LEMBAR JAWABAN

SKILLAB EVIDENCE BASED MEDICINE (EBM)

Nama
NIM

: Ita Rahmatika
: 04011281320048

1. Nilai Abnormalitas

Valid
Missin
g

Mean
Std.
Deviation
1.1

Statistics
SGOT/SG Hemoglo Trigliseri TotalKolest
PT
bin
d
rol
200
200
200
200
0

26.290

12.472 115.305

13.9232

.3238 20.0475

137.235 89.440 74.640

17.119 13.634
32.4054
3
1

Rata-rata
26.29
12.47
115.30
137.24
89.44
74.64

Standar Deviasi
Parameter
SGOT/SGPT
Hemoglobin
Trigliserid
TotalKolestrol
HDL
LDL

1.3

LDL
200

Harga Rerata
Parameter
SGOT/SGPT
Hemoglobin
Trigliserid
TotalKolestrol
HDL
LDL

1.2

HDL
200

Standar Deviasi
13.92
0.32
20.04
32.40
17.12
13.63

Nilai Abnormalitas
Parameter
SGOT/SGPT
Hemoglobin
Trigliserid

Rata-rata 2SD
26.29 +2(13.92)=54.13
12.47 2(0.32)=11.83
115.30 + 2(20.04)=

Nilai Abnormalitas
54.13+0.05 = 54.18
11.83 0.05= 11.78
155.39 + 0.05 = 155.46

TotalKolestrol

155.39
137.24 + 2(32.40) =

202.04+0.05=202.09

HDL

202.04
89.44 - 2 (17.12) =

55.22 0.05 = 55.17

LDL

55.22
74.64 + 2 (13.63) =

101.90 + 0.05 = 101.95

101.90
2. PICO
2.1. PICO
P

Older patients reporting memory loss and concerned

about the onset of dementia
I
Mini Cog Screening test
C
Mini-Mental State Examination (MMSE)
O
Accurate in detecting Alzheimers disease or dementia
Tabel 1. PICO
2.2.

Clinical question
In older adults with early sign/symptoms of cognitive
impairment is the Mini-Cog test as the Mini-Mental State
Examination (MMSE) in diagnosing dementia or Alzheimer
Disease

2.3.

Search Term/Search/Keyword
(Mini-Cog or minicog) AND (Mini-Mental State Examination or
MMSE) AND (Alzheimers Disease or Dementia)

1.4
1.5

Searching
Result of searching/ Abstract Article
Cognitive tests for dementia: MMSE, Mini-Cog and ACE-R

In this systematic review and meta-analysis, Tsoi and colleagues

from Hong Kong aimed to assess the relative effectiveness of
common cognitive tests at diagnosing dementia.
Dementia is an umbrella term for a number of different brain
diseases that progressively affect a persons ability to think and
function independently. Alzheimers disease, for example, is the
commonest cause of dementia. The symptoms and the impairment
caused by dementia are a result of progressive damage to the
brain and a loss of brain cells and connections.
The symptoms a particular person with dementia develops
depends on where in the brain the disease is affecting. For
example, early on in the disease course Alzheimers affects an area

of the brain called the hippocampus, which is involved in storing

memories about our lives. For this reason patients with Alzheimers
disease get memory problems early on. By comparison,
frontotemporal dementia affects the frontal area of the brain first
and, as a result, these patients often have changes in personality
and difficulties in planning long before they have difficulties with
memory.
The way we diagnose and detect dementia, therefore, is by
systematically assessing the function of various brain regions by
using cognitive tests. Cognitive here means the higher brain
functions I alluded to earlier; things like memory, numeracy,
visual perception, personality change and planning, to name
a few.
Obviously, an exhaustive assessment of a persons cognitive
function would take a very long time hours, if not longer! While
researchers may have hours to spend with patients, most busy
clinicians do not and so the Holy Grail is finding a good, brief
screening test of cognitive function that allows us to diagnose
dementia.
The commonest cognitive test used is called the Mini-Mental
State Examination (MMSE). In this test you can score up to 30
points by answering a range of questions that test your orientation
to time and place, your memory, attention and so on. The test
itself takes about 10 minutes to complete. As the authors of this
paper state, the performance of the MMSE in detecting dementia
as compared to other tests has not been systematically assessed
and so, that is what they set out to do. One of the reasons to
assess the relative merits of the MMSE is that it is a proprietary
instrument, owned by Psychological Assessment Resources
meaning that it is not actually free for organisations to use.
In this paper, the authors completed a systematic review of the
literature for studies that:

Assessed the performance of the MMSE at being able to correctly

detect dementia; and

Compared it to other measures that fell into three categories;

tests that took less than 5 minutes to complete, 10 minutes and
20 minutes

This systematic review compares the MMSE with other tools for
detecting dementia. [Interlocking-Pentagons used in the MiniMental State Exam].
Methods
The reviewers included studies that:

Looked for patients with either Alzheimers, vascular dementia or

Parkinsons disease in any clinical setting

Assessed patients or carers face-to-face

Used a standardised diagnostic criteria to diagnose dementia

Published the outcome measures they were interested in.

