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Clinical Rehabilitation2016, Vol. 30(2) 134 –144© The Author(s) 2015Reprints and permissions: sagepub.co.uk/journalsPermissions.navDOI: 10.1177/0269215515578295cre.sagepub.com
CLINICALREHABILITATION
Introduction
Cognitive motor intervention is becoming an increasingly popular means of enhancing gait and balance ability.1 Cognitive motor intervention is where a cognitive exercise and a motor exercise are conducted simultaneously, such as performing bal-ance exercise while doing cognitive exercise.2 In fact, most daily activities require the ability to maintain balance while performing various tasks.
Cognitive motor intervention for gait and balance in Parkinson’s disease: systematic review and meta-analysis
Xue-Qiang Wang1*, Yan-Ling Pi2*, Bing-Lin Chen1, Ru Wang1, Xin Li1 and Pei-Jie Chen1
AbstractObjective: We performed a systematic review and meta-analysis to assess the effect of cognitive motor intervention (CMI) on gait and balance in Parkinson’s disease.Data sources: PubMed, Embase, Cochrane Library, CINAHL, Web of Science, PEDro, and China Biology Medicine disc.Methods: We included randomized controlled trials (RCTs) and non RCTs. Two reviewers independently evaluated articles for eligibility and quality and serially abstracted data. A standardized mean difference ± standard error and 95% confidence interval (CI) was calculated for each study using Hedge’s g to quantify the treatment effect.Results: Nine trials with 181 subjects, four randomized controlled trials, and five single group intervention studies were included. The pooling revealed that cognitive motor intervention can improve gait speed (Hedge’s g = 0.643 ± 0.191; 95% CI: 0.269 to 1.017, P = 0.001), stride time (Hedge’s g = -0.536 ± 0.167; 95% CI: -0.862 to -0.209, P = 0.001), Berg Balance Scale (Hedge’s g = 0.783 ± 0.289; 95% CI: 0.218 to 1.349, P = 0.007), Unipedal Stance Test (Hedge’s g = 0.440 ± 0.189; 95% CI: 0.07 to 0.81, P =0.02).Conclusions: The systematic review demonstrates that cognitive motor intervention is effective for gait and balance in Parkinson’s disease. However, the paper is limited by the quality of the included trials.
KeywordsCognitive motor intervention, Parkinson’s disease, gait, balance, systematic review
Received: 11 October 2014; accepted: 14 February 2015
1 Sport Medicine & Rehabilitation Center, Shanghai University of Sport, Shanghai, China
2 Department of Rehabilitation Medicine, Shanghai Punan Hospital, Shanghai, China
*These authors contributed equally to this study.
Corresponding author:Pei-Jie Chen, Sport Medicine & Rehabilitation Center, Shanghai University of Sport, Changhai Rd 399, Shanghai 200438, China. Email: [email protected]
578295 CRE0010.1177/0269215515578295Clinical RehabilitationWang et al.research-article2015
Article
Wang et al. 135
Therefore, falling could be prevented by training to perform cognitive motor tasks simultaneously.
Parkinson’s disease is a neurodegenerative dis-ease that often leads to movement impairments, particularly gait and balance dysfunction.3 de Bruin showed that cognitive motor intervention, conversing whilst the music accompanied walks, can improve the gait and motor function of patients with Parkinson’s disease.4 And a recent systematic review with 15 randomized controlled trials demonstrated that cognitive motor interven-tion could be effective for improving gait speed, stride length, cadence and balance function for patients with stroke.5 Many studies found exer-cise was an effective strategy for improving gait and balance function.6–8 However, the effect of cognitive motor intervention on the gait and bal-ance of Parkinson’s disease patients remains unclear.
A published systematic review,9 which included 28 articles, reported that limited evidence is availa-ble on the ability of cognitive motor intervention to promote physical function in patients with neuro-logical impairments. And another systematic review, which covered 30 randomized controlled trials with 1,206 subjects, showed that cognitive motor inter-vention was more effective than no intervention or single-task exercise for improving gait and balance function in older people.10 However, this review did not focus on Parkinson’s disease.
To date, no systematic review or meta-analysis has been conducted on cognitive motor interven-tion in relation to the gait and balance function of patients with Parkinson’s disease. Moreover, the extent of cognitive motor intervention’s effective-ness to improve the gait and balance in Parkinson’s disease remains unclear. Thus, the aim of this sys-tematic review and meta-analysis is to assess the effect of cognitive motor intervention for gait and balance functionin Parkinson’s disease.
