The effect of cognitive behaviour therapy for chronic fatigue
syndrome on self-reported cognitive impairments and
neuropsychological test performance
Hans Knoop, Judith B Prins, Maja Stulemeijer, Jos W M van der Meer, Gijs Bleijenberg
............................................................... ............................................................... .....
J Neurol Neurosurg Psychiatry 2007;78:434–436. doi: 10.1136/jnnp.2006.100974
Background: Patients with chronic fatigue syndrome (CFS)
often have concentration and memory problems.
Neuropsychological test performance is impaired in at least a
subgroup of patients with CFS. Cognitive behavioural therapy
(CBT) for CFS leads to a reduction in fatigue and disabilities.
Aim: To test the hypothesis that CBT results in a reduction of
self-reported cognitive impairment and in an improved
neuropsychological test performance.
Methods: Data of two previous randomised controlled trials
were used. One study compared CBT for adult patients with
CFS, with two control conditions. The second study compared
CBT for adolescent patients with a waiting list condition. Self-
reported cognitive impairment was assessed with question-
naires. Information speed was measured with simple and
choice reaction time tasks. Adults also completed the symbol
digit-modalities task, a measure of complex attentional func-
Results: In both studies, the level of self-reported cognitive
impairment decreased significantly more after CBT than in the
control conditions. Neuropsychological test performance did
Conclusions: CBT leads to a reduction in self-reported cognitive
impairment, but not to improved neuropsychological test
performance. The findings of this study support the idea that
the distorted perception of cognitive processes is more central
to CFS than actual cognitive performance.
known organic disease or ongoing exertion, and not alleviated
by rest. According to the Centre for Disease Control definition
of CFS, impaired concentration and/or memory is an additional
symptom criterion.1The level of self-reported cognitive impair-
ments in CFS is high2and contributes to the social and
occupational dysfunctions of patients with CFS.3
patients with CFS with neuropsychological tests yielded
conflicting results.4Reduced speed of (complex) information
processing is the most consistently found impairment.3 5 6
However, several studies found no cognitive impairments7
and other studies identified a subset of patients with defective
Fatigue-related cognitions and behaviour can perpetuate
CFS.10Several controlled trials have shown that cognitive
behavioural therapy (CBT) aimed at these perpetuating factors
leads to a reduction in fatigue and disabilities.11
The first hypothesis tested was that CBT for CFS also results
in a reduction of self-reported cognitive impairments. The
hronic fatigue syndrome (CFS) is characterised by severe
fatigue, lasting longer than 6 months and leading to
functional impairment. The fatigue is not the result of a
second hypothesis was that the neuropsychological test
performance of patients with CFS improves after CBT. Data of
two previous CBT trials12 13were used to test the hypotheses.
MATERIALS AND METHODS
The first study from which data were used compared the effects
of CBT for adults with CFS with natural course and support
Assessments were done at baseline, and at 8 and 14 months.
An intention-to-treat analysis showed a reduction in fatigue
and functional impairment after CBT. In two of the three
participating treatment centres, neuropsychological tests were
part of the assessments. Consequently, data from neuropsy-
chological test performance were available for a subset of 233
(78 CBT; 76 natural course; 79 support group) of the total group
of 278 patients. The mean (SD) age of this group was 36.8
(10.2) years, 182 (78%) were female and median illness
duration was 41 months. The second study was a randomised
controlled trial comparing CBT for adolescents with CFS13with
a waiting list condition. A total of 69 patients were randomly
assigned to the conditions. Assessments were done at baseline
and at 5 months. The results showed a greater decrease in
Neuropsychological data of 67 patients were available (33
CBT; 34 waiting list). The mean (SD) age of the group was 15.6
(1.3) years, 59 (88%) were female and median illness duration
was 18 months.
in theCBT group.
Questionnaires assessing self-reported cognitive
Checklist individual strength-concentration
In both studies, the severity of concentration problems over the
past 2 weeks was assessed with the subscale concentration of
the checklist individual strength (CIS) that consists of five
items on a seven-point scale. The score can range between 5
and 35.3 12 13
Sickness impact profile-alertness behaviour
In adults, the self-observed effect of cognitive impairments on
daily functioning was assessed with the subscale sickness
impact profile-alertness behaviour (SIP-ab) of the sickness
impact profile.14The subscale has 10 items, each item is
weighed and the score can range between 0 and 777. No such
instrument was available for adolescents.
