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Validity and Reliability of a PersianTranslation of the Minimal Assessmentof Cognitive Function in MultipleSclerosis (MACFIMS)Arman Eshaghi a , Sadjad Riyahi-Alam a , Tina Roostaei a , GhazalHaeri a , Aida Aghsaei a , Mohammad Reza Aidi a , Hamid RezaPouretemad b c , Mojtaba Zarei d , Sara Farhang a , RoghayehSaeedi a b c , Arash Nazeri a , Habib Ganjgahi d , Farnaz Etesam a ,Amir Reza Azimi a , Ralph HB Benedict e & Mohammad Ali Sahraiana

a Sina MS Research Center, Brain and Spinal Injury Research Center,Tehran University of Medical Sciences, Tehran, Iranb Department of Psychology, Shahid Beheshti University, Tehran,Iranc Institute for Cognitive Science Studies, Tehran, Irand Brain Mapping Research Center, Tehran University of MedicalSciences, Tehran, Irane Department of Neurology, State University of New York atBuffalo, Buffalo, NY, USA

Available online: 11 Jun 2012

To cite this article: Arman Eshaghi, Sadjad Riyahi-Alam, Tina Roostaei, Ghazal Haeri, AidaAghsaei, Mohammad Reza Aidi, Hamid Reza Pouretemad, Mojtaba Zarei, Sara Farhang, RoghayehSaeedi, Arash Nazeri, Habib Ganjgahi, Farnaz Etesam, Amir Reza Azimi, Ralph HB Benedict &Mohammad Ali Sahraian (2012): Validity and Reliability of a Persian Translation of the MinimalAssessment of Cognitive Function in Multiple Sclerosis (MACFIMS), The Clinical Neuropsychologist,DOI:10.1080/13854046.2012.694912

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The Clinical Neuropsychologist, 2012, 1–10, iFirst

http://www.psypress.com/tcn

ISSN: 1385-4046 print/1744-4144 online

http://dx.doi.org/10.1080/13854046.2012.694912

Validity and Reliability of a Persian Translation of theMinimal Assessment of Cognitive Function in MultipleSclerosis (MACFIMS)

Arman Eshaghi1, Sadjad Riyahi-Alam1, Tina Roostaei

1,

Ghazal Haeri1, Aida Aghsaei1, Mohammad Reza Aidi

1,

Hamid Reza Pouretemad2,3, Mojtaba Zarei4, Sara Farhang

1,

Roghayeh Saeedi1,2,3, Arash Nazeri1, Habib Ganjgahi

4,

Farnaz Etesam1, Amir Reza Azimi

1, Ralph HB Benedict

5, and

Mohammad Ali Sahraian1

1Sina MS Research Center, Brain and Spinal Injury Research Center, Tehran University of

Medical Sciences, Tehran, Iran2Department of Psychology, Shahid Beheshti University, Tehran, Iran3Institute for Cognitive Science Studies, Tehran, Iran4Brain Mapping Research Center, Tehran University of Medical Sciences, Tehran, Iran5Department of Neurology, State University of New York at Buffalo, Buffalo, NY, USA

Cognitive dysfunction is common in multiple sclerosis (MS) and validated batteries are

limited in languages other than English. We aimed to translate, cross-culturally adapt,

validate, and assess reliability of Minimal Assessment of Cognitive Function in MS

(MACFIMS) in Persian. The MACFIMS is a well-constructed battery in the MS literature.

The battery was adapted to Persian in accordance with available guidelines. A total of 158

MS patients and 90 controls underwent neuropsychological assessment. For reliability

assessment the battery was re-administered in a subset of 41 patients after a short interval

using alternate forms to mitigate practice effects (approximately 10 days). Patients

performed significantly worse than controls in all cognitive tests, supporting discriminant

validity of our adapted battery. Approximately half of patients (46.2%) showed cognitive

impairment as defined by the impairment in two or more tests. The Symbol Digit Modalities

Test was the most robust test by ROC analysis. All tests showed acceptable to good level of

reliability. This is the first validation of gold-standard cognitive testing in Persian. The

Persian MACFIMS shows nearly the same psychometrics as its English counterpart.

Keywords: Multiple sclerosis; Cognitive assessment; MACFIMS.

INTRODUCTION

Cognitive dysfunction is common in MS patients (R. H. Benedict &Zivadinov, 2011; Chiaravalloti & DeLuca, 2008; Prakash, Snook, Lewis, Motl, &Kramer, 2008) but comprehensive assessment of cognition is expensive, timeconsuming, and often absent in neurology clinics outside of the US and WesternEurope. In 2001 an expert panel of neuropsychologists from English-speakingcountries proposed a battery of seven neuropsychological (NP) tests covering theprimary domains commonly impacted by MS associated cerebral injury.

