Transcript Document

DELIRIUM, DEMENTIA, AND
AMNESTIC and OTHER
COGNITIVE DISORDERS
Second Year Medical School
J. Wesson Ashford, M.D., Ph.D.
University of Kentucky
VAMC, Lexington
February 12, 2003
Slides at: www.medafile.com/demdx03a.ppt
Dementia Definition
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Multiple Cognitive Deficits:
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Memory dysfunction
 especially new learning, a prominent early symptom
At least one additional cognitive deficit
 aphasia, apraxia, agnosia, or executive dysfunction
Cognitive Disturbances:
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Sufficiently severe to cause impairment of occupational
or social functioning and
Must represent a decline from a previous level of
functioning
Differential Diagnosis: Top Ten
(commonly used mnemonic device: AVDEMENTIA)
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
Alzheimer Disease (pure ~40%, + mixed~70%)
Vascular Disease, MID (5-20%)
Drugs, Depression, Delirium
Ethanol (5-15%)
Medical / Metabolic Systems
Endocrine (thyroid, diabetes), Ears, Eyes, Environ.
Neurologic (other primary degenerations, etc.)
Tumor, Toxin, Trauma
Infection, Idiopathic, Immunologic
Amnesia, Autoimmune, Apnea, AAMI
Diagnostic Criteria For Dementia Of The
Alzheimer Type (DSM-IV, APA, 1994)
A. Multiple Cognitive Deficits
1. Memory Impairment
2. Other Cognitive Impairment
B. Deficits Impair Social/Occupational
C. Course Shows Gradual Onset And Decline
D. Deficits Are Not Due to:
1. Other CNS Conditions
2. Substance Induced Conditions
E. Do Not Occur Exclusively during Delirium
F. Not Due to Another Psychiatric Disorder
ALZHEIMER’S DISEASE
Estimate MMSE as a function of time
MMSE score
30
25
20
15
10
5
0
-10
-8
-6
-4
-2
0
2
4
6
Estimated years into illness
AAMI / MCI
DEMENTIA
8
10
Alzheimer’s Disease versus
Dementia
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50 - 70% of dementias are AD
Probable AD - 30% of cases, 90% correct
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Possible AD - 40% of cases, 70% correct
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20% have other contributing diagnoses
40% have other contributing diagnoses
Unlikely AD - 30% of cases, 30% are AD

80% have other contributing diagnoses
Vascular Dementia
(DSM-IV - APA, 1994)
A. Multiple Cogntive Impairments
1.
2.
Memory Impairment
Other Cognitive Disturbances
B. Deficits Impair Social/Occupational
C. Focal Neurological Signs and Symptoms or
Laboratory Evidence Indicating Cerebrovascular
Disease Etiologically Related to the Deficits
D. Not Due to Delirium
Factors Associated with Multi-infarct Dementia
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History of stroke (especially in Nursing Home)
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Abrupt onset, Step-wise deterioration
Cardiovascular disease - HTD, ASCVD, & Atrial Fib
Depression (left anterior strokes), personality change
More gait problems than in AD
MRI evidence of T2 changes (?? Binswanger’s disease)
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Followed by onset of dementia within 3 months
Basal ganglia, putamen
Periventricular white matter
SPECT / PET show focal areas of dysfunction
Neuropsychological dysfunctions are patchy
SCORE
VASCULAR DEMENTIA CHANGE ON
THE MINI-MENTAL STATE EXAM
OVERTIME
30
20
10
0
< event
< event
< event
-5
0
5
AVERAGE TIME OF ILLNESS (years)
10
Post-Cardiac Surgery
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53% post-surgical confusion at discharge (delirium)
42% impaired 5 years later (dementia)
May be related to anoxic brain injury, apnea
May be related to narcotic/other medication
May occur in those patients who would have
developed dementia anyway (? genetic risk)
Cardio-vascular disease and stress may start
Alzheimer pathology
Any surgery may have a similar effect related to peri-op or
post-op anoxia or vascular stress
Newman et al., 2001, NEJM
Drug Interactions
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Anticholinergics: amitriptyline, atropine,
benztropine, scopolamine, hyoscyamine, oxybutynin,
diphenhydramine, chlorpheniramine, many antihistaminics
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May aggravate Alzheimer pathology
GABA agonists: benzodiazepines, barbiturates,
ethanol, anti-convulsants
Beta-blockers: propranolol
Dopaminergics: l-dopa, alpha-methyl-dopa
Narcotics: may contribute to dementia
Drug Toxicity

