CPG on Dementia : Approach to diagnosis and management

1. CPG ON DEMENTIA
(2nd edition):
APPROACH TO DIAGNOSIS
AND MANAGEMENT
DR NORAZAM BIN HARUN
CONSULTANT PSYCHIATRIST,
KOTA BHARU

2. OUTLINE
1.
DEFINITION
2.
EPIDEMIOLOGY DATA
3.
DEMENTIA AND THE BRAIN
4.
HOW TO RECOGNISE DEMENTIAs
5.
CAUSES OF DEMENTIAs
6.
TYPES OF DEMENTIAs
7.
COMORBID CONDITIONS
8.
INVESTIGATIONS
9.
FUNDAMENTALS OF MANAGEMENT

3. 1. DEFINITION
WHAT IS DEMENTIA?

4. DEMENTIA: DEFINITION
(ICD10)
• Dementia
– is a syndrome due to disease of the brain, usually
of a chronic or progressive nature, in which there
is disturbance of multiple higher cortical functions,
including memory, thinking, orientation,
comprehension, calculation, learning capacity,
language and judgement. Consciousness is not
clouded. Impairments of cognitive function are
commonly accompanied and occasionally
preceded, by deterioration in emotional control,
social behaviour or motivation.
– This syndrome occurs in Alzheimer’s disease, in
cerebrovascular disease and in other conditions
primarily or secondarily affecting the brain.

5. ALZHEIMER’S DISEASE: DSM
IV
• Multiple cognitive deficits (‘4As’)
– memory impairment (Amnesia) – impaired ability
to learn new in or to recall previously learned info
– Aphasia (language disturbance)
– Apraxia (impaired ability to carry out motor
activities)
– Agnosia (failure to recognise objects)
– disturbance in executive function (planning,
organising, sequencing, abstracting)
• These lead significant impairment in social,
occupational functioning

6. ALZHEIMER’S DISEASE:
NINCDS-ADRDA
POSSIBLE:
PROBABLE:
•
Established by clinical
examination and documented by
neuropsy tests,
•
Deficits in 2 or more areas of
cognition i.e. aphasia, apraxia,
agnosia,
•
Progressive worsening
•
No disturbance in conciousness
•
Absence of systemic or brain d/s
•
Absence of neuro, psych or
systemic d/o to cause
dementia
•
DEFINITE:
• Evidence obtained from
histopathology biopsy
and/or autopsy

7. 2. EPIDEMIOLOGY
WHAT IS THE BURDEN?

8. ELDERLY IN MALAYSIA (>60)
(Statistik Malaysia 1990)
YEAR
NUMBERS
%
1990
1 047 000
5.7
2010
2 094 000
7.5
2020
3 261 000
9.8
2035
3 261 000
9.8

9. PREVALENCE OF AD:
INCREASING WITH AGE
Age
Prevalence
65-74
3%
75-84
18.7%
>85
47.2%
5x

10. AD: EPIDEMIOLOGY
(ADI report 2006)
Region
Preval
ence
(60+,
%)
Inciden
ce (mil
per
annum,
2001)
2001
(million)
2020
(million)
2040
(million)
Proporti
onate
increas
e in
number
s
(20012020)
Proporti
onate
increas
e in
number
s
(20012040)
WPRO B
(incl China,
Malaysia)
4.0
1.21
6.0
11.7
26.1
96
336
Indonesia
Thailand,
Sri Lanka
2.7
0.14
0.6
1.3
7
100
325

11. DEMENTIA BURDEN
ADI report 2006, Wimo et.al. Alz Dis Asso Dis 2003;17(2):63-7,
Ferri CP Lancet 2005;366:2112-7
Grey hair population
Dementia
•
10% total population >65 yo
•
6.1% popn >65 suffers from AD
(0.5% total population)
•
635mil people in 2002
•
24.3 million worldwide
•
Expected to increase 30% in
2050
•
Double every 20 years
•
Care of an AD person: USD
18400-36000 p.a.
•
Total care USD 1 bilion p.a.
•
47% male Malaysian pilgrim has
cognitive impairment (Harun N
2003)
•
Mostly in developing
countries

12. 3. DEMENTIA AND
THE BRAIN
WHERE IS IT?

13. THE BRAIN
•
Average adult brain size is
about medium sized
cabbage
•
Weight: 1-1.5kg
•
Number of neurons: 100
000 000 000 (100billion)
•
Number of synapse: 100
000 000 000 000 (100trilion)

14. PARTS OF BRAIN INVOLVED
AND MANIFESTATION
AD pathology starts at Nucleus Basalis of Meynert at temporal region
then expands to parietal, frontal & whole brain including subcortical
structures.

