dementia
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DEMENTIADEMENTIAAN APPROACH TO AN APPROACH TO
MANAGEMENT AND MANAGEMENT AND PREVENTIONPREVENTION
DR. HASANAH CHE ISMAILPSYCHIATRIST
SCHOOL OF MEDICAL SCIENCESUNIVERSITI SAINS MALAYSIA
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Definition of the dementiasyndrome
• Multiple cognitive deficits – memory loss – aphasia – apraxia – agnosia – disturbance in executive function
• These lead to functional decline
DEMENTIA
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Causes of dementia
• Common causes: – Depression– Drug toxicity
• Common causes: – Alzheimer's disease– Vascular dementia
• Other causes– Lewy body disease– Pick's disease (dementia
of the frontal lobe type) – Parkinson's disease with
dementia
Reversible dementias Irreversible dementias
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Differentiating AD from other dementias
Cognitive impairment
Dementia
Alzheimer's disease
Exclude other causes (e.g. delirium and depression, etc)
Exclude other dementias
Differentiating AD from other dementias
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DEMENTIA
• AD represents over 50% of all dementia cases
• AD prevalence doubles every 5 years after 60 years of age
• AD affects 15 million people worldwide
Alois Alzheimer
Short history
1907 Alzheimer reports the first case of August D
1960s Re-emergence of interest in dementia
1970s Cholinergic deficits in AD identified
1980s First trials of cholinergic enhancing therapies
1994 First cholinesterase inhibitor licensed
Present First launches of Reminyl, a cholinesterase inhibitor and nicotinic modulator
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Prevalence of Alzheimer’s disease
Kurz A. Eur J Neurol 1998; 5(Suppl 4): S1-8Wimo A et al. Int J Geriatr Psychiatry 1997; 12: 841-56
0
10
20
30
40
50
60
60-64 65-69 70-74 75-79 80-84 85+ 95+
Age (years)
Pre
vale
nce (
%)
1% 2% 4%8%
16%
30%
50%
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Clinical features of AD
• Loss of cognition– short-term memory– language– visuospatial functions
• Loss of daily function– instrumental activities of daily living (ADL)– self-maintenance skills
• Abnormal behaviour
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‘‘Normal’ ageing Normal’ ageing vs.vs. dementia dementia
• Multiple cognitive domains affected• Decline of language and orientation• Deterioration in common activities of daily living
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IPA AD Conference, 1996
Functionalimpairment * IADL * ADL
Insidious onset Cognitive decline* Memory loss * Aphasia * Apraxia * Agnosia * Executive function difficultiesBehavioral signs
* Mood swings * Agitation* Wandering
Age over 60 years
No gait difficulties
AD
Clinical features of AD
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Natural history of Alzheimer’s disease
1 2 3 4 5 6 7 8 9
0
5
10
15
20
25
30
Time (years)
Symptoms
Diagnosis
Loss of functional independence
Behavioural problems
Nursing home placement
Death
Min
i-Men
tal S
tate
Exa
min
atio
n (M
MS
E) Early diagnosis Mild-to-moderate Severe
Feldman and Gracon. The Natural History of Alzheimer’s Disease. London: Martin Dunitz, 1996
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Anatomical features of AD
• Gross atrophy
– shrinkage of brain
– thinning of gyri
– widened sulci
Normal brain
Alzheimer brain
The pathological cascade of ADThe pathological cascade of AD
Clinical symptoms
Neurodegeneration
Neurofibrillary tangles
-amyloid
Environmental risk factors
Genetic risk factors
Apo-E
Pathogenetic mutations
APP
PS1,2
Cholinergic dysfunction
TAU hypophosphorylation
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Acetyl CoAAcetyl CoA++
CholineCholine
AcetylcholineAcetylcholine
N receptorN receptor
The cholinergic system
Presynaptic nerve terminal
Postsynaptic nerve terminal
ChATChAT
ChAT = choline acetyltransferase
AChE = acetylcholinesterase
N = nicotinic
M = muscarinic
N receptorN receptor
M receptorM receptor
M receptorM receptor
= acetylcholine
Important in:Memory and learningSensory and attentional functions
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Cholinergic dysfunction in AD
Cholinergic neurons Choline uptake Acetylcholine release Choline acetyltransferase Nicotinic receptors
= progressively impaired memory
and cognition
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NEUROTRANSMITTERACETYLCHOLINENucleus basalis ofMeynert
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Need for earlydiagnosis
Consistent onset, clinicalpresentation and disease progression
Practicalassessmentmethods
New symptomatictreatments
Patient and caregiver support
Making a diagnosis of AD
IPA AD Conference, 1996
