Using computers to conduct
mass screening for dementia
- practical issues and ethics April 15, 2011
International Association of Geriatrics and Gerontology
J. Wesson Ashford, M.D., Ph.D.
Clinical Professor (affiliated) of Psychiatry & Behavioral Sciences
Stanford University
Senior Research Scientist
Stanford/VA Aging Clinical Research Center,
VA Palo Alto Health Care System
Palo Alto, California
Slides at: www.medafile.com/IAGG2011.ppt
Two issues to be covered
• Establishing the Cost-Worthiness of
dementia screening (ethical issues)
• Demonstrating a practical dementia screen
• Slides at:
www.medafile.com/IAGG2011.ppt
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
AD - Dementia Continuum
Normal
0
MCI
AD
0.5
1
CDR (clinical dementia rating scale)
3004153-1
Introducing the time-index model
of the course of Alzheimer’s disease
Estimate MMSE as a function of time
(calculated from the CERAD data set)
MMSE score
30
25
20
The best model to fit the progression,
both mathematically and biologically,
is the Gompertz survival curve
(99.7% fit to mean changes over time):
15
10
5
0
S(t) = exp(Ro/alpha *(1- exp (alpha * t)))
-10
-8
-6
-4
-2
0
2
4
6
8
10
Estimated years into illness
(Time-Index Scale)
AAMI / MCI/ early AD -- DEMENTIA
Ashford et al., 1995
Is it worth screening for memory
problems or Alzheimer’s disease?
“If there was treatment for AD, I'd recommend screening,
but there is no disease-modifying therapy."
Anonymous Alzheimer expert -2008
“All older adults benefit from memory screening because
it detects cognitive problems before memory loss is noticeable.”
Anonymous Alzheimer expert -2008
Healthy Aging, 2008; repost, 2010
“Memory Screening: Is it Worth It?”
http://healthy-aging.advanceweb.com
http://healthy-aging.advanceweb.com/Patient-Resource-Center/DiseaseManagement-and-Prevention/Memory-Screening-Is-it-Worth-It.aspx
Alzheimer's Disease Is
Under-diagnosed
• Early AD 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%–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 substantially improve overall course
• No definitive laboratory test for diagnosing AD exists
– Efforts to develop biomarkers, early recognition by brain scan
Why Memory Screening Is
Important to Consider
• Cognitive impairment is disruptive to human well-being
and psychosocial function
• Cognitive Impairment is potentially a prodromal condition
to dementia and Alzheimer’s disease (AD)
• Dementia is a very costly condition to individuals and
society (issue of who is paying for screening, patient care)
• With the aging of the population, there will be a
progressive increase in the proportion of elderly individuals
in the world (must consider costs to society)
• Screening will lead to better care (more cost-effective care)
No Testing:
What happens without screening?
Total Population
Risk=P
P’
Do not have AD
P
Have AD
No effective intervention
Helena Kraemer, 2003
Testing: What happens with testing?
Helena Kraemer, 2003
Total Population
P’
Specificity = Sp
Sensitivity = Se
P
AD
No AD
Sp’
Sp
Unnecessary intervention
$ Testing
$ Intervention
$Testing
Se
Se’
OK
No effective intervention
$ Testing
Effective intervention
$ Testing
$ Intervention
Iatrogenic Damage?