Abbreviations: CBT, cognitive behavioural therapy; CFS, chronic fatigue
syndrome; CIS, checklist individual strength; CIS-conc, checklist individual
strength-concentration; SDMT, symbol digit modalities task; SIP-ab,
sickness impact profile-alertness behaviour; SOCI, self-observation of
Self-observation of cognitive impairment
In adolescents, the frequency of cognitive impairments was
determined with a structured diary. Patients rated both
concentration and memory impairment separately on a daily
self-observation list four times a day for 12 days (0=no
impairment; 1=impaired). The percentage of concentration
problems and memory problems (both number of assessments
with a problem divided by 48 times 100) were added and then
divided by two to calculate the mean percentage of incidents of
Reaction time task
The reaction time task consisted of two subtests, simple and
choice reaction time tasks. Both are described in detail
elsewhere.8 15In a previous study, the reaction times of patients
with CFS were slower than that of healthy controls on both
Symbol digit modalities task
The symbol digit modalities task (SDMT)16was used in the
adult study as a measure of complex attention. In previous
studies, patients with CFS scored lower than a matched healthy
control group.8 9
Significance was assumed at p,0.05. A multivariate analysis
of variance was performed with self-reported cognitive impair-
ment and reaction time as dependent variables and treatment
as fixed factor. Univariate tests and post hoc analysis are
reported if the multivariate test was significant. For the SDMT,
a univariate analysis was performed, as data were available for
a subset of 174 patients as the SDMT was added later to the test
battery. In the adult study, the dependent variables were the
change scores at 14 months from baseline and in the adolescent
study, it was at 5 months from baseline. Reaction times were
transformed by a logarithm transformation. For adults, if data
at 14 months were missing and data 8-months post-treatment
were available, the second were used. In all other cases, missing
data were replaced with estimates derived by single imputation
analysiswas performedusingSPSS V.12.01.
(missing variable analysis regression in SPSS with baseline
value as predictor). For significant treatment effects, effect sizes
Nineteen adult patients (8%) had missing checklist individual
strength-concentration (CIS-conc) and SIP-ab post-treatment
data. One patient had missing data on both reaction time tasks
at baseline, for 44 (19%) patients only baseline data and for 30
(17%) patients only a baseline SDMT score was available.
Two adolescent patients had no SOCI scores at baseline. For 4
(6%) patients the CIS-conc and SOCI at second assessment
were missing. Two patients had no baseline reaction time and
for 13 (20%) adolescents the reaction times at the second
assessment were missing.
In both studies, there were more data missing from
neuropsychological tests than from questionnaires as some
patients were willing to mail the questionnaires, but refused to
undergo a second neuropsychological assessment.
Self-reported cognitive impairments
The multivariate test (Pillai’s trace) showed a significant
change in self-reported cognitive impairments (F(4,460)=4.76;
p=0.001). The univariate tests showed a significant effect of
treatment on the change in CIS-conc and SIP-ab (F(2,230)=
8.94; p ,0.001 and F(2,230)=4.42; p=0.013). Following CBT,
the decrease in CIS was significantly greater than in both the
natural course (p,0.001) and the support group (p=0.001;
table 1). There was a significantly greater decrease in SIP-ab
score after CBT compared with natural course (p=0.004). The
difference between CBT and support group failed to reach
The multivariate test showed a significant treatment effect on
self-reported cognitive impairments (F2,62=5.03; p=0.009).
Univariate tests showed that the decrease in the CIS-conc and
SOCI score was significantly larger in the CBT group
(F(1,63)=6.4; p=0.014 and F(1,63)=6.28; p=0.015).
Estimated treatment effect in change score (95% CI) on the dependent variables
Self-reported cognitive impairments
27.4 (29.1 to 25.7)?