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PERUBAHANPERUBAHANKOGNITIFKOGNITIF::
INGATANINGATANBAHASABAHASAPERTIMBANGANPERTIMBANGAN
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PERUBAHANPERUBAHANPADA PADA PERSONALITI,PERSONALITI,KELAKUANKELAKUAN::JUGA GEJALAJUGA GEJALAPSIKIATRIPSIKIATRISEPERTISEPERTIDELUSI &DELUSI &HALUSINASIHALUSINASI
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PERUBAHANPERUBAHANMOTORMOTOR => =>TERBARINGTERBARINGDI ATAS KATILDI ATAS KATIL=>MENELAN=>MENELANTERGANGGUTERGANGGU=>MAUT=>MAUT
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Dementia * Insidious onset with unknown date* Slow, gradual, progressive decline* Generally irreversible* Disorientation late in illness* Slight day-to-day variation* Less prominent physiological changes* Consciousness clouded only in late stage* Normal attention span* Disturbed sleep wake cycle; day night
* Psychomotor changes late in illness
Delirium * Abrupt, precise onset, known date * Acute illness, lasting days or weeks * Usually reversible * Disorientation early in illness * Variable, hour by hour * Prominent physiological changes * Fluctuating levels of consciousness * Short attention span * Disturbed sleep wake cycle; hour-to-hour variation * Marked early psychomotor changes
OR
Dementia or delirium
Ham, 1997
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Dementia * Insidious onset * No psychiatric history * Conceals disability * Near-miss answers * Mood fluctuation day to day * Stable cognitive loss * Tries hard to perform but is unconcerned by losses * Short-term memory loss * Memory loss occurs first * Associated with a decline in social function
Depression * Abrupt onset * History of depression * Highlights disabilities * ’Don't know' answers * Diurnal variation in mood * Fluctuating cognitive loss * Tries less hard to perform and gets distressed by losses * Short- and long-term memory loss * Depressed mood coincides with memory loss * Associated with anxiety
OR
Dementia or depression
Ham, 1997, modified from Wells CE, 1979
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Clinical History
Ask the following questions: * How did it start? Was it sudden or gradual? * How long has it been going on? * Is the situation progressing? If so, how rapidly? * Is it step-wise or continuous? * Is it worsening, fluctuating or improving? * What changes have you noticed? * Has there been a change in personality? * Has the patient suffered any delusions or hallucinations? * Does the patient become agitated or wander?
Diagnosing AD in primary careclinical history, questioning
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Functional Assessment
Functional Activities Questionnaire (FAQ)1. Dealing with financial matters, paying bills, writing checks2. Keeping records of taxes, business affairs3. Shopping for everyday necessities: groceries, clothes, etc4. Hobbies or playing games5. Making tea, turning the kettle on and off6. Cooking a balanced meal7. Perception of current events8. Level of attention and understanding: books, television9. Memory: remembering appointments and medications10. Getting about: driving or taking public transport
Pfeffer et al 1982
ScoreMaximum
3333333333
Total 30
ScoreActual
Diagnosing AD in primary carefunctional assessment
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Physical examination
* Life-threatening conditions, e.g. mass lesions, vascular lesions and infections * Blood pressure and pulse * Vision and hearing assessments * Cardiac and respiratory function * Mobility and balance * Sensory and motor system examination (tone, reflexes, gait and coordination) and depressive symptoms (sleep and weight)
Diagnosing AD in primary carephysical examination
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Laboratory tests
All patients* Complete blood count* Thyroid function* Vitamin B12 and folate* Syphilis serology * BUN and creatinine * Calcium * Glucose * Electrolytes * Urinalysis * Liver function tests
Most patients * ECG* Chest X-ray
Diagnosing AD in primary carelaboratory tests
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Neuroimaging
Various CT scan reports in AD * Normal examination for the patient's age * Generalized cerebral atrophy * Small vessel changes, areas of leucoencephalopathy* No signs of subdural hematoma (if head trauma suspected) * Absence of specific areas of cerebral infarctions or evidence of stroke
Diagnosing AD in primary careneuroimaging, computed (axial)
tomography (CT)
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Cognitive Assessment
Cognitive areaMini Mental State Examination: test outline and scoring
Orientation *What is the (date, day, month, year, season)? * Where are you (clinic, town, country)?
