DEMENTIA

EUFEMIO E. SOBREVEGA, MD
FELLOW, PHIL. NEUROLOGICAL ASSOCIATION
FELLOW, PHIL. PSYCHIATRIC ASSOCIATION

APPROACH TO PATIENTS COMPLAINING OF

FORGETFULLNESS
Primary Care Visit

Diagnosis

Evaluation

Treatment

PRIMARY CARE VISIT

Patient complains of
worsening of cognitive functioning
or caregiver/clinician notices
cognitive impairment in the patient.

suggestive of

DEMENTIA?

APPROACH TO PATIENTS COMPLAINING OF

FORGETFULLNESS
Primary Care Visit

Diagnosis

Evaluation

Treatment

DIAGNOSIS
CONFIRM DEMENTIA:

CLINICAL ASSESSMENT
INTERVIEW WITH CAREGIVER/PATIENT
NEUROPSYCHOLOGICAL EXAMS
ANCILLARY PROCEDURES

DIAGNOSIS Diagnostic Tests

Exclude treatable causes which may be
dementia:

- BLOOD CHEMISTRIES
- CT SCAN
- MRI
- CSF EXAM

contributing to the

DIAGNOSIS - Exclusion

A.

Potentially treatable causes of dementia

Infections
- MENINGITIS

- HIV encephalitis
- Neurosyphilis
- Creutzfeldt-Jakob Disease

DIAGNOSIS - Exclusion
B.

Metabolic and Toxic

- Alcoholism
- Hypothyroidism
- Hepatic or renal failure
- Psychoactive medications
- Vitamin B12 or folate deficiency

DIAGNOSIS - Exclusion
C.

Neoplastic
- Brain tumors
- Carcinomatosis
Others:
- Subdural Hematoma
- Normal pressure hydrocephalus

DIAGNOSIS
General Cognitive Screening Tests

1.
2.

Mini-Mental State Examination

Clock drawing test

MINI MENTAL STATE

EXAMINATION

MINI MENTAL STATE EXAMINATION

ORIENTATION

TIME
PLACE

5PTS
5PTS

REGISTRATION
3PTS
ATTENTION AND CALCULATION 5PTS
RECALL
3PTS
LANGUAGE

NAMING
REPETITION
3 STAGE COMMAND
READING
WRITING
COPYING

TOTAL = 30PTS

2PTS
1PT
3PTS
1PT
1PT
1PT

A.1. Orientation
What is the
Year?
Season?
Date?
Day?
Month?

Points
1

Score
1
1

1
1
1
TOTAL = 5PTS

1
1
1
1

A.2. Orientation
Where are we?
Province?
Country?
Town or City?
Hospital?
Floor?

Points
1
1
1
1

Score
1
1
1
1

1
TOTAL=5PTS

B. Registration (Total points = 3)

Name three (3) objects, taking one second
to say each (e.g.
apple, table, coin).
Then ask the patient all three (3) after
you have said them.
Repeat the answers until the patient learns
trials

Give one point for each correct answer

three(3), up to 6

C. Attention and Calculation

(Total points = 5)
Serial sevens. Instruct patient to subtract 7
from 100 in increments.
Stop after 5
answers. Alternate: Spell WORLD
backwards (e.g.
DLROW = 5, DLRW = 4, DLW = 3, OW = 2, DRLWO = 1 )
Give one(1) point for each correct answer or

number of letter.

D. Recall (Total points =3)

Ask for names of three (3) objects

learned in section B
( e.g. apple, table, coin).

Give 1 point for each correct answer.

E. 1. Language Naming
(Total points = 2)

Point to a pencil and a watch.

