This PPT is a seminar on the Alzheimer's disease which was prepared for sensitizing post graduate psychiatry students on the day of World Alzheimer's Day.
2. WHAT IS ON PLATE TODAY?
What is Dementia?
What is Alzheimer’s Disease?
Symptomatology
Clinical Assessment
Management: Brief
3. WHAT IS DEMENTIA?
Dementia refers to a spectrum of brain disorders all of
which involve cognitive impairment but vary widely in
terms of cause, course and prognosis.
Progressive loss of cognitive/intellectual functions.
Without impairment of consciousness.
There is disturbance of multiple higher cortical
functions, including memory, thinking, orientation,
comprehension, calculation, learning capacity, language,
and judgment.
4. DEMENTIA: BACKGROUND
Dementia : De = Out from + mens = the mind
Loss of intellectual abilities of sufficient severity to interfere with
social or occupational functioning
Usually irreversible disorder
Egyptians and Greeks of the period 2000-1000 BC were aware of
age related memory decline
India : Dementia : Smiriti Bhransh : 800 BC
: Sathiya Gaye (Turned 60)
: Satar- Batar (Turned 70)
: “Chinan” in South India
5. EPIDEMIOLOGY
AD is the most common cause of dementia amongst people aged
65 and older
Prevalence among people over 60 years–5% to 8 %
Starting with 0.5% prevalence at 55 yrs., it goes on doubling every
five years (60yrs-1%; 65yrs-2%; 70yrs- 4%; 75yrs- 8% and so on)
Risk at the age of 80 years is around 15 to 20%
At present nearly 47.5 million people worldwide with dementia. It
is expected to be 74.7 million by 2030 and 131.5 million by 2050.
About 7.7 million new cases of dementia each year.
A new case detected in every 3 seconds somewhere in world.
(WHO)
Average prevalence of dementia in India: 3.7%
6. DEMENTIA OF ALZHEIMER’S TYPE
Alzheimer’s disease (AD) is the most common form
of dementia, representing approximately 55-60% of all
cases.
In 1907, Alois Alzheimer first described the condition
that later assumed his name.
It is a cortical dementia characterized by a slow,
progressive loss of cognitive functions.
AD is the fourth leading cause of death in USA. No
Indian data is available regarding it.
7. DEMENTIA OF ALZHEIMER’S TYPE
Characterized by:
Progressive loss of cortical neurons
Formation of amyloid plaques (beta-amyloid is
major component)
Intra-neuronal neurofibrillary tangles (hyper
phosphorylated tau proteins is major
constituent)
8. PATHOGENESIS AND
PATHOPHYSIOLGY
AD is characterized by generalized cerebral cortical atrophy
with widespread cortical neuritic (or senile) plaques (NPs) and
neurofibrillary tangles (NFTs). Following mechanisms have been
attributed for the development of Alzheimer’s dementia
Amyloid cascade theory
Neuronal loss
Cholinergic hypothesis
Excitotoxicity
Genetic factors
9. DIAGNOSIS OF AD (DSM IV TR)
A. The development of multiple cognitive deficits manifested by both
1. Memory impairment (impaired ability to learn new information or to recall previously learned
information)
2. One (or more) of the following cognitive disturbances:
A. Aphasia (language disturbance)
B. Apraxia (impaired ability to carry out motor activities despite intact motor function)
C. Agnosia (failure to recognize or identify objects despite intact sensory function)
D. Disturbance in executive functioning (i.e., planning, organizing, sequencing, abstracting)
B. The cognitive deficits in Criteria A1 and A2 each cause significant impairment in
social or occupational functioning and represent a significant decline from a
previous level of functioning.
C. The course is characterized by gradual onset and continuing cognitive decline.
D. The cognitive deficits in Criteria A1 and A2 are not due to any of the following:
1. Other central nervous system conditions that cause progressive deficits in memory and
cognition (e.g., cerebrovascular disease, Parkinson's disease, Huntington's disease, subdural
hematoma, normal-pressure hydrocephalus, brain tumor)
2. Systemic conditions that are known to cause dementia (e.g., hypothyroidism, vitamin B12 or folic
acid deficiency, niacin deficiency, hypercalcemia, neurosyphilis, HIV infection)
3. Substance-induced conditions
E. The deficits do not occur exclusively during the course of a delirium.
10. DIAGNOSTIC TYPES
Early onset: < 65 years; familial types; 1, 14 and 21
chromosomes.
