Dementia

DEMENTIA AND HOW THE
DEMENTIC PATIENTS’ ARE?
Chairperson - Prof M A Hayee
Presenter - Dr. Khurshida Khanam Almi
Dr. Md. Shariful Alam

Brief History of Dementia

A woman in her early 50’s was admitted to a hospital because of
increasingly odd behavior. Her family reported that she had been showing
memory problems and strong feelings of jealousy. She also had become
disoriented at home and was hiding objects. During a doctor's examination,
the woman was unable to remember her husband's name, the year, or how
long she had been at the hospital. She could read but did not seem to
understand what she read, and she stressed the words in an unusual way. She
sometimes became agitated and seemed to have hallucinations and irrational
fears.

This woman, known as Auguste D., was the first person reported to have the
disease now known as Alzheimer's disease * (AD)
Alois Alzheimer – German
Neuropathologist
Auguste D.- 1
st
A D Patient
Brief History of Dementia
US PRESIDENT RONALD REGAN
FORMER PRESIDENT DR. IAS UDDIN AHMED
They are suffered from Dementia
but,
What about you?

So, lets know about Dementia
What is Dementia?
Þ Dementia:
It is defined as an acquired persistent
and progressive decline in intellectual function
that is severe enough to compromise social or
occupational functioning.



Key points of Dementia
Key points:
Þ Impairment of multiple domains of cognitive functions:
Þ Memory impairment - Must----- a. New material learning
Þ b. Forget previous learning
Þ With at least one of the following cognitive disturbance:
Þ i. Aphasia-language disturbance
Þ ii. Apraxia - impaired ability to carry out motor activities despite
intact motor function
Þ iii. Agnosia - failure to recognize/ identify familiar object despite
intact sensory function
Þ iv. Disturbence in executive functions
Þ Significant impairment of social & occupational functioning- decline
from previous level

Þ Gradual onset, continuing cognitive decline with alert & normal arousal.
Epidemiology
The prevalence of dementia has been estimated to be approximately
5.7% in over 65 years old.

O The prevalence rate of Alzheimer’s Disease (AD) for population
over 65 years old range from 5-7 per cent for moderately or severely
affected people.
O Prevalence rate approximately double with every additional 5 years
of age from about 1 percent at 65, rising to about 8-10 per cent at age
80 and 30-40 per cent at age 90 years.

There are currently an estimated 18 million people in the world with
dementia. This figure is expected to rise dramatically to 34 million
by the year 2025. The increase will be greatest in developing
countries.

Prevalence of Dementia in Bangladesh

Bangladesh

+ No exact epidemiological data
+ Incidence – 54/100000/year
+ Peak age – 54 yrs.

Hasan M, Khan B
Risk Factors for Dementia
Non Modifiable
• Age: 60-70 years
• Learning Disability: Down’s syndrome
• Gender: AD- F>M, VaD-M>F
• Genotype: Autosomal dominant form,
mutations in the amyloid precursor protein,
presenilin 1 and presenilin 2 genes
• Family history of dementia

Risk Factors for Dementia (CONT..)

O Alcohol consumption
O Smoking
O Obesity
O HTN
O Heart diseases : AF, IHD
O DM
O Stroke


O Hypercholesterimia
O Head Injury
O Low foliate and raised
homocysteine levels
O Hormone Replacement
therapy
O Depression
O NSAID Use
O Low educational status
and mental stimulation
Potentially modifiable risk factors



Classification of Dementia
Classification of Dementia
Primary degenerative dementia
- Cognitive impairment is the major
presenting features

Dementia plus Syndrome (Secondary)
- Cognitive impairment just one face
of more wide spread disorder

Primary degenerative dementias
Þ Alzheimer’s disease
Þ Frontotemporal Dementia &
Pick’s disease
Þ Dementia with Lewy bodies

Dementia plus Syndrome (Secondary)
VITAMINS D4
V: Vascular
Multi infarct dementia
Lacunar state
Binswanger disease
CADASIL
Amyloid angiopathy

I: Infectious-
Viral
# AIDS dementia complex
# Encephalitis – HSV
# SSPE
# PMLE

Dementia plus Syndrome
(Secondary CONT...)
Þ T: Traumatic
Þ Subdural hematoma
Þ Dementia pugilistica
Þ A: Autoimmune
Þ CNS Vasculitis
Þ SLE, PAN
Þ Sarcoidosis
Þ M: Metabolic
Þ Endocrine
Þ Hepatic
Þ Renal

