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OVERVIEW ON ALZHEIMER DISEASE

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Alzheimer s disease is the most common form of dementia. ... 2nd Edition by Professor S. Gauthier, 1999, Martin Dunitz Publishers (Taylor & Francis Group) ... – PowerPoint PPT presentation

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Title: OVERVIEW ON ALZHEIMER DISEASE


1
OVERVIEW ON ALZHEIMER DISEASE
  • NABIL NAJA M.D
  • GERIATRIC MEDECINE
  • DAIH- CMC- AAL

2
What is dementia?
  • Dementia is a general term used to describe a
    group of diseases that affect the brain.
    Alzheimers disease is the most common form of
    dementia. The damage caused by all types of
    dementia leads to a progressive loss of brain
    tissue. As brain tissue cannot be replaced,
    symptoms become worse over time. These generally
    reflect a loss of skills and increased Dependance.

3
How common is dementia?
  • Prevalence of dementia of 6.4 in people 65 years
    of age or over
  • Under age 60, dementia is rare
  • At the age of 8599, 45 of people could be
    expected to have dementia

Jorm et al 1987 Kokmen et al 1989 Lobo et al
2000 Ritchie Kildea 1995
4
What causes dementia?
  • The different causes of dementia are
  • Alzheimers disease (AD)
  • vascular dementia (VaD)
  • mixed dementia
  • Lewy body dementia
  • Parkinsons disease
  • severe alcohol abuse
  • Creutzfeldt-Jacob disease
  • Huntingtons disease
  • frontal lobe or fronto-temporal lobe dementia
    (including Picks disease)
  • AIDS
  • Other conditions Reversible causes

5
Prevalence of four major types of dementia
6
Potentially reversible causes of DEMENTIA
  • D Drugs
  • E Eyes, ears
  • M Metabolic
  • E Emotion (i.e. depression)
  • N Normal pressure hydrocephalus
  • T Tumor
  • I Infection (e.g. neurosyphilis)
  • A Anemia (i.e. B12 deficiency)

7
ALZHEIMERS DISEASE
  • Alois Alzheimer
  • German neuro-psychiatrist and neuropathologist
  • Described several brain diseases causing dementia
  • Importance of his discovery not appreciated in
    his lifetime

8
Auguste D.
  • 1906 / 1907 Dr Alzheimer reported patient
    Auguste D.
  • 53 years old at onset
  • Cognitive decline
  • Psychosis
  • Died within 5 years

9
Charles Bronson
Perry Como
Thomas Dorsey
Rita Hayworth
Famous People with Alzheimer's
Norman Rockwell
Barry Goldwater
Charlton Heston
Sugar Ray Robinson
Alfred Van Vogt
Ronald Reagan
Iris Murdoch
10
CLINICAL PROGRESSION OF ALZHEIMERS DISEASE
  • Insidious Onset
  • progressive disease
  • Duration between 2 and 10 years
  • Median duration5-7 years.

Henderson Jorm 2000
11
AD Stages
12
Causes of AD and Risk Factors
  • The precise cause is unknown
  • Established risk factors are
  • Old Age
  • A family history of AD
  • Gender
  • Apolipoprotein E (ApoE)
  • Education
  • Head trauma

13
AD pathology
  • -Neuronal degradation in AD is associated with
    accumulation of
  • Neurofibrillary tangles (NFTs)
  • Amyloid plaques (APs)
  • -These changes are accompanied by
  • Reduction in brain volume
  • Disruption of neurotransmitter systems

  • APs
    NFTs

14
Neurochemical changes in AD
  • Several changes in neurotransmitter balance
    accompany the microscopic changes in the AD brain
  • The two neurotransmitters that have gained most
    prominence in recent years are
  • Acetylcholine
  • Glutamate
  • Other neurotransmitters affected by AD are
  • Noradrenaline
  • Dopamine
  • Serotonin

Gsell et al. Curr Pharm Des 2004 10 265293
15
Care Givers Burden
16
Alzheimers The Devastating Impact
  • Family/spouse fears, concerns and frustrations
  • Gradual loss of their loved one
  • Loss of companionship/sexuality
  • Regrets about broken plans
  • Concerns about changes in behaviour, increased
    dependence, care giving needs
  • Behaviour causing embarrassment and/or
    frustration
  • The mortality of their loved one
  • Own mortality, leaving loved one on their own
  • Sleep disturbances
  • Restriction of caregiver's social life
  • Financial burden