Methods
Relevant articles dated June 1980 to January 2015 were identified from the following databases: PubMed, Embase, Cochrane Library, Ebsco (CINAHL), Web of Science, PEDro, and China
Biology Medicine disc. The electronic search strategies for all of the databases are provided in supplementary material Appendix 1. Manual searching was also performed. The protocol was registered on the international prospective register of systematic reviews (PROSPERO registration number: CRD42012002606).
Inclusion criteria were as follows: types of stud-ies were randomized controlled trials (RCTs) and non-RCTs; we included studies on patients with Parkinson’s disease; types of outcome measures were gait variables, such as gait speed and stride length, and balance function, such as Berg Balance Scale, center of pressure sway. Inclusion criteria interventions: (1) subjects who performed cogni-tive motor intervention were compared with those who underwent other therapies or no intervention; (2) subjects who performed cognitive motor inter-vention and were assessed before and after treat-ment. In cognitive motor intervention, subjects perform a motor task (e.g., balance exercise) while accomplishing a cognitive task exercise (e.g., addi-tion/subtraction questions, 8 + 5 = 13).2 Other forms of feedback and attention strategies can also be included in cognitive motor exercise, such as the use of virtual reality techniques and electronic gaming (e.g., Wii).9
Two authors independently used the same selec-tion criteria to screen titles, abstracts, and full papers of the relevant articles. Studies that failed to meet the inclusion criteria were removed. Any disagree-ment is resolved through discussion. A third author was consulted if any disagreement persisted.
A standardized form was used to extract the data from the included studies. The following data were extracted: study characteristics (e.g., author and year), participant characteristics (e.g., age and number of subjects), description of interventions, duration of trial period, and types of outcomes assessed. The data extraction was performed by the same two authors who selected the studies.
The Physiotherapy Evidence Database scale11 (with scores from 1 to 10) was used to assess the quality of the RCTs and non-RCTs with a control arm. We used modified Downs and Black tool12 to evaluate the quality of the single-group interven-tional studies. The modified Downs and Black
136 Clinical Rehabilitation 30(2)
tool comprised 27 questions about study descrip-tion, external validity, internal validity, and statis-tical power.
Two review authors independently used a stand-ardized assessment form to assess the methodo-logical quality of each study. A third author was consulted if any disagreement occurred.
A standardized mean difference (SMD) ± stand-ard error and 95% confidence interval (CI) were calculated for each study by using Hedge’s g to quantify the treatment effect. The means and stand-ard deviations could be estimated if the data are reported in a graph rather than a table. Authors were contacted if their standard deviations were not provided. Only the data from the cognitive motor intervention group were used in the pooled analyses if the trials estimated the treatment con-trast of cognitive motor intervention versus an alternative intervention.
We used the Comprehensive Meta-analysis soft-ware (version 2.0, Biostat, Englewood, NJ, USA)13 to analyze effect sizes, forest plots, and heteroge-neity. Cohen14 suggested that an effect size greater than 0.5 is large, that ranging from 0.2 to 0.5 is moderate, and that lower than 0.2 is small. Q statis-tic and I2 statistic were used to assess heterogeneity among the studies. We used the random effects model. We considered P < 0.05 to be statistically significant. If a meta-analysis was not possible, the results from the clinical trials were described qualitatively.
Results
Figure 1 shows the process of identifying eligible trials. Basing on their titles and abstracts, we included 43 potentially eligible studies (n = 181 patients) from 1048 identified records. After the full papers were reviewed, nine articles 9, 15–22 satis-fied the inclusion criteria. The remaining 34 trials were excluded, because the participants considered had other neurological illness (e.g., cognitive impairment and stroke), no intervention or other interventions. Protocol articles were also excluded. Four RCTs conducted a comparison between an intervention group (cognitive motor intervention) and a control group (no treatment or other
interventions). Five articles were single-group intervention trials, in which all of the subjects were subjected to cognitive motor intervention. Table 1 presents the characteristics of each included study.