The Clinical Neuropsychologist, 2012, 1–10, iFirst

http://www.psypress.com/tcn

ISSN: 1385-4046 print/1744-4144 online

http://dx.doi.org/10.1080/13854046.2012.694912

Validity and Reliability of a Persian Translation of theMinimal Assessment of Cognitive Function in MultipleSclerosis (MACFIMS)

Arman Eshaghi1, Sadjad Riyahi-Alam1, Tina Roostaei

1,

Ghazal Haeri1, Aida Aghsaei1, Mohammad Reza Aidi

1,

Hamid Reza Pouretemad2,3, Mojtaba Zarei4, Sara Farhang

1,

Roghayeh Saeedi1,2,3, Arash Nazeri1, Habib Ganjgahi

4,

Farnaz Etesam1, Amir Reza Azimi

1, Ralph HB Benedict

5, and

Mohammad Ali Sahraian1

1Sina MS Research Center, Brain and Spinal Injury Research Center, Tehran University of

Medical Sciences, Tehran, Iran2Department of Psychology, Shahid Beheshti University, Tehran, Iran3Institute for Cognitive Science Studies, Tehran, Iran4Brain Mapping Research Center, Tehran University of Medical Sciences, Tehran, Iran5Department of Neurology, State University of New York at Buffalo, Buffalo, NY, USA

Cognitive dysfunction is common in multiple sclerosis (MS) and validated batteries are

limited in languages other than English. We aimed to translate, cross-culturally adapt,

validate, and assess reliability of Minimal Assessment of Cognitive Function in MS

(MACFIMS) in Persian. The MACFIMS is a well-constructed battery in the MS literature.

The battery was adapted to Persian in accordance with available guidelines. A total of 158

MS patients and 90 controls underwent neuropsychological assessment. For reliability

assessment the battery was re-administered in a subset of 41 patients after a short interval

using alternate forms to mitigate practice effects (approximately 10 days). Patients

performed significantly worse than controls in all cognitive tests, supporting discriminant

validity of our adapted battery. Approximately half of patients (46.2%) showed cognitive

impairment as defined by the impairment in two or more tests. The Symbol Digit Modalities

Test was the most robust test by ROC analysis. All tests showed acceptable to good level of

reliability. This is the first validation of gold-standard cognitive testing in Persian. The

Persian MACFIMS shows nearly the same psychometrics as its English counterpart.

Keywords: Multiple sclerosis; Cognitive assessment; MACFIMS.

INTRODUCTION

Cognitive dysfunction is common in MS patients (R. H. Benedict &Zivadinov, 2011; Chiaravalloti & DeLuca, 2008; Prakash, Snook, Lewis, Motl, &Kramer, 2008) but comprehensive assessment of cognition is expensive, timeconsuming, and often absent in neurology clinics outside of the US and WesternEurope. In 2001 an expert panel of neuropsychologists from English-speakingcountries proposed a battery of seven neuropsychological (NP) tests covering theprimary domains commonly impacted by MS associated cerebral injury.

Address correspondence to: Dr. Mohammad Ali Sahraian, Sina MS Research Center, Sina

hospital, Tehran University of Medical Sciences, Tehran, Iran. E-mail: msahrai@tums.ac.ir

Accepted for publication: May 8, 2012. First published online: June 11, 2012.

� 2012 Psychology Press, an imprint of the Taylor & Francis group, an Informa business

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This battery was coined the Minimal Assessment of Cognitive Function in MS(MACFIMS) (R. H. B. Benedict et al., 2002). The battery is a collection ofpreviously published tests that includes the Rao (1991a, 1991b) adaptation of thePaced Auditory Serial Addition Test (PASAT) (Gronwall, 1977), Symbol DigitModalities Test (SDMT) (Smith, 1982), the California Verbal Learning Test secondedition (CVLT-II) (Delis, Kaplan, & Ober, 2000), and Brief Visuospatial MemoryTest-Revised (BVMT-R) for memory assessment (R. H. B. Benedict, 1997) as wellas the Controlled Oral Word Association Test (COWAT) (Benton, Sivan, Hamsher,Varney, & Spreen, 1994), Judgment of Line Orientation Test (JLO) (Benton, 1994),and the Delis-Kaplan Executive Function System (D-KEFS) Sorting Test (Delis,Kaplan, & Kramer, 2001) for assessing language, spatial processing, and executivefunction, respectively. These tests have good reliability (R. H. B. Benedict, 2005) aswell as validity, in that they generally correlate well with brain MRI metrics(Houtchens et al., 2007) and employment status (R. H. Benedict et al., 2006).

