DEMENTIA: Alzheimers 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 bodys 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 Alzheimers disease
Amnestic

Mild cognitive
impairment Alzheimers disease
Multiple domains ? normal aging
slightly impaired

Frontotemporal dementia
Mild cognitive
Lewy body dementia
impairment
Primary progressive aphasia
Single non-
memory domain Parkinsons disease
Alzheimers 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 patients 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, cant
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 Alzheimers 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)

8/28/2017
 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

8/28/2017
 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 Alzheimers
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. Dont argue or try to convince.
Acknowledge requests and respond to them.
Try not to take behaviors personally. Remember: its
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 Alzheimers 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 Rsrepeat, 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 Alzheimers
disease dementia can be determined on
enough certainty