TOPICAL REVIEW
Cognitive Impairment in Multiple Sclerosis:
A Review of Neuropsychological Assessments
Nikolaos Korakas, MD, and Magda Tsolaki, MD, PhD
Abstract: Of the more than two million people worldwide with
multiple sclerosis, 40% to 65% experience cognitive impairment,
many of them early in the course of the disease. Cognitive im-
pairment has been found in patients with all subtypes of multiple
sclerosis. Because both pharmacologic and nonpharmacologic in-
terventions may improve patients’ brain function, cognitive assess-
ment should be a routine part of the clinical evaluation. Traditional
paper-and-pencil neuropsychological tests and batteries can help
detect and monitor patients’ cognitive problems. Computerized
cognitive batteries also show promise. Controversy continues over
which test is most reliable at assessing cognitive impairment in both
everyday clinical practice and research. Each battery has possible
disadvantages, such as practice effects, poor sensitivity and
specificity, and questionable applicability to multiple sclerosis.
Based on our review of the literature, we describe the tests that are
currently being used or that might be used in assessing cognitive
deficits in patients with multiple sclerosis, and we summarize the
strengths and limitations of each.
Key Words: multiple sclerosis, neuropsychology, cognition,
cognitive impairment, neuropsychological assessment
(Cogn Behav Neurol 2016;29:55–67)
BICAMS = Brief International Assessment of Cognition for
Multiple Sclerosis. BRB-N = Brief Repeatable Battery–
Neuropsychology. EPT = Everyday Problems Test. FST =
Faces Symbol Test. MMSE = Mini-Mental State Examination.
MoCA = Montreal Cognitive Assessment. MS = multiple scle-
rosis. NPSBMS = Neuropsychological Screening Battery for
Multiple Sclerosis. PASAT = Paced Auditory Serial Addition
Test. PROMIS = Patient-Reported Outcomes Measurement
Information System. RBANS = Repeatable Battery for the
Assessment of Neuropsychological Status. SDMT = Symbol
Digit Modalities Test.
Received for publication December 21, 2014; accepted July 8, 2015.
From the Third Department of Neurology, General Hospital “G.
Papanicolaou,” Aristotle University of Thessaloniki, Thessaloniki,
Greece.
Present address: Nikolaos Korakas, Knappschaftskrankenhaus, Klinikum
Westfalen, Dortmund, Germany.
The authors declare no conflicts of interest.
Reprints: Nikolaos Korakas, MD, Arkadioupoleos 36, 62125 Serres,
Greece (e-mail: nickakor@gmail.com).
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Cogn Behav Neurol  Volume 29, Number 2, June 2016
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INTRODUCTION
Multiple sclerosis (MS) is an inflammatory neuro-
degenerative disease of the central nervous system
(Hernández-Pedro et al, 2013) in which inflammatory
cells attack and destroy the myelin, the protective in-
sulation surrounding the nerves (Rahn et al, 2012). Typ-
ically, MS symptoms first appear between the ages of 20
and 40 years (Ortiz et al, 2013), although 2.7% to 5% of
patients are diagnosed as children (MacAllister et al,
2013). Newly developed magnetic resonance imaging
sequences and other studies have shown gray matter
demyelination and microglia activation in the disease’s
earliest stages (Klaver et al, 2013) and even at its very
start (Schutzer et al, 2013). As a result, many people with
MS experience physical, sensory, and emotion-regulation
difficulties (Katz Sand and Lublin, 2013).
Diagnosis of MS follows the 2010 McDonald cri-
teria (Polman et al, 2011), which focus on symptoms and
neurologic findings. The diagnosis starts with a patient’s
description of symptoms typical of an MS attack, eg,
optic neuritis, intranuclear ophthalmoplegia, and partial
transverse myelitis. These symptoms should be combined
with objective findings from a neurologic examination
and testing. Important to the diagnosis are a determi-
nation that multiple areas of the central nervous system
are involved and evidence that disease activity is con-
tinuing (Katz Sand and Lublin, 2013).
Cognitive Impairment in MS
In addition to their physical symptoms, an esti-
mated 40% to 65% of people with MS experience some
degree of cognitive impairment (Klaver et al, 2013; Rahn
et al, 2012). This impairment can have serious effects on
daily life, interfering with such basic and instrumental
activities of daily living as housekeeping, social life, and
employment (Chiaravalloti and DeLuca, 2008). The most
commonly affected cognitive domains are complex at-
tention, information processing, executive function, pro-
cessing speed, and long-term memory (Helekar et al,
2010). Patients first show deficits in verbal fluency and
verbal memory, followed by a decline in visuospatial and
recall skills, and, still later, a deterioration in attention
and information processing speed (Achiron et al, 2005).
Verbal learning can also be affected; this deficit has been
associated with apolipoprotein E epsilon 4 (Koutsis et al,
2007). Helekar and colleagues (2010) speculated that
people with MS overcome their primary structural deficits
through a neuroplastic reorganization of their functional
www.cogbehavneurol.com | 55
Korakas and Tsolaki
networks, or they use alternative strategies to cope with
cognitive tasks.
Even though cognitive impairment is not a core
symptom of MS and the McDonald criteria do not re-
quire it for diagnosis (Katz Sand and Lublin, 2013), pa-
tients may have cognitive impairment in the early stages
of the disease, even before the first characteristic physical
symptoms appear (Lovera and Kovner, 2012). In fact, a
2013 survey by Achiron et al estimated that cognitive
impairment may precede other symptoms by 1.2 years.
Clinically isolated syndrome, the mildest form of
MS, can be a precursor to a more severe form. Reuter
et al (2011) studied patients with clinically isolated syn-
drome and found that 24% had cognitive dysfunction at
the very onset of MS. In general, patients with clinically
isolated syndrome have cognitive problems similar to
those in patients with the more severe forms of MS, al-
though with relatively intact verbal learning and memory
capacity (Potagas et al, 2008).
Cognitive dysfunction affects patients with all MS
subtypes. The highest frequency is in those with sec-
ondary progressive MS; the rate is lower in primary
progressive MS, still lower in relapsing-remitting MS, and
lowest in clinically isolated syndrome (Achiron et al,
2013). Amato et al (2001) reported that cognitive decline
in MS is unlikely to subside; rather, it progresses
slowly. Borghi et al (2013) wrote that the frequency of
impaired cognition gradually increases as patients pro-
gress through their disease course, and that patients with
the progressive forms have more severe cognitive im-
pairment than do patients with the relapsing-remitting
form. In a recent survey of 1500 patients with
MS, Achiron et al (2013) found that those with the sec-
ondary progressive form showed greater cognitive decline
than those with the other forms, in all domains except for
the visuospatial. In a 6-year follow-up study of patients
newly diagnosed with MS, Hankomäki et al (2014) ob-
served quite stable overall cognitive function, but deteri-
oration in attention and processing speed.
