Most Populous Countries 2007 CountryPopulation (million) China1,331 India1,171 United States307 Indonesia243 Brazil191 Pakistan181 Bangladesh162 Nigeria153

Most Populous Countries 2007

Country Population (million)

China 1,331

India 1,171

United States 307

Indonesia 243

Brazil 191

Pakistan 181

Bangladesh 162

Nigeria 153

Russia 142

Japan 128

2050

Country Population (million)

India 1,748

China 1,437

United States 439

Indonesia 343

Pakistan 335

Nigeria 285

Bangladesh 222

Brazil 215

Congo, Dem Rep 189

Philippines 150

Population Reference Bureau 2009

On January 1, 2011, as the baby boomers begin to celebrate their 65th birthdays, 10,000

people will turn 65 every day—this will continue for 20 years.

Alliance for Aging Research

Dementia

Auguste Deter, the “first” case

Auguste Deter, the “first” case

Goals

Epidemiology Memory in typical aging Mild cognitive impairment Risk Factors for Dementia Types of Dementia Mental Status and functional Assessments Laboratory Evaluations Hierarchical Approach to Diagnosing Dementia Treatment

Prevalence

Incidence of dementia

Rorsman et al (1986); Hofman et al (1991)Swedish data Role of APOE

Incidence of dementia (%)

0

10

20

30

65-74 75-79 80-84

Age group (years)

Liverpool, UK

Rochester, MN, USA (men)

Rochester, MN, USA (women)

Incidence

Prevalence of dementia in developing countries

Problems with cross-cultural assessment of dementia

language

culture

assessment

differential morbidity and mortality

Chandra et al (1994)

Dementia

Memory Impairment* PLUS

Aphasia - disorder of language Agnosia - disorder of recognition Apraxia - impaired execution of tasks Executive Dysfunction - impaired abstraction,

sequencing, monitoring

Asso AP, 1993 DSM 4th ed. McKhann G et al,Neurology 1984;34:939-944

Function

Cognition

Behavior

Dementia

Memory in normal aging vs. dementia

Slow Accurate recall Remedied by cues e.g.

appointment calendars and lists

Stable Does not interfere with

function

Slow Inaccurate recall Reminders fail

eventually, recall poor despite cueing

Progressive decline Interferes with function

Memory in normal aging vs. dementia

Misplaces items infrequently

Independent retrieval possible

Can follow directions; oral or verbal

Capable of self-care

Misplaces personal items frequently

Needs help from others to find items

Can hardly follow directions even with guide

Gradually incapable of self-care

Memory declines with age

Age

Memoryand

Cognition

* Education* Cognitive demand

* I.Q.

Normal

Abnormal

MCI

Memory System

Encoding

Registration

Retrieval

Dementia

Normal aging

NeuronsCourtesy of The National Institute on Aging

Slide 14

Dendrites

Neuron

Axon

Electrical Im

pulses

NeurotransmitterMolecules

Receptor Synapse

Mild cognitive impairment

Cognitive decline accompanies normal ageing

Memory in health

Cognitive speed

Memory in dementia

Age

0 20 30 40 50 60 70

Definitions

Mild cognitive impairment has been classified in a number of ways

AAMI = Age-associated memory impairment (most widely studied)

MCI = Mild cognitive impairment

BSF = Benign senile forgetfulness

Subjective memory loss

Subjective memory loss does not predict dementia or mortality

Factors associated with subjective memory loss

mood state

use of memory strategies

personality factors

Best-fit equation Jorm (1997)Study measurements

Mild cognitive impairment

Easy to recognize MCI ( a large intermediate zone between the cognitively normal elderly and those with dementia

Impairment in at least 1 cognitive domain (usually recent memory) but who function independently in daily affairs.

Mild cognitive impairment (MCI)

2 Variants Recognized− Amnesic type

Most common Preclinical manifestation of AD Most common - Impaired performance on

delayed recall

− Multiple cognitive domains - localized impairment of other cognitive domains

Less common Signal non-AD clinical syndromes

Predicting which patients with MCI will become demented

Psychological tests verbal recall visuospatial recall object function recognition task object identification task

Genetic tests ?APOE or other susceptibility loci

Neuroimaging atrophy & activation in hippocampal & parahippocampal areas

Risk factors and protective factors

Using epidemiology to understand aetiology

Risk-modifying factors for AD age

family history

head injury

vascular factors

diabetes

education

depression

dietary factors

heavy metals

maternal age

smoking

Prevalence of dementia

Hofman et al (1991)Prevalence differences in Europe

Prevalence (%)

0

5

10

15

20

25

30

35

40

30-59 60-64 65-69 70-74 75-79 80-84 85-89 90-94 95-99

Age group (years)

Definition of prevalence

Age specific dementia prevalence (Frangitioni, 99 & Sahadevan, 08)

Prevalence of Dementia in USA

Ages 40-65 1 in 1000

Ages 65-70 1 in 50

Ages 70-80 1 in 20

Age 80+ 1 in 5

Head injury

Increases risk of AD (relative risk 1.8)

Increases A deposition in the brain

Increases tangle formation when repeated and severe

Mehta et al (1999); Nicoll et al (1995)

Vascular risk factors

Hypertension

Evidence of cardiac disease

Peripheral atherosclerosis

. . . increase risk of AD

What does this mean for vascular dementia?

