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ARTICLE Multiple Sclerosis 2006; 12: 187 195 /

Cognitive impairment in patients with multiple


sclerosis using the Brief Repeatable Battery-
Neuropsychology test
J Sepulcre1, S Vanotti2, R Hernández1, G Sandoval2, F Cáceres2, O Garcea2 and
P Villoslada1

Aims To assess the cognitive impairment of multiple sclerosis (MS) patients using the Brief
Repeatable Battery-Neuropsychology (BRB-N) test.
Methods The performance of 59 patients with MS in the BRB-N test was assessed and compared
with 152 matched healthy controls (HC).
Results In most tests, MS patients performed worse than controls. Age and educational level
strongly influenced the performance of the subjects. The Symbol Digit Modality Test (SDMT) best
correlated with the other individual tests and contributed most to the general BRB-N factor. Further-
more, a correlation between physical disability and performance in some BRB-N tests was observed.
Indeed, patients with progressive MS and greater physical disability performed worse in some tests
than less disabled patients with relapsing MS. By creating a global BRB-N Z score, we found that
patients generally performed 0.7 standard deviation (SD) below the level of controls. We obtained
cut-off values stratified by age and education to determinate cognitive impairment in MS patients.
Conclusions Our data show that cognitive impairment is prevalent amongst MS patients, and that a
single cognitive measurement might be useful for monitoring patients during the progression of this
illness. Multiple Sclerosis 2006; 12: 187 /195. www.multiplesclerosisjournal.com

Key words: Brief Repeatable Battery; cognitive impairment; multiple sclerosis; neuropsychology;
stratified cut-offs

Introduction shown to be of little use in MS [10], the Brief


Repeatable Battery-Neuropsychology (BRB-N) test
Multiple sclerosis (MS) is one of the major causes was developed as a short and sensitive test to
of disability in young adults [1], with cognitive and identify disturbances of cognitive domains in MS
psychiatric disturbances appearing in half of the patients [11]. The BRB-N has become the most
cases [2 /4]. The spectrum of clinical manifestations widely used neuropsychological battery for MS
depends mainly on the location and extension of [12], and it is now being applied in clinical trials
the plaques in the central nervous system. The to monitor cognitive changes [13]. In this study, we
cognitive functions that are most often affected assessed the relationship of the BRB-N with the
are memory, the speed of information processing, physical disability of MS patients and healthy
controls (HC) and obtained the cut-off values
as well as attention and executive functions, visuo-
stratified by age and education to determinate
spatial perception or object naming [4 /7].
cognitive impairment in MS. Furthermore, we
Neuropsychological manifestations can be de- were interested in developing a unified cognitive
tected in patients even during early stages of the measurement that might be useful for clinical
disease [8,9], highlighting the need to screen for studies and that would be easier to administer
cognitive deficits. As the Mini-Mental test has been in practice.

1
Department of Neurology, Multiple Sclerosis Centre, Clinica Universitaria, University of Navarra, Navarra, Spain;
2
Neuroimmunology Clinic, Ramos Mejia Hospital, Argentina
Author for correspondence: Pablo Villoslada, Department of Neurology, Multiple Sclerosis Centre, Clı́nica
Universitaria de Navarra, Pio XII 36, 31008, Pamplona, Navarra, Spain. E-mail: pvilloslada@unav.es
Received 3 September 2004; accepted 6 July 2005