We used the Physiotherapy Evidence Database scale (with scores from 1 to 10) to assess the meth-odological quality of RCTs. The PEDro score (mean ± SD) for the RCTs was 5.5±1. Three arti-cles9,15,16 attempted to blind the assessors to the allocated treatment; one article17 reported alloca-tion concealment; one article15 performed inten-tion-to-treat analysis; and no article blinded the subjects and the therapist. The modified Downs and Black tool was used to evaluate the quality of the single-group interventional studies. The D owns and Black score (mean ± SD) for the single-group interventional studies was 15.5±1.30.
Gait variables: three studies9,18,19 with six com-parisons were included to assess the effect of cog-nitive motor intervention on gait speed. The results showed that cognitive motor intervention improves the gait speed of patients with Parkinson’s disease (Hedge’s g = 0.643 ± 0.191; 95% CI: 0.269 to 1.017, P = 0.001) (Figure 1A). Two studies 9,18 with four comparisons were included to assess the effect of cognitive motor intervention on stride length. We found that stride length presented no signifi-cant difference between pre- and post-intervention in Parkinson’s disease (Hedge’s g = 0.245 ± 0.181; 95% CI: –0.110 to 0.600, P = 0.176) (Figure 2B). Three studies9,18,19 with six comparisons were included to assess the effect of cognitive motor intervention on stride time. The results showed that cognitive motor intervention improves stride time (Hedge’s g = −0.536 ± 0.167; 95% CI: –0.862 to –0.209, P = 0.001) (Figure 2C). One study9 with two comparisons was included to estimate the effect of cognitive motor intervention on cadence. The results showed that cadence exhibited no sig-nificant difference between pre- and post-interven-tion (Hedge’s g = 0.484 ± 0.308; 95% CI: –0.118 to 1.087, P = 0.115) (Figure 2D).
Balance function: three studies9,16,18 were included to assess the effect of cognitive motor intervention on the Unified Parkinson’s Disease Rating Scale. We found that cognitive motor inter-vention improves Unified Parkinson’s Disease
Wang et al. 137
Figure 1. Flow chart of the study selection procedure.
138 Clinical Rehabilitation 30(2)
Tab
le 1
. C
hara
cter
istic
s of
incl
uded
stu
dies
.
Stud
y, s
tudy
typ
ePa
tient
s ch
arac
teri
stic
Inte
rven
tion
Dur
atio
n of
tri
al
peri
odO
utco
me
Qua
lity
asse
ssm
ent
Yen
201
115
RC
TSo
urce
: hos
pita
l 42
patie
nts
(G1=
14, G
2=14
, G3=
14).
Mea
n ag
e (S
D):
G1=
70.4
y (
6.5)
, G
2=70
.1 y
(6.
9), G
3=71
.6 y
(5.
8)H
oehn
and
Yah
r st
ages
: 2 t
o 3
G1:
cog
nitiv
e m
otor
ex
erci
seG
2: c
onve
ntio
nal b
alan
ce
trai
ning
G3:
No
inte
rven
tion
Tw
ice
a w
eek
for
6 w
eeks
Bala
nce
perf
orm
ance
(C
OP
sway
)PE
Dro
: 7
de B
ruin
2010
9
RC
T
Sour
ce: n
ot s
peci
fied
22 p
atie
nts
(G1=
11, G
2=11
).M
ean
age
(SD
): G
1=64
.1 y
(4.
2),
G2=
67.0
y (
8.1)
Hoe
hn a
nd Y
ahr
stag
es: 2
to
3
G1:
cog
nitiv
e m
otor
ex
erci
seG
2: r
egul
ar a
ctiv
ities
Thr
ee t
imes
a
wee
k fo
r 13
w
eeks
Gai
t (g
ait
spee
d,
stri
de le
ngth
, str
ide
time,
cad
ence
), U
PDR
S sc
ore
PED
ro: 5
Pom
peu
2012
16
RC
TSo
urce
: not
spe
cifie
d 22
pat
ient
s (G
1=11
, G2=
11).