15. 4. HOW TO RECOGNISE
DEMENTIA?
DIAGNOSIS SUBTYPES AND THE DIFFERENTIALS

16. ASSESSMENT
• Standard interview and clinical data collection
• History of presenting illness, current problems, why
now.
A – ADL
B – behaviour problems
C – cognitive problems
• Investigate physical status
• CVS, CNS, MS, endocrine problems, DM, thyroid,
infections, nutrition, elimination.

17. MAKING A DIAGNOSIS

18. Algorithm for diagnosis of dementia:
2nd CPG of Management of Dementia
(2010)

19. 5. CAUSES OF
DEMENTIA

20. CAUSES
REVERSIBLE
•
Depression
•
Delirium
•
Drug toxicity incl alcohol
•
Metabolic d/o e.g. hypoNa
•
Hypothyroidism
•
Vit B12/folate def
•
Normal pressure hydrocephalus
•
Infection e.g. HIV, CJD
•
Hypoxia: sleep apnoea
IRREVERSIBLE
•
Alzheimer’s d/s
•
Vascular dementia
•
Lewy body dementia
•
FrontoTemporal Lobe
dementia
•
Parkinson’s d/s dementia
•
Huntington’s d/s dementia

21. RISK FACTORS
NON-MODIFIABLE
•
1. AGE
MODIFIABLE
•
• Increase 5x >85yo
• <0.1% in <65yo, 1-5% >65yo, 2530% in >85
•
•
•
•
•
•
•
2. GENDER
• F>M
• Female higher risk of AD
• Male higher risk of VaD
3. GENETIC
• Genetic loading in young onset –
APOE4, chromosome 1, 14, 21 as
in Down syndrome
1. CARDIOVASCULAR RISK
FACTORS:
•
Hypertension
DM
CVA
Hyperlipidaemia
Homocysteine
2. LIFESTYLE FACTORS:
•
•
•
•
•
•
Low education
Smoking
Alcohol
Obesity
Exercise
Social network

22. CHOLINERGIC THEORY:
DEPLETION OF ACETHYLCHOLINE
•
Neurons communicate with
each other by
neurotransmitter to activate
the receiving neurons
•
AD causes depletion of
neurotransmitters
particularly acetylcholine
(Ach) which a/w memory.

23. TAU THEORY:
ABNORMAL DEPOSITION OF TAU PROTEINS
• Tau protein is to
maintain the structure of
the axon of neurons
• Intraneuronal NFT
containing excessive tau
protein
• Distruption of Tau
proteins via abnormal
hyper-phosphorylation
which leads to deposition
of neurofibrillary tangle
(NFT) eventually death
of neurons

24. AMYLOID THEORY:
EXCESSIVE DEPOSITION OF AMYLOID
PLAQUE
• Extracellular amyloid
plaques containing Aβ
amyloid
• Plaque formed by
abnormal degradation
of a large protein
(Amyloid Precursor
Protein APP) into
insoluble protein AB42
• Genetic factor APOE4
may contribute
• Neuronal cell death

25. MACROSCOPIC CHANGES IN AD
•
Loss of overall volume of
the brain
•
Marked atrophic changes,
widening of sulci,
prominent gyri,
enlargement of ventricles

26. BRAIN PATHOLOGY IN VaD
•
Infarction or death of brain
tissue from blockage of
cerebral arteries by
thrombosis or embolism
•
Ischaemic or hemorrage
•
Large or small vessels
•
Strategically located vessels
involved

27. 6. DEMENTIA TYPES
WHY IS IT IMPORTANT TO DETERMINE SUBTYPES?
To determine treatment modalities

28. TYPES OF DEMENTIAS
• Most common types:
• Alzheimer’s disease
• Vascular dementia
(Mixed AD/VaD)
• Dementia Lewy Body
• Frontotemporal lobe dementia
• Others: PDD, CJD, Huntington
50%
25%
15%
5%
1%

29. SPECIAL FEATURES OF
DEMENTIA TYPES
•
ALZHEIMER’S DISEASE DEMENTIA
– 4As: Amnesia, Aphasia, Apraxia, Agnosia and poor executive function
•
VASCULAR DEMENTIA
– Step-wise deterioration, emotional lability, evidence of vascular disease
•
FRONTOTEMPORAL LOBE DEMENTIA
– Behaviour, personality and language problems are predominant features
(Disinhibition, Apathetic, Stereotypic type)
•
DEMENTIA OF LEWY BODY
– Fluctuation of cognitive decline, visual hallucination, sensitive to
neuroleptics, unsteady gait
•
HUNTINGTON’S DISEASE DEMENTIA and PARKINSON DISEASE
DEMENTIA
– Specific Movement d/o