Borghi et al (2013) looked at each subtype of MS
but were unable to discern subtype-specific patterns of
cognitive impairment. This finding suggests a global
pattern of cognitive dysfunction independent of disease
course.
Cognitive impairment correlates strongly with brain
lesions. Brain imaging studies of patients with MS have
identified several potential sources of cognitive
impairment. Tsolaki et al (1994) examined patients with
MS using magnetic resonance imaging and nine neuro-
psychological scales, and found that cognitive dysfunc-
tion correlated with lesions in the hippocampus and with
enlargement of the third ventricle. Cognitive impairment
is also related to brain atrophy. Implicated in particular
have been thalamic atrophy and hippocampal damage
(Sicotte, 2011), as well as atrophy of the basal ganglia and
cerebral cortex (Batista et al, 2012). Furthermore, ele-
vated volume of the third ventricle is a strong biomarker
of cognitive decline (Houtchens et al, 2007). Riccitelli et al
(2011) reported that patients with the progressive form of
56 | www.cogbehavneurol.com
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Cogn Behav Neurol  Volume 29, Number 2, June 2016
MS lost gray matter in cortical regions, while patients
with the relapsing-remitting form lost deep gray matter
structures. Specifically for the relapsing-remitting form,
however, Papadopoulou et al (2013) found that white
matter lesions seemed to be an essential factor for cog-
nitive problems.
No significant relationship has been found between
overall cognitive impairment and physical disability in
MS (Amato et al, 2008b), duration of the disease (Amato
et al, 2010), or education or age (Solari et al, 2002).
However, a recent survey reported a connection between
cognitive problems and patients’ levels of education and
physical disability (Ben Ari Shevil et al, 2014).
About half of patients with MS have depression
(Marrie et al, 2009; Sadovnick et al, 1996), with 25.7% of
all patients suffering from major depression (Patten et al,
2003). Anxiety has been reported in 23.5% to 41% of
patients with MS (Wood et al, 2013). Anxiety has been
shown to interfere with cognitive performance in patients
with MS (Goretti et al, 2014). Researchers are divided,
however, on whether depression does so: The COGIMUS
study found no significant correlation between depression
and cognitive dysfunction in patients with MS (Patti et al,
2009), but Borghi et al (2013) reported that impaired
cognitive performance and depression might be linked in
MS, and Sundgren et al (2013) found that even mild de-
pressive symptoms affected cognition in MS.
Even if depression does not affect the objective
neuropsychological performance of patients with MS,
some evidence suggests that it influences their subjective
perception of cognitive impairment (Kinsinger et al,
2010). According to Brassington and Marsh (1998),
however, other researchers claim that depression does not
affect neuropsychological efficiency and that objective
cognitive function and depression vary according to an
individual patient’s coping style. Although this issue is
not resolved, Kinsinger et al (2010) concluded that spe-
cific domains, such as speed of information processing,
may be related to depressive symptoms in MS.
Cognitive Impairment in Pediatric-Onset MS
Cognitive dysfunction is also a core symptom of
pediatric-onset MS (Till et al, 2013), and may be found in
children with clinically isolated syndrome (Julian et al,
2013). Within the first 2 years after onset of clinically
isolated syndrome, 30% of children experience significant
cognitive dysfunction (Bigi and Banwell, 2012).
Children diagnosed with MS at a very young age
have an especially high risk of experiencing cognitive
impairment within the first years of the disease (Bigi and
Banwell, 2012). Cognition in children with MS worsens
relatively fast (Jongen et al, 2012), and the impairment
can be more dramatic than in adults with MS (Ozakbas
et al, 2012). Because children’s central nervous system
myelin is still developing, the pathologic process can in-
terfere with the ongoing maturation of the white matter
pathways, destroying the neural networks involved in
cognition (Ozakbas et al, 2012). However, children have
significant brain plasticity and repair mechanisms, which
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Cogn Behav Neurol  Volume 29, Number 2, June 2016
might help them recover from the neurodegeneration
more efficiently than can adults (Ozakbas et al, 2012).
The cognitive domains most likely to be affected in
children with MS are verbal and visuospatial memory,
complex attention, and executive function (by contrast,
most patients with adult-onset MS retain their verbal
skills) (Bigi and Banwell, 2012). Processing speed seems to
be one of the most sensitive and disturbed domains in
both pediatric and adult-onset MS (Penner et al, 2013).
Not only may patients with childhood-onset MS show
cognitive deficits during the first years of the disease, but they
are also at risk for a lower intelligence quotient. Children’s
cognitive impairment and low intelligence quotient scores
can jeopardize their current and future academic perfor-
mance as well as their ability to cope with life difficulties and
psychosocial challenges (Amato et al, 2008a).
Clinicians should be aware that a child with MS
may have cognitive impairment caused by the MS, but
may also have depression and/or anxiety that can com-
plicate the diagnosis of the cognitive impairment; alter-
natively, a child with MS may have depression and/or
anxiety that can manifest as cognitive impairment
(Weisbrot et al, 2014). Cognitive fatigue may lead chil-
dren to perform poorly on cognitively effortful tasks, and
they may need counseling to help with their everyday
activities (Goretti et al, 2012). Nevertheless, Goretti et al
(2012) found no connection between general or cognitive
fatigue (evaluated with subjective scales) and overall
cognitive impairment. Bigi and Banwell (2012) found no
connection between cognitive dysfunction in children
with MS and their disability status, number of relapses, or
disease duration.
Management of Cognitive Impairment in MS
Amato and colleagues (2013) published a position
paper that examined in great detail the state of treatment
for cognitive impairment in MS. They reported that some
studies showed benefit from symptomatic drug treatment,
but could not be replicated. As for disease-modifying
treatments, relevant research is slight, and the few pub-
lished studies show minimal benefit (Amato et al, 2013).
Despite the limitations of the relevant studies,
behavioral techniques have markedly improved learning
and memory performance in people with MS-related
cognitive impairment. Even though more data are needed,
clinical trials to date have shown that, for some patients,
behavioral interventions may slow the deterioration of
cognition or even improve the already affected brain
functions (Amato et al, 2013; Portaccio et al, 2013).
Surprisingly, Amato et al (2013) found no studies evalu-
ating behavioral treatment for processing speed deficits in
patients with MS, despite the fact that processing speed is
one of the major affected domains in MS. In the domain
of long-term memory, Leavitt et al (2014) showed that
aerobic exercise may be effective treatment.