Despite well-documented psychometrics in English, the MACFIMS is notvery easily applied in non-English-speaking cultures. More than 80 million people inIran, Afghanistan, and Tajikistan, as well as these countries’ expatriates, speakPersian as their first language. Tehran, the biggest city in Iran, is a high-risk area forMS that had an increasing MS incidence (8.3-fold) during the last two decades andstill has an increasing trend in MS incidence (Elhami, Mohammad, Sahraian, &Eftekhar, 2011). Iranian immigrants show higher risk of MS than other immigrantsin Western countries that may be due to a susceptibility gene in this group(Guimond et al., 2010).

In this study we set out to translate the MACFIMS tests to Persian and theninvestigate psychometrics of this Persian MACFIMS. Our study is the first tovalidate MACFIMS in a language other than English. This paper shows ourendeavor in translation, cross-cultural adaptation, and assessment of validity andreliability of MACFIMS in Persian.

METHOD

Participants

Studied were a convenience sample of 158 MS patients receiving care in theMS Clinic at Sina Hospital in Tehran. Only two patients who met inclusion criteriawere excluded. One patient was not able to complete the battery due to motorproblems and one other patient was not motivated enough to continue the test.Therefore a final sample size of 156 was considered for further analysis.

Inclusion criteria included: (1) MS diagnosis by revised McDonald criteria(Polman et al., 2005), (2) no neurologic/psychiatric diagnosis other than MS andMS-related behavioral changes, (3) no IV corticosteroid use or MS relapse within 6weeks of assessment, (4) no history of developmental disorder, (5) Persian as thefirst language, (6) no history of drug or alcohol abuse, (7) relapsing remitting (RR)or secondary progressive (SP) course (Lublin & Reingold, 1996). Patients wereunder routine treatment and we did not include or exclude patients based onmedications. Patients had a mean age (�SD) of 34.05� 9.09 years, disease durationof 6.07� 5.08 years, education of 14.13� 2.97 years, and Expanded Disability

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Status Scale (EDSS) (Kurtzke, 1983) median of 2.5 (mild severity) (range 7.5).Almost all patients (n¼ 154, 99%) were of Persian descent and 71.2% (n¼ 111)were female. Most patients had relapsing-remitting disease course (n¼ 127, 81%)while 29 patients (18%) had secondary progressive disease course.

There were 90 age, sex, and education-years matched controls that wererecruited from local community through advertisement with a mean age of33.65� 9.48 years. Most (93.4%, n¼ 84) were of Persian descent and 63.3% (n¼ 57)were female (see Table 1 for other demographics). All healthy volunteers completedthe battery and were considered for further analysis. There were no significantdifferences in age, education, or gender.

A random subgroup of 41 patients (33 RR MS and 8 SP MS including 34females) underwent retest for reliability assessment. There was no significantdifference in demographics of this subgroup compared to the total group in terms ofage (p¼ .66), gender (p¼ .07), and years of education (p¼ .56).

All research participants gave informed written consent in accordance withDeclaration of Helsinki (World Medical Association, 2008).

Translation and cross-cultural adaptation

Tests were adapted to Persian according to available guidelines (Perneger,Leplege, & Etter, 1999; Reichenheim & Moraes, 2007). Every attempt was made tomaintain conceptual, item, semantic, and operational equivalence between adaptedand original versions (Reichenheim & Moraes, 2007). To preserve semanticequivalence, first bilingual translators with a good understanding of Persian andEnglish translated tests into Persian. Next, back translation into English wasperformed by independent translators (healthcare researchers) with a good under-standing of Persian and English. To assure their equivalence, original and back-translated versions were compared. In the case of DKEFS and CVLT-II an iterativeprocess of administering draft versions and subsequent modifications, includingcultural adaptation of some words, was undertaken as these tests emphasize verbalstimuli. Patients and clinician feedback during pilot study led to final versions, withalternate forms of CVLT-II, BVMT-R, DKEFS, and COWAT. In the case ofDKEFS card set 1 and 2 were adapted and used as the primary form, and card set3 and 4 as the alternate form. For CVLT-II standard and alternative formswere adapted as the primary and alternate forms respectively (Delis et al., 2000).