Have the patient name the

as you point.

object

E. 2. Language Repetition
(Total point = 1)
Ask the patient to repeat the phrase,
No ifs, ands or buts after you.

E.3. Language 3 Stage Command

(Total points = 3)

Have the patient follow a 3-stage

command:

1. Take the paper in your right hand

2. Fold the paper in half
3. Put the paper on the floor

E.4. Language Reading

(Total point = 1)
Have the patient read and obey the following: (1 point)

CLOSE YOUR EYES

(Write it in LARGE LETTERS)

E. 5. Language Writing
(Total point = 1)
Have the patient write a sentence of his or
point)

her own choice. (1

(The sentence should contain a subject

and a verb and should
make sense.
Ignore spelling errors when scoring)

E.6. Language - Copying

(total point = 1)
Have the patient copy the figure below. (Give one (1)point if all sides
and angles are preserved and if the intersecting sides form a
quadrangle)

SCORES
Maximum Total Score is 30
Total Score ____
Suggested guidelines for determining the severity
of cognitive impairment
Mild:
MMSE > 21
Moderate:MMSE 10 -- 20
Severe: MMSE < 9
Expected decline in MMSE scores in untreated
mild to moderate Alzheimers patient is 2 to 4
points per year.

APPROACH TO PATIENTS COMPLAINING OF

FORGETFULLNESS
Primary Care Visit

Diagnosis

Evaluation

Treatment

EVALUATION

COMMON CAUSES OF DEMENTIA

1.5%
Medications

19.3% Others

56.8% AD
13.3%
Multi-inflarct
dementia

ALZHEIMERS DISEASE

EVALUATION

ALZHEIMER,S DISEASE

Alzheimers disease
Alzheimers disease (AD) is the most
frequent
cause of
dementia
it represents more than half of all dementia
cases.
AD is most likely to occur in people aged over 6570 years of age (lateonset),
although it can occur earlier (early- onset).

Alzheimers disease
Alzheimers disease (AD) develops slowly over a period of years.
progression of early-onset AD is more

rapid.

AD is associated with general impairment of higher cortical functions.

EVALUATION

Alzheimers disease (AD)

-diagnosis should only be made after

other causes of
dementia have been excluded by lab test, physical and
neurological exams and patient history.

DSM- IV DEFINITION OF DEMENTIA OF

ALZHEIMERS TYPE
MEMORY LOSS
IMPAIRMENT IN AT LEAST 1 OTHER COGNITIVE
DOMAIN
GRADUAL ONSET AND SLOWLY PROGRESSIVE
NOT DELIRIOUS
DISABLING
NO ALTERNATE EXPLANATION

DSM-IV DEFINITION OF DEMENTIA OF

ALZHEIMERS TYPE
MEMORY LOSS:
* INABILITY TO LEARN NEW MATERIAL ;
POOR REMOTE RECALL
IMPAIRMENT IN AT LEAST 1 OTHER COGNITIVE
DOMAIN:
* APHASIA (LANGUAGE)
*
APRAXIA (MOTOR ACTS, VISUOSPATIAL)
* AGNOSIA
(VISUAL RECOGNITION)
* DISTURBED
EXECUTIVE FUNCTION
(PLANNING, ETC.)

MEMORY and the FORGOTTEN SELF

SYSTEMATIC RETROGRADE AMNESIA:
CANNOT LEARN NEW INFORMATION.
RECALL MOST RECENT
INFORMATION.

* CANNOT
LEARNED

PROGRESSIVE RETROGRADE AMNESIA: * ERASING

THE LINE OF LIFE FROM
NEAREST TO OLDEST.
* LOSS OF SEMANTIC (FACTUAL) AND
EPISODIC (PERSONAL) MEMORY.

CRITERIA FOR DIAGNOSIS OF ALZHEIMERS

DISEASE
PROBABLE ALZHEIMERS DISEASE:
* DEMENTIA BY DSM-IV AND MMSE
* PROGRESSIVE MEMORY IMPAIRMENT
* NO DISTURBANCE IN
CONCIOUSNESS
* BETWEEN 40 AND 90 AGE OF ONSET
* ABSENCE OF SYSTEMIC
BRAIN DISEASE;
SUPPORTED BY FAMILY
HISTORY;
CEREBRAL ATROPHY BY CT SCAN.