Rationale for This Review
Even when people have been diagnosed with MS by
the McDonald criteria, determining cognitive impairment
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Neuropsychological Assessment in Multiple Sclerosis
is difficult. Health care practitioners need universal
agreement on what constitutes cognitive impairment and
tools to help them assess cognition in early MS (Achiron
and Barak, 2006). Because most of the methods currently
used to assess mental ability require both time and special
training to give, cognitive impairment in MS is under-
diagnosed (Patti, 2012). Borghi et al (2013) strongly
support neuropsychological screening for patients with
MS, especially those at high risk for cognitive impairment
based on demographic, clinical, and radiographic
evidence. Zarei and colleagues (2003), arguing for a cor-
tical variant of MS, even proposed including MS in the
differential diagnosis of dementia with cortical features
and the differential diagnosis of depression when it is
early onset, unusual, and persistent.
Our aim in this study was to examine the current
state of knowledge about methods used to assess neuro-
cognitive function in patients with MS. Based on a review
of the literature, we describe the individual tests and
batteries that measure cognitive deficits in MS and we
describe the advantages and limitations of each. We
group noncomputerized and computerized tests sepa-
rately, and within each category we list established cog-
nitive assessments, proposed cognitive assessments, and
functional assessments.
METHODS
Between June and December 2013, we performed an
online search of the PubMed database using the key
words cognitive impairment, multiple sclerosis, and neu-
ropsychological assessment. We searched the key words
first alone and then in combination. Next, we manually
searched all relevant sources cited in the identified ar-
ticles.
Later we added articles suggested by the anonymous
reviewers of our study, and we kept updating the manu-
script with new articles published until June 2015. We
tried to include every article that tested or validated a
neuropsychological test or test battery for patients with
MS.
NONCOMPUTERIZED TESTS
Noncomputerized Cognitive Assessments
Mini-Mental State Examination (MMSE)
The MMSE (Folstein et al, 1975) evaluates ori-
entation to time and place, registration, attention and
calculation, recall, language, and visuoconstruction. A
resident or attending physician, neuropsychologist, or
speech therapist (Benaim et al, 2015) can easily give the
11-question interview with pencil and paper in at most
10 minutes (Folstein et al, 1975). The test is easily scored,
from 0 to 30 (Beatty and Goodkin, 1990). Cutoff scores
for cognitive dysfunction differ.
While the MMSE is not very sensitive in detecting
well-defined dementia in people with MS, the scale is
useful in predicting focal cognitive impairment, especially
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Korakas and Tsolaki
in patients with relapsing-remitting MS who also have
minor physical disabilities (Beatty and Goodkin, 1990).
Montreal Cognitive Assessment (MoCA)
The MoCA (Nasreddine et al, 2005) is also a
screening tool for identifying cognitive impairment. The
short edition is recommended by the US National In-
stitute of Neurological Diseases and Stroke and by the
Canadian Stroke Network. The MoCA has been vali-
dated for cognitive screening in patients with Alzheimer
disease, human immunodeficiency virus, Huntington
disease, parkinsonism, tremors, and epilepsy (Kaur et al,
2013). The test has also been validated for cognitive
evaluation of patients with MS (Dagenais et al, 2013).
The MoCA is a 5-minute verbal test that consists of
an immediate and a delayed five-word memory task, an
orientation test, and a language fluency test of words
starting with the letter F. Patients are awarded one point
for each correct answer, with a maximum score of 30
(Kaur et al, 2013). To determine the value of the MoCA
in MS, Dagenais et al (2013) have suggested that it be
given to a large sample of patients with MS and the re-
sults compared to other sensitive neuropsychological
batteries such as the Minimal Assessment of Cognitive
Function in MS and the Brief Repeatable Battery–
Neuropsychology (BRB-N).
Symbol Digit Modalities Test (SDMT)
The SDMT (Smith, 1982) measures attention and
information processing speed, and can be administered in
5 minutes by nursing or technical personnel. The SDMT
is part of many batteries, such as the Screening Exami-
nation for Cognitive Impairment, BRB-N, and Minimal
Assessment of Cognitive Function in MS.
The top of the SDMT form shows nine typographic
symbols, each matched with a digit in sequence from 1
through 9. Beneath this display is a row of 15 symbols, all
taken from the original set, in a pseudo-randomized se-
quence. Participants are given 90 seconds to say which
digit is paired with which symbol. Scherer et al (2007)
noted that use of the SDMT is limited to cultures that use
Arabic numerals.
The SDMT has been found to correlate with degree
of cerebral atrophy in patients with MS (Christodoulou
et al, 2003). Some researchers have suggested that if only
one neuropsychological test could be given to screen for
cognitive impairment, the SDMT could stand alone
(Amato et al, 2006). Sonder et al (2014) claimed that in
both everyday clinical practice and clinical trials, the
SDMT can be used as a sole neuropsychological tool in
assessing the cognition of patients with MS. The SDMT
has even been found to be a significant predictor of
cognition and automobile driving performance in people
with MS (Schultheis et al, 2010). Furthermore, the test is
relatively free of practice effects.
Digit Symbol Substitution Test
The Digit Symbol Substitution Test (Wechsler,
1981) is similar to the SDMT both in format and in
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Cogn Behav Neurol  Volume 29, Number 2, June 2016
evaluating information processing speed and attention, as
well as concentration. As with the SDMT, the top of the
Digit Symbol Substitution Test form shows symbols, each
paired with a digit. In this test, however, beneath the
display the form shows the digits pseudo-randomized,
and participants have to draw (instead of say) the cor-
rectly paired symbol underneath each digit. Like the
SDMT, the Digit Symbol Substitution Test is limited to
cultures that use Arabic numerals (Scherer et al, 2007).
Faces Symbol Test (FST)
The FST (Scherer et al, 2007) evaluates working
memory and sustained attention using the same testing
principle as the SDMT, except that participants match
symbols to faces rather than to Arabic numerals. The test
is brief, easily administered as part of a routine neurologic
examination, and well accepted by patients. Before par-
ticipants take the FST, their hand function and visual
acuity are evaluated to ensure that they are adequate for
the test. During the actual FST, participants are given 90
seconds to draw each symbol as quickly as possible be-
neath the corresponding face. The sensitivity is 84% and
the specificity is 85% (Scherer et al, 2007).