– 2006 Edward Arnold (Publishers) Ltd 10.1191/1352458506ms1258oa


188 J. Sepulcre et al.

Patients and methods individuals had been previously studied with this
battery and none of the subjects refused to perform
We studied 59 consecutive patients with MS (Poser any of the tests (including PASAT 2-3). The BRB-N
criteria [14]) and 152 HC, proportionally matched was administered once, thus training-effects are
by sex, age and education in two MS centres. HC not applicable.
with cognitive impairment identified with Fol- Statistical analyses were performed using the
stein’s Mini-Mental [15], were also excluded. MS SPSS 11.0 software package (SPSS Inc., Chicago, IL,
related disability was evaluated with the Extended USA), applying the following tests: ANCOVA (ad-
Disability Status Scale (EDSS) [16], and the Multiple justed by age and education), unvaried correlation,
Sclerosis Functional Composite Measure (MSFC) multivariate analysis (multiple lineal regression-
[17,18], which includes: the Nine Hole Peg Test stepwise method, P to enter 0.05 and P to exit
(9-HPT); the Timed Walk Test (TWT); and PASAT 3. 0.1), factor analysis (principal components method)
Only one patient with complete paralysis of his and Z scores. A factor analysis was performed to
dominant hand was excluded for the 9-HPT. In this assess the principal distribution components of the
study, we included only individuals with no history battery in HC compared to MS, and not with the
of psychiatric or neurological disease other than intention to reduce variables. Correlation between
MS, no visual or auditory deficits, and no history the BRB-N tests and the patient’s disability scales
of alcohol or drug abuse, or any other major were assessed using the Pearson correlation test (all
medical illness. Individuals with psychiatric distur- variables had a normal distribution, as assessed by
bances identified with Cummings’ Neuropsychia- the Kolmogorov /Smirnov test). The level of sig-
tric Inventory [19], or Hamilton’s Depression Scale nificance was set at P B/0.05. To obtain cut-off
[20], were excluded from the study. values, we used three different criteria: 1 standard
MS patients were categorized by their EDSS as deviation (SD), 1.5 SD and 2 SD below the mean
follows: low disability (EDSS: 0 /3.0); medium dis- values of the HC in each test. We also defined the
ability (EDSS: 3.5 /6.5); and high disability (EDSS: pathological performance of MS patients at three
7.0 /9.0). The educational level of the subjects levels as the performance below the cut-off in at
was classified within one of four levels: low (B/8 least one, two or three tests of the battery. For the
years of education: elementary school); middle-low development of cut-off levels, the decimal values
(between nine and 12 years: high school), middle- were rounded up in the case of a decimal /0.5 and
high (between 13 and 16 years: college) and high down in the case of a decimal 5/0.5.
(/17 years: advanced degrees). The age of the In order to obtain a global cognitive performance
individuals was classified within one of three levels: score, we created a Z score for each cognitive
B/35 years, between 35 and 49 years and /49 years. domain (Z verbal memory (Zv), Z visual memory
Trained personnel carried out the validated (Zvi), Z attention-executive functions (Za) and Z
Spanish translation of the BRB-N in both centres. fluency (Zf)) and Z global cognitive function (BRB-
The two alternative Spanish versions (A or B) of N Z; see equations below). We calculated two sets of
BRB-N were produced for the European Study Z scores, one based on the control group and the
Group on Interferon beta-1b in Secondary Progres- other based on the MS patient group and for each
sive MS [13], and both were administered in alter- cognitive domain, the different subtests were
nating order. The BRB-N includes: the Selective weighted by their Z score to balance the tasks
Reminding Test (SRT) to assess verbal memory; the (e.g., Z SRT-S, Z SRT-R and Z SRT-D to produce the
10/36 Spatial Recall Test (10/36) to assess visual Zv). We obtained the global cognitive function
memory; the Symbol Digit Modalities Test (SDMT) (BRB-N Z) by calculating the mean of the Z scores
to assess attention, visual precision search and from the four cognitive domains.
executive functions; the Paced Auditory Serial
Z-verbal memory (Zv)
Addition Task 2 and 3 seconds (PASAT 2-3) to assess
the maintenance of attention; and the Word List (Z SRT-SZ SRT-RZ SRT-D)=3
Generation (WLG) to assess associative verbal flu- Z-visual memory (Zvi)(Z 10=36Z 10=36D)=2
ency. These tests were selected to explore most Z-attentional=executive (Za)
of the cognitive functions while minimising the
overlap between them. (Z Pasat3Z Pasat2Z SDMT)=3
The SRT-S and SRT-R were performed over six Z-fluency (Zf)Z WLG
trials and the 10/36 over three trials. The delayed BRB-N Z or Z-global (Zg)(ZvZviZaZf)=4
SRT-D and 10/36-D were performed 15 minutes
later. The SDMT, the WLG semantic form (A: The local Ethical Committees of both centres
animals; B: fruits and vegetables), and PASAT 2-3 approved these studies and all participants gave
were performed only once. The SDMT and the WLG their informed consent before being included in
were each performed in 90 seconds. None of the the study.