They excluded:

Non-English language papers

Tests that took longer than 20 minutes to complete

Tests that were only evaluated in four or less papers

Any patients who were visually impaired.

In terms of how the search was performed, it looks very thorough.

They searched MEDLINE, EMBASE, PsychoINFO and Google Scholar
from the earliest available dates stated in the individual databases
until 1 Sep 2014. Two authors independently assessed the search
results and used a standardised data extraction sheet. The studies
were also screened for quality and bias.
As outcomes they chose several different measures of diagnostic
accuracy that can get a bit confusing. The perfect test should be
able to tell you everyone who has the disease and correctly identify
everyone who does not have the diseaseeasier said than done.

To understand what the results of this paper mean it is worth

running through an imaginary scenario.
How do diagnostic tests work?
Lets imagine 100 people come to a GP to get tested for Disease
X. The GP decides to compare a new test hes just bought with the
gold-standard perfect test. Using the gold standard he finds out
that 50 people have the dreaded Disease X and 50 people do not.
He then compares these results with his new test, which you can
see in the table below.

People tested
who do have
Disease X (n =
50)

People tested
who do not
have Disease X
(n = 50)

New test came

back as
positive

35

10

These are true

positives (TP)
this is good

These are false

positives (FP)
this is bad.

New test came

back as
negative

15

40

These are false

negatives (FN)
this is really
bad!

These are true

negatives (TN)
this is good
too.

From these kinds of tables you can work out how good a
new/alternative diagnostic test is. As you can see from this
imaginary scenario, the new test misdiagnosed 20 of the 100
people.
In this paper, they chose to look at a number of different options
for assessing the effectiveness of each of the cognitive tests they
were interested in. Its probably not worth going through all the
measures they used, but its worth knowing about two: sensitivity
and specificity.
Sensitivity and specificity

Sensitivity determines what proportion of people who actually have

the disease get a positive test. Or as a formula

Sensitivity = TP / (TP + FN)

So, in the example above for Disease X the sensitivity of the

new test is 35/(35+15) = 0.7 or 70%

Likewise specificity determines what proportions of people who

actually do not have the disease get a negative test. Or as a
formula:

Specificity = TN/ (TN + FP)

So, in the example above for Disease X the specificity of the

new test is 40/(40+10) = 0.8 or 80%

For both sensitivity and specificity; the higher the number, the
better.
The paper also looks at other measures of the diagnostic accuracy
but they are derived from the sensitivity and specificity. Without
going into detail, the paper also reports Likelihood Ratios,
diagnostic odds ratio and AUC or area-under-the-curve.

Accurate diagnostic tests have high sensitivity and high specificity.

Results
The initial search yielded 26,380 papers! After applying the
inclusion/exclusion criteria they were left with 149 studies, which
covered 11 different diagnostic tests and over 40,000 people from
around the world.
MMSE

The vast majority of the studies looked at MMSE (108 of 149)

Sample size was 36,080 of whom 10,263 had dementia

From these studies the:

o Mean sensitivity was 81% (CI was 78% to 84%)
o Mean specificity was 89% (CI was 87% to 91%)
o All other markers also showed good diagnostic accuracy (LR+
= 7.45, LR- = 0.21, diagnostic OR was 35.4 and AUC was 92%)

Mini-Cog and ACE-R (the best of the rest)

Of the 11 remaining tests, two stood out as being better than

the MMSE

Mini-Cog (brief test <5 min): sensitivity of 91% and

specificity of 86%
ACE-R (20 min test): sensitivity of 92% and specificity of

o
89%

However where the MMSE data was drawn from hundreds of

studies:

Mini-Cog data was drawn from just 9 studies

ACE-R was drawn from just 13 studies

For all three of the above tests, there was found to be a high
degree of heterogeneity. In essence this is a statistical test telling
us that between studies included in the analyses, the results were
quite different from one study to another. Heterogeneity is not a
good thing in systematic reviews.
Further analyses
The reviewers showed that the accuracy of the MMSE was not
affected by geographical location or clinical site (i.e. it was as
effective for hospital patients as community patients).
Finally they looked at the accuracy of diagnosing mild cognitive
impairment (MCI); a risk state that precedes dementia. They
didnt really go into much detail in the methods of how they found
the studies or how they defined MCI.