30. VASCULAR DEMENTIA
•
Sudden onset (<3 months post stroke)
•
Step-wise deterioration
•
Specific neurological signs: physical and/or neuroimaging
evidence
•
SUBTYPES:
– Large or small vessels: Post-stroke or Multi-infarct dementia
(MID)
– Cortical or Subcortical Ischemic VaD (SIVD)
– Ischaemic or hemorrhagic
– Single specific infarct dementia may manifest s/s depending
on location e.g.
• cortical or subcortical (BG, Thalamus, Basal forebrain)

31. LEWY BODY
DEMENTIA
•
LBD is a clinically defined syndrome and consists of a primary
dementia characterised by visuoperceptual and executive dysfx.
Lewy bodies (deposits of synuclein protein) in the brain.
•
Presence of 2 out 3 core clinical features (McKeith IG et.al.
Neurology 2005;65(12):1863-72):
• Prominent visual hallucination
• Fluctuating attention
• Parkinsonism
• ‘One year rule’ to differentiate with Parkinson d/s
dementia
• Increased sensitivity to neuroleptics (suggestive feature)
• Risk of fall(supportive feature)

32. FRONTOTEMPORAL LOBE
DEMENTIA
(Lund-Manchester criteria, Neurology 1998;51: 1546-54)
• Characterised by frontal signs
• Personality changes (Disinhibited type)
• Behaviour problems prominent (Stereotypic type)
• Characterised by temporal signs
• Language problems (Apathetic type)
• Memory problems may present late

33. 7. COMORBID CONDITIONS
IN DEMENTIA
HOW TO DIFFERENTIATE THEM

34. DEMENTIA Vs DELIRIUM Vs DEPRESSION
DEMENTIA
DELIRIUM
DEPRESSION
ONSET
Insidious
Acute
Gradual
DURATION
Years
Hours/days
Weeks/months
COURSE
Progressive (stepwise for
VaD)
Fluctuates, sundowning
Worse in morning
ALERTNESS
Normal
Fluctuates
Normal
ORIENTATION
May be normal
Always impaired
Normal
MEMORY
Impaired recent, maybe
intact remote
Impaired
Recent maybe impaired
but remote good
THOUGHTS
Delusion common in late
stage
Paranoid, bizarre,
disjointed, occur early
Slow response, negative
thoughts
PERCEPTIONS
Hallucination occur late
Illusions, hallucination
Mood congruent
psychosis
EMOTIONS
Shallow, apathetic
Irritable, fearful
Sad, may be agitated
SLEEP
Disturbed diurnal rhythm
Nocturnal confusion
Early morning
awakening
Organic cause
Past h/o mood do
OTHER FEATURES

35. BEHAVIOURAL AND PSYCHOLOGICAL
SYMPTOMS OF DEMENTIA (BPSD)
Medical Research Council Aging Study, 2008
Symptoms
Without
dementia (%)
With dementia
(%)
P value
Apathy
12.1
50.3
<0.001
Sleep problems
43.8
42
0.574
Irritability
12.8
28.8
<0.001
Persecution
8.1
25.4
<0.001
Depression
8.6
20.5
<0.001
Misidentification
3.0
20.3
<0.001
Hallucination
3.7
15.1
<0.001
Wandering
0.3
12.8
<0.001
Elation
3.2
9.5
<0.001
Agitation
3.6
9.0
<0.001
Anxiety
6.3
8.9
<0.001

36. BEHAVIOURAL AND PSYCHOLOGICAL
SYMPTOMS OF DEMENTIA (BPSD)
• Behavioural disturbance is the most significant factor
for institutionalisation:
•
•
•
•
•
•
Psychosis
Wandering
Aggression/agitation
sleep disturbance
Anxiety
Depression
79%
73%
68%
73%
47%
42%
• St Louis Uni BPSD study 1996

37. BPSD SYMPTOMS THAT CAUSED
DISTRESS TO CARERS (Norazam H 2006)

38. COMORBID CONDITIONS: DELUSION
•
Occur in cognitive disorders but not all impaired patients have delusions
•
In A.D. 40-75% patients have some kind of delusional ideas
•
Types of delusions:
-
stealing
-
jealousy
-
mis-identification (house, spouse, impostors)
-
secondary delusions
•
More common in cortical dementias
•
Usually later in course of disease
•
Associated with increasing cognitive decline and aggressive behaviour
•
Mis-identification relate to lesions of right frontal lobe in A.D.
•
Delusions may be related to right temporal lobe lesions