2116 (2156 to 276)`
22.7 (24.4 to 21.0)**
231 (272 to 210)**
23.4 (25.1 to 21.8)**
261 (2100 to 221)
26.8 (210.5 to 23.5)` 20.9 (24.2 to +2.5)*
27.9 (212.8 to 22.9)1 0.9 (24.1 to +6.0)*
Neuropsychological test performance
Simple reaction time (ms)
Choice reaction time (ms)
9 (29 to 27)
224 (251 to 3)
2.8 (0.8 to 4.8)
25 (223 to 14)
227 (254 to 1)
2.3 (0.2 to 4.4)
6 (212 to 24)
226 (253 to 1)
4 (2 to 6)
Simple reaction time (ms)
Choice reaction time (ms)
230 (253 to 28)
212 (229 to 6)
218 (241 to 4)
210 (228 to 8)
CBT, cognitive behavioural therapy; CIS-conc, checklist individual strength-concentration; SDMT, symbol digit modalities
task; SIP-ab, sickness impact profile-alertness behaviour; SOCI, self-observation of cognitive impairment.
* Significantly different from the CBT condition, p,0.05.
**Significantly different from the CBT condition, p,0.01.
?Cohen’s d based on change within treatment condition=1.3.
`Cohen’s d =0.6.
The effect of CBT on cognitive impairments in CFS435
Neuropsychological test performance Download full-text
There was no significant effect of treatment on either reaction
time task (F(4, 458)=0.44; p=0.783). There was no significant
treatment effect on the SDMT (F(2,171)=0.73; p=0.484).
Multivariate tests showed no significant treatment effect on
either reaction time task (F(2,62)=0.34; p=0.714).
decrease after CBT in patients with CFS was confirmed. Only
one comparison in the adult study, measuring cognitive
impairments more indirectly, showed an effect in the expected
direction without reaching significance. The results of the
original adolescent study13already indicated that concentration
problems decrease after CBT. In that study, the concentration
problems were assessed with a single item evaluating these
problems retrospectively over a period of 6 months. This
assessment can be easily influenced by situational circum-
stances and memory biases, which can be prevented by the use
of a diary as in the present study. No support could be found for
the hypothesis that neuropsychological test performance
improves after CBT.
A methodological problem is that in a substantial part of the
patients the neuropsychological data of the second assessment
were missing. Furthermore, in our analysis we assumed that
dropout occurred at random, whereas patients may drop out for
non-random reasons. We repeated the analyses, but only on
patients who completed both assessments. Again, there was no
significant treatment effect. Our interpretation is that this
indicates that improvement in self-reported cognitive impair-
ments after CBT is independent of the change in neuropsycho-
logical test performance.
A discrepancy between subjectively reported disabilities
versus objectively measured performance is not limited to the
current study. Mahurin et al17found that the objective cognitive
functioning of monozygotic twins discordant for CFS did not
differ, whereas the twin with CFS reported more cognitive
impairments. Metzger and Denney18showed that patients with
CFS underestimated their cognitive performance. In the study
by Vercoulen et al,8most patients with CFS reported concentra-
tion and memory problems, whereas only a small percentage
showed an impaired performance. Given the fact that patients
with CFS perceive their cognitive processes as impaired but
underestimate their actual performance, one would expect that
an effective treatment of CFS would lead to a more accurate
perception of one’s performance. The results of the present
study are consistent with this prediction. CBT resulted in
decreased complaints about cognitive functioning, but not in a
change in performance. This is also in line with the hypothesis
that a distorted perception of symptoms and performance is a
crucial element of CFS.10
The authors thank Theo Fiselier for contributing to the selection of
adolescent patients with CFS, Lammy Elving for contributing to the
selection of adult patients and Ria te Winkel and Lida Nabuurs for
assisting in data collection.
Hans Knoop, Gijs Bleijenberg, Expert Centre Chronic Fatigue, Radboud
University Nijmegen Medical Centre, Nijmegen, The Netherlands
Judith B Prins, Maja Stulemeijer, Department of Medical Psychology,
Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Jos W M van der Meer, Department of Internal Medicine, Radboud
University Nijmegen Medical Centre, Nijmegen, The Netherlands
Funding: The Health Insurance Council (College van Zorgverzekeraars)
funded the adult CBT study. The Children’s Welfare Stamps Netherlands
(Stichting Kinderpostzegels Nederland) and the ME Foundation (ME
Stichting) funded the adolescent CBT study.
Competing interests: none.
Correspondence to: H Knoop, Expert Centre Chronic Fatigue, Radboud
University Nijmegen Medical Centre, P O Box 9011, 6525 EC Nijmegen,
The Netherlands; email@example.com
Received 26 June 2006
Revised 14 November 2006
Accepted 15 November 2006
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