Clinical Wash
Clinical Wash
Clinical Gain
Major(?) Loss
Minor (?) Loss
Some gain
True Negative
Minor(?) Loss
Major(?) Gain
False Negative
True Positive
False Positive
Factors for Deciding whether
a Screening Test is Cost-Effective
1) Benefit of a true positive screen
2) Benefit of a true negative screen
3) Cost of a false positive screen
4) Cost of a false negative screen
5) Incidence of the disease (in population)
6) Test sensitivity (in population)
7) Test specificity (in population)
8) Test cost
$W = Cost–Worthiness Calculation
$W > ($B x I x Se) – ($C x (1 - I) x (1 - Sp)) - $T
•
•
•
•
•
•
BENEFIT
– $B = benefit of a true positive diagnosis
• Earlier diagnosis may mean proportionally greater savings
• Estimate: (100 years – age ) x $1000
• Save up to $50,000 (e.g., nursing home cost for 1 year)
– (after treatment cost deduction at age 50, none at age 100)
– (cost-savings may vary according to your locale)
– True negative = real peace of mind (no money)
COST
– $C = cost of a false positive diagnosis
• $500 for further evaluation
– (time, stress of suspecting dementia)
– False negative = false peace of mind (no price)
I = incidence (new occurrences each year, by age)
Se = sensitivity of test = True positive / I
Sp = specificity of test = True negative / (1-I) = (1-False positive/(1-I)
$T = cost of test, time to take (Subject, Tester)
Kraemer, Evaluating Medical Tests, Sage, 1992
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
Benefits of Early Treatment of
Alzheimer’s Disease
• Neurophysiological pathways in patients with AD are still
viable and are a target for treatment
• Opportunity to reduce from a higher level:
– Functional decline
– Cognitive decline
– Caregiver burden
Need to estimate net benefit monetarily
(key factor in determining case for screening)
Estimate benefit = (100 years – age ) x $1000
Dollar savings from delayed nursing
home placement
Estimated Age-related Benefit
of Early Alzheimer Treatment
Benefit = $10,000 - 0
Benefit = $25,000 - 0
Benefit = $50,000 - 0
50000
40000
30000
20000
10000
0
50
60
70
80
AGE (years)
90
100
Value of Diagnosis versus Time-Index
Value across continuum
Value at transition
Value early
Relative value of detection
100%
90%
80%
70%
60%
More sensitive
More specific
50%
40%
30%
20%
10%
0%
-10
-8
-6
-4
-2
0
2
4
6
8
10
Estimated years into illness
(TimeIndex Scale)
- Sharpness of peak relates to increased sensitivity and specificity
- Location of peak relates to point in dementia continuum where recognition
would be most beneficial – adjusting sensitivity versus specificity
Cost of False-Positive Screen
• Referral of normal individual for further testing
– (more specific testing)
• Value of individual’s time
• Cost of additional testing
• Estimate cost = $500 per false-positive screen
• This does not and should not include the cost
of untoward results of misdiagnosis,
medication side-effects, or malpractice
– quality management should address these issues
Other Benefits and Costs
of Screening
• Benefit of true-positive screen = intangible
– Peace of mind
– Plan further into future
• Cost of false-negative screen = wash
– Delay in diagnosis and treatment
– No different from current condition
INCIDENCE OF DEMENTIA
(Hazard per year)
Based on estimate of 4 million AD patients with
dementia in US in 2000, with an incidence
that doubles every 5 years, illness duration of
8 years.
U.S. mortality, dementia, MCI rate
by age (mortality = 2000 CDC / 2000 census)
Males,
1.0000
2t = 8.2yrs
Fem ales, 2t = 7.5 yrs
Hazard / year
dem entia incidence, 2t = 5 yrs
MCI incidence, 2t = 5yrs
0.1000
The Gompertz survival curve explains
99.7% of male and female mortality
Variance between 30 and 95 y/o in US:
0.0100
U(t) = Ro * exp (alpha * t)
0.0010
0.0001
0
10
20
30
40
50
60
70
80
90 100
Age (years)
JW Ashford, MD PhD, 2003; See: Raber et al., 2004
(Incidence for “a” to “a + 1” year)
Relative Risk Factors for Alzheimer’s Disease
(after age, early onset genotypes)
•
•
•
•
•
•
•
•
•
•
•
•
•
APOE-e4 genotype
Family history of dementia
Family history - Downs
Family history - Parkinson’s
Obese, large abdomen
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-blockers
1 allele x 4; 2 alleles x 16
3.5 (2.6 - 4.6)
2.7 (1.2 - 5.7)
2.4 (1.0 - 5.8)
3.6
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
# / yr
U.S.
