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COGNITIVE IMPAIRMENT AND QUALITY OF LIFE IN PATIENTS
WITH MYOTONIC DYSTROPHY TYPE 1
HARUO FUJINO, PhD ,
1,2
HONOKA SHINGAKI, MS,
2
SHUGO SUWAZONO, MD, PhD,
3
YUKIHIKO UEDA, PhD,
4
CHIZU WADA, MD, PhD,
5
TAKAHIRO NAKAYAMA, MD, PhD,
6
MASANORI P. TAKAHASHI, MD, PhD,
7,8
OSAMU IMURA, PhD,
2
and TSUYOSHI MATSUMURA, MD, PhD
9
1
Department of Special Needs Education, Oita University, 700 Dannoharu, Oita, Japan 870-1192
2
Graduate School of Human Sciences, Osaka University, Osaka, Japan
3
Department of Neurology, National Hospital Organization Okinawa Hospital, Okinawa, Japan
4
Okinawa International University, Okinawa, Japan
5
Department of Neurology, National Hospital Organization Akita National Hospital, Yurihonjo, Japan
6
Department of Neurology, Yokohama Rosai Hospital, Yokohama, Japan
7
Department of Functional Diagnostic Science, Osaka University Graduate School of Medicine, Osaka, Japan
8
Department of Neurology, Osaka University Graduate School of Medicine, Osaka, Japan
9
Department of Neurology, National Hospital Organization Toneyama National Hospital, Osaka, Japan
Accepted 27 November 2017
ABSTRACT: Introduction: This study sought to clarify whether
specific cognitive abilities are impaired in patients with myotonic
dystrophy type 1 (DM1) as well as to investigate the relation-
ships among quality of life (QoL), cognitive function, and psy-
chological factors. Methods: Sixty patients with DM1 were
evaluated on cognitive functioning (abstract reasoning, atten-
tion/working memory, executive function, processing speed, and
visuoconstructive ability), apathy, depression, excessive daytime
sleepiness, fatigue, and QoL. QoL was assessed by 2 domains
of the Muscular Dystrophy Quality of Life Scale (Psychosocial
Relationships and Physical Functioning and Health). Results:
More than half of the patients exhibited cognitive impairment in
attention/working memory, executive function, processing
speed, and visuoconstructive ability. The Psychosocial Relation-
ships factor was associated with processing speed, attention/
working memory, and apathy, whereas depression and fatigue
were associated with 2 QoL domains. Discussion: Our study
identified specific cognitive impairments in DM1. Specific cogni-
tive functions and psychological factors may be potential con-
tributors to QoL.
Muscle Nerve 000:000–000, 2017
Myotonic dystrophy type 1 (DM1) is the most
common muscular dystrophy in adults and involves
multisystem organs. DM1 is an autosomal domi-
nant disease caused by unstable cytosine–thymine–
guanine (CTG) triplet repeat expansion. Gener-
ally, longer CTG repeat expansions are associated
with earlier onset and more severe symptoms.
1
No
curative treatment is currently available for DM1,
although gene therapies are being developed.
Thus, optimizing quality of life (QoL) is critical in
the management of DM1 and in the development
of interventions for this patient group.
Several studies have described selective impair-
ments in executive function, visuospatial function,
processing speed, and attention.
2,3
In addition to cog-
nitive deficits, previous studies have also suggested
that emotional disturbances and characteristic person-
ality patterns are present in DM1, although the pro-
portion of patients exhibiting these features varies
among studies.
2–5
Major central nervous system (CNS)
and emotional problems include fatigue, daytime
sleepiness, depression, and apathy.
6
The complexity
of such problems poses difficulties in the clinical man-
agement of DM1.
7
It is possible that cognitive impair-
ments and psychological problems can affect patients’
behaviors toward medical providers and their access
to appropriate care, leading to worse QoL.