Anti-cholinergic
Peripheral: blurred vision, dry mouth, constipation,
urinary obstruction
 Central: confusion, memory encoding block
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Gaba-agonist:
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Muscle relaxant, anti-convulsant, sedative, antianxiety, amnesic, confusion
Medication induced electrolyte imbalance
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Confusion (watch for in nursing home)
Depression
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Onset: rapid
Precipitants: psycho-social (not organic)
Duration: less than 3 months to presentation
Mood: depressed, anxious
Behavior: decreased activity or agitation
Cognition: unimpaired or poor responses
Somatic symptoms: fatigue, lethargy, sleep, appetite
disruption
Course: rapid resolution with treatment,
but may precede Alzheimer’s disease
Delirium Definition
(more often a problem in medical in-patients)

Disturbance of consciousness
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i.e., reduced clarity of awareness of the
environment with reduced ability to focus, sustain,
or shift attention
Change in cognition (memory, orientation,
language, perception)
Development over a short period (hours to
days), tends to fluctuate
Evidence of medical etiology
Delirium
 Susceptibility may be symptom of early dementia, or
delirium may predispose to later dementia
 Predisposing factors - Age, infections, dementia
 Medical conditions
 Infections:
 G.U. - urinary
 Respiratory (URI, pneumonia)
 G.I.
 Constipation
 Drug toxicity
 Fracture (especially related to hip fracture)
Ethanol
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Possibly Neuroprotective
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Accidents, Head Injury
Dietary Deficiency
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Thiamine – Wernicke-Korsakoff syndrome
Hepatic Encephalopathy
Withdrawal Damage (seizures) Delayed Alcohol
Withdrawal
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May not kill neurons directly (?Dietary recommendation?)
Watch for in hospitalized patients
Chronic Neurodegeneration
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Cerebellum, gray matter nuclei
Medical / Endocrine
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Thyroid dysfunction
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Hypothyoidism – elevated TSH
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Hyperthyroidism
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Compensated hypothyroidism may have normal T4, FTI
Apathetic, with anorexia, fatigue, weight loss, increased T4
Diabetes
Hypoglycemia (loss of recent memory since episode)
Hyperglycemia
Hypercalcemia
Nephropathy, Uremia
Hepatic dysfunction (Wilson’s disease)
Vitamin Deficiency (B12, thiamine, niacin)
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Pernicious anemia – B12 deficiency, ?homocysteine
Eyes, Ears, Environment
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Must consider sensory deficits might contribute to the
appearance of the patient being demented
Central Auditory Processing Deficits (CAPD)
Hearing problems are socially isolating
Visual problems are difficult to accommodate by a
demented patient, ?To do cataract op?
Environmental stress factors can predispose to a
variety of conditions
Nutritional deficiencies (tea & toast syndrome)
Neurological Conditions
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Primary Neurodegenerative Disease
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Diffuse Lewy Body Dementia (? 7 - 50%)
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Fronto-temporal dementia (tau gene)
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Impaired attention, behavioral dyscontrol
Decrease blood flow, hypometaboism on SPECT / PET
(Pick’s disease, Argyrophylic grain disease)
Focal cortical atrophy
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Note relation to Parkinson’s disease, symptoms
Hallucinations, fluctuating course, neuroleptic hypersensitivity)
Primary progressive aphasia (many causes)
Unilateral atrophy, hypofunction on EEG, SPECT, PET
Normal pressure hydrocephalus
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Dementia with gait impairment, incontinence
Suggested on CT, MRI; need tap, ventriculography
Other Neurologic Conditions
Subdural hematoma
 Huntington’s disease
 Creutzfeldt-Jakob disease
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Rapid progression
 Characteristic EEG changes
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Multiple sclerosis
 Corticobasal degeneraton
 Cerebellar degeneration
 Progressive supranuclear palsey
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Tumor
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Primary brain tumor
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Meningioma (treatable)
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Glioma (usually not responsive to therapy)
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Metastatic brain tumor
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Remote effects of carcinoma
Toxins
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Heavy metal screen if considered
Trauma
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Concussion, Contusion
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Subdural hematoma
Hydrocephalus:
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Occult head trauma if recent fall
Normal pressure (late effect of bleed)
Dementia pugilistica
Possible contributor to Alzheimer’s disease initiation
and progression (? 4% of cases)
Concern re: physical abuse by caretakers
Infectious Conditions
Affecting the Brain
HIV
 Neurosyphilis
 Viral encephalitis (herpes)
 Bacterial meningitis
 Fungal (cryptococcus)
 Prion (Creutzfeldt-Jakob disease); (mad cow disease)
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AMNESIC DISORDER
DSM-IV
A.
Memory impairment
- inability to learn new information, or
- Inability to recall previously learned information
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Memory disturbance significantly impairs social,
occupational function, deterioration from past
Memory not due to delirium, dementia
Physiological basis or substance induced
- Distinguish from dissociative disorders, dissociative amnesia,
dissociative identity disorders

