Neuropsychologia 44 (2006) 11661174

Verbal fluency deficits in multiple sclerosis

Julie D. Henry a, , William W. Beatty b
a School of Psychology, University of New South Wales, Sydney, NSW, Australia
b University of Oklahoma Health Sciences Center, Department of Psychiatry and Behavioral Sciences, OK, USA
Received 25 August 2005; received in revised form 5 October 2005; accepted 5 October 2005
Available online 15 November 2005

Abstract
A quantitative review of 35 studies with 3673 participants was conducted to estimate and compare the magnitude of deficits upon tests of
phonemic and semantic fluency for participants with multiple sclerosis (MS) relative to healthy controls. Participants with MS were substantially
but similarly impaired on tests of phonemic and semantic fluency. These deficits were larger than deficits on measures of verbal intelligence,
confrontation naming and another widely used measure of executive functioning, the Wisconsin Card Sorting Test, but were of a comparable
or smaller magnitude relative to deficits on the oral version of the Symbol Digit Modalities Test (SDMT). This is consistent with other research
suggesting that measures of verbal fluency and the SDMT may be amongst the most sensitive neuropsychological measures to cognitive impairment
in MS. Increased neurological disability and a chronic progressive (as opposed to a relapsing remitting) disease course were associated with larger
deficits on tests of phonemic and semantic fluency. However, it is suggested that this latter finding is attributable to the distinct clinical features of
chronic progressive and relapsing remitting sub-types. Thus, patients who follow a chronic progressive course tend to be older, have an increased
duration of illness and experience greater neurological disability. Once these variables were controlled for, differences between the two sub-types
were substantially attenuated.
2005 Elsevier Ltd. All rights reserved.

Keywords: Meta-analysis; Fluency; Disease course

1. Introduction
In addition to motor abnormalities, cognitive impairment is
a common feature of multiple sclerosis (MS). Neuropatholog-
ically, MS is associated with multiple focal areas of axonal
demyelination, and diffuse white matter pathology is believed to
be particularly associated with executive dysfunction (Stuss &
Gow, 1992). However, whilst some studies have found that exec-
utive deficits occur with considerable frequency in MS (Benedict
et al., 2002; Marie & Defer, 2001), others have found little evi-
dence that executive dysfunction particularly characterises the
disorder (Bryant, Chiaravalloti, & DeLuca, 2004; Chiaravalloti
& De Luca, 2002).
Tests of verbal fluency have consistently been found to be
more sensitive to impairment in MS relative to other measures
of executive functioning. Rosser and Hodges (1994) have argued
that identical executive processes are involved in the initiation
Corresponding author. Tel.: +61 2 9385 3936; fax: +61 2 9385 3641.
E-mail address: julie.henry@unsw.edu.au (J.D. Henry).
and monitoring of both of these tasks, but that semantic flu-
ency is relatively more dependent on the integrity of semantic
memory (see also Henry & Crawford, 2004). Assessing the rela-
tive prominence of deficits on phonemic and semantic fluency is
therefore important, and bears on whether MS is associated with
executive function impairments and/or semantic memory dys-
function. Whilst there might be more than one reason for equal
impairment in phonemic and semantic fluency tasks, a pattern of
comparable impairment would be consistent with the possibility
that the deficits reflect executive dysfunction. In contrast, greater
impairment on measures of semantic fluency may be indicative
of semantic memory dysfunction. However, whilst some stud-
ies have reported comparable deficits on measures of phonemic
and semantic fluency (Beatty, 2002; Parry, Scott, Palace, Smith,
& Matthews, 2003), others have found phonemic fluency to be
more affected by the disorder (Fischer, unpublished; Nocentini
et al., 2001). Greater impairment on semantic fluency has also
been reported (Foong et al., 1997; Roig et al., unpublished).
It also remains unclear whether fluency deficits in MS qualify
as differential deficits. In particular, MS patients are typically
impaired on the oral version of the Symbol Digit Modalities