A few previous studies have also examined the
relationship between cognitive impairment and QoL
and found inconclusive evidence
8–10
;however,the
majority of these studies did not consider all domains
of cognition, or they used generic QoL measures,
which may not be sensitive to specific issues in DM1.
More studies are required to assess cognitive impair-
ment better, compare disease-specific and generic
questionnaires, and study more diverse patient sam-
ples. This study sought to describe the affected
domains of cognitive functioning in patients with
DM1 and evaluate the relationships between cogni-
tive functioning, psychological factors, and QoL.
Additional supporting information may be found in the online version of
this article.
Abbreviations: CAT, Clinical Assessment for Attention; CNS, central ner-
vous system; CTG, cytosine–thymine–guanine; DM1, myotonic dystrophy
type 1; ESS, Epworth Sleepiness Scale; FAB, Frontal Assessment Battery;
IQ, intelligence quotient; MDQoL, Muscular Dystrophy Quality of Life
Scale; MFI, Multidimensional Fatigue Inventory; MMSE, Mini-Mental State
Examination; NHO, National Hospital Organization; PASAT-2, Paced Audi-
tory Serial Addition Test 2; PHQ-9, Patient Health Questionnare-9; QoL,
quality of life; SRS, Social Responsiveness Scale; TMT-A, Trail Making
Test-A; TMT-B, Trail Making Test-B; VPTA, Visual Perception Test for
Agnosia; WAIS-III, Wechsler Adult Intelligence Scale-III; WCST, Wisconsin
Card Sorting Test.
Key words: central nervous system; cognitive deficit; depression; fatigue;
myotonic dystrophy type 1; quality of life
Funding: This work was supported in part by the Ministry of Health,
Labour, and Welfare of Japan (H28-Nachitou[Nan]-Ippan-030), the Japan
Agency for Medical Research and Development, AMED (Comprehensive
Research on Persons with Disabilities 15dk0310043h0002 and Practical
Research Project for Rare/Intractable Diseases 17ek0109259), and JSPS
KAKENHI (17K14067).
Conflicts of Interest: The authors declare that they have no conflicts of
interest. The funders had no role in the study design, data collection and
analyses, decision to publish, or preparation of this article.
Correspondence to:H. Fujino; e-mail: fjinoh@oita-u.ac.jp
V
C2017 Wiley Periodicals, Inc.
Published online 28 November 2017 in Wiley Online Library (wileyonlinelibrary.
com). DOI 10.1002/mus.26022
Cognition & QoL in DM1 MUSCLE & NERVE Month 2017 1
MATERIALS AND METHODS
Ethical Standards. This study was conducted in accor-
dance with the ethical standards set forth in the World Med-
ical Association 1964 Declaration of Helsinki and its later
amendments and was approved by the research ethics com-
mittees at each represented institution. Written informed
consent was obtained from all participants after the study
procedures had been fully explained.
Participants. Patients were recruited from 5 hospitals
(National Hospital Organization [NHO] Toneyama
National Hospital, NHO Okinawa National Hospital, NHO
Akita National Hospital, Yokohama Rosai Hospital, and
Osaka University Hospital). Although no consensus regard-
ing the clinical classification of DM1 exists, we classified
patients into 4 clinical forms according to the age at onset
using criteria from a recent study; clinical onset from 1
month to 10 years of age 5infantile, 11–20 years 5juvenile,
21–40 years 5adult, and >40 years 5late onset.
11
The num-
ber of CTG repeats was assessed by polymerase chain reac-
tion and Southern blotting.
Assessment of Cognitive Function, Psychological
Factors, and QoL. The following cognitive batteries were
used to evaluate patients’ general cognitive function and 5
specific domains (abstract reasoning, attention/working
memory, executive function, processing speed, and visuo-
constructive ability).
General cognitive function was evaluated with the Japa-
nese version of the Mini-Mental State Examination (MMSE),
and the estimated intelligence quotient (IQ) was calculated
from 2 subtests (Picture Completion and Information) of the
Wechsler Adult Intelligence Scale-III (WAIS-III).