Specify
- Transient – less than 1 month
- Chronic - more than 1 month
Causes of Amnesic Disorders
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Amnesia
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Dissociative: localized, selective, generalized
Organic - damage to CA1 of hippocampus
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Epileptic events
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thiamine deficiency (WKE), hypoglycemia, hypoxia
Partial complex seizures
Specific brain diseases
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Transient global amnesia
Multiple sclerosis
Age-Associated Memory Impairment
vs
Mild Cognitive Impairment
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Memory declines with age
Age - related memory decline corresponds with atrophy
of the hippocampus
Older individuals remember more complex items and
relationships
Older individuals are slower to respond
Memory problems predispose to development of
Alzheimer’s disease
Advances in Alzheimer’s
Disease
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Incidence and prevalence
Search for etiology, genetics
Understanding pathophysiology
Better screening tools for early recognition
Improved diagnosis
Developing interventions
Behavioral conditions and management
U.S. Census 2000 by age
Males,
138,053,563
Females,
143,368,343
2,500,000
2,250,000
# people
2,000,000
1,750,000
1,500,000
1,250,000
1,000,000
750,000
Total = 281,421,906
>65 = 35,008,753
>85 = 4,256,587
500,000
250,000
0
0
10
20
30
40
50
Age
60
70
80
90 100
U.S. mortality by age - 1999
Males, 1,175,460
45,000
Number of people
40,000
Females, 1,215,939
35,000
30,000
25,000
20,000
15,000
10,000
5,000
0
0
10
20
30
40
50
Age
60
70
80
90
www.cdc.gov
100
U.S. mortality rate by age
1999 CDC / 2000 census
Males
1.0000
probability
Females
0.1000
0.0100
0.0010
0.0001
0
10 20 30 40 50 60 70 80 90 100
Age
U.S. mortality rate by age
1999 CDC / 2000 census
Males
probability
1.0000
Females
0.1000
Expon. (Males)
y = 9E-05e 0.0848x
Expon.
(Females)
R = 0.9974
y = 3E-05e 0.0926x
0.0100
0.0010
2
2
R = 0.9973
0.0001
30
40
50
60
70
Age
80
90
100
PREVALENCE of AD

Estimated 4 million cases in US (2000)
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(2000 - 46 million individuals over 60 y/o)
Estimated 500,000 new cases per year
Increase with age
(prevalence)
1% of
 2% of
 4% of
 8% of
 16% of