Multiple Sclerosis 2006; 12: 187 /195 www.multiplesclerosisjournal.com


Cognitive impairment in MS patients 189

Results therefore, were the most important components


of the battery.
Structure of BRB-N and the influence of The values obtained from the HC group (Supple-
demographic variables mentary information S1) were similar to those
found in Dutch and Italian populations [21,22],
The demographic and clinical characteristics of the indicating that language did not influence BRB
HC and MS subjects are shown in Table 1, both performance. Furthermore, we found no differences
groups being homogeneously distributed by age in the performance of the HC subjects with respect
and education. We first assessed the performance of to gender, the BRB-N version used, or between the
BRB-N in the HC group in order to evaluate the two centres in which the tests were performed. We
cognitive performance under normal conditions. As found that age influenced the performance in the
expected, the correlation between tests of the same SRT (three subtests) and SDMT, and that education
cognitive domain was high (r /0.6; between SRT-S, influenced performance in the SRT-S, 10/36 (two
SRT-R and SRT-D in verbal memory, 10/36 and 10/ subtests), SDMT, PASAT 2-3 and WLG tests (P B/
36-D in visual memory, or PASAT 3 and PASAT 2 in 0.05 in all cases).
attention function) and with the exception of the
SDMT, the correlation between tests of different
cognitive domains was low or non-significant. Performance of MS patients in the BRB-N
Indeed, the SDMT had the highest significant
correlation with respect to all other tests of the MS patients performed worse than HC subjects (P B/
different cognitive domains. In HC subjects, we 0.001 in all cases; Supplementary information S1),
found a five-factor solution that explained 90.03% except for WLG, even when assessed by MS sub-
of the total variance and factor 1 was identified as a types (data not shown). We found significant
general factor of the battery. The SRT-S and SDMT differences between patients with relapsing MS
most closely correlated with this factor 1 and, and progressive MS in the three SRT and the
SDMT (P B/0.05 in all cases). We obtained the
Table 1 Demographic and clinical characteristics of both HC BRB-N cut-off scores, stratified by age and educa-
and MS patients tion, using three different criteria ( B/1, B/1.5 or
HC MS patients P values* B/2 SD below the mean values of HC in each test;
Appendix 1 /3) and using such cut-off levels, we
n 152 59 /
Sex (M/F) 44/108 21/38 NS found that cognitive impairment was highly pre-
Age (years) 42.59/11.9 42.69/10.4 NS valent in MS patients. Using a very relaxed criteria
B/35 years 48 17 NS (abnormal result ( B/1 SD in one subtest)), we
35 /49 years 54 25 NS obtained a very high prevalence (89.83%) in the
/17 years 50 16 NS
Education 11.849/3.04 11.989/3.42 NS MS group, but with a big overlap in HC subjects
(years) (64.47% had one abnormal subtest with this cri-
5/8 years 23 11 NS teria). When criteria were set to medium stringency
9 /12 years 53 18 NS
13 /16 years 61 20 NS
(such as abnormal performance (B/1.5 SD) in two
]/17 years 15 10 NS subtests), the prevalence fell to around 60%
EDSS / 3.44 (0 /8.5) (14.47% in HC). However, even when the most
EDSS 0 /3.0 / 34 / stringent criteria were applied, such as an abnormal
EDSS 3.5 /6.5 / 19 /
EDSS 7.0 /9.0 / 6 / result ( B/2 SD) in three tests, cognitive impairment
MSFC / /0.369/1.88 / was still highly prevalent in MS, around 30%
MS subtype (3.94% in HC; Table 2).
RRMS / 37 /
SPMS / 9 /
PPMS / 11 / Table 2 Performance of the BRB-N in MS patients according to
PRMS / 2 / the different strength criteria
*P values between HC cohort and MS patients cohort (x2 or Cut-off levels using different strength criteria
Student’s t-test where appropriate).
Results are expressed as number of HC or MS patients, mean9/ Abnormal
SD (or median and rank for EDSS). subtest B/1 SD (%) B/1.5 SD (%) B/2 SD (%)
ns, Not significant; EDSS, Expanded Disability Status Scale; ]/1 subtest 53 (89.83) 46 (77.96) 39 (66.10)
MSFC, Multiple Sclerosis Functional Composite; RRMS, relap- ]/2 subtest 49 (83.05) 34 (57.62) 24 (40.67)
sing remitting multiple sclerosis; SPMS, secondary progressive ]/3 subtest 43 (72.88) 31 (52.54) 18 (30.50)
multiple sclerosis; PPMS, primary progressive multiple sclerosis;
PRMS, progressive relapsing multiple sclerosis. Results are expressed as number of MS patients and percentage.