Late onset: >65 years usually in 70s; sporadic form;
Chromosome 19.
Mixed: not fitting into above two
Unspecified:
11. STAGES OF ILLNESS
DEVELOPMENT
Stage 1: Normal
Stage 2: Normal aged forgetfulness
Stage 3: Mild Neuro-cognitive disorder (MCI)
Stage 4: Mild Alzheimer’s Disease
Stage 5: Moderate Alzheimer’s Disease
Stage 6: Moderately severe Alzheimer’s Disease
Stage 7: Severe Alzheimer’s Disease
12. FAST SCALE (FUNCTIONAL
ASSESSMENT STAGING)
STAGE 1: No impairment
STAGE 2: Complaints of forgetting location of objects.
Subjective work difficulties
STAGE 3: Decreased job functioning evident to co-
workers. Difficulty in traveling to new places.
Decreased organizational capacity.
STAGE 4: Decreased ability to perform complex tasks,
e.g., planning dinner for guests, handling personal
finances, difficulty in marketing etc.
STAGE 5: Requires assistance in choosing proper
clothing to wear for the day, season or occasion, e.g.,
patient may wear the same clothing repeatedly, unless
supervised.
13. FAST SCALE (FUNCTIONAL
ASSESSMENT STAGING)
Stage 6:
a) Improperly putting on clothes without assistance or
cuing occasionally or more frequently over the past
few weeks
b) Unable to bathe properly
c) Inability to handle mechanics of toileting
d) Urinary incontinence
e) Fecal incontinence
14. FAST SCALE (FUNCTIONAL
ASSESSMENT STAGING)
Stage 7:
a) Ability to speak limited to approximately a half a dozen intelligible
different words or fewer, in the course of an average day or in the
course of an intensive interview.
b) Speech ability limited to the use of single intelligible word in an
average day or in the course of an intensive interview (may repeat
the word over and over)
c) Ambulatory ability lost
d) Cannot sit up without assistance
e) Loss of ability to smile
f) Loss of ability to hold up head independently
15. STAGING OF AD IN 3 CATEGORIES:
Mild: Although work or social activities are significantly
impaired, the capacity for independent living remains,
with adequate personal hygiene & relatively intact
judgment (~1-3 yrs)
Moderate: Independent living is hazardous & some
degree of supervision is necessary (~2-8 yrs)
Severe: Activities of daily living are so impaired that
continuous supervision is required, e.g., unable to
maintain minimal personal hygiene; largely incoherent
or mute.
16. EARLY SYMPTOMS:
Forgetfulness, especially for recent events
Difficulty doing tasks with many steps
Feeling lost or disoriented in familiar places
Difficulty making quick decisions
Problems finding the right words
Moodiness, loss of interest in new projects, social
activities, anxiety, or depression
17. TEN WARNING SIGNS OF AD
1. Memory loss that affects job skills
2. Difficulty performing familiar tasks
3. Problems with language
4. Disorientation to time and place
5. Poor or decreased judgment
6. Problems with abstract thinking
7. Misplacing things
8. Changes in mood or behavior
9. Changes in personality
10.Loss of initiative
(Alzheimer’s
18. NEURO-PSYCHIATRIC SYMPTOMS
IN AD
Neuro-psychiatric domains:
1. Delusions
2. Hallucinations
3. Agitation/Aggression
4. Depression/Dysphoria
5. Anxiety
6. Elation/Euphoria
7. Apathy/Indifference
8. Disinhibition
9. Irritability/Lability
10.Aberrant motor behavior
Vegetative domains:
11.Sleep and Nighttime Behavior
Disorders
12.Appetite and Eating Disorders
Neuro-Psychiatry
Inventory
20. PERSONALITY CHANGES
Loss of awareness and normal responsiveness to
environment
Individuals may become more anxious or fearful
There is flattening of affect and a withdrawal from
challenging situations
Aggressiveness may be exhibited
21. TYPICAL WORK-UP OF AD
PATIENTS:
History taking
Physical and Neurological examination
Mental status
Functional assessment
Laboratory work-up
Neuro-imaging
22. HISTORY TAKING
History taking: Collateral history is very important
From patient
Informant: one who lives with the patient throughout the day, taking
care of patient, helping in daily activities
Another informant: to confirm findings, suspected cases of abuse and
neglect
Attention should be paid to
Mode of onset,
Course of progression,
Pattern of cognitive impairment
Presence of non-cognitive symptoms such as behavioral disturbance,
hallucinations and delusions
23. HISTORY TAKING:
History taking as per ABC:
A: Activities of daily living (ADL)
B: Behavioral and Psychological symptoms of dementia
C: Cognition
25. HISTORY TAKING:
o Activities of daily living: (ADL)
Basic activities:
•Bathing, dressing, toileting, transferring, continence, Feeding
etc.