60 - 65
65 - 70
70 - 75
75 - 80
80 - 85
(10.7m) = 107,000
( 9.4m) = 188,000
( 8.7m) = 350,000
( 7.4m) = 595,000
( 5.0m) = 800,000
U.S. mortality rate by age
1999 CDC / 2000 census
Males
Females
dementia incidence
probability
1.0000
0.1000
0.0100
0.0010
0.0001
0
10 20
30 40 50 60 70
Age
80 90 100
# / yr
U.S. Dementia Incidence
(4 million / 8yr)
male=170,603
16000
14000
12000
10000
8000
6000
4000
2000
0
female=329,115
50
60
70
80
Age
90
100
Proportional risk / yr
Dementia incidence by individual
male=34%
0.016
0.014
0.012
0.01
0.008
0.006
0.004
0.002
0
female=66%
50
60
70
80
Age
90
100
Oeppen & Vaupel, 2002
Oeppen & Vaupel, 2002
ECONOMIC IMPACT OF AD
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2 million AD patients in nursing homes
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Projection to Kentucky – 22,000 (6,000 in Eastern KY)
Nursing homes cost - $120 to $160 per day
Annualized cost of nursing homes ranges from $40 to
$70,000 per year
Care of AD patients costs $80 billion per year
With lost wages of patients and families plus costs for
non-nursing home patients:
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Total costs: $120 billion annually (Am J Publ Hlth)
Projection to Kentucky – $1.5 billion annually!
Etiology
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Age (initial genesis vs response to stress)
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Bigger factor than for mortality
Design in a plastic (memory) system, energy demands
Stressor response (adequate repair mechanisms)
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Genetics (amyloid related)
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Familial, early onset: APP (21), PS (14, 1) (less than 5%)
Late onset: APOE e4 (ch19) (?50% of AD)
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Trauma (head injury), vascular (stroke), surgery, loss, grief, etc.
relation to brain cholesterol metabolism?
APOE e2 may be most protective
many other candidate genes
Relation to vascular factors, cholesterol, BP
Education (? design vs protection)
Environment - diet, exercise, smoking
RELATIVE RISK FACTORS
FOR ALZHEIMER’S DISEASE
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Family history of dementia
Family history - Downs
Family history - Parkinson’s
Maternal age > 40 years
Head trauma (with LOC)
History of depression
History of hypothyroidism
History of severe headache
NSAID use or statin use
3.5 (2.6 - 4.6)
2.7 (1.2 - 5.7)
2.4 (1.0 - 5.8)
1.7 (1.0 - 2.9)
1.8 (1.3 - 2.7)
1.8 (1.3 - 2.7)
2.3 (1.0 - 5.4)
0.7 (0.5 - 1.0)
0.2 (0.05 – 0.83)
Roca, 1994, t’Veldt, 2002
NEUROPATHOLOGY OF AD
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Senile plaques
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Neurofibrillary tangles
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beta-amyloid protein (? Primary problem)
hyper-phosphorylated tau (loss of synapses, dementia)
Neurotransmitter losses
Acetylcholine (Ach) – major loss of nicotinic receptors
 Norepinephrine, serotonin, glutamate, GABAss
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Inflammatory responses
New Neuropath Mechanisms
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Amyloid PreProtein (APP - ch21) (early changes)

metabolism occurs on cholesterol “rafts”
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Cholesterol transport by APOE (ch 19)
alpha-secretase vs beta/gamma secretase metabolism
 influence toward alpha-secretase by Acetylcholine
 gamma-secretase (PreSenilin genes, ch14,1)
 break down - Insulin Degrading Enzyme (ch10), etc.
 prevention of fibril formation by melatonin

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Tau hyperphosphorylation (relation to dementia)
glycogen-synthase-kinase (GSK) 3-beta
 inhibition by Ach, lithium, valproic acid