Breteler et al (1994); Tariska et al (1997)

Education

Low educational level increases risk of dementia and probably AD

Demonstrated by prospective studies and the Nun Study

Snowdon et al (1996)

Diabetes

Late-onset diabetes increases risk of AD

Insulin resistance increases risk of AD

• However. . .

both conditions are common in the elderly and the relative risk is small

Stewart and Liolitsa (1999); Ott et al (1999)

Depression

A history of depression occurs more often in those with dementia

However. . .

Does depression herald dementia?

both conditions are common in the elderly and the relative risk is small

Jorm et al (1991)

Clinical features of Dementia

Delirium versus dementia

The confused patient

Confusion is “the inability to think with one's customary clarity and coherence” (Lishman 1987)

Primary causes of confusion include dementia and delirium

Confusion also arises as a consequence of other events and pathologies

It may be the doctor and not the patient who is confused

DSM-IV: features of dementiaDSM-IV: features of delirium

DSM-IV: features of delirium

Disturbance of consciousness with reduced ability to focus, maintain or shift attention

Change in cognition or perception not accounted for by dementia

Short development period and fluctuating course

Evidence of a general medical condition accounting for the disturbance

American Psychiatric Association (1994)

DSM-IV: features of dementia

Multiple cognitive deficits, including memory and at least one of aphasia, apraxia, agnosia and executive planning

Cognitive deficits give rise to significant impairment in social and occupational functioning

Deficits do not occur only during a delirium and cannot be accounted for by depression


Delirium prevalence

Increases with age; even in the community, prevalence in the elderly is > 10% especially in those with polypharmacy, diabetes, visual impairment and structural brain disease

Prevalence in hospital populations is 10–40%; elderly frail with recent falls and fractures are at particularly high risk

Elderly in long-term care also at high risk; the risk is greater in those with preexisting dementia or other physical illness requiring nursing-home care

Nursing-home prevalenceCommunity prevalence Hospital prevalence

Prevalence of delirium in the community

Prevalence of delirium (%)

0

2

4

6

8

10

12

14

> 18 years

> 55 years

Folstein et al (1991)

> 85 years

Prevalence of delirium in hospital settings


0

10

20

30

40

Medical in-patients 10%(Levkoff et al 1992)

Geriatric in-patients 18%(O'Keeffe and Lavan 1997)

Orthopaedic in-patients 36%(Forman et al 1995)

Prevalence of delirium in long-term settings


0

10

20

30

40

50

All elderly in care or hospital 44%(Sandberg et al 1998)

Intermediate-care home 9%(Rovner et al 1986)

Nursing homes 25%(Sabin et al 1982)

Clinical features of delirium

Impairment of consciousness

Disordered perception

Abnormal thought content

Altered mood

Motor features

Autonomic features

Lishman (1987)

Comparing delirium and dementia

Delirium Alzheimer's disease

Patient 'confused' Patient 'confused'

Patient agitated Patient 'agitated'

Patient anxious (psychic and somatic) Patient anxious (psychic and somatic)

Hallucinations Hallucinations

Rapid onset Gradual onset

Fluctuating Stable

Marked diurnal variation Waking at night or 'sundowning'

Severe attentional deficits Wandering attention

Primary cortical degenerative diseases

Natural history of Alzheimer's disease

Onset gradual, probably imperceptible

Progression slow and gradual, but not linear; progressive amnesia most common

Duration less than 10 years, on average, from diagnosis to death

Alzheimer’s disease

Vascular dementia

Dementia with Lewy bodies

Cognitive function

Time

Clinical symptoms of AD

Amnesia memory loss is early and invariable recent memory loss before remote memory

Aphasia nominal dysphasia early both expressive and receptive dysphasia in moderate stages severely disrupted speech in late phases

Apraxia functional difficulties, initially instrumental, subsequently basic activities of daily living ‘special’ dyspraxias, including topographical dyspraxia

Agnosia difficult to assess, but probably more prevalent than often realised includes autoprosopagnosia (one cause of ‘mirror sign’)

Behavioural and psychiatric symptoms (BPSD) depression psychotic features personality change activity disturbance

Natural history of dementia with Lewy bodies (DLB)

Onset may be gradual, but may also be sudden; in retrospect, onset may have been first diagnosed as delirium

Progression fluctuating Duration some evidence suggests total duration

of illness shorter than for AD


Vascular dementia


Cognitive function

Time

Discovery of a ‘new’ disorder

Discovery of a ‘new’ disorder

Dementia with Lewy bodies was recognised as a separate disorder only relatively recently

Basal Lewy bodies described in Parkinson’s disease Lewy was a co-worker of Alzheimer

Cortical Lewy bodies (LBs) became apparent with immunocytochemical studies of brain

traditional H&E staining does not reveal cortical LBs staining with ubiquitin antibodies illuminates cortical LBs ubiquitin is part of the non-specific cellular mechanism for degrading proteins now recognised that LBs are composed principally of synuclein\

Clinical study demonstrated that these patients had a typical triad of symptoms fluctuating cognitive state visual hallucinations Parkinsonism

Associated features sensitivity to neuroleptic

Clinical symptoms of DLB

Dementia with Lewy bodies is a disorder with a characteristic triad of symptoms

fluctuating confusion

visual hallucinations

parkinsonism

McKeith et al (1996)

