Cognitive study on Chinese patients with idiopathic REM sleep behavior

disorder

Xudong Li, Zhi Zhou, Shuhong Jia, Chunlei Hou, Wenjing Zheng, Pei
Rong, Jinsong Jiao

PII: S0022-510X(16)30240-4
DOI: doi: 10.1016/j.jns.2016.04.047
Reference: JNS 14521

To appear in: Journal of the Neurological Sciences

Received date: 4 October 2015

Revised date: 23 April 2016
Accepted date: 25 April 2016

Please cite this article as: Xudong Li, Zhi Zhou, Shuhong Jia, Chunlei Hou, Wen-
jing Zheng, Pei Rong, Jinsong Jiao, Cognitive study on Chinese patients with idio-
pathic REM sleep behavior disorder, Journal of the Neurological Sciences (2016), doi:
10.1016/j.jns.2016.04.047

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 ACCEPTED MANUSCRIPT

Cognitive study on Chinese patients with idiopathic REM sleep behavior disorder
Xudong Lia, Zhi Zhoub, Shuhong Jiaa, Chunlei Houa,
Wenjing Zhenga, Pei Ronga, Jinsong Jiaoa
a
Department of Neurology, China-Japan Friendship Hospital, Beijing100029, China
b
Department of Senior Official Ward, China-Japan Friendship Hospital,

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Beijing100029, China

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Correspondence: Xudong Li, Department of Neurology, China-Japan Friendship
Hospital, Yinghua East Road, Chaoyang District, Beijing 100029, China

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E-mail: lixd73cj@163.com

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Tel: 0086-10-84205410
Running head: Cognition in iRBD
There are no conflicts of interest.

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The study was supported by the China-Japan Friendship Hospital (2014-4-QN-32).
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The corrections were labelled on red color.
Answers to Reviewer 4:
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The manuscript was edited by the highly qualified native English speaking editors at
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American Journal Experts again.

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Abstract
Aims: We investigated cognitive abnormalities using standard tests in Chinese
patients with idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD)
compared with those in normal controls.

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Methods: Twenty-three patients with iRBD and 23 normal controls were included in
this study. All of the participants underwent one night of video-polysomnography
(PSG) monitoring to certify REM sleep without atonia or abnormal behaviors. The
cognitive assessments were administered and scored according to a standard
procedure, including global cognitive screening and attention/processing speed,

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executive function, memory, language, and visuospatial ability testing.
Results: Patients with iRBD had similar scores of the Mini Mental State Examination

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(MMSE) but lower Montreal Cognitive Assessment (MoCA) scores compared with
controls (p＞0.05, p=0.013). The iRBD patients performed poorly on verbal memory

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tests, which included immediate recall (p＜0.001), delayed recall (p＜0.001), and

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false recognitions (p=0.002) of the Rey Auditory Verbal Learning Test (RAVLT).
The visual memory and visuospatial abilities were also impaired in iRBD patients, as
reflected by the copy (p=0.005) and immediate (p=0.004) and delayed (p=0.003)

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recall of the Rey-Osterrieth complex figure, although no difference was found after
Bonferroni correction. The duration of RBD was 6.98±8.10 years. After controlling
for age, the duration of RBD was only correlated with the Trail Making Test B
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(r=0.613, p=0.045) and block design (r=-0.667, p=0.025).
Conclusions: Impaired verbal memory was observed in iRBD patients who identified
as Chinese. MoCA could detect cognitive abnormalities and serve as a screening scale.
The present study further confirmed cognitive deficits in iRBD as an early clinical
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marker in the prodromal stage of synucleinopathy.