APPs
amyloid
APPs
APP
M1 AGONIST or ACh
M1 mAChR
Gq/11
/-secretase
-secretase
PHF
MAPk
PLC
Hyper-P-TAU
PKC
TAU
GSK-3
beta
Li+
Protein
phosphorylation
Adapted from Fisher, 2000
Genes and Alzheimer’s disease
(60% - 80 % of causation)
(all known genes relate to amyloid)

Familial AD (onset < 60 y/o) (<5%)
Presenilin I, II (ch 14, 1)
 APP (ch 21)
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
Non-familial (late onset)

APOE
Clinical studies suggest 40 – 50% due to e4
 Population studies suggest 10 – 20% cause
 Evolution over last 300,000 to 200,000 years

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At least 20 other genes
APO-E genotype and AD onset
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e2 -- 7% of the population
e3 -- 78% of the population
e4 -- 15% of the population
e3/3 - average age of onset = 74 y/o
e3/4 and e4/4 average age = 69 y/o
APO-E genotype and AD risk
46 Million in US > 60 y/o //// 4 Million have AD
(data from Saunders et al., 1993; Farrer et al., 1997)
GenT %pop %AD
#pop
E2/2
0.5M .004M 0.8%
.4 M
5.5M .18M 3.2%
1.5 M
1% 0.1%
4%
#AD
risk If all US
E2/3
12 %
E3/3
60%
35% 27.6M 1.4M 5.1%
2.3 M
E3/4
21%
42%
8.2 M
E4/4
2%
16%
9.6M 1.7M 18%
.9M
.6M 67%
30.7M
See: Ashford & Mortimer, 2002, Journal of Alzheimer’s Disease
Biopsychosocial Systems
Affected by AD
(all related to neuroplasticity)

Social Systems
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Psychological Systems
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Instrumental ADLs - Early
Basic ADLs - Late
Primary Loss Of Memory
Later Loss Of Learned Skills
Neuronal Memory Systems
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Cortical Glutamatergic Storage
Subcortical (acetylcholine, norepi, serotonin)
Cellular Plastic Processes
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APP metabolism – early, broad cortical distribution
TAU hyperphosphorylation – late, focal effect, dementia related
Why Diagnose AD Early?
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Safety (driving, compliance, cooking, etc.)
Family stress and misunderstanding (blame, denial)
Early education of caregivers of how to handle
patient (choices, getting started)
Advance planning while patient is competent (will,
proxy, power of attorney, advance directives)
Patient’s and Family’s right to know
Specific treatments now available, may delay nursing
home placement longer if started earlier
Early Recognition of AD: Consensus Statement
(AAGP, AGS, Alzheimer’s Association)


AD continues to be missed as diagnosis
AD is unrecognized and under-reported
patients do not realized
 families tend to compensate

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Effective treatment and management techniques
are available
Small et al., JAMA, 1997
Need for Better Screening
and Early Assessment Tools
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Genetic vulnerability testing
Early recognition (10 warning signs)
Screening tools (6th vital sign in elderly)
Positive diagnostic tests
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CSF – tau levels elevated, amyloid levels low
Brain scan – PET – DDNP, Congo-red derivatives
Mild Dementia severity assessments
Detecting early change

predicting progression, measuring rate
Alzheimer Warning Signs
Top Ten
Alzheimer Association
1. Recent memory loss affecting job
2. Difficulty performing familiar tasks
3. Problems with language
4. Disorientation to time or 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
Need for a Brief Screening Test for
Alzheimer’s Disease

Recent evidence of benefits of anticholinesterase agents in the treatment of mild
Alzheimer’s disease
Improvement of cognition
 Slowing of progression

Available Screening Tests

MMSE

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
2 – 4 min
Not sensitive
3 – 5 min
Complex scoring, unclear adequacy
Memory Impairment Screen

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Too complex
Mini-cog
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7 – 10 min
Clock Drawing Test
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Too long
7-Minute Screen