Alzheimer Incidence
(4 million / 8yr)
male=170,603
16000
14000
12000
10000
8000
6000
4000
2000
0
female=329,115
50
60
70
80
Age
JW Ashford, MD PhD, 2003; See: Raber et al., 2004
90
100
Zandi et al., JAMA, November 6, 2002—Vol 288, No. 17 p.2127
Dementia rate, assume Td = 5 yrs
mean rate
Hazard / year
1000
APOE 3/4 (x2)
Using the Gompertz equation
to model rate of dementia
increase with age:
APOE 3/3 (x0.6)
U(t) = Ro * exp (alpha * t)
APOE 4/4 (x7.5)
100
10
Early onset (x200)
1
0.1
0.01
0.001
0.0001
50
60
70
80
Age (years)
JW Ashford, MD PhD, 2003; See: Raber et al., 2004
90
100
Cache County, probability
of incident dementia
Circles – females
Squares - males
Open – ApoE-e44
Gray – ApoE-e4/x
Black – ApoE-ex/x
Miech et al., 2002
Proportion / Year
U.S. AD Incidence by APOE
(proportion of cases)
1
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0
4/4
3/4
3/3
50
60
e4/4 – 2% of pop, 20% of cases
e3/4 - 20% of pop, 40% of cases
e3/3 - 65% of pop, 35% of cases
JW Ashford, MD PhD, 2000
70
Age
80
90
100
Cost Justified for
Dementia Screen
Cost-Worthy Test Evaluation
Benefit = $50,000 - 0; False Pos = $500
600
550
500
450
400
350
300
250
200
150
100
50
0
-50
-100
Se, Sp
.8, .8
.9, .9
.95, .95
1,1
50 55 60 65 70 75 80 85 90 95
AGE
Cost Justified for
Dementia Screen
Cost-Worthy Test Evaluation
Sensitivity = 0.9, Specificity = 0.9
$1,000
$800
$600
$400
$200
$0
-$200
50 55 60 65 70 75 80 85 90 95
AGE (years)
Benefit: $5,000 - 0
Varying Benefit:
Benefit: $10,000 - 0
Benefit: $25,000 - 0
Benefit: $100,000 - 0
Benefit: cure = $240,000
Cost Justified for
Dementia Screen
Cost-Worthy Dementia Screening
Se=0.9; Sp=0.9
Benefit = $25,000 - 0; False Pos = $500
600
500
400
300
200
100
0
-100
50 55 60 65 70 75 80 85 90 95
AGE
mean
ApoE 4/4
ApoE 3/4
ApoE 3/3
MMSE
items
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
The Taxonomy of Long-Term Memory
(Squire and Zola, 1996)
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
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
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
www.medafile.com/bas.htm
Mendiondo, Ashford, Kryscio, Schmitt., 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
Brief Alzheimer Screen (BAS) ROC for Univ. Kentucky ADRC Clinic Cases
Schmitt et al., 2006
Need for Mass Screening
• Alzheimer’s disease, dementia, and memory problems
are difficult to detect when they are mild
– about 90% missed early
– about 25% are still missed late
• There are important accommodations and
interventions that should be made when there are
cognitive impairments
– (like needing glasses or having driving restrictions if you have
vision problems)
Recommendations being considered for
mandatory Medicare screen (April, 2011)
1) Ask patient and significant other (if available) if memory is a
problem
2) Ask patient and significant other (if available) if remembering
to take medications is a problem
3) Ask patient to remember 3 unrelated words, and have the
patient repeat the 3 items twice
4) Ask patient the date (note if off by more than 2 days)
5) Ask the patient to name as many animals as possible in 1
minute (note concern if number is below 10)
6) Ask the patient to draw a clock (note issues)
7) Ask the patient to recall the 3 items that were repeated (note
concern if 2 or 3 items not recalled)
8) Evaluate the clinical responses. If problems noted, consider
possible explanations or need for further evaluation
There is considerable resistance to
implementation of clinical screening