Instrumental activities:
• Ability to use telephone
• Shopping
• Food preparation
• Laundry
• House keeping
• Ability handle finances, responsibility of own medications,
mode of transportation
26. HISTORY TAKING:
o Behavioral and Psychological symptoms of dementia:
Types of delusions encountered in AD: patient
believe that
he/she is in danger ‐ that others are planning to hurt
him/her?
others are stealing from him/her?
his/her spouse is having an affair?
unwelcome guests are living in his/her house?
his/her spouse or others are not who they claim to be?
his/her house is not his/her home?
family members plan to abandon him/her?
television or magazine figures are actually present in the
home? (Does he/she try to talk or interact with them?)
27. HISTORY TAKING:
Past history:
Family history:
Medication history:
Medical history:
Family assessment:
Examination:
General Physical Examination
Systemic examination: Neurological
Mental status examination:
28. COGNITIVE ASSESSMENT:
Can be done by:
MMSE: Mini Mental Status Examination
HMSE: Hindi Mental Status Examination
HCST: Hindi Cognitive Screening Test
Detailed assessment can be done by separate tests for each
cognitive domains
Based on the basic assessment the patient can be categorized into:
Mild: 20-24
Moderate: 10-19
Severe: <10
• CDT (clock drawing test): if the
patient has MMSE more than 24 than
try CDT
• If CDT is abnormal than dementia is
confirmed
• CDT + Delayed recall: MINI Cog
29. RECOMMENDATIONS FOR DIAGNOSTIC
CRITERIA
o DSM-IV or NINCDS-ADRDA criteria should be used for the
diagnosis of Alzheimer’s disease
o The Hachinski Ischemic Scale or NINDS-AIRENS criteria may be
used to assist in the diagnosis of vascular dementia.
o Diagnostic criteria for dementia with Lewy bodies and fronto-
temporal dementia should be considered in clinical assessment.
o Clinical criteria for dementia with Lewy bodies (Consortium for
DLB criteria) fronto-temporal dementia (Lund-Manchester
criteria) are not closely associated with neuropathological
diagnoses but can still provide useful differentiating clinical
features
NINCDS-ADRDA: National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease
and Related Disorders Association
NINDS-AIREN: National Institute of Neurological Disorders and Stroke- Association Internationale pour la Recherche et
l'Enseignement en Neurosciences
30. DIAGNOSIS:
Initial Cognitive Testing:
MMSE is used widely for screening purpose
It provides superficial assessment of memory, language, visuoperceptual
function.
Processing speed and executive function are not tested.
Evidence from a systematic review has shown that the MMSE is suitable for
the detection of dementia in individuals with suspected cognitive impairment
Recommendations: In individuals with suspected cognitive impairment, the
MMSE should be used in the diagnosis of dementia.
Initial cognitive testing can be improved by the use of Addenbrooke’s
Cognitive Examination, Montreal Cognitive Assessment (MoCA)
A questionnaire, such as the IQCODE, completed by a relative or friend may
be used in the diagnosis of dementia (The Informant Questionnaire on
Cognitive Decline in the Elderly)
MoCA assesses executive functions, it is
particularly useful for patients with
vascular
impairment, including vascular
dementia.