10 -- 15 min
4 min
Need for slightly shorter, easier test
(a suitably accurate test that takes less than 2
minutes is not available)
The Progress of Alzheimer’s Disease
30
Early diagnosis
Mild-moderate
Severe
Cognitive symptoms
MMSE score
25
20
Loss of ADL
15
10
5
Behavioral problems
Nursing home placement
Death
0
0 0.5 1 1.5 2 2.5 3 3.5 4 4.5 5 5.5 6 6.5 7 7.5 8 8.5 9
Years
Feldman H, Gracon S. In: Clinical Diagnosis and Management of Alzheimer’s Disease. 1996:239-253.
Ashford et al., 1995
AD all (easiest to hardest at p=.5)
Mini-Mental State Exam items
PROBABILITY CORRECT
1
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0
-4 -3 -2 -1
0
1
2
3
4
5
6
7
8
DISABILITY ("time-index" year units)
9 10
PENCIL
APPL-REP
WATC
LOCATION
PENY-REP
TABL-REP
CLOS-IS
RIT-HAND
CITY
FOLD-HLF
SENTENCE
COUNTY
NO-IFS
FLOOR
SEASON
YEAR
PUT-LAP
MONTH
ADDRESS
DRAW-PNT
DAY
SPEL_ALL
DATE
APPL-MEM
PENY-MEM
TABL-MEM
Total Item Information Function for the MMSE
30
Information
25
20
15
10
5
0
-4 -3 -2 -1
0
1
2
3
4
5
6
7
8
Alzheimer's Severity Horographic Function (time-index year units)
9 10
Brief Alzheimer Screening



Repeat these three words: “apple, table, penny”.
So you will remember these words, repeat them again, twice.
What is today’s date?


“Name as many animals as you can in 30 seconds, GO!”

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A score of 4 or 5 indicate a very low likelihood of dementia.
A score of 2 or 3 suggests that more testing is needed.
A score of 0 or 1 indicate a very high likelihood of dementia.
(palm-pilot scoring under development)
If score of 2 or 3:



1 for each word,
TOTAL (max = 5)


1 point for naming 10 animals
“What were the 3 words I asked you to repeat?” (no prompts)