Table 1. Demographic characteristics of the patient and control groups

MS Control p value

Gender: no. (%) 0.25a

Males 45 (29) 33 (37)

Females 111 (71) 57 (63)

Age

Mean�SD 34.05� 9.09 33.65� 9.48 0.74b

Years of education

Mean�SD 14.13� 2.97 14.27� 3.56 0.77b

aw2 test bt-test. MS, multiple sclerosis; SD, standard deviation.

PERSIAN MACFIMS 3

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Form 1 and form 4 were used as the primary and alternative forms in BVMT-Rrespectively (R. H. B. Benedict, 1997). For the COWAT the Persian lettersapproximating m, b, and t were used for the primary form and n, r, and p for thealternate form.

Other tests (PASAT, SDMT, BVMT-R, and JLO) that employed numbersand figures as stimuli underwent only translation of instructions.

Procedure

MS patient volunteers who fulfilled the eligibility criteria underwent neuro-logical examination for EDSS assessment (Kurtzke, 1983). Participants were notpaid for participation, but transportation to and from our center in Tehran wasprovided when needed. No other incentive was provided. In addition to theMACFIMS all participants completed the Nine Hole Peg Test (9HPT)(Mathiowetz, Volland, Kashman, & Weber, 1985), the 25 Foot Walk (25FW)(Schwid et al., 1997), and Persian Beck Depression Inventory-Fast Screen (BDI-FS)questionnaire (R. H. Benedict, Fishman, McClellan, Bakshi, & Weinstock-Guttman, 2003) that was adapted from a previously validated version of BDI-IIin Persian (Ghassemzadeh, Mojtabai, Karamghadiri, & Ebrahimkhani, 2005). ThePersian Adult Reading Test (PART) (Hagh Shenas, 2001) was also administered.The PART is a reading test of irregularly spelled words for assessment of premorbidintelligence. The examinee is presented with 50 words one at a time and the numberof correctly read words is recorded.

Test order was uniform throughout the study, beginning with the CVLT-IIlearning trials and ending with the JLO while controlling for modality specificinterference where possible. (Test order: CVLT-II learning trials, 25-FW, PASAT,SDMT, CVLT-II delayed recall, BVMT-R learning trials, COWAT, DKEFS,PART, 9-HPT, BVMT-R delayed recall, and JLO.) Administration of PersianMACFIMS takes 90 minutes.

The MACFIMS tests have been described in many prior publications and arewell known to MS researchers. In brief, the CVLT-II is a multiple trial learning testwith 16 words. There are five learning trials. After roughly 25 minutes participantsare asked to recall the list again without another exposure. Outcome measures aretotal learning over five trials and number of correct recalls following the delay.BVMT-R consists of three learning trials and delayed recall of a matrix of sixdesigns. The PASAT is a test of auditory working memory and mental speedinvolving the rapid calculation of sums. SDMT is a test of visual processing speedconsisting of nine abstract symbols paired with a number from 1 to 9. The examineescans the symbol/number pairings at the top of the page and voices numbers as fastas possible in response to unpaired symbols below. The COWAT is a test of verbalfluency that lasts 60 seconds and starts when the examiner asks the patient to say asmany words as possible beginning with a specific letter. The JLO presents a displayof numbered visual angles to which two smaller lines are to be matched. DKEFS is atest of conceptual reasoning. The examinee is asked to sort six different cards intotwo groups in as many different ways as possible. With each sort, the rationale forsorting is explicated by the patient and scored for accuracy. This test is repeated

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with another set of six cards in the same manner. Two dependent variables are thescore for sorting and description over two card sets.

A subset of patients (n¼ 41) underwent retest for reliability assessment. Test–retest interval (�SD) was 10.8 days �3.78. This sub-study employed alternate formsfor CVLT-II, BVMT-R, DKEFS and COWAT because it has been shown thatusing alternate forms improves reliability (R. H. Benedict, 2005). Sequence of testadministration was the same at each session.

Statistical analysis

One-way analysis of variance (ANOVA) was conducted to analyze between-group statistics between patients and healthy controls with an alpha level of 5.05indicating significance. Analysis of covariance (ANCOVA) was performed tocompare cognitive scores between control and patient groups with BDI-FS andPART as covariates. Effect sizes (Cohen’s d) (Cohen, 1988) were calculated for eachtest based on the difference of means divided by pooled SD. A common statisticalapproach for calculating standardized scores (z-score) of patients in relation tomean and SD of controls was conducted. Patients with a score of less than �1.5 SDare considered impaired in each NP test. In accordance with prior research (R. H.Benedict et al., 2006) patients impaired on two or more tests were defined ascognitively impaired. Pearson’s product moment coefficient was used in correlationanalyses. Paired t-test was used to assess practice effects.