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Key Words: idiopathic REM sleep behavior disorder, Cognition, Synucleinopathy,

Polysomnography
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1. Introduction
Rapid eye movement (REM) sleep behavior disorder (RBD) is characterized by a
loss of normal muscle atonia during REM sleep, resulting in undesirable and often
violent motor activity that is associated with dream content [1]. RBD generally affects
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adults, particularly men, aged 50 years and older. The violent nature of these
dream-enactment behaviors may cause severe injuries to individuals with RBD or
their bed partners [2]. There is growing evidence that this disorder is strongly
associated with synucleinopathies. RBD has been reported to occur in approximately
one-third of patients with Parkinson’s disease (PD), 80–95% of patients with multiple
system atrophy (MSA), and 50–80% of patients with dementia with Lewy bodies
(DLB) [3].
Patients with idiopathic RBD (iRBD) can develop synucleinopathies. The
estimated risk of neurodegenerative syndrome in iRBD patients is 17.7–33.1% at five
years, 40.9–75.7% at ten years, and 90.9% at 14 years [4, 5]. Pathological studies have
also shown that 94% of RBD patients with neurodegenerative disorders were
diagnosed with synucleinopathies [6]. Thus, iRBD likely represents the prodromal
stage of synucleinopathy.
Early neurodegeneration signs that possibly represent synucleinopthy, such as
electroencephalographic (EEG) slowing, mild Parkinsonism, olfaction dysfunction,

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color vision impairment, decreased striatal dopamine transporter uptake, substantia

nigra hyperechogenicity and reduced cardiac sympathetic innervation [7-11], have been
observed in patients with iRBD. However, the predictive value of each alteration for
the evolution of a neurodegenerative disease remains unclear. Impaired cognitive
performance in iRBD was also considered to be a manifestation of the
presymptomatic stage of neurodegeneration [12]. Increasing evidence has demonstrated

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that iRBD patients perform poorly on neuropsychological tests, but the results have

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varied with different studies. This discrepancy may be the consequence of a small
sample size and use of different cognitive tasks with variable sensitivities and

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specificities. Previous studies have focused on the populations of western countries.

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There has been no cognitive research of this condition in an Asian population,
particularly the Chinese population.
Here, we investigated cognitive abnormalities by standard tests in Chinese

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patients with iRBD and compared them with normal controls.
2. Methods
2.1 Subjects
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Twenty-three previously untreated patients with iRBD (19 men and 4 women;
mean age 72.48±6.78 years; range 60 to 88 years) were recruited from sleep disorder
clinics and the inpatient wards of our department between 2011 and 2014.
Twenty-three healthy controls (19 men and 4 women; mean age 72.52±6.72 years;
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range 62 to 86 years) were also selected from community and general neurological
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clinics and were matched for age, gender, and education. All participants underwent
routine assessments, including standardized history taking regarding sleep, physical
and neurological examinations, necessary laboratory tests, and CT or MRI. Based on
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one night of polysomnographic recordings and clinical history, the iRBD patients
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fulfilled the diagnostic criteria of the revised version of the International

Classification of Sleep Disorders (ICSD-2) [13], which includes excessive phasic or
tonic electromyography (EMG) activity during recorded REM sleep, a history of
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injurious or disruptive sleep behavior or documentation of abnormal behavior during

REM sleep on laboratory PSG, and no EEG epileptiform activity during REM sleep.
None of the iRBD patients had neurodegenerative disease, particularly PD or
dementia.
Exclusion criteria for the patients and controls included severe medical illness,
neurological disorder, psychiatric disease, head trauma, severe obstructive sleep apnea
and abnormalities on cranial MRI. Participants who were prescribed psychiatric drugs
were also excluded.
Participants and their families were given an explanation about the objectives of
this research, and written informed consent was obtained. The research was also
approved by the ethics committee of the China-Japan Friendship Hospital.
2.2 Polysomnography
All of the participants underwent one night of video-PSG monitoring recorded
by a 32-montage electroencephalograh (9200K; Nihon Kohden, Japan).
Polysomnography (PSG) included electroencephalography (EEG) with 16 montages,
and the leads were positioned according to the International 10–20 System (i.e., FP1,

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FP2, F3, F4, C3, C4, P3, P4, O1, O2, F7, F8, T3, T4, T5, T6, and a common reference)
to rule out epilepsy. Additionally, electrooculography (EOG) was used to record
horizontal and vertical eye movements. EMG was performed on the chin and the
bilateral triceps and anterior tibialis muscles, while electrocardiography and nasal
airflow through thermocouples that were located at the nostrils were measured.