Because the FST uses faces instead of digits, pa-
tients’ education and culture have minimal effect on their
performance. However, the use of faces instead of digits
means that participants cannot reply orally but must
draw the symbols (Scherer et al, 2007). Thus, patients
who have hand or vision dysfunction cannot take the test
and should be given the SDMT or Paced Auditory Serial
Addition Test (PASAT) instead. Researchers with the
Berlin Multi-Centre FST Validation Study have recom-
mended using the FST as a screening tool for MS-related
cognitive decline, and the patients who show deficits
should undergo a more comprehensive neuro-
psychological assessment (Scherer et al, 2007).
Paced Auditory Serial Addition Test (PASAT)
Like the SDMT and the Digit Symbol Substitution
Test, the PASAT (Gronwall, 1977; Gronwall and Sampson,
1974) evaluates information processing speed and attention.
Also like the SDMT, the PASAT is included in many bat-
teries, such as the Neuropsychological Screening Battery for
Multiple Sclerosis (NPSBMS) and BRB-N.
The PASAT is a complex test involving language
functions, visualization of numbers, and calculation
(Yaldizli et al, 2014). The test asks participants to add
together two randomized single digits: the digit they just
heard and the one they had heard immediately before it.
The digits are presented by a voice on a compact disk or
audiocassette. In the PASAT-3, the voice presents a digit
every 3 seconds; in the PASAT-2, the rate is one digit
every 2 seconds. The maximum number of correct an-
swers is 60.
Like the other tests that use Arabic numerals, the
PASAT is not culture-free (Scherer et al, 2007). It is such
a difficult test for patients to take that in Aupperle et al’s
(2002) study, 11 (17%) of participants refused to take the
PASAT and four (6%) tried but quit before completing it.
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Cogn Behav Neurol  Volume 29, Number 2, June 2016
Scherer et al (2007) found the SDMT to be more
sensitive than the PASAT in differentiating between pa-
tients with MS and healthy controls, and reported that
the two tests had similar reliability and practice effects.
Other studies, however, have shown substantial practice
effects for the PASAT (Parmenter et al, 2007). Re-
searchers do not agree on which of the two tests is better
for cognitive screening, and whether either of them can be
given alone (Amato et al, 2006). Brooks et al (2011) ar-
gued that the PASAT is unpleasant to take and its results
in patients with MS can be compromised by sleep dis-
orders, fatigue, depression, anxiety, and systemic diseases.
However, Williams et al (2006) maintained that the
SDMT is not an equal substitute for the PASAT. Sonder
et al (2014) studied the long-term validity of the PASAT
and SDMT, and found the SDMT to be superior.
Free Recall and Recognition Test
The Free Recall and Recognition Test (Wahlin et al,
1995) has two parts. In the recall section, the tester shows
the patient a list of 12 concrete nouns while reading them
aloud at a rate of 3 seconds per noun (Claesson et al,
2007). Then the tester withdraws the list, asks the patient
to say the nouns in any order, and records the correct
answers. In the recognition section, the tester presents the
same nouns in the same format as in the recall section, but
now the nouns are mixed randomly with 12 distractors.
The tester asks the patient to answer “yes” or “no” as to
whether each noun appeared during the earlier pre-
sentation (Claesson et al, 2007).
The Free Recall and Recognition Test has several
advantages over other tests. It takes less than 5 minutes to
give, has no floor or ceiling effects, and is accepted by
most patients (Claesson et al, 2007). In contrast to the
MMSE and PASAT, this test can discriminate among
mild, moderate, and severe MS (Claesson et al, 2007). The
test is easily administered by master’s- and doctoral-level
staff with knowledge of neuropsychology and proper
training, and the results may indicate whether the patient
needs a more comprehensive neuropsychological assess-
ment (Claesson et al, 2007).
Multiple Sclerosis Neuropsychological Screening
Questionnaire
This Questionnaire (Benedict et al, 2003) consists of
15 items assessing neuropsychological performance in
daily activities. The Questionnaire has two forms, one for
patients and the other for informants. It is self-ad-
ministered and takes only 5 minutes.
To evaluate the validity of the Questionnaire,
Benedict and colleagues (2003, 2004) gave it to patients
and informants, and also gave the patients a compre-
hensive neuropsychological test battery. The patients’
Questionnaire responses correlated strongly with mea-
sures of depression, but not with neuropsychological
function. The informants’ scores, by contrast, correlated
with the patients’ cognitive function but not with de-
pression. For this reason, the Questionnaire would be
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Neuropsychological Assessment in Multiple Sclerosis
most valid if the patient and an informant completed it at
the same time (Parmenter et al, 2007).
Brief International Assessment of Cognition for Multiple
Sclerosis (BICAMS)
The BICAMS (Langdon et al, 2012) is a 15-minute
battery comprising, in the following sequence, the SDMT,
the California Verbal Learning Test 2nd ed (Delis et al,
2000) (the first five recall trials), and the Brief Visuospa-
tial Memory Test Revised (Benedict, 1997) (the first three
recall trials). Advantages of the BICAMS are that it can
be administered by appropriately trained nonspecialist
staff, it is given easily with just pencil and paper, and the
only prerequisite is background information on the pa-
tient.
Clinicians should evaluate BICAMS results taking
into account that performance is influenced by demo-
graphic factors, physical impairment (eg, dysarthria, im-
paired vision, pain), concurrent medical disorders,
medications, fatigue, and, to some extent, depression
(Langdon et al, 2012).
A limitation of the BICAMS is that it should not be
given within 1 month after a patient recovers from a re-
lapse or within 1 month after a patient takes a steroid
medication, since these would affect the scores.
Neuropsychological Screening Battery for Multiple
Sclerosis (NPSBMS)
The NPSBMS (Rao et al, 1991) consists of, in the
following sequence, a verbal learning test, a spatial
learning test, the PASAT, and a letter fluency task. An
option is to add the SDMT, which slightly increases the
battery’s sensitivity, even though it adds time. Advan-
tages of the NPSBMS are a short administration time
(mean = 31.7 minutes) (Aupperle et al, 2002) and high
sensitivity (71%) and specificity (94%) (Rao et al, 1991).
Two major drawbacks: Administration of the
NPSBMS requires trained subdoctoral professionals,
and, as noted earlier, a component of the battery, the
PASAT, is a very difficult test for patients to take.
Screening Examination for Cognitive Impairment
The Screening Examination for Cognitive Impair-
ment (Beatty et al, 1995) consists of a vocabulary test, a
verbal reasoning test, a verbal memory test, and the oral
version of the SDMT. The tests are given as three learning
trials and a delayed recall trial of a list of 10 concrete
nouns, along with the Shipley Institute of Living Scale
Vocabulary Test (Zachary, 1986), the Shipley Institute of
Living Scale Verbal Abstraction Test (Zachary, 1986),
and the SDMT. The Screening Examination lasts about
30 minutes, with a mean administration time of 22.6 min-
utes (Aupperle et al, 2002), and can be performed in a
single session that participants tolerate well (Solari et al,
2002). The high sensitivity and specificity are similar to
those of the NPSBMS.