www.multiplesclerosisjournal.com Multiple Sclerosis 2006; 12: 187 /195


190 J. Sepulcre et al.

Relationship between BRB-N and physical Discussion


disability
Although fully developed dementia is rare in MS
All BRB-N subtests, except for the WLG test, showed patients, at least half of MS patients have some
a moderate correlation with the EDSS and MSFC degree of cognitive impairment [2 /4]. We found
scales in MS patients (r / /0.395 to /0.598, P B/ that cognitive impairment was indeed highly pre-
0.05 for EDSS; and r /0.276 /0.477, P B/0.05 for valent in our cohort of MS patients, depending on
MSFC). Interestingly, the SDMT had the strongest the degree of disability, and the MS subtype.
correlation with both the EDSS (r / /0.598; P B/ Although different cognitive batteries have been
0.001) and MSFC (r /0.477; P B/0.001). This finding proposed to assess cognitive impairment in MS
was striking because the correlation of the PASAT 3 [10,11,22 /24], the BRB-N has now become widely
with the MSFC was slightly lower, despite the fact accepted for clinical studies and even in clinical
that PASAT 3 is included in the MSFC (r /0.423; practice. In our study with the Spanish version of
P/0.001). This association between SDMT and the the BRB-N, we found that the values from HC were
disability scales was not due to hand impairment similar to those obtained in Dutch [21], and Italian
because an independent association was main- [22], populations indicating that this battery is little
tained after adjusting for the dominance of the influenced by language or cultural differences,
9-HPT score (r /0.610, P B/0.001 for EDSS; and r/ thereby validating its use in different populations.
0.469, P B/0.001 for MSFC). According to the However, as previously reported, age and educa-
categories of the EDSS scale, patients with low tional level did strongly influence BRB-N perfor-
disability (EDSS: 0 /3.0) performed better than mance. In this study, we excluded subjects with
patients with medium disability (EDSS: 3.5 /6.5) in depression and therefore this variable did not affect
the SRT and SDMT (P B/0.05 in all cases), and better BRB-N performance. Since, in clinical practice,
than the highly disabled patients (EDSS: 7.0 /9.0) patients with mood disorders might perform differ-
in the SRT (three subtest), 10/36 (two subtest), ently in this battery, we recommend that cognitive
SDMT, PASAT 2 and 3 tests (P B/0.05 in all cases). deficits should not be assessed during this period.
Interestingly, MS patients with medium and high A degree of controversy exists regarding the
disability performed similarly in all tests. In addi- correlation between cognitive impairment and
tion, the performance of patients with very low the degree of physical disability measured with
disability (EDSS:5/1.5) was similar to that of HC the EDSS scale [4,9,21 /30]. We found a moderate
subjects, no differences being observed in any test correlation between the BRB-N and both physical
in the battery. disability scales analysed, EDSS and MSFC. We
found that the SDMT correlated with the other
tests in the battery, it had the strongest correlation
with disability scales, and weighed most heavily in
Developing a global cognitive score the general factor of BRB-N in MS patients. It may
be that the relevance of this test is due to its multi-
As expected when using the HC reference values
modal character [31]. Moreover, this test might be
(see Supplementary information 2), the distribution sensitive to changes in the disease, as reflected by
of the mean BRB-N Z score of MS patients was its ability to discriminate between relapsing and
skewed 0.7 SD towards a poorer performance progressive disease [12,25]. Indeed, SDMT correlates
than the HC group. Moreover, the difference was with the degree of cerebral atrophy measured by
highest (/0.85 SD) when considering only the MRI [26]. Taking all these data into account, we
cognitive domains that best discriminated the propose that if only one neuropsychological test
groups (abbreviated BRB-N Z score: calculated were to be used to screen for cognitive impairment,
with verbal and visual memory tests and the tests the SDMT would be the most appropriate test and
of attention-executive domains). However, when could even substitute for the PASAT in the MSFC.
using reference values from the MS patient group When the MSFC was developed, the inclusion of
(see Supplementary information 2), the distribution the PASAT test was based on the fact that, at that
of BRB-N from an individual patient reflected time, more data was available for the PASAT test
a better or worse performance than an average than any other at that time [18].
patient. This latter approach seems to be more In our study, all the tests of the BRB-N were
intuitive and sensitive to clinical changes with significantly different between HC and MS patients
time, and as such, it was adopted for the MSFC except for the WLG. This lack of sensitivity of
[17]. Finally, the BRB-N Z score correlated signifi- WLG supports the previously established idea that
cantly with the disability scales EDSS (r / /0.540; language function is more resistant to deterioration
P B/0.01) and MSFC (r /0.456; P B/0.01). in MS than other cognitive tasks [9,32]. However, it