CRITERIA FOR THE DIAGNOSIS OF

ALZHEIMERS DISEASE
DEFINITE ALZHEIMERS DISEASE:
* CLINICAL

CRITERIA FOR
PROBABLE
ALZHEIMERS D.
*
HISTOPATHOLOGIC EVIDENCE
(AUTOPSY OR BIOPSY)
NINCDS-ADRDA

Neuropathological changes
characteristic of AD
Normal

AD

AP

AP = amyloid plaques
NFT = neurofibrillary tangles

NFT

Courtesy of George Grossberg, St Louis University, USA

Hippocampus
Amygdala

Entorhinal region and

the nucleus basalis of
Meynert

Near regions
of cortex

Hippocampus

DISEASE PROGRESION

frontal
Lobe

Parietal
Lobe

Neuritic
plaque

Neuron

The neuron
eventually dies

Paired
helical
filament

NTFs
Abnormal
Tau protein
Microtubules

Phosphate
accumulation on
tau protein leads to
development of
paired helical
filaments

2 Paired helical
filaments
accumulate in
neuron

4 Abnormal tau protein

These develop into NTFs, w/c

build up in the neuron, disrupting
function

and paired helical

filaments also promote
development of
neuritic plaques

Structural Changes in Alzheimers D. Brain

Neuron Loss
Large Cortical Neurons
Amygdala
Hippocampus
Entorhinal cortex
Basal forebrain cholinergic
nuclie
Locus ceruleus
Dorsal raphe neurons

Structural Alterations
Neuritic plaques
Neurofibrillary tangles
Amyloid deposition
Inflammation
Neuropil threads

Two Important Histological Markers

Neurofibrillary Tangles

Neuritic Plaques
Amyloid Precursor
Protein(APP)

Extracellular deposit

6-10nm fibrils

Derived from Tau protein

A 1-42

Microtubule associated protein

(MAP)
Collection of paired helical
filaments (intracellular)

Neuritic
Plaques

Neuronal
Dysfunction and
Synapse Loss

Acetylcholine and
Other
Neurotransmitter
Deficiencies

Clinical
Symptoms

Neurofibrillary
Tangles

Peter Whitehouse, MD 1997

Amyloid cascade

Histologic changes

Biochemical deficits

Dementia syndrome

Jeffrey L. Cummings, MD

Amyloid
Cascade

Regional
Cell Loss

Reticulofrontal

Delirium

Frontal
and
Temporal
Psychosis

Agitation

Regional
Cholinergic
Deficiency

Orbitofrontal

Medial
Frontal

Disinhibition

Apathy

OTHER DEGENERATIVE DEMENTIAS

PICK DISEASE
RARE TYPE OF DEMENTIA CHARACTERIZED BY SELECTIVE ATROPHY OF THE FRONTAL
AND TEMPORAL LOBES OF THE BRAIN

DEMENTIA WITH LEWY BODIES

DEMENTIA IN THE ELDERLY
Presence of Lewy bodies in the neurons of the brainstem and cerebral cortex

OTHER DEGENERATIVE DEMENTIAS

HUNTINGTONS DISEASE (CHOREA)
HEREDITARY DEGENERATIVE DISEASE (AUTOSOMAL DOMINANT) CHARACTERIZED BY:

COGNITIVE DISTURBANCES,
SLOWLY PROGRESSIVE DEMENTIA,
EXTRAPYRAMIDAL MOTOR SYPTOMS OF CHOREA,
RIGIDITY, BRADYKINESIA

APPROACH TO PATIENTS COMPLAINING OF

FORGETFULLNESS
Primary Care Visit

Diagnosis

Evaluation

Treatment

TREATMENT
Non-pharmacological
Pharmacotherapy
Non-cognitive symptoms

TREATMENT

Non-pharmacological
- Patient, caregiver and healthcare workers
education

- Caregiver support
- Patient psychosocial treatment

Pharmacological Treatment of AD
Practice Recommendations:(AAN 2001)
should be
in mild to moderate
(standard).

Cholinesterase inhibitors

considered
AD patients

(1000 IU po bid) should be

considered
in an attempt to slow
progression of AD
(guideline).