39. COMORBID CONDITIONS: DEPRESSION
Alzheimer’s Disease
- 10-20%
Parkinson’s Disease
- 47%
Huntington’s Disease
- 38%
Stroke
- 20-40%
•
Depression is more prevalent in subcortical diseases and where major
pathology is in the striatum and frontal lobes, particularly the left
•
Depression occur early in dementias, often before onset of defining
cognitive or motor features and argues for a neuropathological
relationship, rather than a psychological reaction to the disease

40. COMORBID CONDITIONS: WANDERING
• MILD DEMENTIA
• SEVERE DEMENTIA
• PROBLEM TO CARERS
POSSIBLE CAUSES
- being lost
- catastrophic reaction
- relocation anxiety
- boredom
- psychosis
- agitated depression
- medication side-effects
- dementia pathology
18%
50%
40%

41. 8. INVESTIGATIONS

42. INVESTIGATIONS
All patients
Most patients
•
Full blood count
•
ECG
•
Thyroid function
•
Chest X-ray
•
Vitamin B12 and folate
•
Neuroimaging
•
BUN and creatinine
•
Syphilis serology
•
Calcium
•
Glucose
•
Electrolytes
•
Urinalysis
•
Liver function tests
•
Lipid profile

43. PSYCHOLOGICAL AND
FUNCTIONAL
INVESTIGATIONS
COGNITIVE
NON-COGNITIVE
•
Elderly Cognitive Assessment Qs (Kua
et.al)
•
Geriatric Depression Scale
(Yesavage)
•
MMSE (Folstein et.al.)
•
Cornell Depression scale
•
Symptoms of Dementia Screener (for
carer)
•
Neuropsychiatric Inventories (NPI)
- Cummings
•
Clock Drawing Test
•
Zarit Burden Scale (carer)
•
Abbreviated Mental Test
•
•
Clinical Dementia Rating (Morris)
Activity of Daily Living (ADL) –
Barthel, Katz
•
CIBIC
•
Instrumental ADL – Barthel,
Lawton
•
ADAS-COG
•
Hatchinski Scale (Vascular)
•
CAMCOG

44. 9. FUNDAMENTALS
OF MANAGEMENT
WHAT TO DO AND HOW TO DO IT

45. MANAGEMENT
1. Drugs to palliate primary cognitive symptoms of
dementias
2. Treatment of non-cognitive symptoms (BPSD) –
depression, delirium, BPSD, psychosis
3. Psychosocial and environmental strategies
4. Preventions
5. Care for carers

46. MANAGEMENT
• Assess the patient
• Assess family/caregivers
• Identify target symptoms
• Utilise evidence
• Weigh risks and benefits
• Avoid polypharmacy
• Psychosocial and pharmacological treatments can be
used together
• Review!

47. COGNITIVE ENHANCERS
FOR DEMENTIAs
(CPG on the Mx of Dementias 2nd Ed)
•
CHOLINESTERASE
INHIBITORS (for mildmoderate AD)
• Tacrine THA(Cognex) –
withdrawn because of s/e
• Donepezil (Aricept)
• 5-10mg OD
• Rivastigmine (Exelon)
• 1.5-6mg BiD
• 4.6mg-9.5mg patch/24hrs
• Galantamine (Reminyl)
• 4-8mg BiD
•
N-METHYL D-ASPARTATE
ANTAGONIST (for severe AD)
• Memantine (Ebixa)
• 5-20mg OD

48. RIVASTIGMINE AND
IMPROVEMENT IN ADAS-COG
(Emre et.al. NEJM 2004;351;2509-18)
*
Change from baseline, ADAS-cog
–2.5
Rivastigmine (n = 329)
–2.0
**
Placebo (n = 161)
Improvement
–1.5
–1.0
–0.5
Baseline
0
0.5
Deterioration
1.0
Week: 0
16
24

49. ARICEPT IN MILD –
MODERATE AD
(Winblad et.al. 2006)

50. MANAGEMENT FOR BPSD
Non pharmacology management should be
institute first before pharmacology Mx
• Activity programmes appear successful, but
interventions vary in style and content
• Music appears most promising when
personalised to individual taste and
background
• Bright light exposure decreases daytime sleep
and sundowning

51. NON – PHARMACOLOGY MANAGEMENT FOR
BPSD
• Reality orientation therapy
• Reminiscence therapy
• Validation therapy
• Behavioural modification – stimulus control
• Sensory stimulation - aromatherapy
• Motor activity – OT, PT, podiatrist, massage
• Snoezelen room
• Therapeutic buildings includes wandering path

