DEMENTIA: Alzheimers

Disease and Vascular

Dementia
Christian Kamallan
Neurologist

SKD
I

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
Multiple domains
slightly impaired

Mild cognitive
impairment
Single nonmemory domain

Alzheimers disease
? normal aging

Frontotemporal dementia
Lewy body dementia
Primary progressive aphasia

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
FUNCTI
ON

BEHAVI
OR

COGNITI
ON

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 Workup

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
with dementia
history
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 .. 510
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:
CBC
FBS, liver and renal
function tests
Thyroid stimulating
hormone (TSH)
Serum B12

Ancillary:
EEG
CSF analysis
Serology for
syphilis
HIV testing
Heavy metal
screen

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.
3.
4.
5.

Stereotypy of speech
Echolalia
Perseveration
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)
12/30/15

Hachinski Ischaemic Score

Item No.

12/30/15

Description

Value

Abrupt onset

2
3

Stepwise deterioration
Fluctuating course

1
2

4
5
6

Nocturnal confusion
Preservation of personality
Depression

1
1
1

7
8

Somatic complaints
Emotional incontinence

1
1

9
10

History of hypertension
History of stroke

1
2

11
12

Associated atherosclerosis
Focal neurological symptoms

1
2

13

Focal neurological signs

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

function

Focal neurological symptoms

and signs

Unlikely to respond to
treatment

May respond to a drug which

modifies microcirculation and
enhance cerebral tissue
perfusion

A good teacher is a perpetual learner

Potentially Reversible
Dementia
1.
2.
3.
4.
5.
6.
7.
8.

Hypothyroidism
Pernicious anemia
Chronic Subdural Hematoma
CNS infections: TB, Cryptococcal, viral,
HIV, syphilis
Tumors
Normal pressure hydrocephalus
Drug intoxication
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
antidepressants:
specific serotonin reuptake inhibitors
(citalopram, sertraline)

VIDEO

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

Manage BPSD

Support
patient/family

Increased
quality of
life for
patient and
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
Depressive symptoms
Anxiety
Agitation/irritability/
aggression
Psychotic symptoms
Delusions
Hallucinations

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

Disinhibition
Euphoria
Loss of appetite
Sleep disturbances
Stereotyped
behaviors (eg,
pacing, wandering,
rummaging, picking

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
REACTION

CATASTROPHIC

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