1) Clinicians are concerned that they don’t have time to
screen
2) Certain organizations recommend use of warning
signs, which have not been studied or ever shown to
be effective for recognizing early cases
3) There needs to be a technique for easy recognition of
memory problems in an at-risk individual
4) Audience memory screening is available
5) Memory tests are available on the WEB
6) Computerized testing is more effective and efficient
Issues for Memory Screening
• Memory (neuroplasticity) is the fundamental deficit of
Alzheimer’s disease
• Current testing for memory problems is based on having
a tester sit in front of a subject for a prolonged period of
time and administer unpleasant tests
• Testing must be
– Inexpensive (minimal need for administrator)
– Fun (so people will return for frequent testing)
– More precise, reliable, and valid
• To improve sensitivity
• To improve specificity
Audience Screening:
CONTINUOUS RECOGNITION TEST
• Presentation of complex pictures (that are easily
remembered normally) are useful for detecting memory
difficulties
• Testing memory using a pictures approach needs
standardization for population use
• Picture memory is less affected by education
• Picture memory can be tested by computer
• Audiences can be shown slide presentations
Answer Sheet for Memory Screening (back of sheet)
Carefully look at each picture. If you see a picture that you have seen before, mark the
circle next to the number of the repeat picture. For the main test, you will see 50
pictures. Each picture is numbered. The pictures will stay on the screen for 5 seconds.
25 pictures are new, 25 pictures are repeated.
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
THE
END
Please note the number on your answer sheet,
then hand it in.
MEMTRAX Memory Test
116 subjects – mostly elderly normals, some young, some dementia patients
False positive errors (false recognition) – 33(64);6(58);47(27)—4,18,23,34(1);1,2,8(0)
False negative errors (failure to recognize) – 35(33);27(20);5(16)—32(4);24(3);45(3)
249 - False Positive Responses for Each Slide, by Slide Number Order
(116 subjects voluntarily participating at local informational talks)
# false positives/116 subjects
70
60
50
40
30
20
10
0
1 2 3 4 6 7 8 13 14 15 17 18 19 22 23 25 28 29 33 34 36 37 41 44 47
242 - False Positive Responses by Slide Number, by Number of Errors
(116 subjects voluntarily participating at local informational talks)
# false positives/116 subjects
70
60
50
40
30
20
10
0
33 6 47 36 13 22 44 25 41 19 14 28 37 7 15 17 29 2 4 18 23 34 8 1 2
249 - False Negative Responses for Each Slide, by Slide Number Order
(116 subjects voluntarily participating at local informational talks)
35
30
25
20
15
10
5
0
5 9 10 11 12 16 20 21 24 26 27 30 31 32 35 38 39 40 42 43 45 46 48 49 50
249 - False Negative Responses for Each Slide, by Number of Errors
(116 subjects voluntarily participating at local informational talks)
# false negative/116 subjects
35
30
25
20
15
10
5
0
35 27 5 12 16 9 10 31 43 46 11 30 20 21 42 48 40 49 26 38 39 50 32 24 45
Performance in 116 subjects
Probable Normal
Number False positive
25
? fronto-temporal
dementia
? MCI
20
15
? dementia
10
Random
Performance
Regression
5
0
0
5
10
15
20
Number False negative
25
Test Performance
for 1018 subjects
•
•
•
•
•
82 (8%) had perfect scores,
230 (23%) made 1 error (98% correct),
700 (69%) made 5 or fewer errors (>90% correct),
132 (13%) made 6 – 10 errors (80 – 88% correct),
186 (18%) made > 10 errors (<80% correct).