12
The WAIS-
III is the latest version available in Japan because the Japanese
version of the WAIS-IV has not yet been published. Abstract
reasoning was evaluated with the WAIS-III Similarities subtest
and the Visual Perception Test for Agnosia (VPTA) Story Tell-
ing subtest.
13
Attention/working memory was evaluated with
the Clinical Assessment for Attention (CAT) subtests (Digit
Span [forward], Digit Span [backward], Tapping Span [for-
ward], Tapping Span [backward], Auditory Detection task
[%correct and %hit], Memory Updating 3, and Paced Audi-
tory Serial Addition Test 2 [PASAT-2]).
14
Executive function
was evaluated with the number of categories achieved on the
Wisconsin Card Sorting Test (WCST), the Frontal Assessment
Battery (FAB) total score,
15
the Trail Making Test (TMT)-B
(completion time), the CAT Position Stroop test (completion
time), the semantic fluency test (animal), and the phonemic
fluency test. Processing speed was evaluated with the TMT-A
(completion time) and 2 CAT subtests (Visual Cancellation
task [Ka; completion time] and Symbol Digit Modalities test).
Visuoconstructive ability was evaluated using the WAIS-III
Block Design and the VPTA subtests (Copying Figures, Copy-
ing Flowers, and Bisection of Lines). The CAT and VPTA are
test batteries developed by the Japan Society for Higher Brain
Dysfunction. The CAT assesses a wide range of cognitive func-
tions associated with attention, such as working memory and
processing speed.
14
The VPTA was developed to assess the
visual perception of patients with higher brain dysfunction.
13
Four subtests of the VPTA were included in the current study
to assess abstract reasoning (Story Telling) and visuoconstruc-
tive ability (Copying Figures, Copying Flowers, and Bisection
of Lines).
The 5 specific domains of psychological function mea-
sured were apathy, depression, excessive daytime sleepiness,
fatigue, and social responsiveness. Apathy was evaluated with
the Apathy Scale,
16
excessive daytime sleepiness with the
Epworth Sleepiness Scale (ESS),
17
severity of depression with
the Patient Health Questionnaire-9 (PHQ-9),
18
fatigue with
the Multidimensional Fatigue Inventory (MFI),
19
and social
responsiveness with the Social Responsiveness Scale (SRS).
20
The Apathy Scale, ESS, PHQ-9, and MFI are self-report mea-
sures, whereas the SRS is completed by raters (e.g., family
members or specialists familiar with the patient’s personal
life).
QoL was estimated with the Muscular Dystrophy Quality
of Life Scale (MDQoL),
21
a patient-reported measure con-
sisting of 11 subscales (Psychological Stability, Activities of
Daily Living, Environment, Hope, Activity, Health, Relation-
ships, Family, Sexuality, Breathing, and Defecation), devel-
oped for Japanese patients with muscular dystrophies,
including DM1, to evaluate their self-reported QoL. The
MDQoL has been used in studies conducted with Japanese
patients with muscular dystrophy.
22
The scores range from 0
to 100, with higher scores indicating a better QoL.
Cognitive tests and questionnaires were completed over
2–3 days. Patients received questionnaires at the time of
their first examination and were required to complete them
by their final examination.
Means and SD for the Japanese general population were
obtained from published manuals and previous studies that
had used cognitive tests and measured psychological varia-
bles.
13,14,23–32
Age-specific scores were used for the CAT, FAB,
TMT, and WAIS-III subtests.
14,23,31,32
Significant impairment
in general cognitive functioning was defined by a cutoff score
of 23 on the MMSE.
33
Scores that were 2 SD below or above
those of the general population, as determined by the direc-
tion of abnormality in each test, were considered to indicate
severe cognitive impairment, severe psychological symptoms
(apathy and depression), excessive daytime sleepiness, exces-
sive fatigue, and deficiencies in reciprocal social behavior, in
line with previous studies.