Drawbacks: The exam must be administered by
practitioners with subdoctoral education and brief spe-
cific training. Because the practice effects are not known,
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Korakas and Tsolaki
the exam is recommended for only a one-time screening
of patients (Aupperle et al, 2002).
Repeatable Battery for the Assessment of
Neuropsychological Status (RBANS)
The RBANS (Randolph et al, 1998) is a short
battery (average administration time = 23.8 minutes)
(Aupperle et al, 2002) that examines immediate and de-
layed memory, language, attention, and visuospatial
function. Professionals use its 12 short tests to identify
cognitive impairment in patients with Alzheimer disease,
Huntington disease, subcortical vascular dementia, and
Parkinson disease with dementia.
Patients with MS or Parkinson disease who have
normal scores on the MMSE share similar patterns of
cognitive impairment. When patients with Parkinson
disease and normal MMSE scores took the RBANS, they
did poorly, indicating that the RBANS was more sensi-
tive than the MMSE in revealing the patients’ cognitive
deficits (Beatty et al, 2003). For this reason, Aupperle et al
(2002) gave the RBANS to a group with MS who had
scored normally on the MMSE, but they found that the
RBANS was no more sensitive than the MMSE for the
patients with MS.
Another important limitation of the RBANS is that
it does not estimate executive function. To address exec-
utive function, Aupperle et al (2002) added the Wisconsin
Card Sorting Test (Berg, 1948). This combination of tests
might be completed in an hour (Aupperle et al, 2002).
Brief Repeatable Battery–Neuropsychology (BRB-N)
The BRB-N (Rao and the Cognitive Function
Study Group of the National Multiple Sclerosis Society,
1990) is a battery consisting of five tests, carefully selected
to assess most cognitive functions with minimal overlap.
The Selective Reminding Test (Buschke, 1973) evaluates
verbal memory. The 10/36 Spatial Recall Test (Rao et al,
1990) assesses visual memory. The SDMT measures at-
tention, executive function, and information processing
speed. The PASAT-2 and PASAT-3, with numbers given
every 2 or 3 seconds, assess sustained attention. The
Word List Generation Test (Rao et al, 1990) evaluates
verbal fluency.
A major strength of the BRB-N is that it is a brief
(about 20 minutes) (Amato et al, 2006) and sensitive
measure of cognitive impairment in the earliest stages of
all MS subtypes, even clinically isolated syndrome
(Potagas et al, 2008). The BRB-N’s sensitivity is 71% and
its specificity is 94% (Rao et al, 1991).
The battery can be given by appropriately trained
nonspecialist staff. Although the other elements of the
BRB-N are well accepted by patients (Solari et al, 2002),
as noted they find that the PASAT is quite difficult to take
(Aupperle et al, 2002). To minimize practice effects, the
BRB-N is available in two versions. Since frontal lobe
executive function is underrepresented in the BRB-N, the
Stroop Color and Word Test (Stroop, 1935) can be
added.
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Cogn Behav Neurol  Volume 29, Number 2, June 2016
The greatest weakness of this battery is that per-
formance is strongly affected by the patient’s age and
education. Furthermore, because depression might also
affect performance, patients should not be tested when
they show mood disorders (Sepulcre et al, 2006).
Minimal Assessment of Cognitive Function in MS
The Minimal Assessment of Cognitive Function in
MS (Benedict et al, 2006) is one of the batteries most
widely accepted by clinicians. It has seven tests (including
the SDMT) that help assess five cognitive domains: lan-
guage, spatial processing, learning new information and
memory, processing speed and working memory, and
executive function.
Despite the advantage of high reliability and validity
in identifying cognitive impairment, the Assessment has
major drawbacks (Becker et al, 2012). It takes about 2 hours
to administer and requires highly trained professional test-
ers. Furthermore, its strictly standardized testing environ-
ment may fail to reflect cognitive function in everyday life,
in which tasks are complex and require more than one
ability (Willis et al, 1992). The test results can be affected by
psychoeducational interventions that patients have received
to improve their everyday lives (Becker et al, 2012).
Proposed Noncomputerized Batteries Not Yet
Validated
Battery Proposed by Aupperle et al (2002)
After evaluating the effectiveness of the NPSBMS,
RBANS, and Screening Examination for Cognitive
Impairment, Aupperle and colleagues (2002) proposed a
new battery that would comprise the Consistent Long-
Term Retrieval test (part of the Selective Reminding Test
[Buschke, 1973]), the PASAT-3, and the SDMT. This pilot
battery has the advantage of brevity (about 30 minutes,
similar to the Screening Examination for Cognitive Im-
pairment), but its drawbacks include the need to control for
practice effects on the PASAT and the lack of studies to
measure sensitivity and specificity (Aupperle et al, 2002).
Battery Proposed by the Pediatric Multiple Sclerosis
Centers of Excellence (Julian et al, 2013)
The Pediatric Multiple Sclerosis Centers of Ex-
cellence (Julian et al, 2013) used the following compre-
hensive network battery for neuropsychological
assessment of children with MS:
 Wechsler Abbreviated Scale of Intelligence (Wechsler,
1999) two subtests for Vocabulary and Matrix Rea-
soning: to assess general ability level
 Wechsler Individual Achievement Test, 2nd ed (Wechs-
ler, 2001) Pseudoword Decoding, Expressive One-Word
Picture Vocabulary Test, and Wechsler Abbreviated
Scale of Intelligence (Wechsler, 1999) Vocabulary
subtest: to evaluate reading and language
 Digit Span test from the Wechsler Adult Intelligence
Scale, 4th ed (Wechsler, 2008) (for ages 16 years and
older) or the Wechsler Intelligence Scale for Children,
4th ed (Wechsler, 2003) (for ages younger than 16), and
the Digit Symbol-Coding test from the Wechsler Adult
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Cogn Behav Neurol  Volume 29, Number 2, June 2016
Intelligence Scale or Wechsler Intelligence Scale for
Children: to measure attention, working memory, and
processing speed
 Contingency Naming Test (Taylor et al, 1987) and
Delis-Kaplan Executive Function System Trail Making
Test (Delis et al, 2001): to evaluate executive function
 California Verbal Learning Test, 2nd ed (Delis et al,
2000) or Children’s Version (Delis et al, 1994): to assess
verbal episodic learning and recall
 Beery-Buktenica Developmental Test of Visual-Motor
Integration, 6th ed (Beery and Buktenica, 1997) and
the Wechsler Abbreviated Scale of Intelligence (Wechs-
ler, 1999) Matrix Reasoning test: to evaluate visuo-
spatial function
 Grooved Pegboard Test (Kløve, 1963) and Delis-
Kaplan Executive Function System (Delis et al, 2001)
Trail Making Test Motor Speed Condition: to assess
fine motor speed and coordination
The battery was given by a clinical neuro-
psychologist or a trained and supervised psychometrician.