Vitamin E

Treatment - Pharmacotherapy
A.

B.

Mild to moderate AD
- Cholinesterase inhibitors
(e.g. Rivastigmine, Donepezil and
Moderate to severe AD
- NMDA receptors
( e.g. Memantine)

Galantamine)

Treatment: Pharmacotherapy

A.

Cognitive Symptoms
Cholinesterase Inhibitors
- considered for mild to moderate AD
Mechanism of Action:
*all inhibit cholinesterase in the synaptic
cleft thereby
enhancing central
cholinergic function.
(e.g. Rivastigmine, Donezepil,
Galantamine)

Treatment: Pharmacotherapy
A. Cholinesterase Inhibitors
1.

Rivastigmine (exelon):

- inhibits both acetylcholinesterase and

butyrylcholinesterase.
- initial dose: 1.5 mg PO BID; may increase
3 mg PO BID after > if tolerated.
- may increase dose by 1.5 mg/dose every
weeks as tolerated.
- maximum dose: 12 mg/day

to
2

Treatment: Pharmacotherapy
A.

Cholinesterase Inhibitors

2. Donepezil (aricept):
- inhibits acetylcholinesterase but not
butyrylcholinesterase which may be
component of neuritic plaques and
tangles.
- initial dose: 5mg PO once daily at HS;
may increase to 10 mg PO OD at HS
4-6 weeks, if tolerated.
- maximum dose: 10mg/day

after

Treatment: Pharmacotherapy
A.
2.

Cholinesterase Inhibitors
Galantamine (reminyl):

- inhibits acetylcholinesterase and provides

allosteric modulation of nicotinic
receptors which may have a diseasemodifying benefit.
- initial dose: 4mg PO BID X 4 weeks; if
tolerated, increase to 8 mg PO BID X
> or
equal to 4 weeks; if still
tolerated,
increase to 12 mg PO BID.

Treatment: Pharmacotherapy
B. NMDA receptor antagonist
1. Memantine (abixa):
- considered in patients with moderatesevere AD.
ACTIONS:
- low to moderate affinity, uncompetitive
N-methyl-D-aspartate receptor
antagonist that block the pathological
but
not physiological activation of NMDA
receptor.

Treatment: Pharmacotherapy
Memantine

DOSAGE:-

* 1st week > 5 mg PO OD

* 2nd week > 5 mg PO BID
* 3rd week > 10 mg PO am and 5 mg
PO in the evening
* 4th week & thereafter > 10 mg PO BID

Treatment: Pharmacotherapy
Memantine

EFFECTS:
- to decrease the decline cognition and daily
functioning in patients with moderate to severe
AD.
- combination with cholinesterase inhibitors has
been shown to be safe and effective with
cholinesterase
inhibitor alone.

Treatment: Pharmacotherapy

Vitamin E
- considered in AD patients to slow disease
progression.
ACTION:
- antioxidant; it slows nerve cell damage.
EFFECT:
- decrease the rate of functional decline of AD
patients.
- few drug interactions or side effects.

TREATMENT
Non-cognitive symptoms

- Antipsychotics
- Benzodiazepines
- Antidepressants

Treatment
Non-cognitive symptoms

Rationale:
To minimize psychotic symptoms
(paranoia, hallucinations )or
independent symptoms (e.g.
screaming, violence).
To help to increase comfort and
safety of patients and families.

Treatment :Non-cognitive symptoms

for psychosis and agitation

Principles in Tx:
-Intervention used should be directed
by the level of anguish experienced by
the patient and risk to caregivers and
patient.
-Violent behavior needs to be treated
with pharmacotherapy.

Treatment :Non-cognitive symptoms

For psychosis and agitation
Principles in Tx:

Agitation needs to be investigated

further to reveal underlying causes.
If agitation continues repeatedly,
psychosocial measure should be the
1st line therapy.

