mild cognitive impairment differential diagnosis j. wesson ashford, m.d., ph.d. stanford / va...
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MILD COGNITIVE IMPAIRMENTDIFFERENTIAL DIAGNOSIS
J. Wesson Ashford, M.D., Ph.D.
Stanford / VA Alzheimer’s Center
VAMC, Palo Alto, California
May 14, 2004
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MILD COGNITIVE IMPAIRMENT CRITERIA (Amer. Acad. Neurology)
(Petersen et al., 2001 – Neurology 56:1133)
1. Memory complaint, preferably corroborated by an informant
2. Objective memory impairment3. Normal general cognitive function4. Intact activities of daily living5. Not demented
- Earlier descriptions by: Jonker, Hooyer, 1990 Flicker, Ferris, Reisberg, 1991 Zaudig, 1992
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MILD COGNITIVE IMPAIRMENT ISSUES IN DEFINITION
(Petersen et al., 2001 – Neurology 56:1133)
Study Mean Age
Criteria Annual conversion rate to AD %
Mayo 81 MCI 12
Toronto 74 Memory Impairment 14
Columbia
66 Questionable dementia
15
MGH 72 CDR 0.5 6
Seattle 74 Isolated memory loss 12
NYU 71 GDS 3 25
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0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
Age
Perc
enta
ge AD
MCI
Non-Affected
Yesavavage et al., 2002Markov Chain model
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Estimate MMSE as a function of time
0
5
10
15
20
25
30
-10 -8 -6 -4 -2 0 2 4 6 8 10
Estimated years into illness
MM
SE
scor
e
AAMI / MCI DEMENTIA
ALZHEIMER’S DISEASE
Ashford et al., 1995
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Age-Associated Memory Impairmentvs
Mild Cognitive Impairment
• Memory declines with age – need to consider relative to APOE genotype!
• 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• Thus --- screening for MCI / early AD must consider age!
– And should consider APOE genotype!
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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
• Effective treatment and management techniques are available – (AChEIs FDA approved)– Several other approaches are beneficial
Small et al., JAMA, 1997
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DIAGNOSTIC CRITERIA FOR DEMENTIA OF THE ALZHEIMER TYPE
(DSM-IV, APA, 1994)
A. DEVELOPMENT OF MULTIPLE COGNITIVE DEFICITS
1. MEMORY IMPAIRMENT
2, OTHER COGNITIVE IMPAIRMENT
B. THESE IMPAIRMENTS CAUSE DYSFUNCTION IN
IN SOCIAL OR OCCUPATIONAL ACTIVITIES
C. COURSE SHOWS GRADUAL ONSET AND DECLINE
D. DEFICITS ARE NOT DUE TO:
1. OTHER CNS CONDITIONS
2. SUBSTANCE INDUCED CONDITIONS
F. DO NOT OCCUR EXCLUSIVELY DURING DELIRIUM
G. ARE NOT DUE TO OTHER PSYCHIATRIC DISORDER
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Differential Diagnosis: Top Ten
(commonly used mnemonic device: AVDEMENTIA)1. Alzheimer Disease (pure ~40%, + mixed~70%)2. Vascular Disease, MID (5-20%)3. Drugs, Depression, Delirium4. Ethanol (5-15%)5. Medical / Metabolic Systems6. Endocrine (thyroid, diabetes), Ears, Eyes, Environ.7. Neurologic (other primary degenerations, etc.)8. Tumor, Toxin, Trauma9. Infection, Idiopathic, Immunologic10. Amnesia, Autoimmune, Apnea, AAMI11. VA – consider PTSD, Gulf War Syndrome
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Dementia Definition
• Multiple Cognitive Deficits:– Memory dysfunction
• especially new learning, a prominent early symptom
– At least one additional cognitive deficit• aphasia, apraxia, agnosia, or executive
dysfunction
• Cognitive Disturbances:– Sufficiently severe to cause impairment of
occupational or social functioning and – Must represent a decline from a previous
level of functioning
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Alzheimer’s Disease versus Dementia
– 50 - 70% of dementias are AD– Probable AD - 30% of cases, 90% correct
– 20% have other contributing diagnoses
– Possible AD - 40% of cases, 70% correct– 40% have other contributing diagnoses
– Unlikely AD - 30% of cases, 30% are AD– 80% have other contributing diagnoses
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Vascular Dementia(DSM-IV - APA, 1994)
A. Multiple Cogntive Impairments1. Memory Impairment2. 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
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Factors Associated with Multi-infarct Dementia
• History of stroke (especially in Nursing Home)– Followed by onset of dementia within 3 months
• 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)– Basal ganglia, putamen– Periventricular white matter
• SPECT / PET show focal areas of dysfunction• Neuropsychological dysfunctions are patchy
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VASCULAR DEMENTIA CHANGE ON THE MINI-MENTAL STATE EXAM