Memory *Name three objects. Ask the patient to repeat them
Attention*Serial sevens. Alternatively ask the patient to spell world backwards (dlrow)
Folstein et al 1975
ScoreMaximum
55
3
5
ScoreActual
Diagnosing AD in primary carecognitive assessments, MMSE
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Cognitive Assessment
Cognitive areaMini Mental State Examination: test outline and scoring
Recall *Ask for the three objects mentioned above to be repeated
Language*Name a pencil and watch*Repeat, 'No ifs, ands or buts’*A three stage command*Read and obey CLOSE YOUR EYES*Write a sentence*Copy a double pentagon
ScoreMaximum
3
213111
Total 30
ScoreActual
Folstein et al 1975
Diagnosing AD in primary carecognitive assessments, MMSE (continued)
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Cognition * Recall/learning* Word finding* Problem solving* Judgement* Calculation
Function* Work* Money/shopping* Cooking* Housekeeping* Reading* Writing* Hobbies
Behavior* Apathy* Withdrawal* Depression* Irritability
IMPAIRMENT
Adapted from Galasko, 1997
Clinical features of ADMild stage of AD (MMSE 21 30)
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Cognition * Recent memory (remote memory unaffected) * Language (names, paraphasias)* Insight* Orientation* Visuospatial ability
Function* IADL loss* Misplacing objects* Getting lost* Difficulty dressing (sequence and selection)
Behavior * Delusions* Depression* Wandering* Insomnia* Agitation* Social skills unaffected
IMPAIRMENT
Clinical features of ADModerate stage of AD (MMSE 10 20)
Adapted from Galasko, 1997
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Cognition * Attention* Difficulty performing familiar activities (apraxis)* Language (phrases, mutism)
Function* Basic ADLs Dressing Grooming Bathing Eating Continence Walking Motor slowing
Behavior* Agitation Verbal Physical* Insomnia
Clinical features of ADSevere stage of AD (MMSE <10)
Adapted from Galasko, 1997
IMPAIRMENT
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The Clock Draw Test
Cognitive Assessment
Time: 5.00 Score: 7 (normal)
Time: 'no real time' Score: 2 (demented)
Thalmann et al 1996.
Time: .10.30 Score: 3 (demented)
Time: 1/4 past 25 Score: 3 (demented)
Diagnosing AD in primary carecognitive assessment
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AD prognosisOptimal case
Min
i Men
tal S
tate
Exa
min
atio
n s
core
1 2 3 4 5 6 7 8 9
25 ---------------------| Symptoms
20 |----------------------| Diagnosis
15 |-----------------------| Loss of functional independence
10 |--------------------------------| Behavioral problems
5 |-------------------------------------------|
0 Death |------------------------------------------
Nursing home placement
Feidman and Gracon, 1996Years
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NEUROPSYCHIATRIC SYMPTOMS @ BPSD
APATHY 72% AGITATION 60%IRRITABILITY 42% PACING ETC 38%DEPRESSION 38% ANXIETY 40%DELUSION 22% HALLUCINATION 10%EUPHORIA 8% DISINHIBITION 38%
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BPSD
DELUSION :
CROSS SECTIONAL STUDIES 20-50%LONGITUDINAL STUDIES 50-70%
• THEFT• INFIDELITY
• CAPGRAS• PHANTOM BOARDERS
• PICTURE SIGN
37Neuropsychiatric disturbances in
AD
0
10
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60
70
80
Pat
ien
ts (
%)
Mega MS et al. Neurology 1996; 46: 130–5
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BEHAVIOURAL CORRELATES
•AGGRESSIVE•ACTIVITY DISTURBANCES
COGNITIVE CORRELATES
•DEMENTIA SEVERITY•LANGUAGE, MEMORY &EXECUTIVE FUNCTION
39Successful cholinergic enhancing strategies in AD
Reduced breakdown of acetylcholine
+
Increased release of ACh into synapse
=
Increased availability of ACh at synapse
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Patient flow
• AD is prevalent among primary care patients• However, patients and general practitioners
(GPs) are often not aware of this• The diagnosis of AD comes too late• 30 memory clinics in Germany• Patients are normally followed up by GPs
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Reasons for delayed diagnosisReasons for delayed diagnosis
• Cognitive decline seen as age-related• GPs feel unsure about diagnosis of AD• Lack of practical diagnostic tools• Expected benefits of treatment are low
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Diagnostic problems and pitfallsDiagnostic problems and pitfalls
• Inadequate diagnostic tools• ‘Normal’ ageing vs. dementia • Interpretation of cerebrovascular findings• Problems of mixed pathologies
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Diagnostic problems and pitfallsDiagnostic problems and pitfalls
• Inadequate diagnostic tools• ‘Normal’ ageing vs. dementia • Interpretation of cerebrovascular findings• Problems of mixed pathologies
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Problems of mixed pathologiesProblems of mixed pathologies
• Stroke superimposed on AD• Alzheimer’s plus Parkinson’s disease• Dementia with Lewy bodies
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• RISPERIDONE: 1-2 mg
• OLANZEPINE: 5-10 mg
• QUETIAPINE: 25-250 mg
• HALOPERIDOL: 0.5-3 mg
ANTIPSYCHOTICS
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AGITATION
• physical aggression• verbal aggression• active resistance to care giversRx: ANTIPSYCHOTIC ANTICONVULSANT