After classifying patients to two groups of impaired and non-impaired oncognitive functioning using the whole MACFIMS battery, we evaluated theclassification accuracy of each MACFIMS subtest to cognitive impairment usingthe entire battery as the gold standard. For this we employed Receiver-Operating-Characteristic (ROC) analysis.

RESULTS

All MACFIMS tests showed a significant difference between patients andcontrols (Table 2). The MS group showed a trend toward depression whencompared with the healthy controls, as assessed by BDI-FS, but the comparison didnot reach the level of significance (p¼ .06). Patients and controls were notsignificantly different on estimated premorbid intelligence (PART scores p¼ .15).As predicted, differences remained significant after controlling for BDI-FS andPART scores (p5 .001) for all test measures except for JLO (p¼ .19).

Based on the global impairment designation (z score5�1.5 in at least twocognitive tests), 46.2% of patients were classified as impaired in cognitivefunctioning (Table 3). SDMT showed the highest correlations with physicaldisability indices including EDSS (r¼�.34, p5 .001) and 9-Hole Peg test (r¼�.42,p5 .001) and only a small correlation with 25-foot walk (r¼�.21, p¼ .01). OnROC analysis, SDMT demonstrated the most robust performance for the detectionof cognitive dysfunction as shown in Figure 1.

The test–retest data are presented in Table 4. Note that despite using alternateforms, modest practice effects were encountered on some tests, reliable as per thewithin-participants analysis of mean differences. Pearson product–moment

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correlation analyses yielded modest to strong test-retest correlations (range¼ 0.66to 0.82).

DISCUSSION

Recognizing the need for psychometric assessment of MS patients in Iran, wetranslated the MACFIMS into Persian and assessed its validity and reliability.These Persian-adapted tests showed good discriminant validity when comparinghealthy controls and MS patients, even after controlling for the effects of premorbidintelligence and depression. Effect sizes show medium to large group differences formost tests. Using the same criterion for overall impairment as in prior US work withthe same test battery, we found that approximately half of MS patients wereimpaired on testing.

Table 2. Between-group statistics for the MACFIMS tests and additional measures

Measure MS mean MS SD Control mean Control SD Cohen’s d p value

BDI-FS 4.68 3.96 3.74 3.60 �0.41 0.06

25-FW 7.07 6.61 4.56 0.88 �2.40 50.001*

9-HPT 27.08 13.08 19.66 2.44 �1.87 50.001*

PART 40.11 4.97 41.25 5.74 0.32 0.11

CVLT-II Total Learning 49.23 10.39 55.31 8.46 0.6 50.001*

CVLT-II Delayed Recall 10.51 3.45 12.48 2.52 0.6 50.001*

PASAT 42.27 12.15 49.19 10.32 0.6 50.001*

SDMT 43.93 16.55 55.58 16.48 0.7 50.001*

BVMT-R Total Learning 20.88 7.65 25.01 7.38 0.6 50.001*

BVMT-R Delayed Recall 8.14 3.11 9.59 2.76 0.5 50.001*

COWAT 27.08 10.85 34.68 12.87 0.7 50.001*

DKEFS Description Score 26.76 12.30 33.54 11.99 0.6 50.001*

DKEFS Total Sorting Score 7.30 3.05 9.04 3.13 0.6 50.001*

JLO 20.94 5.22 22.24 4.75 0.3 0.05*

CVLT-II, California Verbal Learning Test; PASAT, Paced Auditory Serial Addition Test; SDMT,

Symbol Digit Modalities Test; BVMT-R, Brief Visuospatial Memory Test Revised; DKEFS, Delis-

Kaplan Executive Function System; COWAT, Controlled Oral Word Association Test; JLO, Judgment

of Line Orientation Test.

