Transcript Recognizing and Screening for Dementia and Alzheimer’s Disease

Dementia and
Alzheimer’s Disease:
Recognition and Diagnosis
J. Wesson Ashford, M.D., Ph.D.
Stanford / VA Alzheimer’s Center
VAMC, Palo Alto
California
May 5, 2006
Slides at: www.medafile.com (Dr. Ashford’s lectures)
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
Alzheimer’s Disease
• First described by Alois Alzheimer,
a German neuropathologist, in 1907
• Observed in a 51-year-old female
patient with paranoia, memory loss,
disorientation, and hallucinations
• Postmortem studies characterized senile
plaques and neurofibrillary tangles
(NFTs) in the cerebral cortex
– Senile plaques: Extracellular
accumulation of insoluble
fragments of beta-amyloid (A1-42)
– NFTs: Intracellular accumulation
of hyperphosphorylated
tau strands
Relative Risk Factors for
Alzheimer’s Disease
•
•
•
•
•
•
•
•
•
•
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
History of “statin” use
NSAID use
– Use of NSAIDs, ASA, H2-blcks
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)
0.3
0.2 (0.05 – 0.83)
0.09
Roca, 1994; ‘t Veld et al., 2001, Breitner et al., 1998, Wolozin et al., 2000
Epidemiology of AD
• Prevalence estimate 4 million cases in US (2000)
• (2000 - 46 million individuals over 60 y/o)
• Incidence estimate 500,000 new cases per year
• Doubles every 5 years (see Jorm & Jolley, 1998)
• Increase with age
–
–
–
–
–
–
–
1% of
2% of
4% of
8% of
16% of
32% of
64% of
60 - 65 (10.8m)
65 - 70 ( 9.5m)
70 - 75 ( 8.9m)
75 - 80 ( 7.4m)
80 - 85 ( 4.9m)
85 – 90 ( 2.8m)
90 - 95 ( 1.1m)
prevalence incidence
=
=
=
=
=
=
=
108,054
191,000
354,000
593,000
791,000
893,000
712,000
13,000
23,000
42,000
70,000
92,000
102,000
89,000
ECONOMIC IMPACT OF AD
• 2 million AD patients in nursing homes in U.S.
– Projection to California (2005) – 240,000
• Nursing Home Care of AD patients - costs
– $40,000/year in U.S. = $80 billion per year
– $55,000/year in California (2005) = $13 billion per year
– Average patient is in nursing homes for an average of about 3
years
– Life-time nursing home cost (CA) – about $165,000 per patient
avg.
• The majority of patients live at home and
are cared for by family and friends
• With lost wages of patients and families plus costs for
non-nursing home patients:
– Total costs in U.S.: $120 billion annually (Am J Publ Hlth)
– Projection to California – $20 billion annually!
United States, 440 Congressional Districts
year
US population
District average population
% > 65
# > 65
# Alzheimer’s Disease
# Other Dementia
Cost / Yr in US
2000
281,421,906
639,595
12.4
34,896,316
3,489,632
2010
308,935,581
702,126
13
40,161,626
4,016,163
2030
363,584,435
826,328
19.7
71,626,134
7,162,613
1,744,816
2,008,081
3,581,307
$157,033,423,548 $180,72,7314,885 $322,317,601,628
Benefits of Early Alzheimer Diagnosis
Social
• Undiagnosed AD patients face avoidable problems
• social, financial
• Early education of caregivers
• how to handle patient (choices, getting started)
• Advance planning while patient is competent
• will, proxy, power of attorney, advance directives
• Reduce family stress and misunderstanding
• caregiver burden, blame, denial
• Promote safety
• driving, compliance, cooking, etc.
• Patient’s and Family’s right to know
• especially about genetic risks
• Promote advocacy
• for research and treatment development
Benefits of Early Alzheimer Diagnosis
Medical
• Early diagnosis and treatment and appropriate
intervention may:
– improve overall course substantially
– lessen disease burden on caregivers / society
• Specific treatments now available
(anti-cholinesterases, memantine)
– Improve cognition
– Improve function (ADLs)
– Delay conversion from Mild Cognitive Impairment to AD
– Slow underlying disease process, the sooner the better
– Decreased development of behavior problems
– Delay nursing home placement, possibly over 20 months
– Delay nursing home placement longer if started earlier
AD is Under-diagnosed
• Early Alzheimer’s disease is subtle, the diagnosis
continues to be missed
– it is easy for family members to avoid the problem and compensate for the patient
– physicians tend 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
– Diagnoses are missed at all levels of severity: mild, moderate, severe
• Undiagnosed AD patients often face avoidable social,
financial, and medical problems
• Early diagnosis and appropriate intervention may lessen
disease burden
– Early treatment may improve overall course substantially
• No definitive laboratory test for diagnosing AD exists
– Efforts to develop biomarkers, early recognition by brain scan
Evans DA. Milbank Quarterly. 1990; 68:267-289
Need to Develop Better Tools for
Early Assessment
• Genetic vulnerability testing (trait risk)
• Vulnerability factors (education, occupation, head injury)
• Early recognition (10 warning signs)
– Activities of Daily Living (ADLs), behavior changes, forgetting
• Developing suspicion - screening tools
– 6th vital sign in elderly
• Positive diagnostic tests
– CSF (cerebrospinal fluid) – tau levels elevated, amyloid levels low
– Brain scan – PET – DDNP, Congo-red derivatives
• Mild Dementia severity assessments
• Detecting early change over time
– measuring rate, predicting progression
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
Anim als nam ed in 1 m in (m m s>19) - CERAD data set
12
percent of total
10
8
6
4
2
0
0
10
20
30
num ber of anim als nam ed
Normal Controls, CS = 1, n = 386
Alzheimer patients, CS = 0, n = 380
40
Animals name d in 30 se conds (mms>19)
16
14
percent of total
12
10
8
6
4
2
0
0
5
10
15
number of animals named
Normal Controls, n=386
JW Ashford, MD PhD, 2001
Mild Alzheimer Patients, n=380
20
25
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 + 4.75 x D + 2 x S
www.medafile.com/BAS
Mendiondo et al., J Alz Dis 5:391, 2003
Percent of Validation Sample
90
80
Mild AD
70
Control
60
50
40
30
20
10
0
3-22
JW Ashford, MD PhD, 2001
23
24
25
BAS Score
26
27-39
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)
JW Ashford, MD PhD, 2003
90 100
$W = Cost–Worthiness Calculation
•
•
•
•
•
I = incidence (new occurrences each year, by age)
$T = cost of test, time to take (Subject, Tester)
Se = sensitivity of test = True positive / I
Sp = specificity of test = True negative / (1-I)
Cost:
– $B = benefit of a true positive diagnosis
• Estimate: (100 years – age ) x $1000
• Save $50,000 NH cost / 1year (after treatment cost deduction)
– $C = cost of a false positive diagnosis
• $500 for further evaluation (time, stress of suspecting dementia)
– True negative (real peace of mind) (no money)
– False negative = false peace of mind (no price)
$W = ($B x I x Se) – ($C x (1-I) x (1-Sp)) - $T
Kraemer, Evaluating Medical Tests, Sage, 1992
Diagnostic Criteria For Dementia Of
The Alzheimer Type
(DSM-IV, APA, 1994)
A. Memory Impairment
1. Multiple Cognitive Deficits
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
Full Dementia Assessment – 1 hour

