LEMBAR JAWABAN

SKILLAB EVIDENCE BASED MEDICINE (EBM)

Nama
NIM

: Muhamad Mardian Safitra

:04011181320059

1. nilai abnormalitas
Tabel 1. Nilai Abnormalitas
parameter
SGOT/SGPT
Hemoglobin
Trigliserid
Total Kolestrol
HDL
LDL

Rata-rata +2SD
26,290 + 2 x (13,92) = 54,13
12,47 - 2 x (0,32) = 11,18
115,31+ 2 x (20,04)=155,39
137,24+ 2x (32,40)= 202,04
89,44+2x (17,11)= 55,22
74,64 + 2x(13,63) = 101,90

Nilai Abnormalitas
54,13 + 0,05 = 54,18
11,18 + 0,05 = 11,78
155.39+005= 155,46
202,04+0,05=202,09
55,22-0,05 = 55,17
101,90+0,05=101,95

2. PICO
Tabel 2. PICO
P
I
C
O

Older elderly with early sign/symtoms of Cognitive impairment

Mini-Cog screening test
Mini-Mental State Examination (MMSE)
Acurate Diagnosis Of Dementia Or Alzhaimers Disease

2.2 Clinical Question

In Older elderly with early sign/symtoms of Cognitive impairment. Is the MiniCog test as accurate as the Mini-Mental state Examination in Diagnosing dementia Or
Alzheimers disease.

2.3 Search Term/Search Keyword/Search Strategy

(Mini-Cog OR Minicog) AND (Mini-Mental State Exam* OR MMSE OR

SMMSE) AND (Alzheimers Disease)
2. 6 Paste-kan abstrak artikel
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
whodo hav
e Disease X
(n = 50)

New
test
came
back as
positive

People
tested
whodo
not have
Disease
X
(n = 50)

35
These
are true
positives
(TP) this
is good

10
These
are false
positives
(FP)
this is
bad.
New
15
40
test
These
These
came
are false
are true
back as
negatives
negative
negative
(FN) this
s (TN)
is really
this is
bad!
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 areaunder-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).

o
o

o
o

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:
a sensitivity of only 62%
and a specificity of 87%.
An alternative test, the MoCA, was found to perform better (in 9 studies)
with:
a sensitivity of 89%
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 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.
- See more at: http://www.nationalelfservice.net/mentalhealth/dementia/cognitive-tests-for-dementia-mmse-mini-cog-and-ace-r/?
referer=TripDatabase&keywords=%28Mini-cog%20OR%20minicog
%29%20AND%20%28Mini-Mental%20State%20Exam*%20OR%20MMSE
%20OR%20SMMSE%29%20AND%20%28Alzheimer*%20OR%20dementia
%29#sthash.Z5CWe2mF.dpuf
2.6 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

Importance

Applicabilit
y

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)
MMSE :
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.
Hasil penelitian dapat diterapkan

3. Data Dianostik
3.1 Creatinin Kinase

Classification: MCI
100
90
80
70
60

Sensitivity (%)
Specificity (%)

50
40
30
20
10
0
40

50
60
70
KretaininKinase

80

3.2 Visually the graph show value of creatinkinase more than 80 and less than 90 is the
cut off point.

3.3 Diagnostic Value

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

Classification variabl

KretaininKinase
MCI

e
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)

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

0.9195
>69.1098

Criterion values and coordinates of the ROC curve [Hide]

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. Randomize clinical tria/control trial inhibitor

Table 1. Angka Kematian MCI Keompok Pacebo dan Ace Inhibitor
Treatment
Ace Inhibitor
Placebo
Total

4.1

Alive
44
37
81

Death
6
13
19

Nilai importance
Importance values
EER
CER
ARR = CER-EER

Hasil
0.12
0.26
0.14

Total
50
50
100

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

RRR = ARR/CER
NNT = 1/ARR
4.2

0.53
7.14

Kesimpulan
Pemberian ACE inhibitor dapat mencegah kematian akibat MCI 14% (ARR= 1.14)

5. Data Therapy Effectiveness

Sembuh
26

Enalapril+ASA
Treatment Isosorbid prodiprogel
9
+ diuretik
Total
35
Tabel 6. Tabel 2 x 2 data therapy effectiveness
5.1

Outcome
Tidak sembuh
24

Total
50

41

50

65

100

Nilai importance

EER
0.52
CER
0.18
ABI = EER-CER
0.34
RBI = ABI/CER
0.19
Tabel 7. Nilai importance data therapy effectiveness
5.2

Kesimpulan

Pemberian Enalapril+ASAlebih efektif dalam menyembuhkan MCI dibandingkan

dengan pemberian Isosorbid prodiprogel + diuretik sebesar 34% (ARR= 0.34)