Age
ran
ge: 6
0 to
85
yH
oehn
and
Yah
r st
ages
: 1 t
o 2
G1:
cog
nitiv
e m
otor
ex
erci
seG
2: b
alan
ce t
rain
ing
Tw
ice
a w
eek
for
7 w
eeks
Bala
nce
(BBS
, UST
) an
d U
PDR
S sc
ore
PED
ro: 5
Ma
2011
17
RC
TSo
urce
: hos
pita
l 31
patie
nts
(G1=
17, G
2=16
).A
ge r
ange
: 50
to 7
5H
oehn
and
Yah
r st
ages
: 2 t
o 3
G1:
cog
nitiv
e m
otor
ex
erci
seG
2: c
onve
ntio
nal b
alan
ce
trai
ning
1 ho
ur p
er t
rail
for
60 t
rails
Mov
emen
t tim
ePE
Dro
: 5
Mir
elm
an20
1118
Sing
le g
roup
in
terv
entio
n tr
ail
Sour
ce: n
ot s
peci
fied
20 p
atie
nts.
Age
ran
ge: 5
5 to
79
Hoe
hn a
nd Y
ahr
stag
es: 2
to
3U
PDR
S m
otor
sco
re m
ean
(SD
) =
26
.5 (
7.6)
Cog
nitiv
e m
otor
exe
rcis
eT
hree
tim
es a
w
eek
for
6 w
eeks
Gai
t (g
ait
spee
d,
stri
de le
ngth
, str
ide
time)
,bal
ance
(FS
ST)
and
UPD
RS
scor
e
Dow
ns a
nd
Blac
k: 1
5
Yog
ev 2
0121
9
Sing
le g
roup
in
terv
entio
n tr
ail
Sour
ce: h
ospi
tal 7
pat
ient
s.A
ge r
ange
: 50
to 9
0H
oehn
and
Yah
r st
ages
: 2 t
o 3
Cog
nitiv
e m
otor
exe
rcis
eT
hree
tim
es a
w
eek
for
4 w
eeks
Gai
t (g
ait
spee
d,
stri
de t
ime)
Dow
ns a
nd
Blac
k: 1
6
(Con
tinue
d)
Wang et al. 139
Stud
y, s
tudy
typ
ePa
tient
s ch
arac
teri
stic
Inte
rven
tion
Dur
atio
n of
tri
al
peri
odO
utco
me
Qua
lity
asse
ssm
ent
Mha
tre
2013
20
Sing
le g
roup
in
terv
entio
n tr
ail
Sour
ce: h
ospi
tal 1
0 pa
tient
s.M
ean
age:
67.
1 y
Hoe
hn a
nd Y
ahr
stag
es: 2
.5 t
o 3
Cog
nitiv
e m
otor
exe
rcis
eT
hree
tim
es a
w
eek
for
8 w
eeks
Bala
nce
(BBS
, D
GI,S
RT
, ABC
, CO
P sw
ay)
Dow
ns a
nd
Blac
k: 1
7
Escu
lier
2012
21
Sing
le g
roup
in
terv
entio
n tr
ail
Sour
ce: n
ot s
peci
fied
11 p
atie
nts.
Age
ran
ge: 4
8 to
80
yU
PDR
S m
otor
sco
re m
ean
(SD
) =
18
.4 (
7.6)
Cog
nitiv
e m
otor
exe
rcis
eT
hree
tim
es a
w
eek
for
6 w
eeks
Bala
nce
(ST
ST,
TU
GT
, PO
MA
, CBM
, A
BC, U
ST, 1
0m w
alk
test
)
Dow
ns a
nd
Blac
k: 1
4
dos
Sant
os20
1222
Sing
le g
roup
in
terv
entio
n tr
ail
Sour
ce: h
ospi
tal 1
6 pa
tient
s.M
ean
age
(SD
): 68
.6 y
(8.
0)H
oehn
and
Yah
r st
ages
: 1 t
o 2
Cog
nitiv
e m
otor
exe
rcis
eT
wo
times
a
wee
k fo
r 7
wee
ksBa
lanc
e (F
RT
)D
owns
and
Bl
ack:
14
ABC
: Act
iviti
es-S
peci
fic B
alan
ce C
onfid
ence
sca
le, B
BS: B
erg
Bala
nce
Scal
e, C
BM: C
omm
unity
Bal
ance
and
Mob
ility
ass
essm
ent,
CO
P: C
ente
r of
pre
ssur
e, D
GI:
Dyn
amic
Gai
t In
dex,
FR
T: F
unct
iona
l Rea
ch t
est,
FSST
: Fou
r Sq
uare
Ste
p T
est,
PED
ro: P
hysi
othe
rapy
Evi
denc
e D
atab
ase,
PO
MA
: Tin
etti
Perf
orm
ance
Ori
ente
d M
obili
ty A
sses
smen
t, R
CT
: ra
ndom
ized
con
trol
led
tria
l, SR
T: S
harp
ened
Rom
berg
Tes
t, ST
ST: S
it-to
-Sta
nd t
est,
TU
GT
: Tim
ed U
p an
d G
o te
st, U
PDR
S: U
nifie
d Pa
rkin
son’
s D
isea
se R
atin
g Sc
ale,
UST
: U
nipe
dal S
tanc
e T
est.