-------------------------------------------------------------------• 70 (7%) scored < 80% correct for True Negatives
– 19 (6%) males, 51 (8%) females
• (false positive responses = saying a picture is repeated when not),
•
79 (8%) scored < 80% correct for True Positives
– 25 (7%) males, 54 (8%) females
• (false negative responses = failure to recognize/recall repeat picture)
Number Correct
True Negative Performance
25
24
23
22
21
20
19
18
17
16
15
14
13
12
40.0
y = -0.0352x + 25.564
2
R = 0.039
y = -0.0597x + 27.24
R2 = 0.141
Male trueFemale trueLinear (Male true-)
Linear (Female true-)
50.0
60.0
70.0
80.0
90.0
100.0
Age (years)
Number Correct
True Positive Performance
25
24
23
22
21
20
19
18
17
16
15
14
13
12
40.0
y = -0.0438x + 27.029
2
R = 0.0617
y = -0.0418x + 26.746
2
R = 0.0605
Male true+
Female true+
Linear (Male true+)
Linear (Female true+)
50.0
60.0
70.0
Age (years)
80.0
90.0
100.0
False Positives (incorrect guesses)
12
y = -0.0935x + 3.7674
Number Wrong
10
2
R = 0.0153
y = -0.021x + 2.5605
8
2
R = 0.0007
6
Male False+
4
Female False+
2
Linear (Male False+)
Linear (Female False+)
0
6
8
10
12
14
16
18
20
Education (years)
False Negatives (memory failures)
12
y = -0.0042x + 1.4457
2
Number Wrong
10
R = 3E-05
8
y = -0.0398x + 1.255
2
R = 0.02
6
Male False-
4
Female False-
2
Linear (Male False-)
Linear (Female False-)
0
6
8
10
12
14
Education (years)
16
18
20
The relationship between discriminability (d′) and age
on the audience-based continuous recognition test of
memory for 868 individuals with all information.
4
3
d'
2
1
0
40
-1
60
80
Age (years)
100
The relationship between discriminability
performance (d′) and age in 868 individuals on
the continuous recognition test of memory.
4
d' ± 1 SEM
3
2
1
29
68
135
239
359
38
0
40-49
50-59
60-69
70-79
Age (years)
80-89
90-99
The relationship between discriminability
performance (d′) and age in 868 individuals on
the continuous recognition test of memory.
d' ± 1 SD
4
3
2
1
29
68
135
239
359
38
0
40-49
50-59
60-69
70-79
Age (years)
80-89
90-99
The relationship between discriminability index
(d′) and education in 868 individuals on the
continuous recognition test of memory.
4
d' (± SEM)
3
*
2
1
82
198
279
6-12
13-15
198
111
17-19
20-21
0
16
Education (years)
The relationship between the number of intervening
items (between initial and first repeat presentations)
and percent correct on those items on the continuous
recognition test of memory.
% Correct (+/- SEM)
100
90
80
70
1
3
5
7
8
9
10
13
Number of Items Between Study and Test
25
The relationship between percent correct and
item repetition in 868 individuals on the
continuous recognition test of memory.
Percent Correct (+/- SEM)
100
95
90
1
2
Repetition Number
WEB-based Screening
On-line Testing
• Same test paradigm as Audience Screening
• Testing can be faster – 1-2 minutes for 50 image
• Many different variations of the test can be given
• Other aspects of cognition can be tested
• Test can be repeated several times to decrease variance
• Test can be taken over time to detect changes
• Improved anonymity to protect private information
MEMTRAX - Memory Test
(to detect AD onset)
• New test to screen patients for AD:
– World-Wide Web – based testing
– CD-distribution
– KIOSK administration (grocery stores, drug stores)
•
•
•
•
Determine level of ability / impairment
Test takes 2 to 3 minutes
Test can be repeated often (e.g., weekly, quarterly)
Any change over time can be detected
MemTrax WEB Testing
• Blueberry Study
– 12 subjects – no health problems reported