0028-3932/$ see front matter 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.neuropsychologia.2005.10.006
 J.D. Henry, W.W. Beatty / Neuropsychologia 44 (2006) 11661174
Test (SDMT), and this has been interpreted as reflecting a
reduction in information processing speed (Beatty, Goodkin,
Beatty, & Monson, 1989; Beatty, Goodkin, Monson, & Beatty,
1989; Huijbregts et al., 2004). Since tests of verbal fluency also
impose substantial demands upon speed of information process-
ing (Salthouse, Atkinson, & Berish, 2003), fluency deficits may
simply reflect a more generalized reduction in processing speed,
and not specific executive decline.
Two previous meta-analyses have quantified executive
impairment in relation to MS (Wishart & Sharpe 1997; Zakzanis,
2000). Both suggest that fluency measures are more sensitive to
the presence of MS relative to other executive measures. They
also raise the possibility of a semantic memory deficit upon
tasks that additionally impose substantial demands upon cogni-
tive speed. Zakzanis (2000) found semantic fluency to be more
impaired than phonemic fluency, whilst in both reviews, phone-
mic fluency was more impaired than confrontation naming, a
non-speeded measure that is very sensitive to the integrity of
semantic memory. However, since neither study quantified mean
effects specifically for the oral version of the SDMT, it remains
unclear whether fluency deficits are disproportionate relative to
measures of information processing that do not impose substan-
tial demands on motor abilities. It is also problematic that in both
meta-analyses different studies assessed each of the constructs
of interest. This raises a potentially important problem, as there
may have been substantive differences between the patients with
MS contributing to each statistic.
1.1. Aims of the current meta-analysis
Following on from these meta-analyses, the relative promi-
nence of deficits on tests of phonemic and semantic fluency will
be investigated using a methodology that restricts studies in each
comparison to only those that assess both measures to be com-
pared.
The first aim is to derive effect size estimates for phonemic
and semantic fluency for patients with MS relative to healthy
controls, and assess the relative prominence of deficits on each.
The second aim is to assess whether either of these deficits
qualify as differential deficits relative to the oral version of
the SDMT (Smith, 1982). The oral SDMT is considered to tap
information processing speed, but minimises confounds aris-
ing from motor disturbances. It is also important to address
the possibility that phonemic and semantic fluency deficits sim-
ply reflect a current general impairment in verbal abilities (see
Crawford & Henry, 2005). Thus, the pattern of deficits across
fluency versus verbal intelligence (VIQ) as measured by the
WAIS (Wechsler, 1955, 1981) Verbal and Vocabulary scales
(VIQ) will be compared. Performance on tests of verbal flu-
ency will also be compared with scores on the Boston Naming
Test (BNT; Kaplan, Goodglass, & Weintraub, 1983), a mea-
sure of confrontation naming. The Wisconsin Card Sorting Test
(WCST) will also be included for comparison standards, as like
verbal fluency, the WCST is considered to impose substantial
demands upon executive processes. The third aim is to assess the
relationship between fluency performance with patients level of
neurological disability, age and disease course.
1167
2. Method
2.1. Sample of studies
A search involving the Web of Science, Psych Lit CD-ROM and Science
Direct databases was undertaken, using the terms: letter fluency, FAS, semantic
fluency, category fluency, controlled oral word association, COWA(T), word flu-
ency, verbal fluency, oral fluency, phonemic fluency, executive test, frontal test
and multiple sclerosis. A manual search of issues of Neuropsychologia, Mul-
tiple Sclerosis, The Journal of the International Neuropsychological Society,
Neuropsychology, The Clinical Neuropsychologist, Neuropsychiatry, Neuropsy-
chology and Behavioural Neurology, Journal of Neuropsychiatry and Clinical
Neurosciences and the Journal of Clinical and Experimental Neuropsychology
was also conducted. The search was completed in December 2004.
The inclusion criteria were that the study had to include: (1) a patient group
consisting entirely of adults with MS, (2) a healthy control group free from
neurological or psychiatric disease and (3) a measure of phonemic or seman-
tic fluency. Effect size estimates for WCST CC, WCST PE, BNT, oral SDMT
and VIQ were derived from studies that also reported fluency results. The study
must also have (4) presented precise statistics convertible to effect size. Some
studies could not be included because only a total score collapsed across phone-
mic and semantic fluency was reported (Tsolaki et al., 1994), others because
despite inclusion of an MS group and a healthy control group, precise statis-
tics convertible to effect size for the fluency measure(s) of interest were not
reported (Cohen & Fisher, 1989; Grossman et al., 1995; Oliveri et al., 1999).
One study was excluded as it was not entirely clear what word generation
referred to (van Dijk, Jennekens-Schinkel, Caekebeke, & Zwinderman, 1992).
Finally, some studies were excluded because they reported data for MS patients
that were already included in another eligible study (Beatty & Monson, 1989;
Foong et al., 1999; Ryan, Clark, Klonoff, & Paty, 1993).
2.2. Statistical analysis
The basis of meta-analysis is the effect size, a standardized statistic that
quantifies the magnitude of an effect. In the present study, the effect size r was
used. For each construct, effects were pooled using a random effects model to
derive an estimate of the mean, with each effect weighted for sample size to
correct for sampling error. To estimate the degree of heterogeneity of the effects
contributing to each mean, the homogeneity statistic Q was estimated, as well
as the S.D. of random effects, and the 95% confidence intervals (CI) within
which random effects can be expected to fall. To test whether differences in the
magnitude of mean effects were significant paired t-tests were computed using
the number of studies (K) as the d.f. For a fuller outline of these statistics, see
Henry, Crawford, and Phillips (2004).
3. Results
3.1. Participant characteristics
Thirty-five research articles published or conducted between
1985 and 2004 contributed to the present analyses, in which there
were a total of 2339 patients and 1334 controls. Demographic
information for patients and controls is presented in Table 1; it
can be seen that they are closely matched for age, education and
gender. Clinical characteristics of patients are also presented
in Table 1. Patients mean score on the Expanded Disability
Status Scale (EDSS; Kurtzke, 1983), an index of disease sever-
ity that categorises level of neurological disability, is 3.8; this
means that the average patient was fully ambulatory without aid
despite relatively severe disability. In Appendix A, effect sizes
for phonemic and semantic fluency, as well as information relat-
ing to demographic and clinical variables, are presented for each
individual study that contributed to the meta-analysis.
1168 J.D. Henry, W.W. Beatty / Neuropsychologia 44 (2006) 11661174