31. DETAILED ASSESSMENT:
o Alzheimer’s Disease Assessment Scale- Cognitive and
Non-Cognitive Sections (ADAS-Cog, ADAS Non-Cog)
o Cambridge Assessment of Memory and Cognition (CAM
Cog)
o PGI Battery of Brain Dysfunction (PGIBBD)
o NIMHANS neuropsychological battery for elderly
o AIIMS comprehensive neuropsychological battery in
Hindi: assessment of Lobar functions
32. RECOMMENDATIONS FOR
NEUROPSYCHOLOGICAL TESTING
Assessment of cognition is useful in both the initial and differential
diagnosis of dementia
It is possible to detect even very early Alzheimer’s disease using
neuropsychological testing.
Neuropsychology is superior to imaging in discriminating people
with AD from controls.
Neuropsychological testing also aids in the differential diagnosis of
dementia:
• FTD is characterized by deficits of semantic memory and
attention/executive function rather than the episodic memory deficit seen
in AD
• Dementia with Lewy bodies has more pronounced visuoperceptual and
frontal impairment compared to AD
• Vascular dementia exhibits executive dysfunction
• Depression shows a subcortical pattern of cognitive impairment
33. RECOMMENDATIONS FOR
NEUROPSYCHOLOGICAL TESTING
o Recommendation: Neuropsychological testing should
be used in the diagnosis of dementia, especially in
patients where dementia is not clinically obvious.
o It may be useful to repeat neuropsychological testing
after six to 12 months in patients where:
The diagnosis is unclear
Measurement of the progression of deficits in a typical
pattern supports a diagnosis of dementia and helps in
differential diagnosis.
34. LABORATORY WORK UP:
Routine Blood Examination:
o CBC
o RFT
o LFT
o RBS
o Lipid profile
o Vit. B12 and folate (based on affordability)
o Vit. D3 (Based on affordability)
o Serum Homocysteine level (if Vascular risk factors present)
o Urine Routine and microscopic examination
• ECG and CXR: When needed
• HB1AC: Diabetes, when RBS is increased
• Screening for syphilis: only in high risk
individual
• HIV screening: only in high risk
individual
Screening for Genetic
markers: Not recommended
35. THE ROLE OF CEREBROSPINAL FLUID
AND ELECTROENCEPHALOGRAPHY:
There is insufficient evidence to support
routine use of CSF markers in the diagnosis of
dementia.
Recommendations:
CSF and EEG examinations are not recommended as
routine investigations for dementia.
CSF and EEG examinations may be useful where CJD
is suspected.
36. IMAGING:
The use of Imaging:
The ability of clinical examination (for example, history-taking and
physical examination) to predict a structural lesion has been reported
as having sensitivity and specificity of 90%.
Imaging can be used to detect reversible causes of dementia and to
aid in the differential diagnosis of dementia. The choice of imaging
technique varies widely, and includes CT scan, MRI, SPECT and PET.
Assessment of delayed recall is at least as good as volumetric MRI in
distinguishing people with probable AD from controls.
Recommendation: Structural imaging should ideally form part of the
diagnostic workup of patients with suspected dementia.
Recommendation: CT may be used in combination with CT to aid the
differential diagnosis of dementia when the diagnosis is in doubt.
37. PHARMACOLOGICAL INTERVENTIONS:
Core symptoms:
Cognitive decline: all cholinesterase inhibitors
Functional decline: all cholinesterase inhibitors
Social decline: no evidence
Associated symptoms:
Agitation: Trazodone and ? SSRI
Aggression: Antipsychotics
Depression: Antidepressants
Psychosis: Donepezil, Rivastigmine, Antipsychotics
Repetitive vocalization: no evidence ? SSRI
Sleep disturbance: no evidence
Non-specific behavior disturbance: all cholinesterase inhibitors and
antidepressants
38. PHARMACOLOGICAL INTERVENTIONS:
DONEPEZIL
Recommendations for Donepezil:
o Donepezil, at daily doses of 5 mg and above, can be used to
treat cognitive decline in people with Alzheimer’s disease.
o Age and severity of Alzheimer’s disease should not be
contraindications to the use of donepezil.
o A systematic review of the use of donepezil in people with
vascular dementia demonstrated some benefit to patients with
mild to moderate cognitive impairment examined over a six
month period.
o Donepezil, at daily doses of 5 mg and above, can be used for the
management of associated symptoms in people with Alzheimer’s
disease.