Treatment :Non-cognitive symptoms

For psychosis and agitation
Principles in Tx:

If psychosocial measures are

unsuccessful or if agitation is thought
to be dangerous to patient/caregiver
then pharmacotherapy is warranted.

Treatment :Non-cognitive symptoms

For psychosis and agitation
1. ANTIPSYCHOTICS
- 2nd line therapy to control
agitation in
demented patients.
- ATYPICAL agents are BETTER
antipsychotics.

psychosis or

tolerated than typical

Treatment :Non-cognitive symptoms

For psychosis and agitation

1. Antipsychotics
- choice of agent is based on the
side effect profile that is most
suited to the patient.
- administered in the evening to help
sleep and treat sundowning
effect.

Treatment :Non-cognitive symptoms For

psychosis and agitation

1. Antipsychotics
- oral route is preferred
- start with low doses; increase dose
carefully and cautiously.
* elderly are more sensitive to the side effects of
antipsychotic.

Treatment :Non-cognitive symptoms For

psychosis and agitation

Atypical or Novel Anti-psychotics

*Olanzapine (Zyprexa)
*Quetiapine (Seroquel)
*Clozapine (Leponex)
*Risperidone (Risperdal)
*Aripiprazole (Abilify)

Treatment :Non-cognitive symptoms For

anxiety and agitation
2. Benzodiazepines
- for agitation, where anxiety is a prominent
- useful as start doses for occasional
sedation is needed.
- risk of disinhibition, over sedation falls or

feature.
agitation or when
delirium.

Treatment :Non-cognitive symptoms For

anxiety and agitation
2. Benzodiazepines
- start with low doses; increase dose
cautiously.
- short acting agents that do not require
activation are
preferred.
- elderly are more sensitive to the side
benzodiazepines.

carefully and
metabolism for

effects of

Treatment :Non-cognitive symptoms

for depression and apathy
3. Tricyclic antidepressants (TCA), MAOIs and SSRI
- may be used to treat depression
- SSRI are preferred agents
- occasionally cognitive deficits, may
recover partially or
fully ( in pseudodementia) with treatment of
depression.

Treatment :Non-cognitive symptoms

for depression and apathy
1. Tricyclic antidepressants (TCA), MAOIs and SSRI
- choice of agents depends on drug interactions, side effects and desired
action:
a. TCAs have significant CVS side effects
and anticholinergic
properties.
b. SSRI have better side effect profile
c. Dietary restrictions (high tyramine food),
drug interactions and
side effects
tend to limit the usefulness of MAOIs.

Treatment :Non-cognitive symptoms

for depression and apathy

Tricyclic antidepressants (TCA), MAOIs and

SSRI
- Start with low doses; increase dose
carefully and cautiously.
- elderly are more sensitive to the
side effects of antidepressants.

1.

Treatment :Non-cognitive symptoms

for depression and apathy

Selective Serotonin Re-uptake Inhibitors

*Fluoxetine (Prozac)
*Sertralline (Zoloft)
*Citalopram (Lupram)
*Paroxetine (Seroxat)

Treatment :Non-cognitive symptoms

for depression and apathy

Selective Norepinephrine Serotonin

Reuptake Inhibitor
* Duloxetine (Cymbalta)
* Venlafaxine (Efexor)

Treatment :Non-cognitive symptoms

for depression and apathy

Tricyclics
*Imipramine (Tofranil)
*Maprotilline (Ludiomil)
*Dothiapine (Prothiadine)

Treatment :Non-cognitive symptoms

for depression and apathy

Reversible MAO-Inhibitor A
*Meclobemide (Aurorix)
Other Antidepressants
*Tianeptine (Amineptine)
*Mirtazapine (Remeron)
*Trazodone (Depresil)

Long Term Goals Of Alzheimers

Disease Management
Monitor treatment of cognitive symptoms.
Detect and treat non-cognitive symptoms.
Balance supervision with meaningful activity.
Educate and advise regarding prognosis and transitions.

APPROACH TO PATIENTS COMPLAINING OF

FORGETFULLNESS
Primary Care Visit

Diagnosis

Evaluation

Treatment