Tab
le 1
. (C
ontin
ued)
140 Clinical Rehabilitation 30(2)
Figure 2. Meta-analyses of cognitive motor intervention on gait function. A: gait speed, B: stride length, C: stride time and D: cadence. 95% CI=95% confidence intervals. CMI: cognitive motor intervention.*represents the performance under dual task test condition.
Wang et al. 141
Rating Scale (Hedge’s g = −0.492 ± 0.21; 95% CI: –0.903 to –0.081, P = 0.019) (Figure 3A). Two stud-ies15,20 with four comparisons were included to assess the effect of cognitive motor intervention on center of pressure sway. We found that center of pressure sway significantly improved between pre- and post-intervention (Hedge’s g = −0.438 ± 0.071; 95% CI: –0.576 to –0.299, P < 0.001) (Figure 3B). Two studies16,20 were included to assess the effect of cognitive motor intervention on Berg Balance Scale. The results showed that cognitive motor interven-tion improved Berg Balance Scale after intervention (Hedge’s g = 0.783 ± 0.289; 95% CI: 0.218 to 1.349, P = 0.007) (Figure 3C). Two studies 16,21 with four comparisons were included to assess the effect of cognitive motor intervention on Unipedal Stance Test. We found that Unipedal Stance Test signifi-cantly improved between pre- and post-intervention (Hedge’s g = 0.440 ± 0.189; 95% CI: 0.07 to 0.81, P =0.02) (Figure 3D).
These studies assessed the effect of cognitive motor intervention on different outcomes, demon-strating that cognitive motor intervention could improve the Four Square Step Test,18 the Dynamic Gait Index,20 the Sit-to-Stand test,21 the Timed Up and Go test,21 the Tinetti Performance Oriented Mobility Assessment,21 the 10 m walk test,21 and the Community Balance and Mobility assess-ment.21 However, no significant difference was found for Sharpened Romberg Test20 between pre- and post-intervention.
Discussion
This systematic review and meta-analysis of arti-cles from four RCTs and five single-group inter-ventional studies, which included 181 subjects, verified the effect of cognitive motor intervention in Parkinson’s disease. Cognitive motor interven-tion was found to significantly benefit the follow-ing outcomes: gait speed, stride time, Unified Parkinson’s Disease Rating Scale, center of pres-sure sway, Berg Balance Scale, Unipedal Stance Test, Four Square Step Test, Dynamic Gait Index, Sit-to-Stand test, Timed Up and Go test, Tinetti Performance Oriented Mobility Assessment, 10 m walk test, and Community Balance and Mobility
assessment. The sizes of the majority of the observed effects between pre- and post-interven-tion were predominantly not large. However, the levels of improvements for gait speed, Unified Parkinson’s Disease Rating Scale, center of pres-sure sway area, Berg Balance Scale, Dynamic Gait Index, Sit-to-Stand test, Timed Up and Go test, 10 m walk test, and Tinetti Performance Oriented Mobility Assessment may signify clinical impor-tance in Parkinson’s disease. Moreover, no adverse events for cognitive motor intervention were found in nine studies.
Various exercise interventions are used to improve the gait and balance function of patients with Parkinson’s disease. Previous most system-atic reviews and meta-analyses23–26 have focused on motor exercise (e.g., resistance exercise and balance exercise). And previous5, 8, 9, 10, 27, 28 sys-tematic reviews of cognitive motor intervention have either focused on qualitative synthesis or have not selected subjects with Parkinson’s dis-ease. However, this work is the first systematic review and meta-analysis that estimates the effects of cognitive motor intervention on gait and bal-ance function in Parkinson’s disease. Compared with previous reviews, the present systematic review and meta-analysis only included subjects with Parkinson’s disease for all articles. Most of the included studies were newly published. Moreover, we performed a meta-analysis of the effects of cognitive motor intervention between pre- and post-intervention of patients with Parkinson’s disease. We conducted a wide range of electronic search for the systematic review.29. No restrictions were placed on language or publica-tion date. Study selection, data extraction, and quality evaluation were independently performed by two authors to minimize transcription errors and bias. In view of the abovementioned points, the results of our meta-analysis are considered extremely robust.