17
What is the societal burden and impact of AD?
  • Impact on society
  • AD is the third most costly disease after cancer
    and heart disease, due to the direct medical
    costs, nursing home and homecare costs
  • Impact on carers
  • Approximately 80 of AD sufferers are living at
    home
  • Carers of people with AD often demoralised,
    isolated and psychologically distressed
  • Nearly 60 of carers reported suffering ill
    health or nervous problems
  • The impact on carers health and work, and the
    consequential cost to society should be
    recognised

Cacabelos et al. Int J Geriatric Psychiatry 1999
14 3-47Fillit Hill. Am J Geriatr Pharmacother
2005 3 (1) 39-49
18
Hours per day caring for person with dementia
current severity
Percentage of early stage patients
Percentage of middle stage patients
Percentage of late stage patients
Georges et al, Int J Geriatr Psychiatry 2008
19
ABCThe Key Symptom Domains of Alzheimers
Disease
  • Activities of Daily Living

Behavior
cognition
20
Diagnosis of AD
  • DSM IV criteria
  • Multiple cognitive deficits
  • - In memory
  • - One or more of language, praxis, gnosis,
    executive functioning
  • Causing
  • - Significant impairment decline in social or
    occupational functioning
  • - Gradual onset and continuing cognitive decline
  • NOT due to
  • - Other nervous system or substance-induced
    conditions
  • - Deficits not exclusively during course of
    delirium not better accounted for by depression
    or schizophrenia

21
Typical clinical presentation of early
Alzheimers disease I
  • Patient usually brought to doctor by relatives
  • Head Turning Sign
  • General anxiousness (During assessment)
  • Tendency to minimize/rationalize symptoms may
    become upset when family describes problems and
    gives examples

22
Typical clinical presentation of early
Alzheimers disease II
  • Patient denying any cognitive impairment, and
    blaming the physician for his idiot questions
  • Patient is repetitive in interview and carer
    reports repetitive questioning
  • Patient does not look ill and health is good
  • Medical/neurological examinations are
    unremarkable, except for higher cortical
    functions with no history of seizures or stroke

23
Diagnosis
  • History
  • Physical Exam
  • Lab.Tests
  • Brain MRI / CT
  • ( Reversible causes Thyroid dys.,NPH,Brain
    tumor,V.B12 def..)

24
MRI scansshowing atrophy also in temporal lobe
  • Normal brain cortex
  • AD patient

25
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26
Neuropsychological Assessment
  • General Principles
  • Standardized Exploration
  • Validated Instruments
  • Normal reference (age / sociocultural level)
  • Material
  • Scales ,Composite instruments (MMS, ADAS,
    Mattis, WAIS)
  • Assessment of specific function (memory, language
    etc)

27
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28
NeuropsychologyClock Drawing Test (CDT)
  • NOT part of the MMSE tests abstraction and
    visual-spatial cognition
  • Draw a circle, and ask the patient to write in
    all the numbers, then tell them to place the
    hands
  • Use the same time used in the original studies
    Please set hands of the clock to 10 after 11
  • Numbers and hands should be both normal

Normal
AbN concrete clock.
29
Clinical disease progression
Mild
Severe
Moderate
30
Cognitive Symptoms
25
Diagnosis
20
Loss of Functional Independence
15
MMSE Score
Behavioral Problems
10
Nursing Home Placement
5
Death
0
0
1
2
3
4
5
6
7
8
9
Years
Reprinted from Clinical Diagnosis and Management
of Alzheimers Disease, 2nd Edition by Professor
S. Gauthier, 1999, Martin Dunitz Publishers
(Taylor Francis Group)
30
Progressive loss of activities of daily living
Mild
Moderate
Severe
0
2
4
6
8
10
Years
Keep Appointments
Use the Telephone
Obtain Meal/Snack
Travel Alone
Use Home Appliances
Find Belongings
Select Clothes
Activities of Daily Living
Dress
Groom
Maintain Hobby
Dispose of Litter
Clear Table
Walk
Eat
25
20
15
10
5
0
Progressive Loss of Function
MMSE Score
Adapted from Galasko D, et al. Eur J Neurol. 1998
31
Most problematic symptoms overview
  • Activities of daily living (68)
  • Showering/bath 25
  • Being left alone 20
  • Incontinence 19
  • Finding belongings 16
  • Moving in general 14
  • Sleeping 12
  • Behaviour (50)
  • Agitation/aggression 16
  • Personality changes 16
  • Irritability 11
  • Wandering/restlessness 10
  • Depression 8
  • Cognition (45)
  • Memory/confusion 32
  • Concentration/attention 12
  • Orientation 12
  • Recognising people 7
  • Communication (36)
  • Following conversation 17
  • Comprehension of language 14
  • Speaking 12
  • Writing/reading 3