Natural history of vascular dementia

Vascular dementia is classically described as a disorder of sudden onset

stepwise deterioration

However, there are problems with the notion as vascular factors are risk factors for AD

mixed disease is common (and may be more common than vascular dementia alone)

relationship between degree of vascular damage and dementia is not direct

progression in vascular dementia is similar to that in AD (although mixed disease may be different from both by showing more rapid decline) (Bowler et al 1997)

vascular dementia is found in many forms (Loeb and Meyer 1996)

Introduction to frontotemporal dementia (FTD)

FTD is a collection of related disorders

Some FTD cases are associated with or are secondary to motor disorders

frontotemporal degeneration with parkinsonism

dementia and ALS (amyotrophic lateral sclerosis; motor neuron disease)

Natural history of frontotemporal dementia

Onset usually age 50–60 years

Clinical onset is insidious

Early stages dominated by

personality changes

changes in social conduct

loss of emotional warmth

progressive loss of speech

Natural history is of a slow and progressive deteriorationGustafson (1993); Neary et al (1998)

Clinical symptoms of FTD

Neuropsychiatric symptoms inertia and loss of motivation loss of organisational abilities lack of insight restlessness

Speech problems early loss of expressive speech stereotyped phrases late mutism and amimia

Cherrier et al (1997); Duara et al (1999); Neary et al (1998)

Clinical symptoms of FTD

Compared with AD FTD: early non-cognitive behavioural changes with relatively spared

cognition AD: early cognitive changes with relatively preserved personality

and behaviour

Compared with vascular dementia better digit span and constructional ability worse verbal fluency and abstractions

Levy et al (1996); Cherrier et al (1997)

Subcortical dementias

Clinical symptoms of subcortical dementias

Bradyphrenia

Perseveration

Executive function deficits

Language and visuospatial preservation

Mild amnesia

Social functioning often preserved

Neurological symptoms of the primary disorder

Cummings (1994); Cummings and Benson (1984); Savage (1997)

Huntington's disease and dementia

4–7/100,000 population

Caused by triple-repeat expansion (autosomal dominant)

Onset usually at age 30–45 years, but may be 15–80 years

Characterised by choreiform movements, depression, psychosis and dementia

CADASIL: cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy

Migraine

Strokes or stroke-like episodes

Psychiatric symptoms (especially depression)

Dementia

MRI shows diffuse leukoencephalopathy with subcortical infarcts

Caused by mutations in Notch3

Onset age 20–40 years

Desmond et al (1999); Kalimo et al (1999)

Binswanger's disease

Disputed entity

onset age 50–70 years

evidence of hypertension or systemic vascular disease

progressive dementia (with predominant subcortical features)

depression

gait abnormalities (especially small stepping gait)

rigidity

neurogenic bladder

Cummings (1994); Pantoni and Garcia (1995)

Parkinson's disease and dementia

Occurs in 20–40% patients

Usually occurs after motor disorder

Mild amnesia

Severe slowing of thought

Depression common

Part of Lewy body disease spectrum

Elwan et al (1996); Hughes et al (1993)

Progressive supranuclear palsy (PSP)(Steele–Richardson–Olszewski syndrome)

Characteristic clinical features of PSP

parkinsonism without tremor

dementia, personality change, emotional incontinence, depression

early postural instability with unheralded falls often misinterpreted as lipothymia, epilepsy, cardiac attacks

spastic and ataxic dysarthria

vertical ocular gaze palsy with vertical saccades

apraxia of lid movement and blepharospasm

poor levodopa response

Progressive SupranuclearPalsy

Facial appearance“Poker face”


Retrocollis(neck extension)


Paresis of vertical gaze(Downward paresis)

Characteristic clinical features of corticobasal degeneration (CBGD)

Asymmetrical motor dysfunction with parkinsonian (rigidity and akinesia) and cortical features

Unilateral/asymmetrical dyspraxia and cortical sensory loss

Loss of control of the involved limb (‘alien limb’ phenomenon)

Early and severe gait and balance problems

Mild global cognitive decline with dysexecutive syndrome, dysphagia and explicit learning deficits

Clinical dementia may be the primary feature

Myoclonus

Relative frequencies of the main dementias

DLB with AD 12%

Pure vascular dementia 5%


Vascular dementia


Frontotemporal dementia

Other dementiaswhite matter dementias subcortical (secondary) dementias transmissible encephalopathies

Gearing et al (1995); Kosunen et al (1996); Nagy et al (1998)

Mixed vascular dementia and AD 10%

Pure DLB 3%

60%

5%5%

Diagnosis and Assessment of Dementia

Diagnosis

Detecting cognitive impairment

Describing the syndrome

Making the diagnosis

Diagnosis: a team approach

clinical management is core to the treatment APA (1997)

interdisciplinary team with key co-ordinator is optimal Alzheimer Society of Canada (1992)

regularly reviewed individual care package important RCGP (Haines and Katona) (1992)

home assessment should be available RCPsych (UK) (1995)

alliance with the patient and family essential APA (1997)

Guidelines insist upon a multidisciplinary approach

Clinical assessment

History

informant

family

personal

Examination

physical

mental

Royal College of Psychiatrists (1999)

Investigations

Routine investigations full blood count serum electrolytes glucose renal function liver function thyroid function tests vitamin B12/folate syphilis serology

Neuroimaging CT MRI SPECT

Special investigations PET CSF

MRI- AD

AD+CVD

FTD CT imaging

Vascular Dementia

Alzheimer’s Disease

Spect Scan

Regional distribution of atrophy in the common dementias

Alzheimer’s disease predominantly parietal and temporal

Frontotemporal dementia predominantly frontal and temporal

Dementia with Lewy bodies as for AD, but with additional subcortical pathology

Vascular dementia vascular distribution

Executive functions

Praxia

Perceptuospatial functionMemory

Language

Functional regionsFTDAD

ALZHEIMER’S DEMENTIA

DSM-IV Diagnostic Criteria for AD

Memory deficit that can be demonstrated objectively on cognitive testing.