Multiple Sclerosis 2006; 12: 187 /195 www.multiplesclerosisjournal.com


Cognitive impairment in MS patients 191

is important to note that we only assessed the 8. Dujardin K, Donze AC, Hautecoeur P. Attention
semantic form of this fluency task, and this could impairment in recently diagnosed multiple sclerosis. Eur J
Neurol 1998; 5: 61 /66.
be responsible for the lack of sensitivity. 9. Ruggieri RM, Palermo R, Vitello G, Gennuso M,
Although it was not the primary aim of our study Settipani N, Piccoli F. Cognitive impairment in
and we might lack power, we found that subjects patients suffering from relapsing-remitting multiple
with progressive MS performed worse than those sclerosis with EDSS B/ or / 3.5. Acta Neurol Scand 2003;
108: 323 /26.
with relapsing MS, which is in agreement with 10. Beatty WW, Goodkin DE. Screening for cognitive
Huijbregts et al . [12] This poorer performance may impairment in multiple sclerosis. An evaluation of the
possibly reflect the amount of brain damage, as Mini-Mental State Examination. Arch Neurol 1990; 47:
highlighted in MRI studies [33]. 297 /301.
The creation of a unified cognitive BRB-N scale 11. Rao SM, in collaboration with the Cognitive
Function Study Group of the National Multiple
could prove to be a useful tool to screen cognitive Sclerosis Society. A manual for the Brief Repeatable
impairment in MS patients and to monitor changes Battery of Neuropsychological Tests in multiple sclerosis .
in cognitive functions over time. For this reason, we Section of Neuropsychology, Medical College of Wiscon-
created a BRB-N Z score. Through this BRB-N Z sin, 1000 N. 92 Street, Milwaukee, WI 53226, 1990.
12. Huijbregts SCKN, de Sonneville LM, de Groot V,
score, we found that patients performed close to 1 Reuling IE, Polman CH. Differences in cognitive
SD worse than HC and that the BRB-N Z score also impairment of relapsing remitting, secondary, and pri-
correlated well with physical disability. One limita- mary progressive MS. Neurology 2004; 63: 335 /39.
tion of our study was that our results were obtained 13. European Study Group on interferon beta-1b in
secondary progressive MS. Placebo-controlled multi-
after a single administration of the battery in
centre randomised trial of interferon beta-1b in treat-
each subject, and the psychometric properties of ment of secondary progressive multiple sclerosis. Lancet
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14. Poser CM, Paty DW, Scheinberg L, McDonald WI,
Davis FA, Ebers GC et al . New diagnostic criteria for
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Acknowledgements Neurol 1983; 13: 227 /31.
15. Folstein MF, Folstein SE, McHugh PR. ‘Mini-mental
We would like to thank the individuals who state’. A practical method for grading the cognitive state
of patients for the clinician. J Psychiatr Res 1975; 12:
participated in our study, the Navarra MS Society
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and the Argentina MS Society for their collabora- 16. Kurtzke JF. Rating neurologic impairment in multiple
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Masdeu, Dr Teresa Gomez-Isla, Dr Manuel Alegre Neurology 1983; 33: 1444 /52.
and Dr Isabel Lamet from the Department of 17. Fischer JS, Rudick RA, Cutter GR, Reingold SC,
Baier ML, Cookfair DL et al . The Multiple Sclerosis
Neurology at the University of Navarra, for their Functional Composite Measure (MSFC): an integrated
advice in the design and analysis of this study. approach to MS clinical outcome assessment. National
MS Society Clinical Outcomes Assessment Task Force.
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18. Cutter GR, Baier ML, Rudick RA, Cookfair DL,
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Appendix 1 Proposed BRB-N cut-off scores stratified by age and education using the criteria of 1 SD below the mean values of the
HC in each test (see methods for details)