Table 1 In Table 3, mean effects for each of the cognitive measures

Descriptive statistics for MS patients and controls are presented, calculated using only those studies that include
MS sample Control sample the particular measure of interest in addition to phonemic flu-
K M S.D. K M S.D.
ency (upper half of Table 3) or semantic fluency (lower half
of Table 3). Thus, for comparisons with WCST CC, WCST PE,
Age 35 41.2 4.38 33 40.8 5.69 BNT, SDMT and VIQ the mean effects for phonemic and seman-
Education 27 13.8 1.18 25 14.1 1.17
Gender (male, %) 28 33.5 12.50 27 33.7 13.40
tic fluency have been re-calculated (these effect sizes appear in
Age at diagnosis 26 32.1 3.45 the last column of Table 3). All mean effects are statistically sig-
Disease duration 26 9.1 3.36 nificant (all p < .05). Relative to the WCST and the BNT, phone-
(since diagnosis) mic and semantic fluency are more impaired, although only the
Disease duration 8 12.6 2.49 comparisons with the BNT attain significance (for phonemic flu-
(since symptom
onset)
ency: t = 3.28, d.f. = 10, p = .008; for semantic fluency: t = 3.89,
Expanded Disability 28 3.8 1.59 d.f. = 7, p = .006). Phonemic fluency is also significantly more
Status Scale sensitive to the presence of MS than VIQ (t = 4.06, d.f. = 10,
p = .002). However, neither phonemic nor semantic fluency is
more impaired than the SDMT.
Table 2
Performance on phonemic fluency (PF), semantic fluency (SF) for MS patients
vs. healthy controls 3.3. Moderators of verbal uency decits in MS
Fluency measure M K N Q S.D. 95% CI
Ms and S.D.s are presented in Table 4 for phonemic and
Lower Upper semantic fluency, sub-divided according to disease course.
Phonemic .42** 16 1060 43.4** .14 .15 .69 Most studies differentiate between relapsing remitting (RR) and
Semantic .42** 16 1060 56.1** .16 .10 .73 chronic progressive (CP) forms of the disease; whilst the former
** refers to patients who experience periods of relapses and remis-
p < .01.
sions, the latter refers to patients whose course is chronically
progressive. The studies that contributed to the following analy-
3.2. Effect sizes for patients with MS relative to healthy ses consisted entirely of patients with either a CP or a RR course,
controls and included tests of both phonemic and semantic fluency. Given
that only three studies contributed to each of these two groups, it
Cohen (1977) defines correlations of .1 as small, .3 as mod- would be inappropriate to conduct inferential statistics compar-
erate and .5 as large. It can be seen in Table 2 that the deficits ing these two groups (statistical power would be low). However,
for phonemic and semantic fluency are of a moderate to large there is a trend for patients presenting with a CP course to be
magnitude (both r = .42), and are both associated with significant more impaired on both phonemic and semantic fluency rela-
heterogeneity. tive to patients presenting with an RR course. Patients with a