At least one other cognitive deficit such as− aphasia , executive function impairment,,

agnosia , or apraxia

Together, these cognitive deficits must result in impairment in performance of daily activities.

DSM-IV Diagnostic Criteria for AD

The course is characterized by gradual onset and continuing cognitive decline.

These deficits must represent a decline from a previous higher level of functioning.

There must not be any other neurological disease that accounts for them.

NINCDS–ADRDA criteria for AD

Criteria for clinical diagnosis of AD include

dementia

deficits in two or more areas of cognition

progressive

no disturbance of consciousness

onset ages 40–90 years

absence of other systemic or brain disease that could account for the condition

McKhann et al (1984)Other (2) Unlikely Possible AD Definite ADOther (1)

Other clinical features compatible with probable AD (1)

Progressive deterioration in specific cognitive areas (e.g. aphasia or apraxia)

Impaired function and altered behaviour

Family history

Normal or non-specific EEG changes

Atrophy on CT

Normal lumbar puncture

Other clinical features compatible with probable AD (2)

Plateau in progression

Other neurological features late in disease

− gait disorder,

− myoclonus or abnormal primitive reflexes

− Seizures

Normal CT

Features making the diagnosis of probable AD unlikely

Sudden apoplectic onset

Focal neurological features

Seizures or gait disturbance early in the disease

Clinical diagnosis of possible AD

May be made on the basis of a dementia syndrome when there are variations in onset, course or presentation in the absence of other systemic or neurological disease sufficient to cause the syndrome

May be made in the presence of other disorder if the disorder is not considered to be the cause of the dementia

Should be used in research studies if a single, gradually progressive, severe cognitive deficit is found in the absence of any identifiable cause

Definite AD

May only be made in the presence of

a clinical diagnosis of probable AD

together with neuropathological

evidence of AD

Molecular pathogenesis of AD

Plaques (1)

tangles

plaques

Plaques (2)

Primitive or diffuse plaque

Mature or neuritic plaque

Tangles (1)

Neuropil Threads /

Dystrophic Neurites

Tangles (2)

Early tangles progress to tombstone tangles

Tombstone tangle

Mature tangle

Early tangle

VASCULAR DEMENTIA

NINDS–AIREN criteria for probable vascular dementia

Dementia

Cerebrovascular disease evident on history, examination or imaging

Two disorders must be related by onset of dementia within 3 months or abrupt, fluctuating or stepwise progression

Roman et al (1993)Uncertain Possible VaD Definite VaDFeatures of VaD

Clinical features supportive of vascular dementia

Early gait disorder (marche à petit pas)

Frequent falls

Urinary incontinence or frequency early in disorder

Pseudobulbar palsy

Personality and mood changes

Features that make the diagnosis uncertain or unlikely

Early memory loss and progressive deterioration in the absence of corresponding focal lesions on imaging

Absence of focal neurological signs

Absence of cerebrovascular lesions on CT or MRI

Possible vascular dementia

Dementia with focal neurological signs, but where imaging is missing

Absence of clear temporal relationship between stroke and dementia

Subtle onset or variable course and evidence of relevant CVD

Definite vascular dementia

Clinical criteria

Histopathological evidence

Absence of AD changes exceeding those expected by age

Absence of other disorder capable of producing dementia

LEWY BODY DEMENTIA

Newcastle criteria for Dementia Lewy Body ( DLB)

Progressive cognitive decline and two of three core features

fluctuation

visual hallucinations

parkinsonism

DLB less likely in the presence of

McKeith et al (1996)Features supporting diagnosis

Features supportive of the diagnosis of DLB

Repeated falls

Syncope

Transient loss of consciousness

Neuroleptic sensitivity

Systemised delusions

Hallucinations in other modalities

A diagnosis of DLB is less likely in the presence of

Stroke disease — evidence as focal neurological signs or on imaging

Other systemic or brain disease sufficient to cause the condition

FRONTO-TEMPORAL DEMENTIA

Manchester and Lund criteria for Fronto-Temopral Dementia (FTD)

Core diagnostic features

insidious onset and gradual progression

early decline in social interpersonal conduct

early impairment in regulation of personal conduct

early emotional blunting

early loss of insight

Neary et al (1998)Language Physical signs InvestigationsBehavioural

Supportive diagnostic features: behavioural disorder

Decline in personal hygiene

Mental rigidity and inflexibility

Distractibility and impersistence

Hyperorality and dietary changes

Perseverative behaviour

Utilisation behaviour

Supportive diagnostic features: speech and language

Altered speech output: aspontaneity or pressure

Echolalia

Perseveration

Mutism

Supportive diagnostic features: physical signs

Primitive reflexes

Incontinence

Akinesia, rigidity, tremor

Low and labile blood pressure

Investigations

Neuropsychology:

− significant impairment on frontal lobe tests

− Language deficits

− absence of severe amnesia, aphasia or visuospatial deficits

Prominent frontal and/or anterior temporal atrophy on neuroimaging

Assessment scales

Why use scales in dementia assessment?