OVERTIME
< event
< event
< event
0
10
20
30
-5 0 5 10
AVERAGE TIME OF ILLNESS (years)
SC
OR
E
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Post-Cardiac Surgery• 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, NEJMNewman et al., 2001, NEJM
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Drug Interactions
• Anticholinergics: amitriptyline, atropine, benztropine, scopolamine, hyoscyamine, oxybutynin, diphenhydramine, chlorpheniramine, many anti-histaminics– 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
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Drug Toxicity• Anti-cholinergic
– Peripheral: blurred vision, dry mouth, constipation, urinary obstruction
– Central: confusion, memory encoding block• Gaba-agonist:
– Muscle relaxant, anti-convulsant, sedative, anti-anxiety, amnesic, confusion
• Medication induced electrolyte imbalance– Confusion (watch for in nursing home)
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Depression• 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
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Delirium Definition(more often a problem in medical in-patients)
Disturbance of consciousness 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
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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)
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Ethanol
• Possibly Neuroprotective– May not kill neurons directly (?Dietary
recommendation?)
• Accidents, Head Injury• Dietary Deficiency
– Thiamine – Wernicke-Korsakoff syndrome• Hepatic Encephalopathy• Withdrawal Damage (seizures)
Delayed Alcohol Withdrawal– Watch for in hospitalized patients
• Chronic Neurodegeneration– Cerebellum, gray matter nuclei
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Medical / Endocrine• Thyroid dysfunction
– Hypothyoidism – elevated TSH• Compensated hypothyroidism may have normal T4, FTI
– Hyperthyroidism• 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)
– Pernicious anemia – B12 deficiency, ?homocysteine
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Eyes, Ears, Environment
• 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)
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Neurological Conditions• Primary Neurodegenerative Disease
– Diffuse Lewy Body Dementia (? 7 - 50%)– Note relation to Parkinson’s disease, symptoms– Hallucinations, fluctuating course, neuroleptic
hypersensitivity)– Fronto-temporal dementia (tau gene)
– Impaired attention, behavioral dyscontrol– Decrease blood flow, hypometaboism on SPECT / PET– (Pick’s disease, Argyrophylic grain disease)
• Focal cortical atrophy– Primary progressive aphasia (many causes)– Unilateral atrophy, hypofunction on EEG, SPECT, PET
• Normal pressure hydrocephalus– Dementia with gait impairment, incontinence – Suggested on CT, MRI; need tap, ventriculography
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Other Neurologic Conditions
– Subdural hematoma– Huntington’s disease– Creutzfeldt-Jakob disease
• Rapid progression• Characteristic EEG changes
– Multiple sclerosis– Corticobasal degeneraton– Cerebellar degeneration– Progressive supranuclear palsey
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• Tumor
– Primary brain tumor• Meningioma (treatable)• Glioma (usually not responsive to therapy)
– Metastatic brain tumor
– Remote effects of carcinoma
• Toxins– Heavy metal screen if considered
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Trauma
– Concussion, Contusion• Occult head trauma if recent fall
– Subdural hematoma– Hydrocephalus:
• 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
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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 DISORDERDSM-IV
A. Memory impairment- inability to learn new information, or- Inability to recall previously learned information
• 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
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Causes of Amnesic Disorders
• Amnesia– Dissociative: localized, selective,
generalized– Organic - damage to CA1 of
hippocampus • thiamine deficiency (WKE), hypoglycemia,
hypoxia
• Epileptic events– Partial complex seizures
• Specific brain diseases– Transient global amnesia– Multiple sclerosis
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Etiology of Alzheimer’s Disease
• Age (initial genesis vs response to stress)– Bigger factor than for mortality– Design in a plastic (memory) system, energy demands– Stressor response (inadequate repair mechanisms)
• Trauma (head injury), vascular (stroke), surgery, loss, grief, immunological response, etc.