Only 21 studies using MMSE were used to assess diagnostic

accuracy for MCI giving:
o a sensitivity of only 62%
o and a specificity of 87%.

An alternative test, the MoCA, was found to perform better (in 9

studies) with:
o a sensitivity of 89%
o and a specificity of 75%

No data was provided on the other tests presumably because

there werent enough studies.

The freely available ACE-R and Mini-Cog instruments may be viable

alternatives to the MMSE for detecting dementia.
Conclusions
In short, the MMSE is not a bad screening tool for dementia but it is
not miles better than the rest; its just really commonly used,
probably for historical reasons. The ACE-R and the Mini-Cog are
both free to use and may be viable alternatives.
The MMSE is less good in mild cognitive impairment.
Strengths and limitations
What were some of the strengths of this paper?
1. The literature search was done well. The authors should be
commended for going through so many papers in such a
systematic way

2. The criteria for inclusion and exclusion were made clear and
papers were assessed for quality and data was extracted in a
reliable way by two authors
3. The meta-analysis itself appears to have been done well
4. The paper collates a huge amount of data pertinent to the
question: data from over 40,000 people were included in the
analysis.
What were the limitations?
1. All meta-analyses inherit the limitations of the papers they
include. In this case the most obvious limitation is the relative
lack of data on alternative cognitive tests like the ACE or MiniCog
2. The authors mention that the cut-off scores for diagnosing
dementia change from study to study. Unlike the example I gave
earlier these tests are not simply positive or negative. They give
a score (from 0 to 30 in the case of the MMSE) and so the cut-off
needs to be determined by the user. In the case of the MMSE,
the commonest cut-off was less than 23 or 24, but this was not
the case in all of the studies included. This has obvious effects
on diagnostic accuracy.
3. The authors chose to include Parkinsons disease in the search
criteria, but not Lewy Body dementia or frontotemporal
dementia, which I cant understand given how common they
are.
4. I
didnt
really
find
the
section
on mild
cognitive
impairment very helpful because it seemed like an
afterthought. The search terms used to collect the data didnt
seem to be wide enough to capture all the relevant studies for
example.
Final thoughts
Its important to add that whilst this paper focussed on cognitive
screening tests, which play an important part in diagnosis, a full
clinical assessment of someone with suspected dementia requires
a much more detailed approach. Combining information from the
history, examination, investigations and cognitive tests greatly
improve the diagnostic accuracy. Also where the screening tests

are not clear, patients can be referred for much more detailed
assessments of cognition performed by neuropsychologists.
Also it is important to remember that the diagnosis of dementia
requires evidence of a progressive illness. This means that
repeating cognitive tests and looking for change is often more
helpful than just a snapshot. This aspect was not covered in this
systematic review.
1.6

Critical appraisal
Validity

1. Validitas seleksi
a. Kriteria seleksi
Data diperoleh dari 149 studi dengan jumlah
sampel lebih dari 40.000 orang dari seluruh
dunia. Penelitian diambil melalui database
online yaitu MEDLINE, EMBASE, PsychoINFO,
dan Google Scholar yang dipublikasikan sejak
tanggal 1 september 2014.
Kriteria inklusi :
penelitian dengan sampel yang merupakan
pasien Alzheimers disease, vascular
dementia atau Parkinsons disease.
Penelitian dilakukan dengan bertatap muka
dengan pasien secara langsung
Kriteria eklusi :
Penelitian yang tidak menggunakan bahasa
Inggris
Lama pengukuran yang lebih dari 20 menit
Pasien yang mengalami gangguan visual
b. Metode alokasi
Penelitian yang digunakan adalah penelitian
yang memenuhi kriteria inklusi dan eklusi.
c. Concealment
Dalam penelitian ini tidak tertulis mengenai
concealment karena bukan merupakan uji klinis
d. Angka DO
Tidak dijelaskan mengenai angka DO pada
sistematik review/meta analisis ini.
e. Jenis analisis
Jenis tulisan berupa sistematik review/meta
analisis yang menggunakan metode cross
sectional.
2. Validitas pengontrolan perancu
Pada tulisan ini, validitas pengontrolan perancu
cukup baik karena memberikan informasi
mengenai kriteria inklusi dan kriteria eklusi pasien
yang dimuat dalam penelitian.