Reliability and validity

Standardisation

Multidisciplinary working

Quantification

Domains assessment using scales

Cognition

Behaviour

Function

Global

Carers

Services

MemoryAttentionLanguage

Visual MemoryVerbal memory

VisuoconstructionVisuomotor SpeedExecutive function

Cognition

Assessment of cognition in dementia

primary care

secondary care

research

specific cognitive deficits

psychometric testing

screening

monitoring change

Scales for:

Screening scales

Which screening scales are suitable for

use in primary care?

AMT

MMSE

clock drawing test

AD-8

TYM

Abbreviated Mental Test Score (AMTS)

Subject interview

3-minute assessment

10 items

Range 0–10

Score < 7-8 suggests dementia

Qureshi and Hodkinson (1974)

Mental Test Score (MTS) / Abbreviated Mental Test Score


Score

Name 0/1Age 0/1Time (to nearest hour) 0/1Time of day 0/1Name and adress for five-minute recall

(this should be repeated by the patient to ensure it has been heard correctly)

Mr John Brown 0/1/242 West Street 0/1/2Gateshead 0/1

Day of week 0/1Date (correct day of month) 0/1Month 0/1Year 0/1Place: Type of place (i.e. hospital) 0/1

Name of hospital 0/1Name of ward 0/1Name of town 0/1

ORIGINAL TEST ITEMS



Score

Recognition of two persons (doctor, nurse, etc.) 0/1/2Date of birth (day and month sufficient) 0/1Place of birth (town) 0/1School attended 0/1Former occupation 0/1Name of wife, sibling or next of kin 0/1Date of First World War (year sufficient) 0/1Date of Second World War (year sufficient) 0/1Name of present Monarch 0/1Name of present Prime Minister 0/1Months of year backwards 0/1/2Count 1-20 0/1/2Count 20-1 0/1/2Total -34

ORIGINAL TEST ITEMS


Quresi and Hodkinson (1974)

1. Age2. Time (to nearest hour)

3.Address for recall at end of test – this should be repeated by the patient to ensure it has been heard correctly: 42 West Street

4. Year5. Name of hospital6. Recognition of two persons (doctor, nurse, etc)7. Date of birth8. Year of First World War9. Name of present Monarch10. Count backwards 20-1(each question scores one mark)

ABBREVIATED MENTAL TEST SCORE

Mini-Mental State Examination (MMSE)

Subject interview

10-minute assessment

30 items

Range 0–30

Score < 24-25 suggests dementia

Assessment of orientation, registration, attention and calculation, recall, language and visual construction


Mini-Mental State Examiniation (MMSE)


Max score Score

ORIENTATION

5 What is the (year) (season) (date) (month) (day)?

5 Where are we: (state) (county) (town) (hospital) (floor)?

REGISTRATION

3 Name 3 objects: (1 second to say each). Then ask the patient all three after you have said them. Give 1 point for each correct answer. Then repeat them until the patient learns all 3. Count trials and record.

Number of trials

ATTENTION AND CALCULATION

5 Serial 7s. 1 point for each correct. Stop after 5 answers. If the patient refuses, spell ”world” backwards.

RECALL

3 Ask for 3 objects repeated above. Give 1 point for each correct.

The copyright in the Mini Mental State Examination is wholly owned by the Mini Mental Ilc, a Massachusetts limited company.

© 1975, 1988 Mini Mental Ilc.

Mini-Mental State Examiniation (MMSE)


The copyright in the Mini Mental State Examination is wholly owned by the Mini Mental Ilc, a Massachusetts limited company.

© 1975, 1988 Mini Mental Ilc.

Max score Score

9

Alert Drowsy Stupor Coma

Write a sentence. (1 point)

Copy a design. (1 point)

Total Score

LANGUAGE

Name a pencil; name a watch. (2 points)

Repeat the following: ”No ifs, ands or buts.” (1 point)

Follow a three-stage command: ”Take this paper in your right hand, fold it in half, and put it on the floor.” (3 points)

Read and obey the following: ”Close your eyes.” (1 point)

Assess level of consciousness along a continuum

MMSE Modification

Modifications were made for Singapore populations:− For “season” substitute “time of day”

− For “state” substitute “region of Singapore”

− For “county” substitute “nearby housing estate”

− For “no ifs ands or buts” substitute “44 stone lions”

Montreal Cognitive Assessment (MoCA)

Subject interview


30 items

Range 0–30

Score < 26 suggests MCI and AD

Designed to be more sensitive to mild cognitive deficits than MMSE (Sensitivity MoCA 90% vs MMSE 18%) (Nasreddine, et al, 2005).

Consists of 8 cognitive subtests: visuospatial /executive, naming, memory, attention, language, abstraction, delayed recall, orientation.

Alzheimer’s Disease Assessment Scale cognitive section (ADAS–cog)

Subject interview

30–45-minute assessment

11 sections on cognition

70-point scale

Rosen et al (1984)

ADAS-cog

1.

2.

3.

4.

5.

6.

High: 1 2 3 4 Fingers: Thumb

Medium: 1 2 3 4 Pinky Index

Low: 1 2 3 4 Middle Ring

Cognitive items

Naming: objects, fingers

Following commands

Word-finding difficulty

Recall of test instructions

Comprehension of spoken language

Spoken language ability


ADAS-cog


7.

1 2 3 4

Yes No

8.

1 2 3 4 5

9.

Day Year Person

Date Month Season

10.

11.

