LEMBAR JAWABAN

SKILLLAB EVIDANCE BASED MEDICINE (EBM)

NAMA

: TRI LEGINA OKTARI

NIM

: 04011181320111

1. NILAI ABNORMALITAS
TABEL 1. Nilai Abnormalitas
PARAMETER

Rata-rata +2SD

Nilai Abnormalitas

SGOT/SGPT

26.29+2(13.92)=54.13

54.13+0.05=54.18

Hemoglobin

12.47-2(0.32)=11.83

11.83-0.05=11.78

Trigliserida

115.31+2(20.04)=155.39

155.39+0.05=155.46

Total Kolesterol

137.24+2(32.40)=202.04

202.04+0.05=202.09

HDL

89.44-2(17.11)=55.22

55.22-0.05=55.17

LDL

74.64+2(13.63)=101.90

101.90+0.05=101.95

2.Dari data clinical scenario

2.1 Tabel PICO
P

Older adults with erarly sign/symptoms of cognitive impairment

Mini-cog screening test

Mini-Mental State Examination

Accurate diagnosis of dementia or Alzheeimers disease

2.2 Clinical question

In Older adults with erarly sign/symptoms of cognitive impairment. Is mini-cog test as
accurate as Mini-Mental State Examination in diagnosis dementia or alzheimers disease.
2.3 Search Term/Search/Keyword
(Mini-cog OR minicog) AND (Mini-Mental state exam* OR MMSE OR SMMSE) AND
(Alzheimer* OR dementia)
2.4 Result of searching

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 Mini-Mental 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
People tested who do not have Disease X
have Disease X (n =
50)
(n = 50)
35

10

New test came back These are true

These are false
as positive
positives (TP) this positives (FP) this
is good
is bad.
15

40

New test came back These are false

These are true
as negative
negatives (FN) this negatives (TN) this
is really bad!
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
o Mini-Cog (brief test <5 min): sensitivity of 91% and specificity of 86%
o ACE-R (20 min test): sensitivity of 92% and specificity of 89%

However where the MMSE data was drawn from hundreds of studies:
o Mini-Cog data was drawn from just 9 studies
o 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 MiniCog 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 Mini-Cog
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.

A full clinical assessment of someone with suspected dementia involves much more than a
simple cognitive test.

Links
Primary paper
Tsoi KF, Chan JC, Hirai HW, Wong SS, Kwok TY. Cognitive Tests to Detect Dementia: A
Systematic Review and Meta-analysis. JAMA Intern Med. Published online June 08, 2015.
doi:10.1001/jamainternmed.2015.2152. [Abstract]

Other references
Alzheimers Society.The Mini Mental State Examination (MMSE). Website last accessed 27 Jan
2016.

2.5.Critical appraisal
:
Step 1: Are the results of this diagnostic study valid?
Apakah ada uji baku standard
yang dapat dibandingkan dengan
uji diagnostik?

Ya, dalam hal ini baku standar adala MMSE.

Apakah uji baku standar juga

diaplikasikan pada sampel
penelitian?

Ya, test dilakukan pada pasien yang di diagnosis

dengan alzheimers atau dementia

Apakah sampel termasuk dalam

spektrum yang sesuai dengan
pasien yang akan dilakukan uji
diagnostik?

Ya, sampel adalah pasien yang didiagnosis secara

klinis dengan dementia atau alzheimers

Apakah cara dan teknik

melakukan uji diagnostik yang
sedang diteliti dijelaskan?

Ya, pasien didiagnosis dengan dementia akan dilihat

keadaannya, dilakukan tes bakunya, dengan cepat
akan di dapatkan hasil. Mini-cog akan lebih cepat
mendapatkan hasil dibanding MMSE

Kesimpulan step 1: Hasil uji diagnostik valid

Step 2: Are the valid results of this diagnostic study important?

HASIL UJI
DIAGNOSTIK

PENYAKIT (DISEASE)

JUMLAH

ADA

TIDAK

POSITIF

35 (a)

10 (b)

45

NEGATIF

15 (c)

40 (d)

55

50

50

100

JUMLAH
SAMPLE CALCULATIONS :
Sensitivity = a/ (a+c) = 35/50 x 100% = 70%
Specifity = d/ (b+d) = 40/50 x 100% = 80%

Positive predictive value = a/a+b = 35/45 x 100 %= 78 %

Negative predictive value = d/b+d = 40/50 x 100 % = 80 %
likelihood positif = sensitifitas/1-spesifisitas = 0.7/1-0.8 = 35 %
likelihood negative = 1-sensitivitas/spesifisitas = 1-0.7/0.8 = 37,5 %
Kesimpulan step2: Hasil uji diagnostik ini penting dan memiliki kepentingan klinis
dimana MMSE,Mini-cog,ACE-R memiliki sensitivitas dan spesifitas yang tinggi
untuk mendiagnosis dementia atau Alzheimer.