History Of Dementia Development (30 min)







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, Activities of Daily Living
Physical Examination (5 minutes)
 Neurological Examination (5 minutes) (vibration sense)
 Neuropsychological Assessment (20 minutes)
 Routine Laboratory Tests
 Brain Scan (CT at minimum, add PET optimally)

LABORATORY TESTS (routine)
• BLOOD TESTS
– electrolytes, liver, kidney function tests, glucose
– thyroid function tests (T3, T4, FTI, TSH)
– vitamin B12, folate (consider homocysteine)
– complete blood count, ESR
– VDRL, HIV (if indicated)
• EKG (if indicated)
• CHEST X-RAY (if indicated)
• URINALYSIS
• ANATOMICAL BRAIN SCAN – CT (cheaper ?), MRI
– Scripps = $880 (min); Modesto = $6,600 (max)
• Functional Brain Scan – SPECT / PET
– PET approved by Medicare for differential from fronto-temporal
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, Delirium
4.
Ethanol (5-15%)
5.
Medical / Metabolic Systems
6.
Endocrine (thyroid, diabetes), Ears, Eyes, Environment
7.
Neurologic (other primary degenerations, etc.)
8.
Tumor, Toxin, Trauma
9.
Infection, Idiopathic, Immunologic
10. Amnesia, Autoimmune, Apnea, AAMI
Adapted from Yesavage, 1979
Alzheimer’s Disease
versus
Dementia
– 50 - 70% of dementias are due to AD
– Probable AD - 30% of cases, 90% neuropath - correct
– 20% have other contributing diagnoses
– Possible AD - 40% of cases, 70% are AD at neuropath
– 40% have other contributing diagnoses
– Unlikely AD - 30% of cases, 30% are AD at neuropath
– 80% have other contributing diagnoses
– Alzheimer’s disease is a pathological condition
– Dementia is a clinical condition frequently caused by AD
• The AD dementia has some characteristics and some heterogeneity
THE TOP TEN TREATMENTS
FOR PREVENTING ALZHEIMER’S DISEASE
www.medafile.com
1. Take blood pressure regularly, assure systolic pressure is always < 130.
2. Watch your cholesterol; if cholesterol is above 200, talk to your clinician about
3.
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6.
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8.
9.
10.
treatment. Consider “statin” medications. Increase dietary intake of omega-3-fatty
acids. Add deep sea fish, nuts, olives. Avoid excess red meat, animal products.
Exercise your body, mind, and spirit regularly. Physical exercise best 10-30 mins
after each meal for 10-30 minutes, 3 times per day. Maximize your education. Do
mental puzzles (like crossword puzzles). Stay active.
Physically protect your brain. Wear your car seat-belt. Wear a helmet when riding a
bicycle or participating in activity where you might hit your head.
Decrease your risk of type II diabetes. Monitor your fasting blood sugar yearly. Keep
your BMI (Basal Metabolic Index) in the optimal range (19-25) by controlling food
intake and exercise. If you have diabetes, make sure that blood sugar is controlled.
Consult your clinician about pains (treat arthritis with ibuprofen, sulindac, or indocin).
Take your vitamins daily (folate - 400mcg, B12 - 25mcg, C - 250 mg, and E - 200iu's).
Check yearly that your homocysteine levels are low and no signs of B12 deficiency.
Eat your veggies.
Discuss sex-hormone replacement therapy with your clinician.
For sleep difficulty, try 3 - 6 milligrams of melatonin at bedtime.
Monitor your memory regularly. If you have significant difficulty with your memory,
talk to your clinician. Consider therapy with cholinesterase inhibitors and memantine.