Time of day

Place

Word recognition: mean error score

Cognition total

Word recall: mean error score

Ideational praxis

Step correct:

Orientation

Construction: drawing

Figures correct

Closing in:

ADAS-cog

12. Tearful

13. Appear / reports depressed mood

14. Concentration, distractibility

15. Uncooperative to testing

16. Delusions

17. Hallucinations

18. Pacing

19. Increased motor activity

20. Tremors

21. Increase / decrease appetite

Non-cognition total

Non-cognitive items


ADAS-cog


Total

Rating x = not assessed

0 = not present

1 = very mild

2 = mild

3 = moderate

4 = moderately severe

5 = severe

Word recall

Word recognition

Non-cognitive behaviour

Total scores

Cognitive behaviour

ADAS-cog

Score 0 – 5 steps correct

1 – 4 steps correct




5 – cannot do one step correct

Spoken language – quality of speech, NOT quantity

Comprehension – do NOT include responses to commands

Do NOT include finger or object naming


ADAS-cog


Name fingers of dominant hand and high / medium / low frequency objects

0 = all correct; one finger incorrect and / or one object incorrect

1 = two-three fingers and / or two objects incorrect

2 = two or more fingers and three-five objects incorrect

3 = three or more fingers and six-seven objects incorrect

4 = three or more fingers and eight-nine objects incorrect

Ability to copy circle, two overlapping rectangles, rhombus and cube

ADAS-cog


Five components in sending self a letter

1 = difficulty or failure to perform one component

2 = difficulty and / or failure to perform two components

3 = difficulty and / or failure to perform three components

4 = difficulty and / or failure to perform four components

5 = difficulty and / or failure to perform five components

Date, month, year, day of week, season, time of day, place and person

Non-cognitive behaviour is evaluated over preceding week to interview

Function

Instrumental Activities of Daily Living Scale (IADL)

Interview with carer


8 items

Lawton and Brody (1969)


1. Operates telephone on own initiative – looks up and dials numbers, etc

2. Dials a few well-known numbers

3. Answers telephone, bud does not dial

4. Does not use telephone at all

A. Ability to use telephone

The Gerontological Society of America (1969)

1. Takes care of all shopping needs independently

2. Shops independently for small purchases

3. Needs to be accompanied on any shopping trip

4. Completely unable to shop

B. Shopping


1. Plans, prepares and serves adequate meals independently

2. Prepares adequate meals if supplied with ingredients

3.Heats, serves and prepares meals, or prepares meals, but does not maintain adequate diet

4. Needs to have meals prepared and served

C. Food preparation

1. Maintains house alone or with occasional assistance (e.g. ’heavy work domestic help’)

2. Performs light daily tasks such as dishwashing, bedmaking

3. Performs light daily tasks, but cannot maintain acceptable level of cleanliness

4. Needs help with all home maintenance tasks

5. Does not participate in any housekeeping tasks

D. Housekeeping



1. Does personal laundry completely

2. Launders small items- rinses stockings, etc

3. All laundry must be done by others

E. Laundry

1. Travels independently on public transport or drives own car

2. Arranges own travel via taxi, but does not otherwise use public transport

3. Travels on public transport when accompanied by another

4. Travel limited to taxi or automobile with assistance of another

5. Does not travel at all

F. Mode of transport



1. Is responsible for taking medication in correct dosages at correct time

2. Takes responsibility if medication is prepared in advance in separate dosage

3. Is not capable of dispensing own medication

G. Responsibility for own medications

1.Manages financial matters independently (budgets, writes cheques, pays rent, bills, goes to bank), collects and keeps track of income

2. Manages day-to-day purchases, but needs help with banking, major purchases, etc

3. Incapable of handling money

H. Ability to handle finance


Basic Activities of Daily Living Scale (BADL)

1. Cares for self at toilet completely, no incontinence

2.Needs to be reminded, or needs help in cleaning self, or has rare (weekly, at most) accidents

3. Soiling or wetting while asleep not more than once a week

4. Soiling or wetting while asleep more than once a week

5. No control of bowels or bladder

A. Toilet

1. Eats without assistance

2.Eats with minor assistance at mealtimes and / or with special preparation of food, or help in cleaning up after meals

3. Feeds self with moderate assistance and is untidy

4. Requires extensive assistance for all meals

5. Does not feed self at all and resists efforts of others to feed him

B. Feeding

Physical self-maintenance scale


Basic Activities of Daily Living Scale (BADL

1. Dresses, undresses and selects clothes from own wardrobe

2. Dresses and undresses self with minor assistance

3. Needs minor assistance in dressing and selecting clothes

4. Needs major assistance in dressing, but cooperates with efforts of others to help

5. Completely unable to dress self and resists efforts of others to help

C. Dressing

1. Always neatly dressed, well groomed without assistance

2. Grooms self adequately with occasional minor assistance (e.g. shaving)

3. Needs moderate and regular assistance or supervision in grooming

4. Needs total grooming care, but can remain well groomed after help from others

5. Actively negates all efforts of others to maintain grooming

D. Grooming (neatness, hair, nails, face, clothing)


Basic Activities of Daily Living Scale (BADL

1.

2.

3.

1 Gets in and out without help2 Needs help in getting in and out

4.

5.