Table 3
Performance on phonemic fluency (PF), semantic fluency (SF) and other cognitive measures for MS patients vs. healthy controls
Variable M K N Q S.D. 95% CI

Lower Upper

Studies with PF
WCST CC .25** 8 675 15.9* .12 .02 .48 .34 (K = 8)a
WCST PE .25** 9 911 7.2 .31 (K = 9)a
BNT .22** 11 876 11.2 .04 .15 .29 .36 (K = 11)a
SDMT .48** 6 350 9.3 .10 .29 .67 .41 (K = 6)a
VIQ .18** 11 1692 24.9* .10 .01 .36 .29 (K = 11)a
Studies with SF
WCST CC .29** 5 366 8.1 .11 .08 .51 .33 (K = 5)b
WCST PE .28** 6 400 3.6 .34 (K = 6)b
BNT .27** 8 461 10.3 .08 .11 .44 .44 (K = 8)b
SDMT .41** 6 635 15.2* .12 .18 .65 .42 (K = 6)b

() The random effects variance has been estimated to be zero. Note: For comparisons, the mean effects for PF and SF were recalculated for each comparison of
interest. For example, six studies included both PF and SDMT. In addition to calculating the mean effect for SDMT from these six studies (r = .48), the mean effect
for PF was also recalculated based only on these six studies (i.e. r = .41). Thus, in each comparison exactly the same participants have been tested upon each of the
measures of interest, controlling for any substantive differences between studies, such as in level of dementia severity.
a PF, M.
b SF, M.
* p < .05.
** p < .01.
 J.D. Henry, W.W. Beatty / Neuropsychologia 44 (2006) 11661174 1169

Table 4
Phonemic and semantic fluency mean effects stratified according to disease sub-type
Phonemic fluency Semantic fluency

K Patient, N Duration EDSS M S.E. K Patient, N Duration EDSS M S.E.

Chronic progressive 3 112 15.3 6.4 .54 .05 3 112 15.3 6.4 .47 .10
Relapsing remitting 3 110 6.7 3.5 .30 .07 3 110 6.7 3.5 .38 .06