Age

Education B/35 years 35 /49 years /49 years


5/8 years (low level)
SRT-S 38 40 28
SRT-R 34 32 25
SRT-D 8 8 7
10/36 12 12 12
10/36D 4 4 4
SDMT 32 31 24
PASAT 3 24 24 24
PASAT 2 19 19 19
WLG 15 15 15

9 /12 years (middle-low level)


SRT-S 40 41 33
SRT-R 34 32 25
SRT-D 8 8 7
10/36 15 15 15
10/36D 5 5 5
SDMT 33 36 33
PASAT 3 35 35 35
PASAT 2 26 26 26
WLG 21 21 21

13 /16 years (middle-high level)


SRT-S 43 46 37
SRT-R 34 32 25
SRT-D 8 8 7
10/36 16 16 16
10/36D 5 5 5
SDMT 45 36 36
PASAT 3 40 40 40
PASAT 2 30 30 30
WLG 22 22 22

]/17 years (high level)


SRT-S 50 49 44
SRT-R 34 32 25
SRT-D 8 8 7
10/36 19 19 19
10/36D 7 7 7
SDMT 55 39 40

Multiple Sclerosis 2006; 12: 187 /195 www.multiplesclerosisjournal.com


Cognitive impairment in MS patients 193

Appendix 1 (Continued)
Age

Education B/35 years 35 /49 years /49 years


PASAT 3 46 46 46
PASAT 2 35 35 35
WLG 25 25 25

SRT-S, Selective Reminding Test Long-Term Storage; SRT-R, Selective Reminding Test Long-Term Retrieval; SRT-D, Selective Reminding
Test Delayed Recall; 10/36, 10/36 Spatial Recall Test; 10/36 D, 10/36 Spatial Recall Test Delayed; SDMT, Symbol Digit Modalities Test;
PASAT 2-3, Paced Auditory Serial Addition Task 2 and 3 seconds; WLG, word list generation.

Appendix 2 Proposed BRB-N cut-off scores stratified by age and education using the criteria of 1.5 SD below the mean values of the
HC in each test (see methods for details)

Age

Education B/35 years 35 /49 years /49 years

5/8 years (low level)


SRT-S 34 36 21
SRT-R 27 26 17
SRT-D 7 7 6
10/36 9 9 9
10/36D 3 3 3
SDMT 25 24 20
PASAT 3 18 18 18
PASAT 2 14 14 14
WLG 10 10 10

9 /12 years (middle-low level)


SRT-S 34 36 27
SRT-R 27 26 17
SRT-D 7 7 6
10/36 13 13 13
10/36D 4 4 4
SDMT 24 30 27
PASAT 3 30 30 30
PASAT 2 21 21 21
WLG 18 18 18

13 /16 years (middle-high level)


SRT-S 37 41 31
SRT-R 27 26 17
SRT-D 7 7 6
10/36 13 13 13
10/36D 4 4 4
SDMT 38 29 31
PASAT 3 35 35 35
PASAT 2 25 25 25
WLG 18 18 18