Dementia plus Syndrome
(Secondary CONT...)
Þ I: Iatrogenic/toxin
Þ Substance abuse (chronic)
Þ Alcohol (chronic)
Þ Lead
Þ Co exposure
Þ Organic solvents

Dementia plus Syndrome
(Secondary CONT...)
Þ N: Neoplasm
Þ Primary
Þ Secondary
Þ Paraneoplastic
#Progressive limbic encephalitis
Þ Treatment effect
#Post radiation effect
Þ S: Structural
Þ Normal pressure hydrocephalus
Þ D1: Demyelanating
Þ Multiple sclerosis
Þ D2: Deficiency
Þ Niacin- Pellagra
Þ Vitamin B1
Þ Vitamin B12

Dementia plus Syndrome
(Secondary CONT...)
D3: Degenerative
Þ Parkinson’s disease
Þ PSP
Þ Huntington’s disease
Þ ALS dementia complex
Þ Cortico-basal degeneration
D4: Developmental
Þ Down syndrome
Þ Wilson disease
Þ Porphyria
Þ Homocysteinuria
Þ Mitocondrial cytopathies
Clinical Classification of Dementia
(CONT..)
2. According to prognosis :
> Reversible Dementia:
- D = Drugs, Delirium.
- E = Emotions (depression) & Endocrine disease.
- M = Metabolic disturbances
- E = Eye & ear impairments
- N = Nutritional disorders
- T = Tumors, Toxicity, Trauma to head
- I = Infectious disorders
- A = Alcohol, Arteriosclerosis

> Irreversible Dementia:
- Alzheimer's
- Lewy body dementia
- Pick’s disease (frontotemporal dementia)
- Parkinson’s
- Head injury
- Huntington’s disease
- Creutzfeldt-Jakob disease
Vascular dementia

Þ Vascular dementia is the second most
common cause of dementia in the United
States and Europe, but it is the most
common form in some parts of Asia.

Vascular dementia
Þ Vascular dementia is the onset of cognitive
impairment, that with a stepwise deteriorating
course and a patchy distribution of neurologic
deficits caused by cerebrovascular disease.


Þ The prevalence rate of dementia is 9 times higher
in patients who have had a stroke than in controls.
One year after a stroke, 25% of patients develop
new-onset dementia. Within 4 years following a
stroke, the relative risk of incident dementia is
5.5%.

Types of Vascular dementia
= Many subtypes of vascular dementia have been
described to date. The spectrum includes –

1) Multi-infarct dementia,
2) Binswanger disease,
3) Mild vascular cognitive impairment,
4) Vascular dementia due to a strategic single infarct,
5) Vascular dementia due to lacunar lesions,
6) Vascular dementia due to hemorrhagic lesions,
7) Subcortical vascular dementia, and
8) Mixed dementia (combination of AD and vascular
dementia).

Vascular dementia (CONT..)
Þ In multi-infarct
dementia, the combined
effects of different
infarcts produce
cognitive decline by
affecting the neural nets.
Pathologically, multiple
small infarcts are
observed in the white
matter, thalamus, basal
ganglia, and pons.

Vascular dementia (CONT..)
Þ In single-infarct
dementia, different areas
in the brain can be
affected, which may
result in significant
impairment in cognition.
This may be observed in
cases of anterior cerebral
artery infarct, parietal
lobe infarcts, thalamic
infarction, and cingular
gyrus infarction.
Vascular dementia (Pathophysiology)
g Small vessel disease affects all the small
vessels of the brain and produces 2 major
syndromes, Binswanger disease and lacunar
state. Small vessel disease results in arterial
wall changes, expansion of the Virchow-Robin
spaces, and perivascular parenchymal
rarefaction and gliosis.




Fig: Lacunar Disease (Thalamic Inf.)
Þ Lacunar disease is due to
small vessel occlusions and
produces small cavitary
lesions within the brain
parenchyma secondary to
occlusion of small
penetrating arterial
branches. These lacunae
are found more typically in
the internal capsule, deep
gray nuclei, and white
matter.
Vascular dementia (Pathophysiology)
Binswanger disease (also
known as subcortical
leukoencephalopathy) is
due to diffuse white matter
disease. Here vascular
changes observed are
fibrohyalinosis of the
small arteries and fibrinoid
necrosis of the larger
vessels inside the brain.