CP course also have a longer duration of illness (over twice as 3.4. Assessing the possibility of publication bias
long), and a substantially higher level of neurological disability.
To investigate the relationship between age, duration of ill- Funnel plot diagrams were constructed for each of the fluency
ness and neurological disability with fluency performance, cor- and non-fluency measures of interest. In these diagrams, sam-
relations were calculated. It can be seen in Table 5 that although ple size is plotted against the corresponding study-level effect;
not significant, phonemic and semantic fluency deficits were if statistically non-significant results have been discriminated
weakly correlated with age, and moderately correlated with against, there should be a relative absence of studies with small
duration of illness. Correlations of a large magnitude were sample sizes that report weak effects. For none of the variables
observed in relation to level of neurological disability; r = .47 was there evidence of this bias operating.
and .49 for phonemic and semantic fluency, respectively; whilst
the former correlation was significant (p = .015), the latter just
failed to attain significance (p = .067). 4. Discussion
Raw and partial correlations are also presented in Table 5
between each of the fluency measures with different types of 4.1. Fluency decits in MS
disease course. Using the same methodology as Thornton and
Raz (1997), the percentage of patients who were RR or CP in The only previous meta-analytic review that has quantified
each study was calculated. (Studies that did not indicate disease mean effects for both phonemic and semantic fluency found the
course did not contribute to these analyses.) Consistent with the latter to be substantially more impaired (Zakzanis, 2000), con-
findings reported in Table 4, raw correlations indicate that the sistent with the possibility that MS is associated with deficits
magnitude of impairment on tests of phonemic and semantic flu- in semantic memory. However, as noted earlier, it is important
ency is substantially negatively associated with the percentage of that the patients contributing to the mean effect for semantic flu-
patients presenting with a RR disease course, and substantially ency do not differ from the patients contributing to the mean for
positively associated with the percentage of patients presenting phonemic fluency, if comparisons between these two measures
with a CP disease course (although the correlations with seman- are to be fair. When mean effects were calculated in the present
tic fluency did not attain significance). However, when partial study using this methodology, there was no difference in the
correlations were calculated, controlling for duration of illness, sensitivity of the two measures to the presence of MS (r = .42
neurological disability and age, these correlations were substan- for both measures).
tially attenuated (partial r ranged from .05 to .18). The finding of equivalent phonemic and semantic fluency
deficits has important clinical implications. Verbal fluency tests
provide brief but sensitive measures of cognitive functioning in
Table 5 MS. These tests have the additional advantages of being rel-
Raw and partial correlations (controlling for duration of illness, neurological atively low in stress for patients and minimally affected by
disability and age) between fluency and patient characteristics the motor and visual impairments that are commonly associ-
Variable Raw correlations Partial correlations ated with the disorder. A phonemic fluency test is one com-
ponent of the Brief Repeatable Battery (BRB; Rao, 1990) that
d.f. r p d.f. r p
is widely used in the English-speaking parts of North Amer-
Phonemic fluency ica, Europe and Australasia. However, the frequency of words
Duration of illness 21 .36 .103 that began with a particular letter varies from one language to
EDSS 25 .47* .015
Patients age 31 .24 .188
another and this factor may produce biases in the sensitivity
Relapse remitting (%) 24 .50* .013 11 .03 .924 of the test for patients who speak different languages. Using a
Chronic progressive (%) 24 .47* .019 11 .08 .797 semantic fluency test with a large number of exemplars (e.g.,
Semantic fluency animals and supermarket items) in every language is one solu-
Duration of illness 15 .29 .282 tion that has been adopted in the non-English speaking version
EDSS 14 .49 .067 of the BRB which is used in Europe (Boringa et al., 2001). The
Patients age 19 .17 .484 present findings that phonemic and semantic test are equally
Relapse remitting (%) 16 .38 .146 7 .18 .678
sensitive to MS encourages the view that the results on flu-
Chronic progressive (%) 16 .44 .091 7 .05 .915
ency tests for patients who speak different languages will be
* p < .05. comparable.
1170 J.D. Henry, W.W. Beatty / Neuropsychologia 44 (2006) 11661174
4.2. Evidence for a differential uency decit?
Although relative to VIQ and the BNT, measures of verbal
fluency were substantially more impaired, phonemic and seman-
tic fluency deficits were of a smaller or comparable magnitude to
deficits on the SDMT. These findings therefore suggest that MS
may not be particularly associated with executive dysfunction.
Instead, cognitive slowing appears to be a more prominent fea-
ture of the disorder, and may at least partially underlie deficits on
tests of fluency, and possibly other measures of executive func-
tion. This is because phonemic and semantic fluency have been
shown to be amongst the most sensitive measures of executive
dysfunction (for a review, see Crawford & Henry, 2005), and in
the present study, neither of these deficits were disproportion-
ate relative to deficits on the SDMT. Also inconsistent with the