Step 3: Can u apply this valid, important evidence about a diagnostic test caring for your
patient?
Apakah hasil test dan interpretasinya dapat
memuaskan dalam diagnosis?

Ya, karena sensitivitas dan spesifitasnya

tinggi.

Apakah hasilnya dapat diaplikasikan pada

pasien kita?

Bisa, karena test ini sangat mudah di

lakukan tanpa persiapan waktu dan alat
yang khusus

Apakah hasil test ini dapat digunakan

untuk mengubah manajemen dalam

Ya, dengan adanya hasil penelitian ini yang

valid ini, dokter dokter akan mengaetahui

mendiagnosis alzheimers atau dementia?

tes yang paling efektif dan cepat sebagai

skrining awal dementia atau alzheimers

Apakah hasilnya dapat membantu pasien

jadi lebih baik?

Ya, karena sensitivitas dan spesifitasnya

yang tinggi, sehingga kesalahan diagnosis
dapat diperkecil. Dengan adanya skrining
awal yang lebih cepat akan membantu
penatalaksaan yang akan mencapai hasil
maksimum

Kesimpulan step3 & Kesimpulan keseluruhan:

Hasil uji diagnostik ini valid dalam skrining awal dementia atau alzheimers

3. DATA DIAGNOSTIK
3.1 Grafik Titik Potong

Classification: MCI
100
90
80
70
60

Sensitivity (%)
Specificity (%)

50
40
30
20
10
0
40

50
60
70
KretaininKinase

80

3.2 Perkiraan secara visual nilai titik potong diagnostic dan interpretasi
Visually the graph show value of creatininkinase more than 80 and less than 90 is the cut off
point.
3.3 Nilai diagnostic berdasarkan Medcal

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

ROC curve
Variable

KretaininKinase
KretaininKinase
MCI

Classification variable
Sample size
Positive group :
Negative group :

MCI = 1
MCI = 0

Disease prevalence (%)

100
13
87
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 criterion
Criterion values and coordinates of the ROC curve [Hide]

0.9195
>69.1098

Criterion
40.0886
>69.1098
>70.1641
>72.9038
>73.2495
>75.2407
>76.5148
>76.8872
>77.4574
>77.995
>78.6751

Sensitivity
100.00
100.00
92.31
76.92
69.23
69.23
61.54
53.85
38.46
30.77
0.00

95% CI
75.3 - 100.0
75.3 - 100.0
64.0 - 99.8
46.2 - 95.0
38.6 - 90.9
38.6 - 90.9
31.6 - 86.1
25.1 - 80.8
13.9 - 68.4
9.1 - 61.4
0.0 - 24.7

Specificity
0.00
91.95
93.10
93.10
94.25
96.55
97.70
98.85
98.85
100.00
100.00

95% CI
0.0 - 4.2
84.1 - 96.7
85.6 - 97.4
85.6 - 97.4
87.1 - 98.1
90.3 - 99.3
91.9 - 99.7
93.8 - 100.0
93.8 - 100.0
95.8 - 100.0
95.8 - 100.0

+LR
1.00
12.43
13.38
11.15
12.05
20.08
26.77
46.85
33.46

4. Randomized clinical trial /control trial Ace Inhibitor

Table 1. angka kematian MCI kelompok Placebo dan Ace Inhibitor
Treatment

Alive

Dead

Total

Ace inhibitor (experiment) 44

50

Placebo (control)

37

13

50

Total

81

19

100

4.1 Nilai nilai importance dari data Therapy Bad outcome

Ukuran Importance

RUMUS

NILAI

EER

Jumlah alive kelompok experiment/total experiment

0.88

CER

Jumlah a;ive kelompok control/total control

0.74

RR

EER/CER

1.18

ARR

EER-CER

0.14

RRR

ARR/CER

0.18

NNT

1/ARR

7.14

4.2 KESIMPULAN :
Ace inhibitor dalam mencegah kematian MCI 18 % (tidak efektif)

-LR
0.00
0.083
0.25
0.33
0.32
0.39
0.47
0.62
0.69
1.00

5. Randomized clinical trial /control trial Enalapril + ASA dan Isosorbid+diuretik

Treatment

Sembuh

Total

26

Tidak
sembuh
24

Enalapril+ASA
(experiment)
Isosorbid+Diuretik
(Control)
Total

41

50

35

65

100

50

5.1 Nilai Importance

Ukuran Importance

RUMUS

NILA
I
0.52

EER
CER

Jumlah kelompok
sembuh/total
Jumlah kelompok control/total

RR

EER/CER

2.88

ARI

CER-EER

0.34

RRI
NNT

ARR/CER
1/ARR

0.41
2.94

0.18

5.2 Kesimpulan :
enalapril +ASA dalam mengobati infark miokard sebesar 41 % lebih efektif daripada
kombinasi isosorbid+diuretic.