ONLINE APPENDIX
Methods
Description of the various cognitive tests used in the study
The Montreal Cognitive Assessment (MoCA) is a screening measure of global cognition that
has demonstrated good sensitivity to detect even mild cognitive impairment and covers, via
13 tasks, the following cognitive domains: visuospatial/visuoconstruction (5 points), naming
(3 points), attention/concentration and working memory (6 points), language (3 points),
abstraction (2 points), short-term memory (delayed recall) (5 points), and orientation (6
points). The original cut-off score identifying cognitive impairment was <26/30 in the
validation study (1). However, it has been demonstrated to be too stringent, misclassifying
cognitively normal patients as being impaired. A score below 23 has been proposed to
identify MCI in an elderly population with a high pre-test probability of MCI (1).
The Digit-Symbol Substitution Test (DSST) assesses processing speed and new learning.
Participants are asked to translate numbers to symbols using a key. The score is the total
number of numbers correctly translated to symbols within 90-seconds and the range of
possible scores is 0 to 93 (2).
The Trail Making Test (TMT) Parts A and B evaluate processing speed and executive
function (complex cognitive processing used in problem solving or complex action
sequences). In the former, participants are asked to draw a line connecting circles numbered 1
to 25, randomly distributed on a page as fast as possible. The score is the time (seconds) for
completion of this task with a maximum allotted time of 150s. TMT Part B consists in
connecting the numbers 1 to 13 and the letters A to L that are randomly distributed on a page,
alternating between numbers and letters. The score is the time (seconds) for completion of this
task, with a maximum allotted time of 300 seconds (2).
Word fluency and animal naming tests explore language and executive function (2). Subjects
are asked to generate as many words as possible starting by the letter P (avoiding proper
nouns) and in the animal subcategory respectively. The score is the total number of acceptable
words/animals generated within the 60s allowed for each test.
REFERENCES
1.
2.
Cooley SA, Heaps JM, Bolzenius JD et al. Longitudinal Change in Performance on
the Montreal Cognitive Assessment in Older Adults. Clinical Neuropsychol
2015;29:824-35.
Schneider AL, Sharrett AR, Gottesman RF et al. Normative data for 8
neuropsychological tests in older blacks and whites from the atherosclerosis risk in
communities (ARIC) study. Alzheimer Dis Assoc Disord 2015;29:32-44.
Supplemental Table 1 – Changes in total MoCA and each neuropsychological dimension of the
MoCA over time based on RCI
Changes from short-term to 1 year
Worsened
Stable
Improved
Changes from baseline to short-term
Visuospatial
Worsened: n=4 (7.8)
4 (100)
Stable: n= 44 (86.3)
1 (2.3)
43 (97.7)
Improved: n=3 (5.9)
3 (100)
Naming
Worsened: n=6 (11.7)
4 (66.7)
2 (33.3)
Stable: n=44 (86.3)
1 (2.3)
43 (97.7)
Improved: n=1 (2.0)
1 (100)
Attention
Worsened: n=4 (7.8)
2 (50.0)
2 (50.0)
Stable: n=43 (84.3)
4 (9.3)
35 (81.4)
4 (9.3)
Improved: n=4 (7.8)
1 (25.0)
3 (75.0)
Language
Worsened: n=8 (15.7)
4 (50.0)
4 (50.0)
Stable: n=34 (66.7)
1 (2.9)
31 (91.2)
2 (5.9)
Improved: n=9 (18.6)
1 (11.1)
8 (88.9)
Abstraction
Worsened: n=2 (3.9)
2 (100)
Stable: n=43 (84.3)
3 (7.0)
36 (83.7)
4 (9.3)
Improved: n=6 (11.8)
6 (100)
Short-term memory
Worsened: n=4 (7.8)
3 (75.0)
1 (25.0)
Stable: n=44 (86.3)
1 (2.3)
41 (93.2)
2 (4.5)
Improved: n=3 (5.9)
2 (66.7)
1 (33.3)
Orientation
Worsened: n=1 (2.0)
1 (100)
Stable: n=49 (96.0)
1 (2.0)
47 (96.0)
1 (2.0)
Improved: n=1 (2.0)
1 (100)
Total
Worsened: n=4 (7.8)
2 (50.0)
2 (50.0)
Stable: n=44 (86.3)
1 (2.3)
42 (95.5)
1 (2.3)
Improved: n=3 (5.9)
1 (33.3)
2 (66.7)
Data are presented as number of patients (percentage). Percentages of changes from short-term
evaluation to 1 year evaluation are given for each row representing changes that occurred from
baseline to the short-term evaluation.
MoCA= Montreal Cognitive Assessment; RCI= Reliable change index.