However, several limitations were found in our review. First, high-quality studies remained inade-quate despite our efforts to cover most of the studies within the last three years in our review. Four RCTs and five single-group interventional studies were found. According to their PEDro score, all of the
142 Clinical Rehabilitation 30(2)
Figure 3. Meta-analyses of cognitive motor intervention on balance function. A: Unified Parkinson’s Disease Rating Scale (UPDRS), B: Center of pressure (COP) sway, C: Berg balance scale (BBS) and D: Unipedal Stance Test (UST). 95% CI=95% confidence intervals. CMI: cognitive motor intervention.*represents the performance under dual task test condition. # represents the performance under eye close.
Wang et al. 143
RCTs were of moderate quality. Only one study con-ducted concealed allocation and intention-to-treat analyses. All studies failed to blind the subjects and therapists. Three studies attempted to blind asses-sors. Second, only a limited number of comparisons (one to three) were made in the systematic review with regard to the effect of cognitive motor interven-tion on the following outcomes: cadence, Unified Parkinson’s Disease Rating Scale, Berg Balance Scale, Four Square Step Test, Dynamic Gait Index, Sit-to-Stand test, Timed Up and Go test, Tinetti Performance Oriented Mobility Assessment, 10 m walk test, and Community Balance and Mobility assessment. In fact, the number of articles may be too small to discover the differences between pre- and post-intervention on these outcomes. Furthermore, the total number of subjects was small for the systematic review. Slight differences between pre and post-intervention were also difficult to esti-mate. Third, we intended to perform the meta-analy-sis on long-term gait and balance. However, most of the articles reported short follow-up periods and involved short intervention durations.
Overall, our systematic review lacked high-quality articles. The methodological standards must be improved in future studies to reduce pos-sible biases. We should improve the following standards: conduct random allocation and con-cealed allocation; attempt to blind assessors, therapists, and subjects; perform intention-to-treat analysis; and employ adequate follow-up period. Moreover, studies should be registered to reduce bias and should be conducted in accord-ance with the standards of clinical trials (e.g., the Consolidated Standards of Reporting Trials statement).30
As previously mentioned, most of the studies in this systematic review had small sample size. Thus, additional large-scale RCTs should be performed to evaluate the effect of cognitive motor interven-tion. To estimate the duration for any improvement outcome to be sustained for cognitive motor inter-vention, future studies should have follow-up ses-sions with longer durations. In addition, different training programs for cognitive motor intervention can be used, which may lead to different results. Therefore, a systematic review and meta-analysis
of different cognitive motor interventions should be conducted to determine the optimal intervention program for patients with Parkinson’s disease.
The results of our systematic review and meta-analysis show that cognitive motor intervention can significantly improve the following outcomes: gait speed, stride time, Unified Parkinson’s Disease Rating Scale, center of pressure sway, Berg Balance Scale, Unipedal Stance Test, Four Square Step Test, Dynamic Gait Index, Sit-to-Stand test, Timed Up and Go test, Tinetti Performance Oriented Mobility Assessment, 10 m walk test, and Community Balance and Mobility assessment. Therefore, our review results should be useful for patients with Parkinson’s disease, health-care decision makers, and medical staff.
Clinical messages
•• Cognitive motor intervention is effective for gait and balance function in Parkinson’s disease.
•• In the future, it is necessary to have more high quality RCTs to confirm these results.
Acknowledgements
We would like to thank Prof Chetwyn Chan for his advice.
Conflict of interest
The authors declare that there is no conflict of interest.
Funding
This study was supported by the Key Laboratory of Exercise and Health Sciences (Shanghai University of Sport), Ministry of Education, Shanghai University of Sport; Ministry of Education, the First-class Disciplines of Shanghai Colleges and Universities (Psychology); Shanghai Committee of Science and Technology (14490503800); Shanghai Youth Science and Technology Sail Project (15YF1411400).
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