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Thoracic and abdominal respiratory movements were measured using strain gauges.
Blood oxygen saturation was determined using a pulse oximeter with a finger probe,

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and snoring behavior was detected by a microphone. Sleep architecture and other
parameters were analyzed by Polysmith software and visual analysis. Sleep stages

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were scored with 30-sec epochs according to the criteria of Rechtschaffen and Kales

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[14]
. The presence of REM sleep without atonia was evaluated based on submental and
limb EMG findings according to the scoring criteria of the American Academy of
Sleep Medicine on movement in sleep [15], whereas vocalizations and motor events

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were confirmed via video and microphone.
2.3 Cognitive assessments
The cognitive assessments were administered and scored according to a
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standard procedure. The time required for test administration was approximately 90
minutes.
The test battery included global cognitive screening, attention/processing speed,
executive function, memory, language, and visuospatial abilities. The Mini Mental
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State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) were used
for global cognitive screening [16, 17]. The Digit Span Forward of the Wechsler Adult
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Intelligence Test-Revised Chinese version (WAIS-RC) [18], Trail Making Test A [19],
Stroop Color Word Test (modified version) Part A [19], and Digit Symbol Subtest of
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WAIS-RC [18] were used to assess processing speed/attention. Executive function was
assessed using the Chinese Version of Trail Making Test B [20] and Stroop Color
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Word Test (modified version) Part C [19]. The Digit Span Backward of WAIS-RC [18]
was used to assess working memory. The Rey Auditory Verbal Learning Test
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(RAVLT) included the sum of trials 1 to 5 and measured immediate recall, delayed
recall, and recognition to detect verbal memory [19]. Immediate and delayed recall of
the Rey-Osterrieth complex figure [21] was also used to measure visual memory. The
Semantic Category Verbal Fluency Test (fruit, vegetable, supermarket and animal) [19]
and the Boston Naming Test as modified by Cheung et al [22] assessed language ability.
Visuospatial skills were verified by the Rey-Osterrieth complex figure [21], the Block
Design of WAIS-RC [18], and the Clock Drawing Test (CDT) [23], including the
command and copy conditions, which were scored by the Rouleau system.
2.4 Statistical analysis
Statistical analyses were performed using SPSS, version 17.0 (SPSS Inc., USA).
The data are expressed as the mean±SD unless otherwise specified. The
Kolmogorov–Smirnov test was used to test the normality of distribution before
performing statistical analysis. Independent sample t-test was performed to assess
group differences in demographic and cognitive measures with a normal distribution.
The variables that were not distributed normally were analyzed using the
non-parametric Mann–Whitney U test. A comparison of sex ratio was performed by

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Chi-square test between groups. Spearman correlation coefficient (r) was used to
evaluate the correlations among the age, education, duration of RBD and cognitive
test scores. The significance level was set at p<0.05. Because multiple cognitive tests
were administered, Bonferroni correction for multiple tests was also applied (level of
significance set at 0.0022 accordingly).

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The raw scores were used to calculate Z scores (Z score = ((individual value) -
(control mean))/control SD), which were considered pathological when equal to or

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less than -1.5. Z scores of attention, executive function, language, visuospatial
function, working memory, verbal memory, and visual memory were calculated,

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respectively.

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3. Results
The demographic and clinical data of the patients with iRBD and normal
controls are summarized in Table 1. Age distribution, sex ratio and years of education

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were similar between the iRBD and normal controls (p＞0.05). All of the iRBD
patients and 22 control subjects were right-handed, except one control. The mean
duration of RBD was 6.98±8.10 years.
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Excessive phasic or tonic EMG activities were recorded during REM sleep
stage in all of the iRBD patients. The video and microphone showed obvious
vocalizations and motor events, including talks, shouts, arm raising, kicking,
punching, and elaborate movements, in most of the iRBD patients (78.3%). There
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were no similar events recorded by PSG in the control subjects.