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DEPRESSION
• major depression uncommon• depressive symptoms frequent (40%)• more common with F/H• MD may precede the onset of AD
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• SSRI = FLUVOXAMINE (LUVOX)
• SNRI = VENLAFAXIN (EFFEXOR)
• OTHER NEW ANTIDEPRESSANTS
ANTIDEPRESSANTS
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• APATHY 70%
• IRRITABILITY 42%
• DISINHIBITION 36%
PERSONALITY CHANGES
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• most common behavioural change
• indifference, loss of affection, decrease motivation
• independent of depression
• frontal hypoperfusion (mediofrontal)
=> correlates with cognitive decline
APATHY IN AD
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• ATROPHY OF NUCLEAS BASALIS
• DECREASE CAT SYNTHESIS
• ACETYLCHOLINE DEFICIT
• INTACT CHOLINERGIC RECEPERS
CHOLINERGIC DEFICIT IN AD
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• improve global function
• enhance cognition
• improve behaviour
• delay nursing home placement
CHOLINESTERASE INHIBITOR [ChEI]
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• TACRINE
• DONEPEZIL
• RIVASTIGMINE
• GALANTAMINE
CHOLINESTERASE INHIBITORSChEIs
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Potential caregiver benefits
• No sleep disruption
• Maintenance of ADL
• Suppression of behavioural symptoms
= diminished caregiver burden
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* Define all contributory factors and other illnesses * Discuss the diagnosis, and differentiate other types of dementia * Withdraw non-essential drugs that may interfere with cognition * Treat or manage concomitant illness (e.g. depression, hearing loss)
The role of the primary care physician in mild to moderate AD
Gauthier, Burns and Pettit, 1997
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* Discuss the use of symptomatic therapies * Monitor functional ability e.g. driving, safety * Referral to specialist if appropriate * Advise on will-making and advance directives * Refer to local AD association for support * Managing caregivers
The role of the primary care physician in mild to moderate AD
(continued)
Gauthier, Burns and Pettit, 1997
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The role of the primary care physician in severe AD
* Help caregivers discover and optimize the patient's preserved function * Monitor and treat complications * Facilitate caregiver support (respite and day care programs) * Be aware of caregiver burden and stress * Plan institutionalization, if needed * Assist with end-of-life decisions
The role of the primary care physician in severe AD
Gauthier, Burns and Pettit, 1997
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CASE-FINDINGSymptomssuggestingcognitive
impairment
MANAGEMENT OF AD *Follow-up *Patient and caregiver counseling *Management and symptomatic treatment *Specialist referral if indicated
CLINICAL ASSESSMENT *Clinical history
*Physical examination *Laboratory tests
*Functional assessment *Cognitive assessment
Functional decline and cognitive impairment
DIFFERENTIAL DIAGNOSIS *Exclude delirium depression other causes of dementia *Evaluate evidence for AD (neuroimaging)
YES
AD diagnosis
Diagnosing AD in primary careA systematic approach summary
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ABCs of Behavioural Management Strategies
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Iceberg
80%
20%
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The caregiving burden in AD
Hours dedicated per patient over 1 month(1 month = 720 hours, including 160 working hours)
• Principal (non-professional) caregiver: 280 hours
• Professional caregiver: 36 hours
Rice DP et al. Health Aff (Millwood) 1993; 12: 164–76Boada M et al. Med Clin (Barc) 1999; 113: 690–5
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Caregiver burden
Physical problems
Psychological or emotional
problems
Social problems
Financialproblems
Family members (including principal caregiver)caring for Alzheimer patient
Multidimensional: objective/subjective burden
George, Gwyther, Hoening, Montgomery, Platt
63Spanish National Plan for Patients
with AD & other Dementias
“Plan Nacional de Atencion a los Enfermos de Alzheimer y otras demencias”
Six main areas
1. Health services
2. Social services
3. Legal and economic protection
4. Family support
5. Education and training for professionals
6. Research
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A growing problem
0
5
10
15
20
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1980 2000 2025
Years
Mill
ions 1980
20002025
Projected prevalence of dementia to 2025
Alzheimer’s Disease International
65Qualitative changes in the Alzheimer
population in the next decade
Early diagnosis
Impact of drugs
Improvement ofcare provided
by non- professionals
Medicalprogress
Changes in the structure of society
Health and social services
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Risk factors* Age* Family History of AD (ApoE-4) * Head trauma* Low educational level* Environmental factors* Down’s syndrome
Protective factors * Genetic (ApoE-2)* High educational level* Long-term anti- inflammatory drug use, e.g. NSAIDS* Long-term use of estrogens (in women)
AD risk and protective factors
IPA AD Conference, 1996