possibility of a significant involvement of executive functions
in MS, the other most widely used measure of this construct,
the Wisconsin Card Sorting Test, was less impaired than either
type of fluency. Further, in terms of cognitive demands, tests of
verbal fluency are similar to the BNT in that they also require
access to phonological units and semantic information, but dif-
fer through the addition of a time pressure factor. The greater
impairment on measures of verbal fluency relative to the BNT
therefore also suggests that cognitive slowing and not executive
function impairment may be a particularly prominent feature of
the disorder.
Nevertheless, the fact that fluency deficits do not qualify as
differential relative to the SDMT does not necessarily indicate
that MS deficits in phonemic and semantic fluency are inde-
pendent of executive function deficits. Tasks like the SDMT are
bound to involve aspects of executive function, such as inhibiting
irrelevant aspects of stimuli or switching (between the coding
key and response boxes). The complexity of the SDMT may
underlie some of its sensitivity to so many forms of brain dam-
age.
Indeed, the Paced Auditory Serial Addition Test (PASAT) is
another popular measure for MS that is also often described as
a measure of information processing speed. Insufficient stud-
ies were available involving the PASAT for this measure to be
included in the present meta-analysis. However, it is of interest
that three studies included in the present study reported perfor-
mance for both the PASAT and the oral version of the SDMT: all
three found the PASAT to be substantially less impaired than the
SDMT (DEsposito et al., 1996; Geisler et al., 1996; Huijbregts
et al., 2004).
Like the SDMT, the PASAT may be regarded as a complex
measure of information processing speed. It has, for instance,
been shown to impose substantial demands on working mem-
ory (see Chiaravalloti, Christodoulou, Demaree, & DeLuca,
2003). However, the point is that the nature of the informa-
tion processing speed measure used as the comparison mea-
sure for fluency in the present meta-analysis may have been
an important factor in the failure to identify a differential flu-
ency deficit. Ideally, in assessment of differential deficits simple
reaction time tasks should be used that are relatively free of
executive demands. However, such measures are far less fre-
quently employed in neuropsychological assessment, and are
typically less standardized in format. Thus, it was not possi-
ble to include such comparison measures in the present meta-
analysis.
Nevertheless, it is of interest that Denney, Sworowski,
and Lynch (in press) found that MS patients did not dif-
fer from controls on measures of executive functioning, but
that generalized slowing in speed of information processing
was a prominent feature of the disorder. Further, informa-
tion processing speed was impaired irrespective of whether
the task involved automatic or controlled processing. Deficits
were also identified irrespective of whether speed was an
explicit feature of successful task performance or assessed
covertly while the participant responded to other task demands.
Consistent with the results of the present study, Denney et
al.s (in press) results therefore suggest that cognitive slow-
ing may be a more prominent feature of MS than executive
dysfunction.
4.3. Moderators of uency decits in MS
Although patients age, duration of illness and neurological
disability will inevitably be confounded, it is of interest that
phonemic and semantic fluency deficits were most strongly cor-
related with neurological disability as indexed by the EDSS.
With respect to the relationship between disease course and cog-
nitive impairment, previous meta-analytic reviews have failed
to concur. Zakzanis (2000) found that CP patients were more
likely than RR patients to exhibit deficits in a range of cog-
nitive domains, whilst Thornton and Raz (1997) found that
patients with a CP course presented with more prominent mem-
ory impairment relative to RR patients. However, Wishart and
Sharpe (1997) concluded that there was no significant difference
between RR and CP patients in terms of cognitive dysfunction.
It is suggested that Wishart and Sharpes (1997) findings may
have been attributable to the methodology that they employed,
as vote-counting is known to be biased towards Type II errors.
In the present study, there was a trend for patients presenting
with a CP course to be more impaired on both types of fluency.
This suggests that CP and RR patients do differ in terms of the
prominence of cognitive deficits, at least as indexed by tests of
verbal fluency. Although conclusions need to be cautious given
the relatively small number of studies that contributed to these
particular analyses, it is of note that Zakzanis (2000) also iden-
tified larger deficits on both types of fluency for patients with a
CP relative to an RR course.
However, when partial correlations were calculated, control-
ling for duration of illness, neurological disability and patients
age, these correlations were substantially attenuated. Indeed,
it is striking that differences between RR and CP patients in
terms of the magnitude of fluency deficits were almost entirely
removed once these characteristics were taken into considera-
tion. Thus, although patients with a CP disease course are more
impaired than patients with an RR course on both types of flu-
ency, we would suggest that this may be attributable to the
older age, increased duration of illness and neurological dis-
ability which typically accompanies the CP relative to the RR
course.
 J.D. Henry, W.W. Beatty / Neuropsychologia 44 (2006) 11661174 1171