Sits unsupported in chair or wheelchair, but cannot propel without help

Bedridden more than half the time

E. Physical ambulation

Goes about grounds or city

Ambulates within residence or about one block’s distance

Ambulates with assistance of (check one): ( ) cane, ( ) walker, ( ) wheelchair

1. Bathes self (tub, shower, sponge bath) without help

2. Bathes self with help in getting in and out of tub

3. Washes face and hands only, but cannot bathe rest of body

4. Does not wash self, but is cooperative with those who bathe him

5. Does not wash self and resists efforts of others to keep him clean

F. Bathing


ADCS-ADL Assessment Tool

The commonly used assessment tool was developed by the Alzheimer’s Disease Cooperative Study

Used to assess a person’s functional ability

Physical functioning is usually measured by the ability to accomplish basic activities of daily living (ADL)

Other components of functional well-being measured are their higher functional abilities

Online scale: http://www.medafile.com/cln/ADCSADL.htm

In the past 4 weeks, did subject use a household appliance to do chores?

Yes No Don’t Know

If yes, ask about all of the following , and check those that were used:

If yes, for the most commonly used appliances, which best describes how {s}

usually used them:

4 without help, operating more than on-off controls if needed

3 _ without help, but operated only on/ off controls

2 _ with supervision, but no physical help

1 _ with physical help

Washer _ Dryer _Vacuum

_ Dishwasher Toaster _Toaster Oven

_Range Microwave

_Food Processor

_Other_________________

Global assessment

Functional Assessment Staging (FAST)

Clinician-rated scale

30-minute assessment; 2-minute rating

7 major stages

16 substages

Reisberg (1988)


Reisberg (1988)

Yes Months1 No.

1. No difficulties either subjectively or objectively

2. Complains of forgetting location of objects; subjective work difficulties

3.Decreased job functioning evident to co-workers, difficulty in travelling to new locations

4.Decreased ability to perform complex tasks (e.g. planning dinner for guests, handling finances, marketing)

5. Requires assistance in choosing proper clothing

6a. Difficulty putting clothing on properly

6b. Unable to bathe properly; may develop fear of bathing

6c.Inability to handle mechanisms of toileting (e.g. forgets to flush, doesn’t wipe properly)

6d. Urinary incontinence

6e. Faecal incontinence

© 1984 by Barry Reisberg, M.D.

Note: Functional staging score = highest ordinal value; 1Number of months FAST stage deficit has been noted


Note: Functional staging score = highest ordinal value; 1Number of months FAST stage deficit has been noted

Reisberg (1988)© 1984 by Barry Reisberg, M.D.

TESTER:

COMMENTS:

Yes No.

7a. Ability to speak limited (1 to 5 words only)

7b. All intelligible vocabulary lost

7c. Non-ambulatory

7d. Unable to sit up independently

7e. Unable to smile

7f. Unable to hold head up

Months1

Clinical Dementia Rating (CDR)


Extensive assessment; 2-minute rating

6 domains

4 stages in each domain

Hughes et al (1982)


Hughes et al (1982)

Rating: Score only as decline from previous usual level due to cognitive loss, not impairment due to other factors

None Questionable Mild Moderate Severe

0 0.5 1 2 3

Memory No memory loss or slight inconstant forgetfulness

Consistent slight forgetfulness; partial recollection of events; ’benign forgetfulness’

Moderate memory loss; more marked for recent events; defect interferes with everyday activities

Severe memory loss; only highly learned material retained; new material rapidly lost

Severe memory loss; only fragments remain

Orientation Fully orientated Fully orientated except for slight difficulty with time relationships

Moderate difficulty with time relationships; orientated for place at place at examination; may have geographic disorientation elsewhere

Severe difficulty with time relationships; usually disorientated to time, often to place

Orientated to person only

Impairment



0 0.5 1 2 3

Judgement and problem solving

Solves everyday problems and handles business and financial affairs well; judgement good in relation to past performance

Slight impairment in solving problems similarities and differences

Moderate difficulty in handling problems similarities and differences; social judgement usually impaired

Severely impaired in handling problems, similarities and differences; social judgement usually impaired

Unable to make judgements or solve problems

Impairment

Hughes et al (1982)




0 0.5 1 2 3

Community affairs

Appears well enough to be taken to functions outside a family home

Appears too ill to be taken to functions outside a family home

Impairment

No pretence of independent function outside of home

Independent function at usual level in job, shopping, and volunteer and social groups

Slight impairment in these activities

Unable to function independently at these activities, although may still be engaged in some; appears normal to casual inspection

Hughes et al (1982)




0 0.5 1 2 3

Home and hobbies

Life at home, hobbies and intellectual interests well maintained

Life at home, hobbies and intellectual interests slightly impaired

Mild but definite impairment of function at home; more difficult chores abandoned; more complicated hobbies and interests abandoned

Only simple chores preserved; very restricted interests, poorly maintained

Severe memory loss; only fragments remain

Personal care Needs prompting Requires assistance in dressing, hygiene, keeping of personal effects

Severe difficulty with time relationships; usually disorientated to time, often to place

Impairment

Fully capable of self-care

Hughes et al (1982)


Quality of life

Progressive Deterioration Scale (PDS)


Extensive assessment; 15-minute rating

11 domains

DeJong et al (1989)Progressive Deterioration Scale (PDS)

Summary of content areas for the Progressive Deterioration Scale (PDS)

Extent to which patient can leave immediate neighbourhood

Ability to safely travel distances alone

Confusion in familiar settings

Use of familiar household implements

Participation / enjoyment of leisure / cultural activities

Extent to which patient does household chores

Involvement in family finances, budgeting, etc

Interest in doing household tasks

Travel on public transport

Self-care and routine tasks

Social function / behaviour in social settings

Reprinted by permission of the publisher from Clinical Therapeutics, 11, 545-54. Copyright 1989 by Excerpta Medica Inc.

