Multiple Sclerosis
Table 1: Tests Used in the Minimal Assessment of Cognitive Function in Multiple Sclerosis (MACFIMS)
Neuropsychological Cognitive Domain Test
SDMT (Rao, 1981; Smith, 1982)
Processing speed and working memory
BVMT-R Visual/spatial learning (Benedict, 1997) PASAT
and memory (Gronwall, 1977)
Processing speed and working memory
CVLT-II Auditory/verbal learning (Delis et al., 2000)
and memory
DKEFS – Sorting Test Executive function (Delis, 2001)
JLOT (Benton, 1994) Visual/spatial perception 25 10
COWAT (Benton, 1989) Language and other domains, 5 verbal fluency
BVMT-R = Brief Visuospatial Memory Test (Revised); COWAT = Controlled Oral Word Association Test; CVLT-II = California Verbal Learning Test II; DKEFS = Delis-Kaplan Executive Function System; JLOT = Benton Judgement of Line Orientation Test; PASAT = Paced Auditory Serial Addition Test; SDMT = Symbol Digit Modalities Test. Source: Benedict et al., 2002.35
10 25
Administration Time (minutes) 5
10
There are two cognitive tests of complex attention that are time- dependent and are widely used in MS. The first is the Paced Auditory Serial Addition Test (PASAT), which requires the testee to listen to a string of pseudo-randomly ordered single digits presented aurally at the rate of one every three (or, in the harder version, two) seconds. The testee must add up the last two numbers heard and say the correct total before the next stimulus number is delivered. A sensitivity of 74% and specificity of 65% have been reported for the PASAT.19
The second is the Symbol Digit Modality
Test (SDMT), which presents the testee with nine simple abstract shapes as a ‘key’, each paired with a single digit. Below these shapes, the testee sees rows of the same nine abstract shapes in a random order. The testee must call out the correct number for each shape, looking along each row of shapes systematically, completing as many as possible within 90 seconds. A sensitivity of 82% and specificity of 60% have been reported for the SDMT.20
The SDMT has
been shown to be reliable when administered by nursing staff over several months.21
Figure 1: Potential Shorter Assessment Strategies for Cognitive Impairment in Multiple Sclerosis
PASAT (5 minutes) No impairment SDMT (3 minutes) No impairment SRT (7 minutes) No impairment No cognitive impairment Re-evaluation after follow-up period
Sensitivity 94% Specificity 84%
PASAT = Paced Auditory Serial Addition Test; SDMT = Symbol Digit Modalities Test; SRT = Selective Reminding Test. Source: Portaccio et al., 2009.37
Figure 2: Early and Late Treatment with IFNβ-1b in the BENEFIT Study (Five-year Data) Showed Significant Differences in PASAT Z-scores of Cognitive Function*
0.2 0.3 0.4 0.5 0.6
0.1 0
-0.1 Baseline Year 1 Year 2 Delayed treatment
*p=0.005 by non-parametric analysis of co-variance. Higher scores indicate better performance.
IFN = interferon; PASAT = Paced Auditory Serial Addition Test; SEM = standard error of mean. Source: Kappos et al., 2009.46
Year 3 Year 4 Early IFNβ-1b Year 5 Cognitive Test Batteries
There are a range of cognitive test batteries used for assessing cognition in MS, mainly in research studies. The Brief Repeatable Battery of Neuropsychological Tests (BRB-N)33
is a set of tests of
short duration (30 minutes) with a sensitivity of 71% and specificity of 94%. The battery comprises the SDMT, the PASAT, the Selective
70 EUROPEAN NEUROLOGICAL REVIEW Impairment Impairment Extensive
neuropsychological testing
Long-term memory function is also commonly impaired in MS. Previous work pointed to a primary retrieval deficit rather than a problem with learning the information.26
Impairment
The PASAT is more demanding than the SDMT for both the testee and the tester. The two tests have been directly compared as part of the Multiple Sclerosis Functional Composite (MSFC), a brief assessment designed to ‘sample’ cognition (originally incorporating the PASAT), upper limb function and walking to produce an index of an MS patient’s ability.22
The results have been inconclusive.23,24 There is
some evidence that the SDMT may be less susceptible to practice effects than the PASAT.21,25
However, the primary
Verbal memory is normally assessed by a word list learning task. A frequently used verbal memory assessment is the California Verbal Learning Test-II (CVLT-II).28
As far as individual-specific
information is concerned, MS deficits in memory of episodic autobiographical incidents have been reported to be greater than deficits in memory of personal semantic information (the general facts, meanings and understanding we have about ourselves).29
Executive functions are complex cognitive processes that deal with novelty, are involved with planning and problem-solving and are crucial to goal-directed behaviour. Studies of people with MS have often shown them to be poor on tests of problem-solving, particularly when flexibility is required. A community sample of MS patients in New Zealand demonstrated a variable range of executive dysfunction, with most exhibiting impairment in some executive aspects.30
The
most frequently (and conveniently) tested aspect of executive function is verbal fluency. Phonemic and semantic fluency tests have been shown to be equally effective in MS.31
Executive functions are
clearly involved in complex decision-making, but decline over time in a standardised decision-making task occurred independently of other cognitive test scores.32
registration of information has now been identified as the core deficit.27
Mean (SEM) PASAT z-score
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