4.4. Summary and conclusions
MS was associated with substantial and comparable levels
of impairment on measures of phonemic and semantic flu-
ency, which were matched only in magnitude by deficits on the
SDMT. These results are therefore consistent with other evi-
dence indicating that measures of fluency and cognitive speed
are amongst the most sensitive markers of cognitive impairment
in MS. Deficits on both phonemic and semantic fluency were
larger for patients with greater neurological disability, and who
presented with a CP (as opposed to a RR) course. However,
the latter finding appears to be attributable to clinical features
of these sub-types, and in particular, the increased duration of
illness, greater neurological disability and older age in patients
who follow a CP course of the disease.
Acknowledgements
Acknowledgements must be given to Peter Arnett, John
DeLuca and Allyson Parry for providing us with additional
information on the individual studies that contributed to these
analyses.
Appendix A
Effect sizes for each of the individual studies that contribute
to the meta-analysis

Study Patient characteristics Fluency

N Age Ed. EDSS Duration MS type Manipulation PF SF

Arnett, Polen, Strober, Bruce, and Smith (unpublished) 97 47 14.3 4.6 Mixed .20 .16
Beatty, Goodkin, Monson, Beatty, and Hertsgaard (1988)b 38 49 13.9 6.7 18.2 CP Total group .61 .52
28a 49 14.0 6.5 19.4 CP MMSE 28 .57 .44
10a 49 13.5 7.3 14.9 CP MMSE < 28 .69 .74
Beatty et al. (1989a, 1989b) b 42 38 14.4 2.1 4.3 RR .31 .36
Beatty, Hames, Blanco, Paul, and Wilbanks (1995) b 100 45 14.5 9.9 .44 .44
Caine, Bamford, Schiffer, Shoulson, and Levy (1986)c 30 44 13.8 4.9 RR .37 .50
Camp et al. (1999) d 63 48 PP/TP Matched .30
157a 51 6.0 10.9 PP PP only .23
33a 47 5.5 12.3 TP TP only .30
Chiaravalloti and DeLuca (2002) e 31 45 15.3 10.7 Majority RR .07 .19
Clark et al. (1992) b 123 36 13.6 2.1 5.0 RR .27
Clark et al. (1997) b 196 34 13.5 2.0 RR .18
DeLuca, Gaudino, Diamond, Christodoulou, and Engel (1998)b 40 45 15.6 4.1 8.5 Mixed .30
DEsposito et al. (1996) e 36 39 14.8 3.5 5.4 89% RR .23 .24
Fischer (unpublished) b 45 39 14.2 4.0 4.9 Mixed .43 .26
Foong et al. (1997) b 42 39 6.3 67% SP .51 .65
Franklin, Heaton, Nelson, Filley, and Seibert (1988)c 60 37 14.6 5.3 6.0 CP .12
Friend et al. (1999) b 68 45 15.1 11.6 Mixed Total group .37 .42
30a 47 14.4 14.9 CP CP only .53 .60
38a 43 15.7 9.1 RR RR only .24 .31
Geisler et al. (1996) f 8 43 RR .12
Heaton, Nelson, Thompson, Burks, and Franklin (1985)c 100 37 13.7 3.1 9.4 Mixed Total group .28W
57a RR RR only .19W
43a CP CP only .33W
Huber et al. (1987) b 32 40 13.9 5.3 .42
Huijbregts et al. (2004) b 234 43 4.0 8.4 Mixed Total group .43
108a 36 2.4 3.4 RR RR only .53
71a 45 5.0 12.3 SP SP only .58
55a 54 5.8 13.0 PP PP only .36
Klonoff, Clark, Oger, Paty, and Li (1991)b 86 37 13.7 2.1 5.9 RR .29
Krupp, Sliwinski, Masur, Friedberg, and Coyle (1994)b 20 40 14.5 2.3 Fatigue .34
Laatu, Hamalainen, Revonsuo, Portin, and Ruutiainen (1999)b 12 45 11.4 6.0 11.9 Mixed .76 .79
McIntosh-Michaelis et al. (1991) g,h 147 48 6.0 13.0 .22
Minden, Moes, Orav, Kaplan, and Reich (1990)c 50 41 14.0 4.2 11.3 Mixed .23
Nocentini et al. (2001) b 44 44 11.9 6.1 12.7 SP Total group .46 .24
18a 44 12.4 6.0 13.3 SP No deficits .07 .03
21a 43 11.5 6.1 10.9 SP Specific deficits .81 .19
5a 49 11.4 6.3 15.7 SP General deficits .85 .50
1172 J.D. Henry, W.W. Beatty / Neuropsychologia 44 (2006) 11661174