The total administration time was 2.5 hours, with breaks
as needed (Julian et al, 2013).
Noncomputerized Cognitive Functional
Assessment
Everyday Problems Test (EPT)
The EPT (Willis, 1993) and its revised edition
(Becker et al, 2012) are useful tools for measuring cog-
nitive performance in everyday situations. The original
test consists of 42 written problem-related questions that
assess performance in seven areas: meal preparation and
nutrition, medications, phone use, shopping, financial
management, transportation, and household manage-
ment. The administration time is about 30 minutes. The
revised edition, shortened to 30 questions, takes about
21 minutes, thus reducing patient fatigue and burden
(Becker et al, 2012).
Both versions of the EPT have yielded reliability
coefficients above 80%, and the revised version has cor-
related moderately with standard neuropsychological
tests. Another advantage of the EPT is that testers require
little formal training. However, the revised edition still
needs to be investigated for its sensitivity to changes in
patients’ cognitive function after they have received in-
terventions. Although the EPT can measure everyday
cognitive performance, patients may still need standard
neuropsychological tests to determine if they have cog-
nitive impairment (Becker et al, 2012).
COMPUTERIZED TESTS
Computerized Cognitive Assessments
Computerized Version of the SDMT
In 2011, Akbar et al reported their newly developed
computerized version of the SDMT designed for patients
with MS (Akbar et al, 2011). Their goal was to overcome
methodologic weaknesses of validation in paper versions.
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Neuropsychological Assessment in Multiple Sclerosis
In Akbar et al’s study of their computerized SDMT, they
presented the task to patients with MS and healthy con-
trols on a 19-inch monitor at a distance of 16 inches. As
with the paper version, the participants looking at the
computer screen were first shown the nine different typo-
graphic symbols, each paired with a digit from 1 to 9. In
the next screen, the original display remained, and below
it appeared the nine symbols in a new sequence. For each
symbol, the participants had to say the number that
matched the identical symbol above. The participants
took a total of eight trials, each with a different sequence
of symbols. Participants also completed the 90-second
paper version of the SDMT, among other tests.
The computerized SDMT proved promising (Akbar
et al, 2011). It had a slightly higher sensitivity and slightly
lower specificity than the paper version. The compu-
terized version seemed to be less influenced than the paper
version by participants’ head motion and the speed of
their eye movements. However, results in both versions
could be affected by impaired visual acuity and speech
capability (Akbar et al, 2011).
Computerized Test of Information Processing
The Computerized Test of Information Processing
(Smith et al, 2012; Tombaugh and Rees, 2008) consists of
three reaction-time subtests, each with progressively
greater cognitive requirements. Tombaugh and Rees
(2008) developed the three subtests. The first is the Simple
Reaction Time task, in which participants are asked to
react when the letter X appears on the screen. The second
subtest is the Choice Reaction Time task, in which par-
ticipants are asked to press the right key on a keypad
when the word DUCK appears, and the left key when
they see the word KITE. This subtest requires participants
not only to react but also to make a decision. In the third
and most difficult subtest, Semantic Search Reaction
Time, participants are asked to decide whether or not a
stimulus is a member of a presented semantic category.
Here participants must not only react to the stimulus but
also simultaneously decide and categorize the stimulus
according to its meaning.
The test takes an estimated 10 to 15 minutes
(Mazerolle et al, 2013; Smith et al, 2012). Tombaugh et al
(2010) reported that the Computerized Test of In-
formation Processing can detect defective information
processing ability in people with MS as effectively as the
PASAT does, and can even replace it.
Automated Neuropsychological Assessment Metrics
The Automated Neuropsychological Assessment
Metrics (Reeves et al, 1992, 2007) battery has a particular
strength in assessing processing speed, a crucial element in
evaluating cognitive impairment in MS. This 30-minute
computerized battery includes the Selective Reminding
Test and the Procedural Reaction Time test to evaluate
basic and complex reaction time, respectively. The battery
assesses memory with the Running Memory Continuous
Performance Test, Code Substitution Delayed Memory,
Delayed Matching to Sample, Mathematical Processing,
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Korakas and Tsolaki
and Sternberg Memory Search tests. Information pro-
cessing speed is measured with Code Substitution
Learning and the Running Memory Continuous Perfor-
mance Test. Finally, the Logical Relations test evaluates
verbal reasoning.
Scores on the Automated Neuropsychological As-
sessment Metrics battery are highly concordant (95.8%)
with paper-and-pencil measures of cognitive deficits in
MS (Wilken et al, 2003).
Pellicano et al (2013) used the battery in comparing
cognitive function in patients with MS and healthy con-
trols. The authors chose to test all participants in the
morning to try to avoid potential bias from variability in
fatigue. Still, they found significantly poorer outcomes in
the MS group.
Cognitive Drug Research Assessment System
The Cognitive Drug Research Assessment System
(Simpson et al, 1991) is a computerized cognitive battery
that assesses power of attention, continuity of attention,
quality of working memory, quality of episodic memory,
and speed of memory. The battery comprises the Selective
Reminding Test, choice reaction time, digit vigilance,
numeric working memory, spatial working memory, word
recognition, and picture recognition tasks. Participants
record “yes” and “no” answers with a simple response
box. To minimize the motor demands on patients, the
tester records their responses for word recall. Admin-
istration time is 15 to 20 minutes.
To study the usefulness and validity of the Cogni-
tive Drug Research battery for patients with MS, Edgar
et al (2011) compared the battery with the PASAT and
the Digit Symbol Substitution Test in patients with re-
lapsing-remitting MS, and found similar efficiency. The
authors reported high test-retest reliability and low
practice effects since the computer generates alternative
forms of the tests; however, these alternative forms have
not been specifically assessed for their equivalence with
the original. The authors also cautioned that the Cogni-
tive Drug Research System might not be sensitive in de-
tecting memory deficits, and that the battery has been
validated for use only in the relapsing-remitting form of
MS.
Neurotrax Mindstreamss
The Neurotrax Mindstreamss computerized cogni-
tive battery (http://www.neurotrax.com) (Dwolatzky et al,
2003) was designed to detect mild cognitive impairment.
