early decline in social interpersonal conduct
•C. Early impairment in regulation of personal
conduct
•D. Early emotional blunting
•E. Early loss of insight
 Fronto-temporal dementia
Supportive diagnostic features
A. Behavioral disorder
–1. Decline in personal hygiene and grooming
–2. Mental rigidity and inflexibility
–3. Distractibility and impersistence
–4. Hyperorality and dietary changes
–5. Perseverative and stereotyped behavior
–6. Utilization behavior
 Fronto-temporal dementia
B. Speech and language
1. Altered speech output
–a. A spontaneity and economy of speech
–b. Press of speech

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

A good teacher is a perpetual learner

 Potentially Reversible Dementia
1. Hypothyroidism
2. Pernicious anemia
3. Chronic Subdural Hematoma
4. CNS infections: TB, Cryptococcal, viral,
HIV, syphilis
5. Tumors
6. Normal pressure hydrocephalus
7. Drug intoxication
8. Heavy metal poisoning
 Features suggesting reversibility
• Shorter duration of illness
• Subcortical type of dementia
• Moderately severe disturbance
• Younger age of onset
• Prominent gait disturbance
• Urinary dysfunction
• Focal neurological signs
 Akin To Dementia …

• 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

• “Useful in quantitatively estimating the

severity of cognitive impairment”

• “Useful in serially documenting cognitive

change in serial ”
 Different cognitive domains tested
In seven categories:
•Orientation to time 5 points
•Orientation to place 5 points
•Registration of three words 3 points
•Attention and calculation 5 points
•Recall of three words 3 points
•Language 8 points
•Visual construction 1 point

Total 30 points
 MMSE
Cut-off Score

•24-30 no cognitive impairment

•18-23 mild cognitive impairment
•0-17 severe cognitive impairment
 MMSE
Good points of the MMSE
•Most widely accepted screening test
•Good internal consistency
•Good test-retest reliability
•High validity: good sensitivity and good
•specificity
•Correlates well with other screening tests e.g.
clock drawing test and Short Blessed test
 MMSE
Limitation

•Confounded by age, education and culture

 Clock Drawing Test (CDT)
•A sensitive measure of:
•Visuo-spatial function and constructional praxis.
•Higher ordered cognitive abilities like the
concept of time
Can help differentiate between a
constructional vs. conceptual problem
4-Point Scoring Method
(Nolan KA, Mohs RC, 1994)

•Draws closed circle 1 point

•Places numbers in correct positions 1 point
•Includes all 12 correct numbers 1 point
•Places hands in correct position 1 point
 CDT: Examples
Patients were instructed to draw in the hands at
twenty minutes after eight

•Figure A: by a normal elderly control

•Figure B-E: patients with dementia
 Interpretation: Clinical judgment
• A low score (≤ 3) indicates the need for
further evaluation to source out other
evidences of impairment or correlation with
other tests
 The role of medications in the
management of dementia
1. Cure disease
2. Prevent disease or delay onset
3. Slow progression of disease
4. Treat primary symptoms eg memory
5. Treat secondary symptoms eg
depression, hallucinations
 Medications to treat primary
symptoms

• 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.

Experts encourage caregivers to try non-medical coping

strategies first. However, medical treatment is often available if
the behavior has become too difficult to handle. Researchers
continue to look at both non-medical and medical ways to help
caregivers.
Management of Alzheimer’s Disease

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

Tampi et al. Clinical Geriatrics. 2011;19:41-46.

Managing BPSD

• 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