OVERVIEW ON ALZHEIMER DISEASE

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OVERVIEW ON ALZHEIMER DISEASE

• NABIL NAJA M.D
• GERIATRIC MEDECINE
• DAIH- CMC- AAL

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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.

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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
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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

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Prevalence of four major types of dementia
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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)

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ALZHEIMERS DISEASE

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

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Auguste D.

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

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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
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CLINICAL PROGRESSION OF ALZHEIMERS DISEASE

• Insidious Onset
• progressive disease
• Duration between 2 and 10 years
• Median duration5-7 years.

Henderson Jorm 2000
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AD Stages
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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

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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

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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
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Care Givers Burden
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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

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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
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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
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ABCThe Key Symptom Domains of Alzheimers
Disease

• Activities of Daily Living

Behavior
cognition
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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

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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

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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

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Diagnosis

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

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MRI scansshowing atrophy also in temporal lobe

• Normal brain cortex

• AD patient

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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)

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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.
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Clinical disease progression
Mild
Severe
Moderate
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Cognitive Symptoms
25
Diagnosis
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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)
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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
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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)
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Functional Impairments
ADLs Bathing Dressing Toileting Transfers Contin
ence Feeding
IADLs Using telephone Shopping Food
preparation Housekeeping Laundry Transportation Me
dications Managing money
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Behavioral problems in Alzheimers Disease
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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
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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
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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
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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
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Treatment Management of Alzheimers Disease
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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
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Pharmacological Treatment

• Ache Inhibitors
• Donepezil
• Rivastigmine
• Galantamine
• NMDA receptor antagonist
• Memantine

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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

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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

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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

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Thank you