3,34,35
Statistical Analyses. The sample size required for the
current study was estimated by using R 3.2.0 software
(R Core Team, Vienna, Austria) and was based on a previ-
ous study that investigated the association between QoL and
cognitive performance in DM1.
9
A minimum of 60 patients
would be required to detect moderate associations between
the MDQoL and cognitive measures given strength of
association 50.4, a50.05, and standard power 50.9.
Statistical analyses were performed in SPSS version 22.0
(SPSS Japan, Tokyo, Japan). We conducted exploratory factor
analysis with promax rotation using maximum likelihood esti-
mation to identify the latent structure (i.e., factors) and to
reduce the number of QoL variables used in the correlational
analysis. Promax rotation was used to obtain a simple struc-
ture to facilitate interpretation (e.g., a particular variable
affects only 1 specific factor).
36
Communalities reflect the
proportion of variance that can be explained by the underly-
ing factors. Factor loadings are measures of the degree to
which a variable contributes to a specific factor. High factor
loadings indicate that the dimension of a factor is well
accounted for by the variables. A scree plot was used to deter-
mine the number of factors to extract. The total scores for
each factor were calculated by summing scores that highly
loaded onto each factor. The total score for each factor was
used in subsequent analyses. Internal consistency of the ques-
tionnaire measures was calculated by using Cronbach’s a.
2Cognition & QoL in DM1 MUSCLE & NERVE Month 2017
A test for normality revealed that most variables were
not normally distributed, with exceptions being some cogni-
tive tests and the QoL measure. Therefore, a nonparametric
Spearman’s test was used to examine associations between
QoL, cognitive performance, and psychological variables.
We focused primarily on associations between QoL and cog-
nitive/psychological measures. Additionally, we examined
associations between cognitive functioning and psychologi-
cal measures in a secondary analysis. The Kruskal-Wallis test
was used to compare differences among clinical forms of
DM1. The influence of cataracts and diabetes mellitus on
QoL was examined by using the Mann-Whitney U test. P-
value was adjusted by using the Benjamini and Hochberg
method for multiple testing to control for type I error in
each analysis, with false discovery rate at 0.05.
37,38
RESULTS
A total of 60 patients with DM1 (35 men and
25 women) participated in this study (Table 1). All
patients were Japanese. The mean number of CTG
repeats in the patients was 1,113.2 (SD 51,025.2).
Most patients were classified as having juvenile or
adult forms of DM1.
Some participants were unable to complete the
cognitive tests in their entirety because of time res-
trictions, clinical conditions, or difficulty in under-
standing the tests. The percentage of missing data
was less than 10% for each variable except the TMT-
B (12%), Visual Cancellation Task (12%), PASAT-2
(23%), and SRS (62%). The completion rate on the
PASAT-2 was low because of auditory deficits and
difficulty in understanding task instructions. The
administration rate on the SRS was low (38%)
because this scale was administered only when raters
were able to participate.
The results (mean scores) of most measures indi-
cated that the cognitive functioning of patients was
lower than that of the general population. In particu-
lar, more than half of the patients scored 2 SD lower
than the general population on measures of atten-
tion/working memory (Auditory Detection task for
%hit and %correct, 67% and 60%, respectively),
executive function (Position Stroop test, 79%), proc-
essing speed (Visual Cancellation task and Symbol
Digit Modalities test, 91% and 54%, respectively),
and visuoconstructive ability (Block Design, 64%;
Table 2, Table S1 in the Supplementary Material,
available online). Although patients were markedly
impaired on tasks measuring complex attentional
function (PASAT-2 and Memory Updating 3), they
were not severely affected on tasks measuring simple
attentional function (Digit Span [forward] and Tap-
ping Span [forward]). With regard to psychological
factors, some patients scored 2 SD higher than the
general population on measures of apathy (22%),
depression (23%), and fatigue (15%; Table 3). Cog-
nitive and psychological variables did not differ sig-
nificantly among the clinical forms of DM1.