3. Validitas informasi
a. Blinding
b. Komponen pengukuran variabel penelitian
Variabel yang diukur pada penelitian yang
masuk dalam sistematik review/meta analisis
adalah hasil pengujian pasien demensia dengan
menggunakan mini-cog dibandingkan dengan
menggunakan MMSE
4. Validitas analisis
Tulisan ini berupa sistematik review/meta analisis
dengan hasil dan interpretasi yang baik, sehingga
validitas analisis tulisan ini baik.
5. Validitas internal kausal
Tidak terdapat validitas eksterna karena bukan
merupakan uji klinis
6. Validitas eksterna
Validitas eksterna pada tulisan ini baik karena
menggunakan metode sistematik review/meta
analisis dengan jumlah sampel yang besar yang
berasal dari seluruh dunia dengan data primer
(data diambil secara langsung/face to face)
Importanc MMSE :
e
sensitifitas 62%
spesifisitas 87%.
Mini-Cog :
Sensitifitas 91%
Spesifisitas 86%
Penelitian ini penting karena selanjutnya Mini-Cog
dapat digunakan untuk skrining MCI mengingat
sensitifitasnya yang tinggi.
Applicabili Hasil penelitian dapat diterapkan
ty

2. Dari Data Diagnostik

Kreatinin Kinase dan MCI
2.1
Grafik titik potong Kreatinin Kinase dan MCI

Classification: MCI
100
90
80
70
60

Sensitivity (%)
Specificity (%)

50
40
30
20
10
0
40

50
60
70
KretaininKinase

80

Grafik 1. Titik potong kreatinin kinase dan MCI

2.2
Perkiraan secara visual nilai titik potong Kreatinin Kinase
dan MCI dan interprestasikan
Visually the graph show value of creatinin-kinase more than 80
and less than 90.
2.3
Hitung seluruh nilai diagnostik Kreatinin Kinase dan MCI
dan buat kesimpulan
Kreatinin kinase dapat mendiagnosis MCI dengan sensitifitas
100% dan spesifisitas 92%.

KretaininKinase

100

Sensitivity: 100.0
Specificity: 92.0
Criterion : >69.1098

Sensitivity

80
60
40
20
0
0

20

40
60
80
100-Specificity

100

Grafik 2. Sensitifitas dan spesifisitas kreatinin kinase

ROC curve

Variable

KretaininKinase
KretaininKinase

Classification vari
able

MCI

Sample size

100

Positive grou
p:

MCI =
1

13

Negative gro
up :

MCI =
0

87

Disease prevalenc
e (%)

unknown

Area under the ROC curve (AUC)

Area under the ROC curve (
AUC)
Standard Errora
95% Confidence intervalb
z statistic
Significance level P (Area=
0.5)
a
b

0.973
0.0140
0.919 to 0.995
33.901
<0.0001

DeLong et al., 1988

Binomial exact

Youden index
Youden index J
Associated crite
rion

0.9195
>69.1098

Criterion values and coordinates of the ROC curve[Hide]

Criterion

Sensitivit
y

95% CI

Specificit
y

95% CI

+LR

40.088
6

100.00

75.3 - 100.
0

0.00

0.0 - 4.2

1.00

>69.109
8

100.00

75.3 - 100.
0

91.95

84.1 - 96.7

12.4
3

0.00

>70.164
1

92.31

64.0 - 99.8

93.10

85.6 - 97.4

13.3
8

0.08
3

>72.903
8

76.92

46.2 - 95.0

93.10

85.6 - 97.4

11.1
5

0.25

>73.249
5

69.23

38.6 - 90.9

94.25

87.1 - 98.1

12.0
5

0.33

>75.240
7

69.23

38.6 - 90.9

96.55

90.3 - 99.3

20.0
8

0.32

>76.514
8

61.54

31.6 - 86.1

97.70

91.9 - 99.7

26.7
7

0.39

>76.887
2

53.85

25.1 - 80.8

98.85

93.8 - 100.
0

46.8
5

0.47

>77.457
4

38.46

13.9 - 68.4

98.85

93.8 - 100.
0

33.4
6

0.62

>77.995

30.77

9.1 - 61.4

100.00

95.8 - 100.
0

0.69

>78.675
1

0.00

0.0 - 24.7

100.00

95.8 - 100.
0

1.00

LDL dan MCI

2.4 Grafik titik potong LDL dan MCI

-LR

Classification: MCI
100
90
80
70
60

Sensitivity (%)
Specificity (%)

50
40
30
20
10
0
80 100 120 140 160 180 200
LDL
Grafik 3. Titik potong LDL dan MCI

2.5 Perkiraan secara visual nilai titik potong dan interprestasikan

Visually the graph shows value of LDL more than 50 and less
than 70.
2.6 Hitung seluruh nilai diagnostik dan buat kesimpulan
LDL dapat mendiagnosis MCI dengan sensitifitas 84,6% dan
spesifisitas 47,1%.