Supplemental Table 2 – Individual changes based on RCI in total MoCA and each
neuropsychological dimension of the MoCA from baseline to 1 year according to changes from
baseline to short-term.
Changes from baseline to 1 year
Worsened
Stable
Improved
Changes from baseline to short-term
Visuospatial
Worsened: n=4 (7.8)
4 (100)
Stable: n= 44 (86.3)
2 (4.5)
36 (81.8)
6 (14.0)
Improved: n=3 (5.9)
3 (100)
Naming
Worsened: n=6 (11.7)
1 (16.7)
5 (83.3)
Stable: n=44 (86.3)
4 (9.1)
40 (90.9)
Improved: n=1 (2.0)
1 (100)
Attention
Worsened: n=4 (7.8)
1 (25.0)
3 (75.0)
Stable: n=43 (84.3)
4 (9.3)
38 (88.4)
1 (2.3)
Improved: n=4 (7.8)
4 (100)
Language
Worsened: n=8 (15.7)
2 (25.0)
6 (75.0)
Stable: n=34 (66.7)
1 (2.9)
31 (91.2)
2 (5.9)
Improved: n=9 (18.6)
4 (44.4)
5 (55.6)
Abstraction
Worsened: n=2 (3.9)
2 (100)
Stable: n=43 (84.3)
3 (7.0)
40 (93.0)
Improved: n=6 (11.8)
6 (100)
Short-term memory
Worsened: n=4 (7.8)
1 (25.0)
3 (75.0)
Stable: n=44 (86.3)
1 (2.3)
42 (95.5)
1 (2.3)
Improved: n=3 (5.9)
3 (100)
Orientation
Worsened: n=1 (2.0)
1 (100)
Stable: n=49 (96.0)
8 (16.3)
41 (83.7)
Improved: n=1 (2.0)
1 (100)
Total
Worsened: n=4 (7.8)
1 (25.0)
3 (75.0)
Stable: n=44 (86.3)
5 (11.4)
37 (84.1)
2 (4.5)
Improved: n=3 (5.9)
1 (33.3)
2 (66.7)
Interpretation and abbreviations as in supplementary table 1.
Supplemental Table 3 – Functional status and self-reported quality of life according to various classifications of neurocognitive status and neurocognitive changes.
CD+
CDCD+
CDBl-MOCA
Bl-MOCA
Fu-MOCA Fu-MOCA
ppppTests
MOCA
MOCA
Other tests
Other tests
<23
≥23
< 23
≥23
value
value
value
value
(n=6)
(n=45)
(n=12)
(n=28)
(n=20)
(n=31)
(n=19)
(n=32)
Bl-DASI
17. 3±15.2
20.3±12.5
0.493
23.8±12.1
21.0±13.7
0.382
15.9±8.3
22.5±14.3
0.125
16.9±11.0
21.7±13.4
0.240
Fu-DASI
12.1±7.11
25.4±13.5
0.003
28.9±16.7
22.8±12.0
0.249
21.2±10.2
25.5±15.2
0.521
20.1±11.2
26.0±14.4
0.112
Md-DASI
-5.1±17.9
4.8±12.1
0.08
5.0±16.3
1.8±12.0
0.324
4.6±12.5
3.0±13.6
0.685
2.4±15.9
4.3±11.5
0.634
Bl-EQ5D-USA
0.74±0.19
0.84±0.15
0.255
0.88±0.16
0.80±0.16
0.096
0.83±0.14
0.83±0.16
0.645
0.84±0.15
0.83±0.16
0.882
Fu-EQ5D-USA
0.70±0.20
0.85±0.15
0.037
0.81±0.22
0.83±0.16
0.879
0.87±0.14
0.81±0.18
0.232
0.83±0.16
0.83±0.17
0.952
Md-EQ5D-USA
-0.04±0.18
0.006±0.15
0.765
-0.08±0.16
0.03±0.17
0.128
0.04±0.17
-0.02±0.14
0.191
-0.003±0.14
0.004±0.17
0.674
Bl-EQ5D-Eu
0.66±0.22
0.78±0.20
0.281
0.84±0.20
0.73±0.21
0.085
0.76±0.19
0.77±0.21
0.687
0.77±0.18
0.77±0.21
0.843
Fu-EQ5D-Eu
0.61±0.24
0.81±0.18
0.034
0.77±0.25
0.78±0.20
0.879
0.83±0.17
0.76±0.21
0.225
0.79±0.18
0.79±0.20
0.984
Md-EQ5D-Eu
-0.05±0.23
0.007±0.15
0.401
-0.08±0.16
0.05±0.22
0.108
0.07±0.23
-0.02±0.18
0.148
0.01±0.17
0.02±0.22
0.884
Bl-EQ5D-VAS
53.3±10.3
62.4±15.8
0.179
63.9±20.2
61.1±13.9
0.611
61.8±12.8
61.1±17.2
0.891
63.2±15.9
60.3±15.4
0.531
Fu-EQ5D-VAS
61.0±15.2
72.1±14.4
0.087
69.2±17.9
70.5±13.1
0.850
76.0±11.2
67.7±15.9
0.104
74.2±15.1
69.2±14.4
0.197
Md-EQ5D-VAS
11.0±20.7
9.7±18.7
0.881
5.8±24.6
9.5±15.9
0.579
14.3±15.3
6.8±20.3
0.171
11.4±16.9
8.9±19.8
0.657
Bl= Baseline ; CD+ = Presence of cognitive decline ; CD- = Absence of cognitive decline; DASI= Duke Activity Status Index ; Eu= Index scores based on data from a