Vascular dementia (Pathophysiology)
Vascular dementia (Pathophysiology)

g In cerebral amyloid angiopathy–associated vasculopathy, aneurysm
formation and stenosis in the leptomeningeal and cortical vessels cause
damage to the subcortical white matter. In hereditary cystatin-C amyloid
angiopathy, patients have recurrent cerebral hemorrhages before age 40
years that can lead to dementia.


g Other less common syndromes which may lead to vascular dementia-
¬ Rare arteriopathies such as, inflammatory arteriopathy (eg, polyarteritis nodosa,
temporal arteritis) and noninflammatory arteriopathy (eg, moyamoya disease,
fibromuscular dysplasia) can cause multiple infarcts and can lead to vascular
dementia.

¬ Hypoperfusion due to large vessel or cardiac disease can affect the watershed
areas of the brain and lead to vascular dementia.
Evaluation of the patient with Dementia
Evaluation of the patient with Dementia
Early diagnosis helps to prevent the condition from deteriorating. The following
are the steps involved in the diagnosis of dementia.

Þ Medical History— A detailed family history is gathered from family, friends
and colleagues. This helps to gather more information about signs and symptoms,
general health, diet, nutrition and alcohol intake.

Þ Neurological Examination— This is done to assess proper functioning of the
nervous system. This involves tests for reflexes, coordination and balance, muscle
tone and strength, eye movement, speech and sensation.

Þ Mini-Mental State Examination (MMSE) —This involves a
questionnaire about day-to-day routine activities to access the
mental function.

Þ Psychiatric evaluation— Is necessary to find out the nature of the disorder
such as depression or any other psychiatric disorder.
Evaluation of the patient with Dementia
Þ Basic Medical Tests— This includes:

• Routine laboratory tests Occasionally helpful tests
Thyroid function (TSH) Parathyroid function
Vitamin B
12
Adrenal function
Complete blood count Urine heavy metals
Electrolytes RBC sedimentation rate
Angiogram
Brain biopsy
• Optional focused tests
Psychometric testing
Chest X-ray
Lumber puncture
Liver function
Renal function
Urine toxin screen
HIV
Apolipoprotien E
RPR or VDRL

Þ Brain Imaging— Brain scans like structural imaging (CT/MRI), functional imaging
Electroencephalogram (EEG), single photon-emission computed tomography (SPECT) are
done to identify the changes in brain structure and function.
The Mini-Mental Status Examination
Points
Orientation
Name: season/date/day/month/year 5 (1 for each name)
Name: hospital/floor/town/state/country 5 (1 for each name)

Registration
Identify three objects by name and ask 3 (1 for each name)
patient to repeat

Attention and calculation
Serial 7s; subtract from 100 (e.g., 93-86-70-72-65) 5 (1 for each name)
Recall
Recall the three objects presented earlier 3 (1 for each name)

Language
Name pencil and watch 2 (1 for each name)
Repeat “No ifs, ands, or buts” 1
Follow a 3-step command (e.g, “Take this paper, fold 3 (1 for each name)
it in half, and place it on the table”)
Write “close your eyes” and ask patient to obey 1
written command
Ask patient to write a sentence 1
Ask patient to copy a design 1

Total 30
Interpretation of MMSE
Þ 27-30 = normal
Þ 25-26 = possible
Þ 10-24 = mild-moderate
Þ 6-9 = mod-severe
Þ <6 = severe

Prognosis
Þ Vascular dementia is associated with a higher mortality rate than AD,
presumably because of the coexistence of other atherosclerotic diseases.

Þ The 5-year survival rate is 39% for patients with vascular dementia
compared with 75% for age-matched controls.

Þ Study on causes showed that circulatory system disorders (eg, ischemic
heart disease) is the most common immediate cause of death in vascular
dementia, followed by respiratory system diseases (eg, pneumonia).

Þ The prognosis for MID is usually not very promising. Even though it may
seem that people with MID improve over time, their condition often steadily
declines after ensuing silent strokes.

Complications of Dementia
; Abuse by an overstressed caregiver.
; Increased infections anywhere in the body.
; Loss of ability to function or care for self.
; Loss of ability to interact.
; Reduced life span.
; Side effects of medications used to treat
the disorder.

Strategies for Medical Treatment of Dementia

+ Prevention of disease
+ Delay of onset
+ Slow rate of progression
+ Treat primary symptoms (cognitive)
+ Treat secondary symptoms (behavioral)
Prevention
As there is no definite cure till now for dementia
but we can reduce the risk by leading an active
life with healthy practices.