Table 3. Number of patients and controls impaired on neuropsychological tests

All MS patients (number, percentage)

Controls

(number, percentage)

RR MS

(number, percentage)

SP MS

(number, percentage)

Impairment in 52 tests 72 (80%) 84 (53.8%)

75 (58%) 9 (33%)

Impairment in 2 or 3 tests 12 (13.3%) 36 (23%)

30 (23%) 6 (22%)

Impairment in 4 or more tests 6 (6.7%) 36 (23%)

24 (18.6%) 12 (44%)

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The Persian MACFIMS battery had acceptable reliability in this short-interval repeated measures analysis, using alternate forms for COWAT, CVLT-II,BVMT-R, and DKEFS. This customary approach for evaluating test–retestreliability yields a test–retest correlation where a value of 0.70 is consideredacceptable, and 0.80 is considered good. In this study the lowest r-value was 0.66 forDKEFS and the highest was 0.82 for BVMT-R. The practice effects were minimalwith all d values 0.2 or lower except PASAT, where patients improved by 0.3 SD.This is not unexpected considering that no alternate forms were employed forPASAT and the test is quite novel and challenging when experienced for the firsttime. Overall, we conclude that the MACFIMS has good reliability in its Persianadapted form. More studies are required to determine predictive validity in terms ofdisability and disease progression over time.

A somewhat different picture emerges when we compare the current findingswith prior research, focusing on the pattern of impairment. First we note that thefrequency of impairment is somewhat lower than was encountered in R. H. Benedictet al.’s (2006) study of 291 patients. One explanation may lie in the sample

Figure 1. ROC curves for different subtests. Patients are classified into two groups of cognitively

impaired and intact based on performance on the full MACFIMS battery. Test AUC (95% CI): PASAT

0.77 (0.70–0.84), SDMT 0.90 (0.85–0.95), BVMT-R total learning 0.83 (0.76–0.89), BVMT-R delayed

recall 0.84 (0.78–0.90), DKEFS Description Score 0.83 (0.77–0.90), DKEFS Total Sorting Score 0.83

(0.76–0.89), COWAT 0.79 (0.72–0.86), JLO 0.70 (0.62–0.78), CVLT-II Total Learning 0.86 (0.80–0.92),

CVLT-II Delayed Recall 0.84 (0.77–0.90). ROC, Receiver Operating Characteristic; AUC, Area

Under the Curve; PASAT, Paced Auditory Serial Addition Test; SDMT, Symbol Digit Modalities Test;

BVMT-R, Brief Visuospatial Memory Test Revised; DKEFS, Delis-Kaplan Executive Function System;

COWAT, Controlled Oral Word Association Test; JLO, Judgment of Line Orientation Test; CVLT-II,

California Verbal Learning Test-II.

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composition, test order, and motivation to participate. In the earlier work patientswere largely consecutive, clinically referred patients or patients paid to participate inresearch, and SP MS patients constituted 27% of the sample. In the current studypatients volunteered to participate, and only 17.4% had SP course. Besides, testorder was different and not as optimal as compared with the previous study. Herewe find an impairment rate of roughly 45% which is nearly identical to the findingof Rao et al. (Rao, Leo, Bernardin, & Unverzagt, 1991) whose sample was also acommunity-based volunteer one. Another difference with prior findings is that whileSDMT was the most robust or sensitive test in this study, the effect size was smallerthan in prior research. This may be related to culturally specific differences in theways that participants view or interpret the number/symbol stimuli. Likewise,whereas BVMT-R has been more sensitive than CVLT-II in some studies, here thesensitivity was equivalent. While the sensitivity of the visual processing domain wasnot as marked in our study as in previous reports, we do find that SDMT is the mostrobust subtest and it has good reliability. The validity and reliability of SDMT inpeople of different ethnic backgrounds was established in prior work (Morrowet al., 2010).

There are some limitations in our study. We did not include PP MS patients inour cohort. This phenotype is also associated with cognitive dysfunction andmerited inclusion (Tur et al., 2011). Future studies with higher sample sizes areneeded to determine cognitive functioning in RR, SP, and PP MS. We did notexamine patient disability using unemployment assessment, which would be animportant validity outcome. The test order was not as optimal as the Englishversion, and subsequent studies of the Persian version should adhere to the order oftests administered in the English version of the battery. Also, we administered theCVLT-II in advance of COWAT, which could have induced participants to useCVLT-II words as COWAT responses.

Table 4. Test–retest means and correlations for the subset of patients (n¼ 41) administered the