The results of factor analysis of the MDQoL are
shown in Table S2 (refer to Supplementary Material
available online). Two factors were extracted on the
basis of the scree plot of the eigenvalues. Five sub-
scales, including Relationships, Environment, Psy-
chological Stability, Hope, and Family loaded highly
onto factor 1. Six subscales, including Defecation,
Breathing, Activities of Daily Living, Activity, and
Health loaded highly onto factor 2. The Sexuality
subscale was excluded from the calculation of 2 fac-
tor scores because the subscale did not load highly
onto either of the 2 factors (factor loading <0.40).
Factor 1 was related to psychosocial relationships,
whereas factor 2 reflected physical functioning and
health; therefore, these factors were interpreted as
the Psychosocial Relationships factor and the Physical
Functioning and Health factor, respectively, and were
used in subsequent analyses. Cronbach’s avalues for
the questionnaire measures were high, including the
Apathy Scale (a50.81), PHQ-9 (a50.82), ESS
(a50.76), MFI (a50.84), SRS (a50.95), MDQoL
Psychosocial Relationships (a50.91), and MDQoL
Physical Functioning and Health (a50.92).
The Psychosocial Relationships factor was associ-
ated with performance on the Digit Span (forward)
and Tapping Span (forward; attention/working
memory domain) tests and was negatively associated
with performance on the TMT-A (completion time)
and the Visual Cancellation task (processing speed
domain; Table 4). Additionally, the Psychosocial
Relationships factor was negatively associated with
apathy, depression, and fatigue (Table 5). The Phys-
ical Functioning and Health factor was negatively
associated with depression and fatigue. Apathy was
associated with the FAB (q520.47, adjusted
P<0.024), Visual Cancellation task (Ka; q50.46,
adjusted P50.030), and Auditory Detection task
(%correct); q520.44, adjusted P50.022). The fac-
tors of the MDQoL were not significantly different
between patients with or without cataracts or diabe-
tes mellitus.
Table 1 . Demographic and clinical variables of patients
with DM1
Variable Data
Sex, n, men/women 35/25
Age, y, mean 6SD 47.1 610.8
Education, y, mean 6SD 13.9 63.0
Age at onset, y, mean 6SD 29.0 613.2
Duration of illness, y, mean 6SD 17.2 611.4
CTG repeats, n, mean 6SD 1,113.2 61,025.2
CTG repeats, median (interquartile range) 850 (600–1,250)
Clinical classification, n
Infantile 1
Juvenile 20
Adult 28
Late onset 11
CTG, cytosine–thymine–guanine.
Cognition & QoL in DM1 MUSCLE & NERVE Month 2017 3
DISCUSSION
Our results suggest that a substantial propor-
tion of the patients exhibited specific cognitive
impairments across several domains. Better cogni-
tive ability in attention/working memory and proc-
essing speed were associated with higher QoL,
Tab le 3. Descriptive statistics of psychological variables and QoL in patients with DM1
Psychological variable nMean SD
Frequency, %,
(95% CI): 1 SD below
Frequency, %,
(95% CI): 2 SD below
Apathy
Apathy Scale 59 18.5 6.4 59 (48–70) 22 (14–33)
Depression
PHQ-9 60 8.0 5.5 47 (36–58) 23 (15–34)
Excessive daytime sleepiness
ESS 59 6.6 4.2 31 (21–42) 5 (1–13)
Fatigue
MFI 59 64.2 12.0 46 (35–57) 15 (8–25)
Social responsiveness
SRS 23 56.7 29.7 30 (15–50) 13 (4–30)
QoL (2 factor scores)
Psychosocial Relationships 57 60.4 17.5
Physical Functioning and Health 57 62.2 19.0
CI, confidence interval; ESS, Epworth Sleepiness Scale; MFI, Multidimensional Fatigue Inventory; PHQ-9, Patient Health Questionnare-9; QoL: quality of
life; SRS, Social Responsiveness Scale.