1 point if within 2 days.
Spell World Backwards
Draw a Clock (gives some impression of visuospatial problems)
If continued difficulties, ask questions about ADLs
BRIEF ALZHEIMER SCREEN
(Normal vs Mild AD, MMS>19)
20
True Positive Rate (%) (Sensitivity)
100
27
90
26
25
80
14
13
12
11
10
70
9
60
8
animals 1 m
AUC = 0.868
animals 30 s
AUC = 0.828
MMSE
AUC = 0.965
20
Date+3 Rec
AUC = 0.875
10
BAS
AUC = 0.983
50
40
97
30
6
0
0
10
20
30
40
50
60
70
80
False Positive Rate (%) (1-Specificity)
90 100
BLT/Ashford Memory Test
(to detect AD onset)
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New test to screen patients for Alzheimer’s
disease using the World-Wide Web – based
testing and CD-distribution
Test only takes 1-minute
Test can be repeated often (quarterly)
Any change over time can be detected
Test is at: www.ibaglobal.com/BLT
For info, see: www.medafile.com
Assessment
History Of The Development Of The Dementia
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Ask the Patient What Problem Has Brought Him to See You
Ask the Family, Companion about the Problem
Specifically Ask about Memory Problems
Ask about the First Symptoms
Enquire about Time of Onset
Ask about Any Unusual Events Around the Time of Onset, e.g.,
stress, trauma, surgery
Ask about Nature and Rate of Progression
Physical Examination
Neurological Examination
PHYSICAL/NEUROLOGICAL
EXAMINATION
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CHECK BLOOD PRESSURE
IDENTIFY SYSTEMIC DISORDERS
CRANIAL NERVES
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SENSORY DEFICITS
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Proprioception, vibration
DEEP TENDON REFLEXES
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Olfactory dysfunction, poor eye tracking
Check for hearing, vision deficits
Brisk, check for focal reflexes
PATHOLOGIC REFLEXES
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Hyperactive snout reflex, Gegenhalten
CURRENT APPROACHES TO
SEVERITY ASSESSMENT
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MINI-MENTAL STATE EXAM
CLOCK DRAWING
ANIMAL NAMING (1 minute)
MATTIS DEMENTIA RATING SCALE
ALZHEIMER’S DISEASE
ASSESSEMENT SCALE (ADAS)
ACTIVITIES OF DAILY LIVING
GLOBAL CLINICAL SCALE
CLINICAL DEMENTIA RATING SCALE
GLOBAL DETERIORATION SCALE / FAST
NEUROPSYCHOLOGICAL
TESTING (WAIS, WECHSLER)
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MEMORY: SHORT-TERM, REMOTE
VERBAL FUNCTION, FLUENCY
VISUO-SPATIAL FUNCTION
ATTENTION
EXECUTIVE FUNCTION
ABSTRACT THINKING
ACCOUNT FOR EDUCATION
ACCOUNT FOR PRIOR DISFUNCTIONS
LABORATORY TESTS (routine)
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BLOOD TESTS
 electrolytes, liver, kidney function tests, glucose
 thyroid function tests (T3, T4, FTI, TSH)
 vitamin B12, folate
 complete blood count, ESR
 VDRL, HIV (if indicated)
EKG (if indicated)
CHEST X-RAY (if indicated)
URINALYSIS
ANATOMICAL BRAIN SCAN – CT (cheapest), MRI
SPECIAL LABORATORY TESTS
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FUNCTIONAL BRAIN IMAGING
(SPECT, PET)
EEG, Evoked Potentials (P300)
REACTION TIMES (slowed in the elderly, especially
when complex response is required
CSF ANALYSIS - ROUTINE STUDIES
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ELEVATED TAU (future possible)
DECREASED AMYLOID (future possible)
HEAVY METAL SCREEN (24 hr urine)
GENOTYPING
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APO-LIPOPROTEIN-E (for supporting dx)
AUTOSOMAL DOMINANT (young onset)
Justification for Brain Scan in
Dementia Diagnosis
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Differential Diagnosis: Tumor, Stroke, Subdural
Hematoma, Normal Pressure Hydrocephalus,
Encephalomalacia
Confirmation of atrophy pattern
Estimation of severity of brain atrophy
MRI shows T2 white matter changes
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Periventricular, basal ganglia, focal vs confluent
These may indicate vascular pathology
SPECT, PET - estimation of regions of physiologic
dysfunction, areas of infarction
Helps family to visualize problem
Ashford et al,
2000
UCLA group, J. Amer. Ger. Psych, 2002
Shoghi-Jadid et al., 2002
67-year-old control
Alzheimer patient
PET brain images
2-(4’-methylamino-phenyl)-6-hydroxybenzothiazole (Pittsburgh
Compound)
Are we ready to do genetic testing to
predict AD?
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The family members want it
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Family members can make more powerful financial
decisions based on this knowledge than the relevance of
insurance companies implementing changes in actuarial
calculations
Those at risk can seek more frequent testing
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They consider recommendations against genetic testing to be
“paternalistic”
This is the best opportunity for early recognition
Those at risk will be better advocates for research
Specific preventive treatments can be developed for each
genetic factor
BEHAVIORAL PROBLEMS
IN DEMENTIA PATIENTS
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MOOD DISORDERS – depression – early in AD
PSYCHOTIC DISORDERS
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Particularly paranoia, e.g, people stealing things
INAPPROPRIATE BEHAVIORS (sexual
AGGRESSION: verbal, physical
PURPOSELESS ACTIVITY: verbal, motor
MEAL TIME BEHAVIORS
SLEEP DISORDERS
NEUROPSYCHIATRIC
TREATMENTS
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First treat medical problems
Second environmental interventions
Third neuropsychiatric medications
Cognitive impairment
 Psychotic symptoms
 Depressive symptoms
 Insomnia symptoms
 Anorexia symptoms
 Parkinsonian symptoms
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