– Mean age = 49.3 + 11.7 (range 31-68)
– 2 weeks of testing (5 days each week)
– 11 different tests
– 14 to 18 administrations per subject
d' by Test #
4.5000
4.0000
3.5000
3.0000
d'
2.5000
2.0000
1.5000
1.0000
0.5000
0.0000
0
2
4
6
Test #
8
10
12
y = 0.0076x + 2.8553
R2 = 0.0219
d' by Age
4.5000
4.0000
3.5000
3.0000
d'
2.5000
2.0000
1.5000
1.0000
0.5000
0.0000
30
35
40
45
50
Age
55
60
65
70
y = -0.0067x + 3.2933
R2 = 0.0032
d' by Test Order
4.5000
4.0000
3.5000
3.0000
d'
2.5000
2.0000
1.5000
1.0000
0.5000
0.0000
0
5
10
15
test order #
20
25
Reaction Time by Test #
1200
Correct reaction times
1000
800
600
400
200
0
0
2
4
6
Test #
8
10
12
Reaction Time by Age
y = 1.3554x + 622.79
R2 = 0.0276
1200
Correct reaction times
1000
800
600
400
200
0
30
35
40
45
50
Age
55
60
65
70
Reaction Time by Test Order
y = -0.4084x + 693.39
R2 = 0.0005
1200
Correct reaction times
1000
800
600
400
200
0
0
5
10
15
test order #
20
25
BlueBerry Study – MemTrax – correlation analyses
Gender
Gender
Age
Age
d'
d' Tot
Beta
Total
Beta
Memtrax Faces
RT
RT
O-HAP
-0.20
-
d'
0.01
-0.14
-
d' Total
0.26
-0.38
0.88
-
Beta
0.61
-0.43
0.18
0.52
-
Beta Total
0.61
-0.53
0.33
0.67
0.98
-
Memtrax RT
-0.42
0.29
-0.31
-0.55
-0.67
-0.66
-
Faces RT
-0.23
0.26
-0.59
-0.78
-0.73
-0.74
0.75
-
Offline HAP
0.76
-0.57
0.05
0.32
0.78
0.77
-0.70
-0.47
-
Vis-Accom
0.55
-0.72
0.01
0.19
0.17
0.28
-0.10
0.16
0.57
Correlation coefficient with n-2 (9 for 11 subjects) degrees of freedom is:
significant at p < .10 level with a value of at least 0.521, p < .05 at 0.602,
and p < .01 at 0.735.
Correlations significant at the .10, .05 and .01 level are shown in red, blue, and green type respectively.
Reaction Tim e as a Function of Hearing
y = -1.4941x + 870.94
R2 = 0.3873
1000.0
950.0
Correct Reaction Time (msecs)
900.0
850.0
800.0
750.0
700.0
650.0
600.0
550.0
500.0
20
40
60
80
100
Offline HAP
120
140
160
180
Conclusions
• The ethical concerns of values and harms must be estimated as
costs and benefits
• Incidence, costs, and test accuracy each play a role in determining
whether screening is justified
• Calculations show that screening for memory problems is justified
under specific circumstances, age, and risks
• Memory can be measured in mass settings using an audiencebased system or web administration over the internet
• The remaining question is whether health systems are prepared to
provide the care that will improve the lives of those affected
• In the future, the incidence is climbing, so the problem may be
much worse. Will future treatments be better?
• Legislation is needed to require training of clinicians to properly
diagnose, treat, and manage dementia patients and for mandating
appropriate reimbursements of clinicians for their work
• Screening tests are ready for widespread implementation
Screening Tests Available On-Line
•
•
•
•
www.memtrax.com (clinical)
www.memtrax.net (research)
www.medafile.com (information)
Slides at:
–www.medafile.com/IAGG2011.ppt
• For further information, contact:
– Wes Ashford: washford@medafile.com
Future directions for screening
• Successful prevention of dementia, AD
• APOE genotyping – routine at birth
– Preventive measures based on genetics
• Can amyloid preprotein dysfunction be controlled
by diet, mental stimulation (education), physical
exercises, better sleep, drugs, to prevent AD?
• Longitudinal assessment of memory
– To treat dementia when not prevented
• Computer games to monitor/improve cognition
– Quick, fun, inexpensive, user-friendly, repeated