DeJong et al (1989)

Burden interview

Carer self-report

20-minute rating

29 items

Zarit et al (1980)

Burden interview

1. I feel resentful of other relatives who could, but do not, do things for my spouse

2. I feel that my spouse makes requests which I perceive to be over and above what s/he needs

3. Because of my involvement with my spouse, I don’t have enough time for myself

4. I feel stressed between trying to give to my spouse as well as to other family responsibilities, job, etc

5. I feel embarrassed over my spouse’s behaviour

6. I feel guilty about my interactions with my spouse

7. I feel that I don’t do as much for my spouse as I could or should

8. I feel angry about my interactions with my spouse

9. I feel that, in the past, I haven’t done as much for my spouse as I could have or should have

10. I feel nervous or depressed about my interactions with my spouse


Burden interview

11. I feel that my spouse currently affects my relationships with other family members and friends in a negative way

12. I feel resentful about my interactions with my spouse

13. I am afraid of what the future holds for my spouse

14. I feel pleased about my interactions with my spouse

15. It’s painful to watch my spouse age

16. I feel useful in my interactions with my spouse

17. I feel my spouse is dependent

18. I feel strained in my interactions with my spouse

19. I feel that my health has suffered because of my involvement with my spouse

20. I feel that I am contributing to the wellbeing of my spouse


Burden interview

21. I feel that the present situation with my spouse doesn’t allow me as much privacy as I’d like

22. I feel that my social life has suffered because of my involvement with my spouse

23. I wish that my spouse and I had a better relationship

24. I feel that my spouse doesn’t appreciate what I do for him / her as much as I would like

25. I feel uncomfortable when I have friends over

26. I feel that my spouse tries to manipulate me

27.I feel that my spouse seems to expect me to take care of him / her as if I were the only one s/he could depend on

28. I feel that I don’t have enough money to support my spouse in addition to the rest of our expenses

29. I feel that I would like to be able to provide more money to support my spouse than I am able to now


TREATMENT

NeuronsCourtesy of The National Institute on Aging

Slide 14

Dendrites

Neuron

Axon

Electrical Im

pulses

NeurotransmitterMolecules

Receptor Synapse

Acetylcholinestarase inhibitors− Donepezil ( Aricept) 5mg, 10mg− Rivastigmine (exelon) patch 4.5mg, 10mg− tab 1.5mg, 3mg, 4.5mg− Galantamine (reminyl) 4mg,8mg,12mg

NMDA receptors antagonist * N-methyl-D-aspartate receptor− Memantine 10mg, 20mg

Desirable properties

Competitive inhibitionCompetitive inhibition

Reversible inhibitionReversible inhibition

Low toxicityLow toxicity

Few drug interactionsFew drug interactions

Long active half-lifeLong active half-life

SelectivitySelectivity

McKeith (1999)

Outcome targets

Cognition

Global measures

Function

Behaviour

Quality of life

Health economics

Leber (1990)

Cholinergic transmission

Muscarinic receptor

Nicotinic receptor

ACh

ACh metabolites

Glutamate

Glutamatergic receptors

AChE

Neuronal firing

Second messengers

3

2

1

4

5

67

8

Correcting cholinergic loss in AD

Muscarinic receptor

Nicotinic receptor

ACh

ACh metabolites

AChEIs

Choline

AChELecithin Acetyl

CoA

3

2

1

4

NMDA RECEPTOR ANTAGONIST

Learning and glutamatergic transmission

Ca2+ Ca2+

Rest

Noise

Learning

Signal detected

Noise

Signal

Glutamate

Magnesium

Pathological activation of NMDA-receptors

Rest

Ca2+

Noise

Learning

Signal not detected

Noise

Signal

Signal

Damaged neuron

Ca2+

Pathological activation of NMDA-receptors

Impairment of plastic processes

Chronic neurodegeneration

Ca2+

Glutamate

Magnesium

Mechanism of action of memantine (1)

Both memantine and magnesium allow the physiological activation of the NMDA-receptor due to their:

voltage dependency

rapid unblocking kinetics

BUT

Memantine does not leave the NMDA-receptor channel as easily as magnesium following tonic low level activation of NMDA-receptors

Memantine’s voltage-dependency is not as pronounced as magnesium’s

Mechanism of action of memantine (2)

MPathological activation of NMDA-receptors

Possible neuroprotection by memantine

Memantine improves plastic processes

Rest

Ca2+

Rest Learning

Ca2+M

M

Ca2+

Signal detected

Noise Noise

Signal

Noise

Glutamate

Magnesium

Memantine

?Choice of treatment

Choice of Treatment

Is the patient demented?− No evidence of efficacy in MCI studies

What is the cause of dementia?− Limited efficacy studies in FTD

What is the stage of dementia?− Limited evidence for efficacy of memantine in early dementia− Limited evidence for efficacy of AChEIs in late dementia

What are the symptoms to be targeted?− Efficacy for cognition, global scales− Preservation of ADL− Prevention of emergent behavioral problems

What other issues need to be addressed?− Dysphagia− cost

Alzheimer’s is not justa little memory loss.

It eventually kills,but not before it takes

everything away.

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