Healthy practices include:
O Avoiding alcohol, smoking and drug abuse.
O Healthy diet with low in saturated animal fat.
O Using seat belts when driving.
O Wearing helmets when riding motor cycles.
O Wearing protective headgear when playing contact
sports

Treatment of Dementia

· Pharmacotherapy: The following drugs are used-
• Cholinesterase Inhibitors— Cholinesterase inhibitors are drugs that block the activity of an
enzyme in the brain called cholinesterase. The drugs that come under this class are Tacrine,
Donepezil, Rivastigmine, Galantamine or Galanthamine.

• Antidepressants or Anxiolytics— Antidepressants are a group of drugs used to alleviate
depression. Anxiolytics are drugs that are used to treat anxiety and depression. The drugs
coming under this group are Fluoxetine, Sertraline, Paroxetine and Citalopram.

• Antipsychotics— Antipsychotics are a group of drugs used to treat psychosis. Haloperidol,
Risperidone, Quetiapine, Olanzapine, Ziprasidone are the drugs under this class.

• Anticonvulsants— These are also called antiepileptic drugs and are used in the prevention of
occurrence of epileptic seizures. Valproic acid, Carbamazepine Gabapentin, Lamotrigine.

• Over-the-counter (OTC) drugs— The available OTC drugs for dementia are Diphenhydramine
and nonsteroidal antiinflammatory drugs (NSAIDs) like Aspirin, Naproxen, or Ibuprofen.
Treatment of Dementia (CONT..)
· Alternate Treatment:
• Reminiscence Therapy— This involves discussing about the past events
in groups and helping them to recall using photos or familiar objects.

• Reality Orientation— Helping the patient to remember where he or she is
and letting them know what is going around them.

• Vitamin and Other Supplements—
- VitaminB12 and folic acid, lower the levels of an amino acid in the
blood that is usually high in Alzheimer’s patients.
- Zinc can improve memory, which lacks in elderly people.
- L-arginine, an amino acid increase the blood flow in the brain helping
vascular dementia.
- Alpha-linolenic acid (ALA), borage oil and evening primrose oil
containing essential fatty acids may help to reduce the risk of
Alzheimer’s disease.
- A diet including less animal fats and more fish is helpful.

Treatment of Dementia (CONT..)
· Future possible therapies under evaluation:
× Glycogen syntehtase kinase 3 (GSK 3)
× β-secretase inhibitors
× γ-secretase inhibitors
× α-secretase enhancers
Overview of Anti-cholinesterase Inhibitors
Oldest (and probably most extensively tested): Physostigmine

O Obsolete because- very short lasting (half life 30 mints)
necessitating frequent oral administration
O Potentially serious dose-limiting S/E

In the past: Tacrine
O Again S/E; 50% of the patients treated with tacrine
discontinued treatment because of adverse events esp.
hepatotoxicity.


Overview of ACHE Inhibitors (CONT..)
Recent past: Donepezile
O Launched in the USA in January 1997 and in the UK in
March 1997
O Modest benefits in terms of cognition
O Most common S/E are similar to those seen with tacrine

Very Recent: Rivastigmine
O Launched in the USA in April 2000; received approval for use
in 60 countries including all member states of EU and USA
O Improvements were seen in cognition, ADL & severity of
dementia
O Dose of 6-12 mg/day
O Lower risk of adverse effects

Exelon Patch (Rivastigmine)

Advantages of new Exelon Patch
s Easy to apply
s Reduce patients’ pill burden
s Reduce care giver’s distress
s Achieve optimal therapeutic dose
s Dramatically improved GI Tolerability
s Ensures Continuous & Consistent drug
delivery that results fewer side effects &
Improved efficacy

Dosage guideline for newly
diagnosed patient
Exelon Patch-5
Exelon
4.6 mg/24 h
Patch
Starting dose

4 weeks
One-step dose increase

Exelon Patch-10
Exelon
9.5 mg/24 h
Patch
Target dose

Switching from other therapy
Patient on other medication e.g., Donepezil. First Stop the drug
then
Exelon Patch-5
Exelon
4.6 mg/24 h
Patch
Starting dose

4 weeks
One-step dose increase

Exelon Patch-10
Exelon
9.5 mg/24 h
Patch
Target dose

Exelon Patch: Where to apply?
Þ Exelon Patch can be applied
to:
O Upper or lower back
O Upper arm
O Chest
Þ When replacing the patch, the
new patch should be applied
to a different spot of skin
O Do not use the same spot more than
once every 14 days
Þ Normal daily activities, such
as bathing, are permitted


So, Get back to
normal life
Thanks