Georges et al, Int J Geriatr Psychiatry 2008
Base all respondents (1,181)
32
Functional Impairments
ADLs Bathing Dressing Toileting Transfers Contin
ence Feeding
IADLs Using telephone Shopping Food
preparation Housekeeping Laundry Transportation Me
dications Managing money
33
Behavioral problems in Alzheimers Disease
34
Prevalence of BPSD in AD
  • Very common
  • 50 of AD patients will experience at least one
    behavioural symptom
  • gt80 of people with AD will experience
    behavioural symptoms at any stage in the disease
  • BPSD fluctuate over time, recurrence rate is high
  • BPSD become more frequent as disease progresses
  • Most common BPSD are
  • Apathy, agitation, anxiety, irritability

Wynn Cummings. Dement Geriatr Cogn Disord 2004
17 100108 Howard et al. Int J Geriatr
Psychiatry 2001 16 (7) 714717 Mega et al.
Neurology 1996 46 130135 Levy et al. Am J
Psychiatry 1996 153 14381443
35
The spectrum of Behavioural and psychological
symptoms (BPSD) in AD
Psychotic symptoms Hallucinations1 Delusions1 Mis
identifications2
Behavioural symptoms Aberrant motor
behaviour1 Irritability1 Agitation/aggression1 Nig
ht-time behaviour1 Stereotypes3 Hyperorality4 Appe
tite/eating changes1 Hypersexuality4
Affective symptoms Depression/dysphoria1 Anxiety1
Apathy1 Elation/euphoria1 Disinhibition1
36
Behavioural scalesNeuropsychiatric Inventory
(NPI)
  • Scripted interview with carer that assesses 12
    behavioural disturbances commonly observed in
    dementia
  • Scored from 1 to 144 with severity and frequency
    being independently assessed
  • Requires only 10 minutes to perform
  • A wider range of psychopathology is evaluated
    compared with similar scales
  • Available in most European languages

Cummings et al. Neurology 1994 44 23082314
Cummings. Neurology 1997 48 (5 Suppl 6) S10S16
37
Assessment of behavioural symptomsNPI
  • Apathy
  • Disinhibition
  • Irritability/lability
  • Aberrant motor behaviour
  • Night time behaviour
  • Appetite/eating change
  • Delusions
  • Hallucinations
  • Agitation/aggression
  • Dysphoria
  • Anxiety
  • Euphoria

Cummings. Neurology 1997 48 (5 Suppl 6) S10S16
38
Treatment Management of Alzheimers Disease
39
Alzheimers Disease treatment goals
  • Symptomatic improvements
  • Cognitive, behavioural and functional improvement
  • Modifying the disease process

Cure
Maintenance of function
Cognitive and functional decline
Diagnosis
Slowing of disease progression
Treatment
Symptomaticbenefit
Natural progression
Time
40
Pharmacological Treatment
  • Ache Inhibitors
  • Donepezil
  • Rivastigmine
  • Galantamine
  • NMDA receptor antagonist
  • Memantine

41
Non pharmacological
  • Cognitive enhancement
  • Orientation in time place ( clock, calender,
    signs)
  • Treating non AZHs diseases
  • Preserving autonomy
  • Attention to safety
  • Environmental modification
  • Communication with family, caregivers

42
Managing Anxiety
  • Reassure, dont ignore
  • Distract - engage person in other activities
  • (Music, simple tasks, hobby-type (activities
  • Simplify the environment
  • Cover windows and mirrors use night lights

43
Managing Aggression
  • Identify the cause (noise, fear, etc.)
  • Focus on the persons feelings
  • Avoid getting angry or upset
  • Simplify the environment to limit distractions
  • Music, exercise, etc. as a soothing activity
  • Shift the focus to another activity

44
Thank you
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