• Genetics (amyloid related)– Familial, early onset: APP (21), PS (14, 1) (less than 5%)– Late onset: APOE e4 (ch19) (40% to 90% of AD)
• 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, toxin, smoking, infectious
agent
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AD Is Often Misdiagnosed
Source: Consumer Health Sciences, LLC. Alzheimer’s Caregiver Project. 1999.
Patient initially diagnosed with AD
Patient’s first diagnosis other than AD
Yes 28%
NoNo 72% 72%
21%
7%
9%
14%
14%
35%
Normal aging
Depression No diagnosis
Dementia (not AD) Stroke
Other
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AD is Underdiagnosed• Early Alzheimer’s disease is subtle – it is easy for
family members and physicians to miss the initial signs and symptoms
• Less than half of AD patients are diagnosed– Estimates are that 25% to 50% of cases remain undiagnosed
• Undiagnosed AD patients often face avoidable social, financial, and medical problems
• Early diagnosis and appropriate intervention may lessen disease burden
• No definitive laboratory test for diagnosing AD exists
Evans DA. Milbank Quarterly. 1990; 68:267-289
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AD Can Be Readily Diagnosed
• A diagnosis of Alzheimer’s disease can be made with a high degree of certainty
• Using NINCDS-ADRDA criteria, accuracy in autopsy-verified cases is approximately 90%
• Diagnosis is a 2-step process:– Detection through screening– Confirmation through patient history and
physical, caregiver interview, brain imaging, and appropriate laboratory studies
McKhann G et al. Neurology. 1984;34:939-944. Kazee AM et al. Alzheimer Dis Assoc Disord. 1993;7:152-164.
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Assessment
History Of The Development Of The Dementia– 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
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RELATIVE RISK FACTORS FOR ALZHEIMER’S DISEASE
• Family history of dementia 3.5 (2.6 - 4.6)• Family history – Downs 2.7 (1.2 - 5.7)• Family history - Parkinson’s 2.4 (1.0 - 5.8)• Maternal age > 40 years 1.7 (1.0 - 2.9)• Head trauma (with LOC) 1.8 (1.3 - 2.7)• History of depression 1.8 (1.3 - 2.7)• History of hypothyroidism 2.3 (1.0 - 5.4)• History of severe headache 0.7 (0.5 - 1.0)• NSAID use or statin use 0.2 (0.05 – 0.83)
Roca, 1994, t’Veldt, 2002
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FACTORS INFLUENCING ALZHEIMER’S DISEASE
(age at onset, rate of progression)• age• sex• genotype (presenilin, APO-E)• education• environment (head injury)• surgery• psychological problems: depression,
agitation, anxiety, sleep disturbance• medication
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PHYSICAL/NEUROLOGICAL EXAMINATION
• CHECK BLOOD PRESSURE• IDENTIFY SYSTEMIC DISORDERS• CRANIAL NERVES
– Olfactory dysfunction, poor eye tracking– Check for hearing, vision deficits
• SENSORY DEFICITS – Proprioception, vibration
• DEEP TENDON REFLEXES– Brisk, check for focal reflexes
• PATHOLOGIC REFLEXES– Hyperactive snout reflex, Gegenhalten
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NEUROPSYCHOLOGICAL TESTING (WAIS, WECHSLER)
• MEMORY: SHORT-TERM, REMOTE• VERBAL FUNCTION, FLUENCY• VISUO-SPATIAL FUNCTION• ATTENTION• EXECUTIVE FUNCTION• ABSTRACT THINKING• ACCOUNT FOR EDUCATION• ACCOUNT FOR PRIOR DISFUNCTIONS
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CURRENT APPROACHES TO SEVERITY ASSESSMENT
• 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
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LABORATORY TESTS (routine)
• 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
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SPECIAL LABORATORY TESTS • 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– ELEVATED TAU (future possible)– DECREASED AMYLOID (future possible)
• HEAVY METAL SCREEN (24 hr urine)• GENOTYPING
– APO-LIPOPROTEIN-E (for supporting diagnosis)– AUTOSOMAL DOMINANT (young onset)
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Justification for Brain Scan in Dementia Diagnosis
• 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
– 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
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Shoghi-Jadid et al., 2002
UCLA compound
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2-(4’-methylamino-phenyl)-6-hydroxybenzothiazole (Pittsburgh Compound)
67-year-old control Alzheimer patient
PET brain images
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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)
• Non-familial (late onset)– APOE
• Clinical studies suggest 40 – 50% due to 4• If is considered, may be 95% of causation• Population studies suggest 10 – 20% cause• Evolution over last 300,000 to 200,000 years
– At least 20 other genes
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APO-E genotype and AD risk46 Million in US > 60 y/o //// 4 Million have AD(data from Saunders et al., 1993; Farrer et al., 1997)
GenT %pop %AD #pop #AD risk If all US
E2/2 1% 0.1% 0.5M .004M 0.8% .4 M
E2/3 12 % 4% 5.5M .18M 3.2% 1.5 M
E3/3 60% 35% 27.6M 1.4M 5.1% 2.3 M
E3/4 21% 42% 9.6M 1.7M 18% 8.2 M
E4/4 2% 16% .9M .6M 67% 30.7M
JW Ashford, MD PhD, 2003
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Are we ready to do genetic testing to predict AD?