39. PHARMACOLOGICAL INTERVENTIONS:
GALANTAMINE
Galantamine is effective for the maintenance of cognition in people with
mild to moderate Alzheimer’s disease.
There is evidence of some cognitive benefit to patients with mixed
Alzheimer’s disease and cerebrovascular disease.
Recommendations for Galantamine:
Galantamine, at daily doses of 16 mg and above, can be used to
treat cognitive decline in people with Alzheimer’s disease and people
with mixed dementias.
Galantamine should be used with slow escalation to doses of up to
24 mg.
Galantamine, at daily doses of 16 mg and above, can be used for the
management of associated symptoms in people with Alzheimer’s
disease.
40. PHARMACOLOGICAL INTERVENTIONS:
RIVASTIGMINE
Recommendations for Rivastigmine:
Rivastigmine, at daily doses of 6 mg and above, can be used to
treat cognitive decline in people with Alzheimer’s disease.
Rivastigmine, at daily doses of 6 mg and above, can be used to
treat cognitive decline in people with dementia with Lewy
bodies and dementia associated with Parkinson’s Disease.
Rivastigmine, at daily doses of 6 mg and above, can be used
for the management of associated symptoms in people with
Alzheimer’s disease and dementia with Lewy bodies.
41. PHARMACOLOGICAL INTERVENTIONS:
Memantine:
The efficacy of memantine has been examined in people with
moderate to severe Alzheimer’s disease and mild to moderate
vascular dementia.
Recommendations:
Memantine can be used in the dose of 20 mg per day in a
patient with moderate to severe Alzheimer’s disease.
Antidepressants:
The use of antidepressants for patients with dementia
accompanied by depressive symptoms is widespread, but their
effect on depression and cognitive function is uncertain.
Antidepressants can be used for the treatment of comorbid
depression in dementia providing their use is evaluated
42. PHARMACOLOGICAL INTERVENTIONS:
ANTIPSYCHOTICS
Recommendation: If necessary, conventional antipsychotics may be used
with caution, given their side effect profile, to treat the associated
symptoms of dementia.
The atypical antipsychotics, olanzapine and risperidone are useful in
the management of psychotic symptoms, aggression and other
behavioral problems associated with dementia.
Atypical antipsychotics with reduced sedation and extrapyramidal side
effects may be useful in practice, although the risk of serious adverse
events such as stroke must be carefully evaluated.
In patients on stable antipsychotic regimens, who are free from
behavioral disturbances, withdrawal of antipsychotic treatment may not
be associated with relapse.
An individualized approach to managing agitation in people with dementia is
required.
Where antipsychotics are inappropriate cholinesterase inhibitors may be considered.
43. PHARMACOLOGICAL
INTERVENTIONS:
Trazodone:
One small RCT of trazodone showed reduction in agitation when
accompanied by depressive symptoms in patients with dementia.
Trazodone may be considered for patients with depressive symptoms and
dementia associated agitation.
Clinically Ineffective Interventions:
Anti-inflammatories
Melatonin
Estrogen
Physostigmine
Selegiline
44. PHARMACOLOGICAL INTERVENTIONS:
Intervention lacking evidence of clinical effectiveness
Anticonvulsants:
Anticonvulsants may be considered for the symptomatic treatment of
seizures or myoclonus associated with dementia but are not recommended
for other symptoms of dementia.
Aspirin:
Aspirin is only recommended in people with vascular dementia who have a
history of vascular disease.
Benzodiazepines:
No systematic reviews or RCTs examining the usefulness of
benzodiazepines in the management of associated symptoms of dementia,
including anxiety, were identified.
Lithium
In the absence of concurrent evidence of bipolar affective disorder lithium
45. TREATMENT FOR SLEEP
DISTURBANCES:
o Interventions include maintaining daytime activities and giving
careful attention to sleep hygiene.