Table 2. Descriptive statistics of cognitive test batteries in patients with DM1
Cognitive variable nMean SD
Frequency, %,
(95% CI): 1 SD below
Frequency, %,
(95% CI): 2 SD below
General cognitive function
MMSE 60 26.6 3.1
WAIS-III: Estimated IQ 59 78.8 19.1 63 (51–73) 27 (18–38)
Abstract reasoning
WAIS-III: Similarities 60 7.7 3.2 52 (40–63) 20 (12–30)
VPTA: Story Telling 57 1.7 2.1 30 (20–41) 7 (2–15)
Attention/working memory
CAT: Auditory Detection task (%hit) 58 60.4 26.5 79 (69–88) 67 (56–77)
CAT: Auditory Detection task (%correct) 58 82.7 18.9 67 (56–77) 60 (49–71)
CAT: PASAT-2 46 42.2 26.0 74 (61–84) 41 (29–54)
CAT: Memory Updating 3 57 73.3 22.2 44 (33–56) 30 (20–41)
CAT: Digit Span (backward) 56 4.1 1.2 55 (44–67) 16 (9–26)
CAT: Tapping Span (backward) 57 4.4 1.4 49 (38–61) 9 (4–18)
CAT: Tapping Span (forward) 57 5.7 1.2 26 (17–38) 7 (2–15)
CAT: Digit Span (forward) 56 5.7 1.4 50 (38–62) 5 (1–13)
Executive function
CAT: Position Stroop test 56 134.3 71.6 86 (76–93) 79 (68–87)
TMT-B 53 220.5 174.5 45 (34–57) 34 (23–46)
FAB 59 15.9 2.0 20 (12–31) 14 (7–23)
WCST: Categories Achieved 55 2.7 2.0 44 (32–56) 11 (5–20)
Phonemic fluency 60 23.7 9.0 40 (29–51) 10 (4–19)
Semantic fluency (animal) 60 17.9 4.6 38 (28–50) 8 (3–17)
Processing speed
CAT: Visual Cancellation task (Ka) 53 186.6 99.9 96 (89–99) 91 (81–96)
CAT: Symbol Digit Modalities test 56 36.7 14.0 82 (72–90) 54 (42–65)
TMT-A 59 180.9 117.9 66 (55–76) 47 (36–59)
Visuoconstructive ability
WAIS-III: Block Design 59 4.4 2.5 85 (75–92) 64 (53–75)
VPTA: Copying Figures 56 1.7 1.5 48 (37–60) 48 (37–60)
VPTA: Bisection of Lines 57 1.4 1.5 39 (28–50) 28 (18–39)
VPTA: Copying Flowers 55 2.3 3.3 42 (31–54) 24 (15–35)
CAT, Clinical Assessment for Attention; CI, confidence interval; FAB, Frontal Assessment Battery; IQ, intelligence quotient; MMSE, Mini-Mental State Exami-
nation; PASAT-2; Paced Auditory Serial Addition Test 2; TMT, Trail-Making Test; VPTA: Visual Perception Test for Agnosia; WAIS-III: Wechsler Adult Intelli-
gence Scale-III; WCST: Wisconsin Card Sorting Test.
4Cognition & QoL in DM1 MUSCLE & NERVE Month 2017
whereas higher apathy, depression, and fatigue
were associated with lower QoL.
Affected Domains of Cognitive Function and Psychological
Factors. The results of the current study demon-
strated moderate to severe executive dysfunction,
processing speed impairment, attentional problems,
and visuoconstructive problems in patients with
DM1, in line with the previous studies.
2,3,8,9,39,40
A
recent study suggested that the degree of cognitive
decline can differ depending on the complexity of
the tasks measuring cognitive ability,
41
which may
explain the variation in impairment on these tests.