MACFIMS twice

Test Retest

Test–retest

paired statistics

Pearson’s r p value Mean SD Mean SD Cohen’s d p value

CVLT-II Total Learning 0.78 50.001 49.12 9.92 50.73 11.90 0.2 0.17

CVLT-II Delayed Recall 0.70 50.001 10.56 3.26 10.95 3.83 0.1 0.37

PASAT 0.77 50.001 42.05 12.80 45.71 11.68 0.3 0.01

SDMT 0.79 50.001 44.80 22.51 49.34 22.97 0.2 0.05

BVMT-R Total Learning 0.82 50.001 21.66 8.43 22.59 8.32 0.1 0.24

BVMT-R Delayed Recall 0.75 50.001 8.07 3.29 8.83 2.84 0.2 0.04

COWAT 0.73 50.001 25.85 12.20 28.32 10.52 0.2 0.07

DKEFS Description Score 0.66 50.001 27.6 11.32 26.51 13.07 �0.1 0.45

DKEFS Total Sorting Score 0.72 50.001 7.44 2.92 7.37 3.25 0.0 0.84

JLO 0.74 50.001 20.93 5.120 21.56 4.79 0.1 0.26

CVLT-II, California Verbal Learning Test; PASAT, Paced Auditory Serial Addition Test; SDMT,

Symbol Digit Modalities Test; BVMT-R, Brief Visuospatial Memory Test Revised; DKEFS, Delis-

Kaplan Executive Function System; COWAT, Controlled Oral Word Association Test; JLO, Judgment

of Line Orientation Test.

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Any further validation of this battery should include vocational status, sincecognitive dysfunction has a major burden on level of employment reached. PersianMACFIMS validation in different subtypes of MS also merits further investigation.

ACKNOWLEDGMENT

This study has been funded by a research grant from Merck-Serono. Theauthors would like to acknowledge the cooperation and generosity of all the MSpatients and controls who participated in this study. We are grateful to FatemehJabbari, Mohaddeseh Zera’atalab, and Ruhollah Davari for their support duringthis study.

REFERENCES

Benedict, R. H. (2005). Effects of using same- versus alternate-form memory tests duringshort-interval repeated assessments in multiple sclerosis. Journal of the InternationalNeuropsychological Society, 11(6), 727–736.

Benedict, R. H., Cookfair, D., Gavett, R., Gunther, M., Munschauer, F., Garg, N., et al.(2006). Validity of the minimal assessment of cognitive function in multiplesclerosis (MACFIMS). Journal of the International Neuropsychological Society, 12(4),

549–558.Benedict, R. H., Fishman, I., McClellan, M. M., Bakshi, R., & Weinstock-Guttman, B.

(2003). Validity of the Beck Depression Inventory-Fast Screen in multiple sclerosis.

Multiple Sclerosis, 9(4), 393–396.Benedict, R. H., & Zivadinov, R. (2011). Risk factors for and management of cognitive

dysfunction in multiple sclerosis. Nature Reviews Neurology, 7, 332–342.Benedict, R. H. B. (1997). Brief Visuospatial Memory Test – Revised: Professional Manual.

Odessa, FL: Psychological Assessment Resources, Inc.Benedict, R. H. B. (2005). Effects of using same vs. alternate form memory tests in short-

interval, repeated assessment in multiple sclerosis. Journal of the International

Neuropsychological Society, 11, 727–736.Benedict, R. H. B., Fischer, J. S., Archibald, C. J., Arnett, P. A., Beatty, W. W., Bobholz, J.,

et al. (2002). Minimal neuropsychological assessment of MS patients: A consensus

approach. The Clinical Neuropsychologist, 16, 381–397.Benton, A. L. (1994). Contributions to neuropsychological assessment: A clinical manual.

Oxford, UK: Oxford University Press.Benton, A. L., Sivan, A. B., Hamsher, K., Varney, N. R., & Spreen, O. (1994). Contributions

to neuropsychological assessment (2nd ed.). New York: Oxford University Press.Chiaravalloti, N. D., & DeLuca, J. (2008). Cognitive impairment in multiple sclerosis. Lancet

Neurology, 7(12), 1139–1151.

Cohen, J. (1988). Statistical power analysis for the behavioral sciences. Hillsdale, NJ: LawrenceErlbaum Associates Inc.

Delis, D. C., Kaplan, E., & Kramer, J. H. (2001). Delis-Kaplan Executive Function System.

San Antonio, TX: The Psychological Corporation.Delis, D. C., Kaplan, E., & Ober, B. A. (2000). California Verbal Learning Test. San Antonio,

TX: Psychological Corporation.

Elhami, S. R., Mohammad, K., Sahraian, M. A., & Eftekhar, H. (2011). A 20-year incidencetrend (1989–2008) and point prevalence (March 20, 2009) of multiple sclerosis in Tehran,Iran: A population-based study. Neuroepidemiology, 36(3), 141–147.