52. PHARMACOTHERAPEUTIC APPROACH FOR
BPSD
•
Cholinergic therapies
•
NMDA antagonist therapy
•
Antipsychotics
•
Off-label use of antipsychotics however use with caution because of the
cerebrovascular risk (RR: 1.4-3.5 Douglas IJ et.al BMJ 2008;337;1227)
•
Recommended for aggression, agitation and psychosis
•
Benzodiazepines: use cautiously and for short term
•
Antidepressants: SSRI is recommended for depression
•
Anti-epileptics: Valproate and Carbamazepine for impulsivity
•
Beta adrenergic receptor blockers: propranolol for agitation
•
Hormonal therapy: antiandrogen for sexually disinhibited

53. RECOMMENDED DOSE
OF ANTIPSYCHOTICS
(CPG ON MX OF DEMENTIA 2nd Edition)
NAME
STARTING
DOSE
MAXIMUM
DOSE
ADVERSE
EFFECTS
RISPERIDONE
0.5mg OD
2mg OD
EPS, hyper
prolactinaemia
OLANZAPINE
2.5mg OD
10mg OD
EPS, weight
gain, hyper
lipidaemia/
glycaemia
QUETIAPINE
12.5-50mg OD
200-300mg OD
EPS,
somnolence,
orthostatic
hypotension
15mg OD
EPS, weight
gain, anxiety
ARIPIPRAZOLE 5mg OD

54. PREVENTION
• Prevent modifiable CVS risk factors:
• Hypertension Rx of mid-life HTN reduce 60% risk of
AD Syst-Euro study:– Lancet 1998; 352: 1847-51
• However other studies –ve (PROGRESS, SCOPE,
HOPE, SHEP, MRC)
• DM: controlled DM – less risk of VaD only with other
risk factors Lu FP Plos One 2009;4(1);4144
• Lipid control – midlife TC may have higher risk BUT
statins were not beneficial Szwart et.al Neurology 2007: 69:187380
• Homocysteinanemia: inconclusive results (Cochrane review
2008 October 8)

55. PREVENTION
• GINKGO-BILOBA EGB 761:
• Cochrane Review 2007(2) and NICE did not
recommend as adverse events outweigh benefits
• ANTIOXIDANT:
• Vitamin E: not significant findings (Petersen et.al NEJM
2005;352:2379-88)
• NICE guidelines did not recommend
• NSAIDS:
• ADAPT trial 2006 did not support use
• OESTROGEN:
• HRT has no benefit (Cochrane Review 2004)

56. PREVENTION
• DIET:
• Mediterranean diet may be beneficial (Sofi F et.al BMJ
2008;337;1344)
• EXERCISE:
• ADAS-COG improved among healthy elderly
Lautenschlager et.al. JAMA 2008;300:1027-37
• SMOKING:
• Increased risk of AD in elderly smokers (Rotterdam study,
Neurology 2007;69:998-1005)
• ALCOHOL:
• Moderate red wine (resveratol) may benefit (Gottenburg
Study Am J Epid 2008; 167: 684-91)

57. PREVENTION
• EDUCATION AND MENTAL STIMULATION:
• Higher education may prevent AD (NUN study JAMA
1997;277:813-7) – ‘brain reserve’
• Cognitive stimulation may benefit by 1.2-2.6 points in
MMSE on healthy adults (Valenzuela et.al. Am J Geri
2009;17(3):179-87
• SOCIAL NETWORK:
• Live alone and reduce social may increase risk (HonoluluAsia Aging Study, Am J Epid 2006;163:433-40)

58. HEALTHY LIFE STYLE
PREVENT DEMENTIA BY:
•
Control vascular risk factors: HTN, DM, hyperlipidaemia
•
Healthy Mediterranean diet: fresh vegies, fruits, olive oil, fish, legumes
(e.g. Sardinian people, Okinawan)
•
Stop smoking
•
Reduce weight (within Normal BMI)
•
Regular aerobic exercise (150min/week)
•
Cognitive stimulation
•
Education
•
Active socialisation

59. WHAT PATIENT AND
FAMILY/CARER SHOULD
KNOW?
•
Education in Dementia and Care
• Knowledge, understanding, Rx available and course of disease (mildmoderate-severe phase)
•
Attitude Change – valuing the person
• Sensitive to persons problems and disabilities
• Not blaming the victim – attribute to disease
• Optimism replacing pessimism
• Refute ‘ageism’ via education to person, family, public, health professional
•
Environmental Change
• Orientation – familiar place, familiar faces, familiar routines
•
Dealing with Psychological and Physiological Issues
• Support groups available in the community

60. THANK YOU