Pharmacological intervention could be considered when other approaches
have failed.
o If a patient also requires medication for another psychiatric
condition, an agent with sedating properties, given at bedtime,
could be selected.
o Primarily for the treatment of sleep disturbance, medications
with possible effectiveness include trazodone, zolpidem, or
zaleplon
Benzodiazepines are not recommended for other than brief
use because of risks of daytime sedation, tolerance, rebound
insomnia, worsening cognition, falls, disinhibition, and
delirium.
Diphenhydramine is not recommended because of its
46. NON-PHARMACOLOGICAL
INTERVENTIONS: BRIEF
Non-pharmacological interventions are used to ensure that
underlying causes of behavioral disturbance are explored and to
provide personalized approaches to presenting problems.
CORE SYMPTOMS:
Cognitive decline
Functional decline
Social decline
ASSOCIATED SYMPTOMS:
Agitation
Aggression
Depression
Psychosis
Repetitive Vocalization
Sleep disturbance
Non-specific behavior Disturbance
47. NON-PHARMACOLOGICAL
INTERVENTIONS: BRIEF
COGNITIVE DECLINE:
Cognitive stimulation: may occur informally through
recreational activities, or formally through specific activities
Recommendation: Cognitive stimulation should be offered to
individuals with dementia.
Reality Orientation Therapy: [ROT] The purpose of ROT is to
reorientate the person by means of continuous stimulation and
repetitive orientation to the environment.
Recommendation: Reality orientation therapy should be used by
a skilled practitioner, on an individualized basis, with people
who are disorientated in time, place and person.
48. NON-PHARMACOLOGICAL
INTERVENTIONS: BRIEF
Functional Decline:
Caregiver intervention programs: Caregiver intervention ranges from
the simplest reassurance to the most complex multi-faceted
interaction with the person with dementia, including in one case, a
caregiver residential program.
Improvement in associated symptoms of dementia
Improvement in basic daily activities and other functional activities
Delay in nursing home placement
Recommendation: Caregivers should receive comprehensive training
on interventions that are effective for people with dementia.
Reality orientation therapy has been also found to be effective
Social Decline: No robust evidence identified
49. NON-PHARMACOLOGICAL
INTERVENTIONS: BRIEF
Agitation: Aromatherapy and recreational activities
are beneficial
Aggression: no robust evidence identified
Depression: Behavior management is beneficial
Psychosis: no robust evidence identified
Repetitive vocalization: no robust evidence identified
Sleep disturbance: no robust evidence identified,
sleep hygiene
Non-specific behavior disturbance: Care giver
intervention and training, multisensory stimulation
and recreational activities have shown benefits
50. NON-PHARMACOLOGICAL
INTERVENTIONS: BRIEF
Interventions showing short term benefit but the
benefits are not sustained once intervention stopped:
Aroma therapy
Light therapy
Music therapy
Multi sensory stimulation
Physical activities
Recreational activities
Simulated presence
Validation therapy
51. INFORMATION FOR DISCUSSION WITH
PATIENTS AND CARERS
Supportive information for patients and carers:
Patients and carers should be offered information tailored to the patient’s
perceived needs.
Good communication between healthcare professionals, patients and carers
is essential.
Disclosure of the diagnosis:
Healthcare professionals should be aware that many people with dementia
can understand their diagnosis, receive information and be involved in
decision making.
Healthcare professionals should be aware that some people with dementia
may not wish to know their diagnosis.
Healthcare professionals should be aware that in some situations disclosure
of a diagnosis of dementia may be inappropriate.
The wishes of the person with dementia should be upheld at all times.
The diagnosis of dementia should be given by a healthcare professional skilled in
communication or counselling.
52. INFORMATION FOR DISCUSSION WITH
PATIENTS AND CARERS
Information at other stages of the patient journey:
Information provision at other stages of the patient’s journey of care is generally more focused on
carer needs than that of the patient.
In decision making, people with mild dementia are more involved, largely in a collaborative role.
Beyond that carers generally make final decisions.
Patients and carers should be provided with information about the services and
interventions available to them at all stages of the patient’s journey of care.
Information should be offered to patients and carers in advance of the next
stage of the illness.
Methods of disseminating information which may be
appropriate for people with dementia and their carers
include:
Written information
Individual education programs
Group education programs
Counselling
Telemedicine service
Communication workshops
Cognitive behavior therapy (CBT)
Stress management
Combinations of the above.