• The family members want it– They consider recommendations against genetic
testing to be “paternalistic”• 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– 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
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U.S. Census 2000 by age
0
250,000
500,000
750,000
1,000,000
1,250,000
1,500,000
1,750,000
2,000,000
2,250,000
2,500,000
0 10 20 30 40 50 60 70 80 90 100
Age
# p
eo
ple
Males,138,053,563Females,143,368,343
Total = 281,421,906>60 = 45,809,291>65 = 35,003,844>85 = 4,251,678>100= 62,545
www.census.gov
JW Ashford, MD PhD, 2003
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U.S. mortality by age - 1999
0
5,000
10,000
15,000
20,000
25,000
30,000
35,000
40,000
45,000
0 10 20 30 40 50 60 70 80 90 100
Age
Nu
mb
er
of
pe
op
le
Males, 1,175,460
Females, 1,215,939
www.cdc.gov
JW Ashford, MD PhD, 2003
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JW Ashford, MD PhD, 2003
U.S. mortality rate by age1999 CDC / 2000 census
0.0001
0.0010
0.0100
0.1000
1.0000
0 10 20 30 40 50 60 70 80 90 100Age
Yea
rly
Haz
ard
Males, 2t = 8.2yrsFemales, 2t = 7.5 yrsAlzheimer incidence
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Probability Not Demented
00.10.20.30.40.50.60.70.80.9
1
50 60 70 80 90 100
Age
Pro
po
rtio
n o
f p
op
ula
tio
n
JW Ashford, MD PhD, 2003
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U.S. Alzheimer Incidence
(4 million / 8yr)
02000400060008000
10000120001400016000
50 60 70 80 90 100
Age
# /
yr
male=170,603
female=329,115
JW Ashford, MD PhD, 2003
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JW Ashford, MD PhD, 2003
(Incidence for a to a + 1 year)
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Probability Not Demented
00.10.20.30.40.50.60.70.80.9
1
50 60 70 80 90 100
Age
Pro
po
rtio
n o
f p
op
ula
tio
n
mean rate
APOE 4/4
APOE 3/4
APOE 3/3
JW Ashford, MD PhD, 2003
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JW Ashford, MD PhD, 2000
U.S. AD Incidence by APOE(proportion of cases)
00.10.20.30.40.50.60.70.80.9
1
50 60 70 80 90 100Age
Pro
po
rtio
n /
Yea
r 4/4
3/43/3
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Probability of Dementia Onset
0
0.01
0.02
0.03
0.04
50 60 70 80 90 100
Age (single mortality correction)
pro
b/ y
r *
live
po
pu
lati
on APOE 4/4-M
APOE 4/4-FAPOE 3/4-MAPOE 3/4-FAPOE 3/3-MAPOE 3/3-F
JW Ashford, MD PhD, 2003
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Miech et al., 2002
Cache County, probability of incident dementiaCircles – femalesSquares - malesOpen – ApoE-e44Gray – ApoE-e4/xBlack – ApoE-ex/x
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Why Diagnose AD Early?