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The results of individual neuropsychological tests are also provided in Table 1.

The patients with iRBD (28.20±1.70, 24.90±3.08) had similar scores on the MMSE
but lower MoCA scores compared with the controls (28.64±0.90, 26.91±1.51) (p＞
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0.05, p=0.013).
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iRBD patients performed poorly on verbal and visual memory tests. The total
words in trials 1 to 5 (p=0.05), immediate recall (p＜0.001), delayed recall (p＜0.001),
and false recognitions (p=0.002) of the RAVLT were found to be impaired.
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Immediate (p=0.004) and delayed (p=0.003) recall of the Rey-Osterrieth complex

figure were also poorly executed. The raw scores of the copy Rey-Osterrieth complex
figure (p=0.005) and the animal subset of the Semantic Fluency Test (p=0.019) were
lower than those of controls. The patients with iRBD performed worse on the Digit
Symbol Subtest of WAIS-RC (p=0.057), Trail Making Test B (p=0.082) and
command condition of CDT (p=0.087), although no difference were found.
After applying the Bonferroni correction for multiple tests, statistical
significance was observed only in immediate recall, delayed recall, and false
recognitions of the RAVLT.
The abnormal percentages of every cognitive domain were found by Z scores.
Three of twenty-three iRBD patients (13.0%) were found to be impaired in attention
domain, 5/23 patients (21.7%) in execution function, 3/23 patients (13.0%) in
language abilities, 5/23 patients (21.7%) in visuospatial ability, 5/23 patients (21.7%)
patients in working memory, 10/23 patients (43.5%) patients in verbal memory, 8/23
patients (34.8%) patients in visual memory were also pathological. Ten of
twenty-three iRBD patients (43.5%) were considered pathological in MoCA

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according to the Z score, whereas 13/23 patients (56.5%) were abnormal if traditional
26 was set as the cutoff.
Spearman correlation analysis indicated that there were significant correlations
between age and MoCA scores (r=-0.511, p=0.015), total words of trials 1 to 5
(r=-0.491, p=0.017), immediate recall (r=-0.505, p=0.014), delayed recall (r=-0.491,

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p=0.017), false recognitions of RAVLT (r=-0.436, p=0.042), Trail Making Test A
(r=0.690, p＜0.001) and B (r=0.689, p＜0.001), Digit Symbol Subtest of WAIS-RC

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(r=-0.548, p=0.008), and the CDT (r=-0.683, p=0.035) in the control subjects. In the
iRBD group, there were correlations between age and duration of RBD (r=0.475,

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p=0.022), MoCA scores (r=-0.582, p=0.007), immediate (r=-0.538, p=0.008) and

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delayed recall (r=-0.541, p=0.008) of the Rey-Osterrieth complex figure, Trail
Making Test B (r=0.592, p=0.004), Stroop Color Word Test Part A (r=0.504,
p=0.017), and the Boston Naming Test (r=-0.488, p=0.047). After controlling for age,

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the duration of RBD was correlated only with the Trail Making Test B (r=0.613,
p=0.045) and the Block Design of WAIS-RC (r=-0.667, p=0.025).
4. Discussion
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The present study first investigated the cognitive changes in iRBD patients in
China. MoCA was demonstrated to detect cognitive abnormalities and could serve as
a screening scale. Furthermore, neuropsychological evaluations confirmed the deficits
in verbal memory. Impairments in visual memory and visuospatial function were also
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observed, although no difference was found.