European population; Fu= 1-year follow-up; Md=Mean difference; USA= Index scores based on data from a United States of America population; VAS= Visual analogue
scale
Supplemental Table 4- Outcomes of included and excluded patients
Included patients
Excluded patients
(n=51)
(n=50)
Clinical outcomes – 30 days
Stroke
0 (0)
2 (4.0)
Myocardial infarction
1 (2.0)
3 (6.0)
New-onset atrial fibrillation
5 (9.8)
5 (10.0)
New pacemaker implantation
7 (13.7)
8 (16.0)
Acute kidney injury stage 2 or 3
1 (2.0)
1 (2.0)
Major vascular complication
2 (3.9)
9 (18.0)
Clinical outcomes – from 30 days to 1 year
Stroke
1 (2.0)
0 (0)
Myocardial infarction
1 (2.0)
2 (4.0)
Major or life-threatening bleeding
4 (7.8)
0 (0)
New-onset atrial fibrillation
2 (3.9)
1 (2.0)
Categorical variables are presented as number (percentage).
p-value
0.242
0.362
1.000
0.967
1.000
0.051
1.000
0.617
0.117
1.000
Supplemental Table 5 – Neurocognitive tests of included and excluded patients at baseline
Neurocognitive tests at baseline
Included
Excluded
p-value
patients (n=51)
patients (n=50)
MoCA Dimensions
Visuospatial function
3.73±1.09
3.40±1.58
0.579
Naming
2.57±0.67
2.56±0.58
0.677
Attention, concentration and working memory
4.88±1.29
4.62±1.55
0.526
Language
2.35±0.63
2.14±0.70
0.107
Abstraction
1.37±0.82
1.12±0.90
0.148
Short-term memory (delayed recall)
1.92±1.59
1.76±1.67
0.521
Orientation
5.73±0.57
5.52±1.03
0.455
Total MoCA score
22.71±3.84
21.22±4.78
0.158
Digit-symbol substitution test (n=87)
Trail making test-Part A (n=92)
Time
Number of failure (time > 150s)
Number of errors ≥ 1
Trail making test-Part B (n=82)
Time
Number of failure (time > 300s)
Number of errors ≥ 1
25.56±10.65
19.31±8.69
0.005
66.64±25.76
1 (2.0)
6 (12.0)
95.43±33.80
5 (11.9)
5 (12.2)
<0.001
184.88±78.72
8 (19.5)
24 (58.5)
238.33±73.1
20 (51.2)
25 (64.0)
0.003
Verbal fluency tests
Letter P (n=95)
10.71±3.72
8.77±3.93
Animals (n=96)
12.16±4.19
10.98±4.21
Data are presented as mean ± standard deviation. MoCA= Montreal cognitive assessment.
0.023
0.178
Supplemental Figure 1 – The Duke Activity Status Index (DASI) Questionnaire.
The DASI questionnaire is a 12-item scale ranging from 0 (worst) to 58.2 (best) that evaluates the
ability to perform common activities of daily living.
Supplemental Figure 2 – EQ-5D-3L questionnaire
The EQ-5D-3L questionnaire is a standardized scale to measure quality of life primarily designed for
self-completion. It consists of 2 pages: the EQ-5D descriptive system and the EQ visual analogue
scale (EQ VAS). The EQ-5D-3L descriptive system comprises the following 5 dimensions: mobility,
self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 3 levels: no
problems, some problems, extreme problems respectively coded 1, 2, and 3. The combination of each
response defines the patient’s state, out of 243 possible states (e.g. if all dimensions are coded 1, then
the patient’s state is 11111), which can be transformed in an index score using known value sets
determined in various populations (see : http://www.euroqol.org). The EQ VAS allow the patient to
rate his health state on a 20 cm vertical analogue scale with end points of 0 (worst imaginable state)
and 100 (best imaginable state).