To lessen the burden and difficulty associated with
the administration of such a wide battery of tests,
researchers and clinicians should select measures
that best capture patients’ target characteristics.
42
The Outcome Measures in Myotonic Dystrophy type
Table 4. Correlations between cognitive performance and QoL variables
Psychosocial Relationships Physical Function and Health
Cognitive function Correlation coefficient Adjusted P-value Correlation coefficient Adjusted P-value
General cognitive function
WAIS-III: Estimated IQ 0.27 0.197 0.05 0.850
MMSE 0.16 0.467 0.01 0.975
Abstract reasoning
WAIS-III: Similarities 0.21 0.313 20.05 0.857
VPTA: Story Telling 20.01 0.975 0.02 0.938
Attention/working memory
CAT: Auditory Detection (%hit) 0.08 0.810 0.03 0.938
CAT: Auditory Detection (%correct) 0.18 0.424 20.01 0.976
CAT: PASAT-2 0.21 0.389 0.08 0.810
CAT: Tapping Span (backward) 0.30 0.155 0.16 0.467
CAT: Digit Span (backward) 0.29 0.172 0.11 0.606
CAT: Memory Updating 3 0.33 0.081 0.28 0.194
CAT: Digit Span (forward) 0.39* 0.033 0.13 0.589
CAT: Tapping Span (forward) 0.40* 0.030 0.18 0.424
Executive function
CAT: Position Stroop test 20.25 0.243 0.08 0.810
TMT-B 20.27 0.232 20.15 0.543
FAB 0.20 0.346 0.10 0.654
WCST: Categories Achieved 0.28 0.197 20.04 0.893
Phonemic fluency 0.14 0.557 20.16 0.467
Semantic fluency (animal) 0.22 0.306 20.12 0.589
Processing speed
CAT: Visual Cancellation task (Ka) 20.48* 0.006 20.24 0.275
CAT: Symbol Digit Modalities test 0.22 0.306 0.07 0.810
TMT-A 20.38* 0.033 20.06 0.831
Visuoconstructive ability
WAIS-III: Block Design 0.24 0.243 0.05 0.857
VPTA: Copying Figures 0.03 0.938 0.13 0.589
VPTA: Bisection of Lines 20.24 0.263 20.17 0.447
VPTA: Copying lowers 20.01 0.976 0.07 0.810
CAT, Clinical Assessment for Attention; CI, confidence interval; FAB, Frontal Assessment Battery; IQ, intelligence quotient; MMSE, Mini-Mental State Exami-
nation; PASAT-2, Paced Auditory Serial Addition Test 2; TMT, Trail-Making Test; VPTA: Visual Perception Test for Agnosia; WAIS-III: Wechsler Adult Intelli-
gence Scale-III; WCST: Wisconsin Card Sorting Test
*Significant after adjustment using false discovery rate.
Tab le 5. Correlations between psychological measures and QoL variables
Psychosocial Relationships Physical Function and Health
Psychological measure Correlation coefficient Adjusted P-value Correlation coefficient Adjusted P-value
Apathy: Apathy Scale 20.37* 0.035 20.20 0.343
Depression: PHQ-9 20.52* 0.001 20.65* <0.001
Excessive daytime sleepiness: ESS 20.13 0.589 20.11 0.601
Fatigue: MFI 20.42* 0.014 20.55* <0.001
Social responsiveness: SRS 20.20 0.589 0.10 0.825
ESS, Epworth Sleepiness Scale; MFI, Multidimensional Fatigue Inventory; PHQ-9, Patient Health Questionnare-9; SRS, Social Responsiveness Scale.
*Significant after adjustment using false discovery rate.
Cognition & QoL in DM1 MUSCLE & NERVE Month 2017 5
1 international workshops suggested a different cog-
nitive battery
6,43
; however, the selection of individ-
ual tests depends on the individual study design and
goals.