PERSIAN MACFIMS 9

Dow

nloa

ded

by [

the

Bod

leia

n L

ibra

ries

of

the

Uni

vers

ity o

f O

xfor

d] a

t 12:

12 1

8 Ju

ne 2

012

Ghassemzadeh, H., Mojtabai, R., Karamghadiri, N., & Ebrahimkhani, N. (2005).Psychometric properties of a Persian-language version of the Beck DepressionInventory–Second edition: BDI-II-PERSIAN. Depress Anxiety, 21(4), 185–192.

Gronwall, D. M. A. (1977). Paced auditory serial addition task: A measure of recovery fromconcussion. Perceptual and Motor Skills, 44, 367–373.

Guimond, C., Dyment, D. A., Ramagopalan, S. V., Giovannoni, G., Criscuoli, M., Yee, I.

M., et al. (2010). Prevalence of MS in Iranian immigrants to British Columbia, Canada.Journal of Neurology, 257(4), 667–668.

Hagh Shenas, S. H., Mani, A., & Tahmasbi, S. (2001). Validity of Persian adult reading testfor estimation of premorbid IQ. Iranian Journal of Medical Sciences (IJMS), 26(1), 2.

Houtchens, M. K., Benedict, R. H. B., Killiany, R., Sharma, J., Jaisani, Z., Singh, B., et al.(2007). Thalamic atrophy and cognition in multiple sclerosis. Neurology, 69, 113–123.

Kurtzke, J. F. (1983). Rating neurologic impairment in multiple sclerosis: An expanded

disability status scale (EDSS). Neurology, 33(11), 1444–1452.Lublin, F. D., & Reingold, S. C. (1996). Defining the clinical course of multiple sclerosis:

results of an international survey. National Multiple Sclerosis Society (USA) Advisory

Committee on Clinical Trials of New Agents in Multiple Sclerosis. Neurology, 46(4),907–911.

Mathiowetz, V., Volland, G., Kashman, N., & Weber, K. (1985). Adult norms for the Box

and Block Test of manual dexterity. American Journal of Occupational Therapy, 39(6),386–391.

Morrow, S. A., O’Connor, P. W., Polman, C. H., Goodman, A. D., Kappos, L.,Lublin, F. D., et al. (2010). Evaluation of the symbol digit modalities test (SDMT)

and MS neuropsychological screening questionnaire (MSNQ) in natalizumab-treatedMS patients over 48 weeks. Multiple Sclerosis, 16(11), 1385–1392.

Perneger, T. V., Leplege, A., & Etter, J. F. (1999). Cross-cultural adaptation of a

psychometric instrument: two methods compared. Journal of Clinical Epidemiology,52(11), 1037–1046.

Polman, C. H., Reingold, S. C., Edan, G., Filippi, M., Hartung, H. P., Kappos, L., et al.

(2005). Diagnostic criteria for multiple sclerosis: 2005 revisions to the ‘‘McDonaldCriteria’’. Annals of Neurology, 58(6), 840–846.

Prakash, R. S., Snook, E. M., Lewis, J. M., Motl, R. W., & Kramer, A. F. (2008). Cognitiveimpairments in relapsing-remitting multiple sclerosis: a meta-analysis. Multiple Sclerosis,

14(9), 1250–1261.Rao, S. M. (1991a). A manual for the Brief, Repeatable Battery of Neuropsychological Tests in

Multiple Sclerosis. New York: National Multiple Sclerosis Society.

Rao, S. M. (1991b). Neuropsychological Screening Battery for Multiple Sclerosis. New York:National Multiple Sclerosis Society.

Rao, S. M., Leo, G. J., Bernardin, L., & Unverzagt, F. (1991). Cognitive dysfunction in

multiple sclerosis. I. Frequency, patterns, and prediction. Neurology, 41(5), 685–691.Reichenheim, M. E., & Moraes, C. L. (2007). [Operationalizing the cross-cultural adaptation

of epidemiological measurement instruments]. Rev Saude Publica, 41(4), 665–673.

Schwid, S. R., Goodman, A. D., Mattson, D. H., Mihai, C., Donohoe, K. M., Petrie, M. D.,et al. (1997). The measurement of ambulatory impairment in multiple sclerosis.Neurology, 49(5), 1419–1424.

Smith, A. (1982). Symbol digit modalities test: Manual. Los Angeles: Western Psychological

Services.Tur, C., Penny, S., Khaleeli, Z., Altmann, D., Cipolotti, L., Ron, M., et al. (2011). Grey

matter damage and overall cognitive impairment in primary progressive multiple

sclerosis. Multiple Sclerosis, 17, 1324–1332.

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nloa

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the

Bod

leia

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of

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ity o

f O

xfor

d] a

t 12:

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