This tool assesses verbal and nonverbal memory as well as
verbal fluency, executive function, visuospatial function,
attention, information processing speed, and motor skills.
The test battery is installed on a patient’s local computer
system, and the results are uploaded to and stored in a
secure web-based patient demographic database. The test
battery takes 45 minutes. Patients can take part in mock
sessions before the actual testing.
The strengths of this battery include quick data reg-
istration and the ability to alter the level of task difficulty
according to each patient’s performance, thus minimizing
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Cogn Behav Neurol  Volume 29, Number 2, June 2016
ceiling effects. Dwolatzky et al (2003) gave the Mind-
streamss Mild Impairment Battery to older people with
cognitive impairment or mild Alzheimer disease and found
that the battery successfully discriminated those with mild
cognitive impairment from healthy elderly controls.
Later, Achiron et al (2007) validated the Mindstreamss
Computerized Cognitive Battery for patients with MS, and
concluded that it can be used to evaluate cognitive dys-
function in MS.
Computer-Generated Battery Not Yet Evaluated
Cognitive Screening Battery Proposed by Lapshin et al
(2013)
In 2013, Lapshin and colleagues reported their
formulation and validation of a new computer-generated
battery to screen for cognitive impairment in patients
with MS. The battery contains five tests to evaluate in-
formation processing speed and working memory: the
Stroop Color-Word Test (Stroop, 1935), the compu-
terized version of the SDMT (Akbar et al, 2011), the
Paced Visual Serial Addition Test (Nagels et al,
2005; Sampson, 1956) (a 2- and 4-second visual analogue
of the PASAT), the Simple Reaction Time test
(Tombaugh and Rees, 2008), and the Choice Reaction
Time test (Tombaugh and Rees, 2008). The battery can be
given with standard Windows software and does not re-
quire any special hardware. Testing time is estimated at
20 minutes.
A tester was needed to give the Paced Visual Serial
Addition Test and to supervise the rest of the battery,
even though the computer collected all the participants’
non-Paced Visual Serial Addition Test responses. In
the Lapshin et al (2013) study, the tester was a master’s
degree student, not a neuropsychologist.
The authors found that the computerized version of
the SDMT and Paced Visual Serial Addition Test had
good sensitivity (up to 85.7%) and specificity (up to
100%). The battery was limited by the need to exclude
patients with significant vision impairment, and possibly
by practice effects.
Computerized Functional Assessments
Patient-Reported Outcomes Measurement Information
System (PROMIS)
The PROMIS, a program funded by the US
National Institutes of Health (http://www.nihpromis.
org), is a system of coordinated patient self-assessments
of physical and mental health and social well-being (Cella
et al, 2007). Patients and informants complete PROMIS
questionnaires on paper or a computer screen. Their data
can be sent to the Assessment Center website (http://
www.assessmentcenter.net), where they are scored and
kept in a database for analysis by both clinicians and
researchers. Because the self-reports are standardized
and validated, researchers can compare across domains
and conditions.
Among the PROMIS measures are subscales for
Cognitive Concerns and for Cognitive Abilities (Becker
et al, 2014). Each consists of eight Likert-type items
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Cogn Behav Neurol  Volume 29, Number 2, June 2016
asking for a self-rating from 1 = “not at all” to 5 = “very
much.” The sum of the scores for individual items be-
comes the total score.
Becker et al (2014) confirmed the validity and reli-
ability of the two PROMIS subscales as a neuro-
psychological tool for patients with MS. The authors
recommended future studies to evaluate whether these
scales are sensitive in measuring meaningful cognitive
change after interventions.
Virtual Shopping Test
The Virtual Shopping Test was developed and
tested by Okahashi et al (2013) to assess cognitive dys-
function caused by brain injury, as from stroke or trau-
ma. The creators designed the test to require only a
personal computer and a touchscreen.
After getting instructions and a demonstration,
participants were given 10 seconds to view and memorize
a shopping list of four items. Then they had to organize
the most effective route through a series of 20 different
kinds of shops in order to buy the four items. Ten shops
were placed on each side of a virtual street, and each shop
contained six items. Each of the items on the shopping list
came from a different shop. This meant that four shops
had one correct item and five incorrect items, and 16
shops had no correct items. Okahashi et al selected the
incorrect items to be similar to the correct item in set, use,
phoneme, color, or shape. If participants forgot the items
that they needed to buy, they could get a second try. They
could also use hints, like referring back to the shopping
list.
The Virtual Shopping Test was easy for participants
to use. Including the demonstration, it took 30 minutes to
complete.
The authors reported that the test could detect at-
tention and memory problems in patients with brain
damage, even in one session. A potential advantage of the
test was that it could be used to evaluate cognitive func-
tion while patients were being rehabilitated. The re-
searchers also emphasized the test’s possible ecological
validity, ie, its ability to generalize to real-life situations.
They did not discuss possible application of the test to
patients with MS.
DISCUSSION
Computerized Versus Conventional Tests
Neuropsychological evaluation of patients with MS
is the focus of substantial research. Along with the
available radiologic and clinical data, numerous well-
constructed and validated tests give clinicians a means to
detect and diagnose cognitive deficits early in the course
of the disease. New computerized and online evaluation
tools are joining the mix, like Okahashi et al’s (2013)
Virtual Shopping Test. The advantages and dis-
advantages of computerized neuropsychological testing
versus standard paper-and-pencil tests are part of an
ongoing debate.
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Neuropsychological Assessment in Multiple Sclerosis
The advantages of computers in neuropsychological
evaluation include shorter test administration times,
faster registering of data (in milliseconds), and automa-
tion reducing human error (Woo, 2008). Because com-
puterized batteries are always administered the same way,
they standardize assessments, benefiting both clinicians
and researchers (Woo, 2008). Some computerized bat-
teries prevent floor and ceiling effects by creating a range
of possible scores that keep participants from scoring too
high or too low (Woo, 2008). Finally, computerized bat-
teries can create multiple and randomized versions of the
same stimuli. In general, Schatz and Browndyke (2002)
write that computerized tests are characterized by ease of
use.
Computerized tests also have substantial dis-
advantages. For example, clinicians should be careful
when they use Internet-based neuropsychological tools
because normative data established for conventional
versions of the tests do not necessarily apply, and norms
for online versions have not yet been established
(Buchanan, 2003). Test developers should give clinicians
all specifics on hardware and software requirements
(Schatz and Browndyke, 2002). Another potential prob-
lem is that older patients who are not familiar with
computer technology may experience so much anxiety
while undergoing computerized tests that their perfor-
mance suffers (Leposavić et al, 2010). Computerized
batteries generally cannot be used with patients who have
low vision or poor motor skills. Importantly, because
computerized tests require less interaction between the
patient and the examiner, these tests almost exclude
the clinical interview that is so important to analyzing
the data correctly and planning proper rehabilitation
(Leposavić et al, 2010).