Appendix A (Continued )
Study Patient characteristics Fluency

N Age Ed. EDSS Duration MS type Manipulation PF SF

Norman, Connor, Delis, and Corey-Bloom (unpublished)b 19 41 14.1 .51 .54

Parry et al. (2003) b 10 42 2.0 10.0 80% RR .48 .26
Pozzilli et al. (1991) c 17 31 13.4 1.7 8.0 RR .35
Rao, Leo, and Staubin-Faubert (1989)b 37 45 13.6 4.3 8.2 .46 .32
Rao, Leo, Bernardin, and Unverzagt (1991)g 100 46 13.2 4.1 9.5 Mixed .36
Roig et al. (unpublished) i 31 46 11.2 4.5 10.7 Mixed .42 .58
Ryan, Clark, Klonoff, Li, and Paty (1996)b 177 36 13.5 2.0 5.2 RR .19
Sailer et al. (2001) b 34 38 4.2 5.5 Mixed Total group .45
12a 38 3.4 4.5 Mixed Low lesion volume .31
12a 39 4.3 6.3 Mixed High volume .50
10a 39 4.9 5.8 Mixed High frontal volume .65
Tong, Yip, and Lee (2002)j 11 37 10.8 13.5 .16
van den Burg, van Zomeren, Minderhoud, Prange, and Meijer (1987)b 40 38 2.6 8.7 Mixed .36

Note: Ed.: years of education received; EDSS: Expanded Disability Status Scale; duration: number of years since diagnosis; MS type refers to the course the disease
has takenRR: relapsing remitting, CP: chronic progressive, PP: primary progressive, SP: secondary progressive and TP: transitional progressive. PF: phonemic
fluency and SF: semantic fluency. For fluency, unless it is indicated that the written version has been administered (superscript letter, W), it has been presumed that
it is the oral version of the test that is administered, as this is the most typical form of administration.
a Some or all of the participant group already entered in table.
b Poser et al.s (1983) criteria for definite MS.
c Schumacher et al. (1965) criteria for definite MS.
d Clinically or laboratory supported MS.
e Clinically definite MScriteria not specified.
f Recruited from MS Care Center.
g Poser et al.s (1983) criteria for definite or probable MS.
h Control group in this study have rheumatoid arthritis.
i Diagnostic criteria not specified.
j Diagnosed by a consultant physician.

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