LDL
100

Sensitivity

80

Sensitivity: 84.6
Specificity: 47.1
Criterion : 143

60
40
20
0
0

20

40
60
80
100-Specificity

Grafik 4. Sensitifitas dan spesifisitas LDL

ROC curve
Variable

LDL

Classification vari
able

MCI

Sample size

100

Positive grou
p:

MCI =
1

13

Negative gro
up :

MCI =
0

87

Disease prevalenc
e (%)

Area under the ROC curve (AUC)

unknown

100

Area under the ROC curve (

AUC)

0.598

Standard Errora

0.0855

95% Confidence intervalb

0.495 to 0.695

z statistic

1.143

Significance level P (Area=

0.5)
a
b

0.2531

DeLong et al., 1988

Binomial exact

Youden index
Youden index J

0.3174

Associated crite
rion

143

Criterion values and coordinates of the ROC curve[Hide]

Criterion

Sensitivit
y

95% CI

Specificity

95% CI

+LR

-LR

<96.39

0.00

0.0 - 24.7

100.00

95.8 - 100.
0

105.6

0.00

0.0 - 24.7

97.70

91.9 - 99.7

0.00

1.0
2

110.39

7.69

0.2 - 36.0

97.70

91.9 - 99.7

3.35

0.9
4

113.41

7.69

0.2 - 36.0

95.40

88.6 - 98.7

1.67

0.9
7

114.34

15.38

1.9 - 45.4

95.40

88.6 - 98.7

3.35

0.8
9

118.88

15.38

1.9 - 45.4

89.66

81.3 - 95.2

1.49

0.9
4

121.17

23.08

5.0 - 53.8

89.66

81.3 - 95.2

2.23

0.8
6

1.0
0

124.45

23.08

5.0 - 53.8

83.91

74.5 - 90.9

1.43

0.9
2

124.98

30.77

9.1 - 61.4

83.91

74.5 - 90.9

1.91

0.8
3

135.63

30.77

9.1 - 61.4

62.07

51.0 - 72.3

0.81

1.1
2

135.71

38.46

13.9 - 68.4

62.07

51.0 - 72.3

1.01

0.9
9

136.43

38.46

13.9 - 68.4

58.62

47.6 - 69.1

0.93

1.0
5

140.21

69.23

38.6 - 90.9

58.62

47.6 - 69.1

1.67

0.5
2

142.73

69.23

38.6 - 90.9

48.28

37.4 - 59.2

1.34

0.6
4

142.79

76.92

46.2 - 95.0

48.28

37.4 - 59.2

1.49

0.4
8

142.91

76.92

46.2 - 95.0

47.13

36.3 - 58.1

1.45

0.4
9

143

84.62

54.6 - 98.1

47.13

36.3 - 58.1

1.60

0.3
3

158.41

84.62

54.6 - 98.1

17.24

10.0 - 26.8

1.02

0.8
9

158.87

92.31

64.0 - 99.8

17.24

10.0 - 26.8

1.12

0.4
5

185.21

92.31

64.0 - 99.8

1.15

0.03 - 6.2

0.93

6.6
9

187.68

100.00

75.3 - 100.
0

1.15

0.03 - 6.2

1.01

0.0
0

192.22

100.00

75.3 - 100.
0

0.00

0.0 - 4.2

1.00

3. Dari Data Therapy Bad Outcome - Randomized clinical trial/ control

trial ACE Inhibitor
Alive

Dead

Total

ACEI
Plasebo
Total
3.1

44
37
81

6
13
19

50
50
100

Nilai Importance
EER = 0.88
CER = 0.74
ARR = 0.14
RRR = 0.189
NNT = 7.14

3.2
Kesimpulan
Pemberian ACE inhibitor dapat mencegah kematian akibat MCI 14%
(ARR= 0.14)
4. Dari Data Therapy Effectiveness
Outcome

Enalapril+ASA
Treatm
ent

Total

Sembuh

Tidak

26

sembuh
24

50

41

50

35

65

100

Isosorbid
prodiprogel +
diuretik
Total

4.1

Nilai Importance
EER = 0.52
CER = 0.18
ARR = 0.34
RRR = 0.188
NNT = 2.94

4.2
Kesimpulan
Pemberian Enalapril+ASA lebih efektif dalam menyembuhkan MCI
dibandingkan dengan pemberian Isosorbid prodiprogel + diuretik
sebesar 34% (ARR= 0.34)