Even though computerized batteries do not always
require a trained neuropsychologist to interpret the
results, Leposavić and colleagues (2010) maintained that
a certified neuropsychologist is essential, not only for
gathering the data, but also for evaluating the history of
illness, the patient’s behavior, and the strategy that the
patient uses in taking the test. These three factors are
fundamental to diagnosing cognitive impairment
(Leposavić et al, 2010). Hence, Leposavić et al concluded
that computerized batteries cannot replace traditional
paper-and-pencil tests, but they can serve as a primary
evaluation tool for clinicians in other fields, who should
refer affected patients to a neuropsychologist.
Limitations
One limitation of our study is that we found no data
on the internal and external validity of the neuro-
psychological tests before and after cognitive inter-
ventions. Very few of the tests have been validated for
their ability to detect minor cognitive changes after in-
tervention.
Another limitation is that most current batteries
measure cognition in a highly standardized environment.
They do not allow the evaluation of cognitive abilities in
everyday life. We could not find data on the ecological
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Korakas and Tsolaki
validity of the tests we presented, and so could not discuss
the tests’ real-world effectiveness.
A further limitation is that we could not find studies
that directly addressed the costs of the neuro-
psychological tests.
An intrinsic limitation of using self-report assess-
ments is that they are somewhat reliable but not sufficient
for longitudinal studies (Gold et al, 2003). Gold and
colleagues concluded, “The common pattern of poor
correlation between self-rated and objective cognitive
function thus appears to be a result of the patients’
(adaptive or maladaptive) coping mechanisms rather than
being due to inaccurate measurement.”
Van der Hiele et al (2012) found that 29% of their
participants with MS underestimated or overestimated
their cognitive abilities. It is noteworthy that in the self-
report tests, the participants evaluated their cognitive
function within the context of a variety of everyday sit-
uations, while the neuropsychological tests evaluated
cognition in a strictly standardized environment. Fur-
thermore, patients may have cognitive deficits that they
and their informants do not report.
Recommendations and Conclusions
Cognitive impairment is a major part of the spec-
trum of clinical manifestations of MS and can have a
serious impact on patients’ quality of life. Thus, cognitive
impairment should be identified as soon as possible, even
before other functional symptoms appear, so that patients
can benefit from early intervention and, possibly, better
rehabilitation.
Helping clinicians confirm their suspicions of cogni-
tive decline in their patients with MS are demographic and
clinical information (Amato et al, 2008a; Ben Ari Shevil
et al, 2014; Bigi and Banwell, 2012; Borghi et al,
2013; Hankomäki et al, 2014; Jongen et al, 2012; Julian
et al, 2013; Kinsinger et al, 2010; Koutsis et al,
2007; Langdon et al, 2012; Ozakbas et al, 2012; Patten et al,
2003; Penner et al, 2013; Potagas et al, 2008; Reuter et al,
2011; Solari et al, 2002; Till et al, 2013) and imaging findings
(Batista et al, 2012; Houtchens et al, 2007; Papadopoulou
et al, 2013; Riccitelli et al, 2011; Sicotte, 2011; Tsolaki et al,
1994). Patients at high risk for cognitive dysfunction in the
course of MS can be identified using cognitive percentile
curves (Achiron et al, 2005). In view of the high prevalence
of brain dysfunction in patients with MS, all diagnosed
patients should undergo neuropsychological testing (Klaver
et al, 2013; Rahn et al, 2012). For these reasons, we en-
courage clinicians to consider the advantages and dis-
advantages of the individual tests and batteries that we have
described and to choose the most suitable battery for each
patient and each clinical situation.
We recommend that clinicians suspect and evaluate
their patients for anxiety and depression, both of which
can affect cognitive test performance (Goretti et al,
2014; Patti et al, 2009, Sundgren et al, 2013). Even if
clinicians do not detect depression, they should be aware
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Cogn Behav Neurol  Volume 29, Number 2, June 2016
that patients with MS are more likely than the general
population to self-report feeling “useless” on the Chicago
Multiscale Depression Inventory (Chang et al, 2003). For
this reason, we endorse the use of a functional perfor-
mance test that has ecological validity.
We also think that the cognitive percentile curves
built by Achiron et al (2005) could be used in the clinical
evaluation of patients’ cognitive performance to predict
their risk of cognitive decline and to guide decisions on
the possible value of neurorehabilitation.
The neuropsychological tests that we have reviewed
can be used to evaluate children with MS. The usefulness
of neuropsychological testing to guide pediatric treatment
decisions is illustrated by a case report by Penner et al
(2013). They affirmed the high sensitivity and clinical
relevance of the testing that they used in their care of a 16-
year-old boy with relapsing-remitting MS. An interesting
finding, however, was that the patient’s SDMT score
appeared normal. This finding led the authors to conclude
that a better choice than the SDMT would have been a
test that measures pure information processing speed
without elements of working memory (Penner et al, 2013).
To overcome the current limitations of neuro-
psychological testing, future research should focus on
constructing a battery that will identify cognitive im-
pairment as early as possible and will not be confounded
by depression, anxiety, or other psychiatric disorders. The
need is great for a test that can differentiate the somatic
symptoms of MS from anxiety and depressive vegetative
disturbances, and help us identify patients in whom
anxiety and depression may affect cognitive evaluation.
Research is needed to examine the validity of the
new batteries, such as those described by Aupperle et al
(2002) and Lapshin et al (2013). We encourage research,
using the tests discussed in this review or even con-
structing new ones, to meet the great need for tests that
can evaluate cognitive changes over time after pharma-
ceutical and cognitive-behavioral therapy. The ecological
validity of new and existing tests is another area that
needs further research; any new tests should be designed
to evaluate patients’ cognitive performance in their ev-
eryday activities. Finally, a review of the costs of cogni-
tive evaluation tools, in both time and money, would be
of great benefit to clinicians who seek guidance in
choosing the best test for their patient.
In summary, because 40% to 65% of people with
MS experience cognitive dysfunction, which may affect
their quality of life and may be treatable, cognitive eval-
uation should constitute a major part of the clinical ex-
amination in MS, especially when impairment seems
likely.
ACKNOWLEDGMENTS
The authors thank the anonymous reviewers for their
insightful comments.
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Cogn Behav Neurol  Volume 29, Number 2, June 2016
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