Several studies have shown that DM1 is associ-
ated with increased depressive symptoms.
4,44
The
prevalence of daytime sleepiness and excessive
fatigue that were observed in this study was higher
than that in the general population but relatively
low compared with previous reports.
3,9,45
Although
the ESS and MFI are both validated measures,
measures that cover target symptoms in the DM1
population are required to capture the patients’
characteristics.
46
Differences in the cognitive per-
formance and psychological variables between the
clinical forms were not detected in contrast to the
previous studies,
47,48
which may have been due to
the limited sample of the current study.
Relationships Among Cognitive Function, Psychological
Variables, and QoL. Impairments in processing
speed and attention led to lower QoL in patients
with DM1,
9,49
whereas the impact of the cognitive
impairments on QoL may differ by affected cogni-
tive domains.
9
Cognitive assessments can provide
useful information for patients, allowing them to
plan for substitutional support in their daily lives.
Cognitive interventions may also contribute to
improvements in the QoL of patients with DM1
because neuropsychological rehabilitation and cog-
nitive remediation have been effective in decreasing
impairments associated with other neurological con-
ditions.
50–52
In addition, apathy may mediate the
influence of cognitive function on QoL, which sug-
gests that the reduction of apathy could lead to bet-
ter cognitive performance or vice versa.
53
Depression and fatigue are the core predictors
of psychological and physical QoL in patients with
muscular diseases.
54,55
In addition, apathy, in con-
junction with fatigue and depression, could pro-
mote social inhibition and the avoidance of social
interactions,
56
leading to the deterioration of QoL.
DM1 management and psychological interventions
should include these factors as potential targets to
improve QoL in patients.
57,58
Results regarding the
influence of daytime sleepiness on QoL in DM1
have been inconclusive in previous studies,
9,49,59
suggesting that subjective evaluation may not cap-
ture the actual impact of daytime sleepiness. Thus,
an objective measure, such as the Multiple Sleep
Latency Test, may be appropriate to investigate the
impact of daytime sleepiness in DM1.
Limitations. Several limitations of this study should
be noted. First, all patients were Japanese and
were recruited from 5 hospitals, which may have
affected the representativeness of the study sample.
Although the age and severity of the patients in the
current study is comparable to that of a previous
multicenter study of DM1 in Japan,
60
the patients in
the current study had relatively severe DM1 in terms
of CTG repeat expansion in comparison with previ-
ous studies
8,9
; this may limit the generalizability of
our findings to samples of patients with relatively
severe DM1. Second, we could not exclude the pos-
sibility that muscular weakness affected participants’
performance on several cognitive tasks. Third, a few
of the cognitive tests and 1 of the psychological
scales had high rates of missing data. Tasks with
higher cognitive loads (i.e., complex tasks requiring
greater mental effort) resulted in lower completion
rates. Fourth, although we included many individual
factors in the current study, we did not examine
environmental factors, such as family support and
public services, which might be potential contribu-
tors to the QoL of patients with DM1.
45
Moreover, a
previous study found that patients with other comor-
bidities had lower QoL,
59
so additional studies are
warranted to explore the potential factors affecting
QoL in DM1. Finally, although the MDQoL was vali-
dated in patients with muscular dystrophies, the
QoL ratings of patients with DM1 may be affected
by CNS involvement associated with the disorder.
The MDQoL, a nondisease-specific instrument, has
inherent limitations as a definitive measure of QoL
in DM1 and is unlikely to cover all aspects that are
important to this population.
61,62
In conclusion, our findings support the notion
that specific cognitive functions, apathy, depres-
sion, and fatigue may be potential contributors to
the QoL of patients with DM1.
The authors greatly appreciate the patients who participated in
this study.
Ethical Publication Statement: We confirm that we have read the
Journal’s position on issues involved in ethical publication and
affirm that this report is consistent with those guidelines.
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