• 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 slow underlying disease process– May delay nursing home placement longer if started
earlier
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Need for Better Screening and Early Assessment Tools
• Genetic vulnerability testing (trait risk)• Vulnerability factors (education, occupation, head
injury)• Early recognition (10 warning signs)• Screening tools (6th vital sign in elderly)• Positive diagnostic tests
– CSF – tau levels elevated, amyloid levels low– Brain scan – PET – DDNP, Congo-red derivatives
• Mild Dementia severity assessments• Detecting early change over time
– predicting progression, measuring rate
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Need for a Brief Screening Test for Alzheimer’s Disease
• Recent evidence of benefits of anti-cholinesterase agents in the treatment of mild Alzheimer’s disease– Improvement of cognition– Slowing of progression
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Alzheimer Warning SignsTop Ten
Alzheimer Association
1. Recent memory loss affecting job2. Difficulty performing familiar tasks3. Problems with language4. Disorientation to time or place5. Poor or decreased judgment6. Problems with abstract thinking7. Misplacing things8. Changes in mood or behavior9. Changes in personality 10. Loss of initiative
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Available Screening Tests• MMSE 10 -- 15 min
• Too long
• 7-Minute Screen 7 – 10 min• Too complex
• Clock Drawing Test 2 – 4 min• Not sensitive
• Mini-cog 3 – 5 min• Complex scoring, unclear adequacy
• Memory Impairment Screen 4 min• Need for slightly shorter, easier test
• (a suitably accurate test that takes less than 2 minutes is not available)
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Animals named in 1 min (mms>19) - CERAD data set
0
2
4
6
8
10
12
0 10 20 30 40
number of animals named
pe
rce
nt
of
tota
l
Normal Controls, CS = 1, n = 386
Alzheimer patients, CS = 0, n = 380
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Animals named in 30 seconds (mms>19)
0
2
4
6
8
10
12
14
16
0 5 10 15 20 25
number of animals named
pe
rce
nt
of
tota
l
Normal Controls, n=386
Mild Alzheimer Patients, n=380JW Ashford, MD PhD, 2001
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Animal naming ROCs (AUC 15: 0.74; 30: 0.83; 45: 0.86; 60: 0.87)
5
6
7
8
7
8
9
10
11
.
10
11
12
13
1415
16 17
0
10
20
30
40
50
60
70
80
90
100
0 10 20 30 40 50 60 70 80 90 100
False Positive Rate (%)
Sen
sitiv
ity (%
) animals in 15 secs
animals in 30 secs
animals in 45 secs
animals in 60 secs
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Brief Alzheimer Screen (BAS)
• Repeat these three words: “apple, table, penny”.• So you will remember these words, repeat them again.• What is today’s date?
• D = 1 if within 2 days.
• Spell the word “WORLD” backwards• S = 1 point for each word in correct order
• “Name as many animals as you can in 30 seconds, GO!”• A = number of animals
• “What were the 3 words I asked you to repeat?” (no prompts)
• R = 1 point for each word recalled
BAS = 3 x R + 2/3 x A + 5 x D + 2 x S
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0
10
20
30
40
50
60
70
80
90Pe
rcen
t of V
alid
atio
n Sa
mpl
e
3-22 23 24 25 26 27-39
BAS Score
Mild AD
Control
JW Ashford, MD PhD, 2001 Mendiondo et al., 2004
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BRIEF ALZHEIMER SCREEN (Normal vs Mild AD, MMS>19)
9
20
1413
1211
10
9
6
7
8
2627
25
0
10
20
30
40
50
60
70
80
90
100
0 10 20 30 40 50 60 70 80 90 100
False Positive Rate (%) (1-Specificity)
Tru
e P
osi
tiv
e R
ate
(%
) (
Se
nsi
tiv
ity)
animals 1 m AUC = 0.868
animals 30 s AUC = 0.828
MMSE AUC = 0.965
Date+3 Rec AUC = 0.875
BAS AUC = 0.983
JW Ashford, MD PhD, 2003
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CONCLUSIONS on the BAS
• A single cut-off score provides reasonable sensitivity and specificity for the diagnosis of AD within 2 – 3 minutes
• Two cut-off points divide the population into 3 tiers– the first cut-off indicates a low likelihood of dementia– the second indicates a high likelihood of dementia– the remaining group falls into a ‘gray area’ in need of
closer scrutiny, follow-up, and more extensive testing
• A suitably short screen can be administered yearly to individuals over 60 y/o as a 6th vital sign
• Next direction – use of IRT to locate level of impairment
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BLT/Ashford Memory Test(to detect AD onset)
• New test to screen patients for AD: – World-Wide Web – based testing, – CD-distribution– KIOSK administration
• Determine level of ability / impairment• Test takes about 1-minute• Test can be repeated often (e.g., quarterly)
• Any change over time can be detected• Test is at: www.ibaglobal.com/BLT• For info, new tests, see: www.medafile.com,
www.brainlane.net