]/17 years (high level)


SRT-S 45 45 41
SRT-R 27 26 17
SRT-D 7 7 6
10/36 17 17 17
10/36D 6 6 6
SDMT 52 33 36
PASAT 3 42 42 42
PASAT 2 30 30 30
WLG 22 22 22

SRT-S, Selective Reminding Test Long-Term Storage; SRT-R, Selective Reminding Test Long-Term Retrieval; SRT-D, Selective Reminding
Test Delayed Recall; 10/36, 10/36 Spatial Recall Test; 10/36 D, 10/36 Spatial Recall Test Delayed; SDMT, Symbol Digit Modalities Test;
PASAT 2-3, Paced Auditory Serial Addition Task 2 and 3 seconds; WLG, word list generation.

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194 J. Sepulcre et al.

Appendix 3 Proposed BRB-N cut-off scores stratified by age and education using the criteria of 2 SD below the mean values of the
HC in each test (see methods for details)

Age

Education B/35 years 35 /49 years /49 years


5/8 years (low level)
SRT-S 30 33 14
SRT-R 21 20 11
SRT-D 6 6 5
10/36 7 7 7
10/36D 2 2 2
SDMT 19 18 16
PASAT 3 12 12 12
PASAT 2 10 10 10
WLG 5 5 5

9 /12 years (middle-low level)


SRT-S 28 32 22
SRT-R 21 20 11
SRT-D 6 6 5
10/36 11 11 11
10/36D 3 3 3
SDMT 15 24 22
PASAT 3 25 25 25
PASAT 2 16 16 16
WLG 15 15 15

13 /16 years (middle-high level)


SRT-S 32 37 25
SRT-R 21 20 11
SRT-D 6 6 5
10/36 10 10 10
10/36D 3 3 3
SDMT 32 26 27
PASAT 3 31 31 31
PASAT 2 20 20 20
WLG 15 15 15

]/17 years (high level)


SRT-S 41 41 39
SRT-R 21 20 11
SRT-D 6 6 5
10/36 15 15 15
10/36D 5 5 5
SDMT 49 29 32
PASAT 3 39 39 39
PASAT 2 26 26 26
WLG 19 19 19

SRT-S, Selective Reminding Test Long-Term Storage; SRT-R, Selective Reminding Test Long-Term Retrieval; SRT-D, Selective Reminding
Test Delayed Recall; 10/36, 10/36 Spatial Recall Test; 10/36 D, 10/36 Spatial Recall Test Delayed; SDMT, Symbol Digit Modalities Test;
PASAT 2-3, Paced Auditory Serial Addition Task 2 and 3 seconds; WLG, word list generation.

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Cognitive impairment in MS patients 195

Supplementary information S1 BRB-N mean scores of HC and MS patients

HC MS P values*
SRT-S 50.919/11.34 40.129/14.5 B/0.001
SRT-R 42.459/13.24 28.469/15.91 B/0.001
SRT-D 9.79/2.04 7.759/2.61 B/0.001
10/36 20.869/5.43 17.059/5.98 B/0.001
10/36D 7.169/2.23 5.669/2.39 B/0.001
SDMT 49.239/14.64 36.869/16.87 B/0.001
PASAT 3 45.969/10.71 36.339/13.93 B/0.001
PASAT 2 36.979/10.69 26.839/11.43 B/0.001
WLG 28.159/7.32 26.159/8.47 NS

Results are expressed as mean9/SD.


*P values between HC cohort and MS patients cohort using ANCOVA test (adjusted by age and education). NS, not significant; SRT-S,
Selective Reminding Test Long-Term Storage; SRT-R, Selective Reminding Test Long-Term Retrieval; SRT-D, Selective Reminding Test
Delayed Recall; 10/36, 10/36 Spatial Recall Test; 10/36 D, 10/36 Spatial Recall Test Delayed; SDMT, Symbol Digit Modalities Test;
PASAT 2-3, Paced Auditory Serial Addition Task 2 and 3 seconds; WLG, word list generation.

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