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As the previous study reported that the MoCA was superior to the MMSE in
detecting mild cognitive impairment (MCI) in iRBD patients, as indicated by good
sensitivity and excellent specificity [24], we found that the MoCA scores in the patients
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were notably lower than those of the control subjects. Even the MoCA scores
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(24.90±3.08) in this study were similar to those of previous studies (24.34±3.50),

although the patients in this study were older. The abnormal percentages were also
similar (56.5%: 55%) if traditional 26 was set as cutoff.
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Various studies have confirmed that episodic verbal memory and non-verbal
learning are the most affected domains in iRBD [25-29]. Our iRBD patients performed
worse on immediate recall, delayed recall and false recognitions of RAVLT. Poorer
performances on immediate and delayed recall of the Rey-Osterrieth complex figure,
which reflects visual memory, were also confirmed, although no difference was found
after Bonferroni correction. Episodic memory impairment was the core feature of AD.
Nevertheless, the deficit of episodic memory was also reported in DLB and PD,
although to a lesser degree than in AD [26]. The early stage of non-demented PD
patients showed episodic verbal memory deficits regardless of whether it was a
clinic-based or population-based study [30, 31]. Episodic memory impairments were
also found in very mild DLB patients (24-30 on MMSE) [32]. The memory disorders in
PD patients contributed to retrieval rather than storage failure, a finding that was
different from that of AD [33, 34]. The episodic memory impairment in very mild DLB
was also due to the deficit of retrieval, while poor memory might be a result of
impaired encoding as well retrieval with the progression of dementia [32]. Verbal
memory impairment in patients with RBD plus dementia has been documented and

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can occur independently of disease duration [35]. Our study found that immediate and
delayed recalls in iRBD were decreased, with relative preservation of correct
recognitions, suggesting a retrieval deficit. Increased false-positive recognitions may
be attributed to encoding impairment. The memory disorders of iRBD were consistent
with those of PD and DLB.

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Visuospatial impairment is a main feature of cognitive involvement in DLB. To
a lesser extent, the same impairment is present in PD [27], in which a progressive

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pattern is observed and dependent on disease severity. Deficits were also found in
visuospatial and visuoperceptual processing in PD patients with RBD compared with

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PD patients without RBD and with controls [28]. iRBD or RBD with PD was

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associated with perceptual closure dysfunction, and the sensory and attentional
aspects of visual information processing were unaffected [36]. Further computerized
tasks demonstrated that iRBD had visuoperceptive impairments that were unrelated to

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attentional, sensory, or phasic dysfunctions [37]. Our cognitive study indicated the
impairment of visuospatial abilities in iRBD, as noted by the copy of the
Rey-Osterrieth complex figure, although the significant difference disappeared after
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Bonferroni correction. Additionally, 21.7% of patients (5/23) were considered
pathological in visuospatial ability according to Z scores, but 47.8% (11/23) were
abnormal based on the copy of the Rey-Osterrieth complex figure. The block design
also had a negative correlation with the duration of iRBD. Some researchers have
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thought that controversial results on visuospatial impairment could be related to the

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extent of cognitive decline.

Attention deficit and executive dysfunction are typical manifestations of both
PD and DLB. Some studies have confirmed this in patients with iRBD [26, 28]. Our
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research only found that the duration of iRBD had an obvious negative correlation
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with the Trail Making B test.

Our iRBD patients presented predominantly episodic memory impairment,
which was different from that of previous studies. The results may reflect the
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heterogeneous cognitive presentations of the prodromal stage of synucleinopathy in

the Chinese population. The heterogeneity of cognitive changes was demonstrated in
PD patients, ranging from cognitively intact with rather high levels of performance in
each cognitive domain to very severely impaired [38].
The longitudinal studies that were performed at sleep disorder centers found
that iRBD was a significant risk factor for developing synucleinopathies. Most of the
patients (80.8%、82%) who were initially diagnosed with iRBD eventually developed
neurodegenerative disease such as PD or DLB, after a longer follow up [39, 40].
Meanwhile, a population-based study that included 651 cognitively normal subjects
between the ages of 70 and 89 years, including 44 individuals with baseline clinical
iRBD, was followed prospectively for a median of 3.8 years. Only one (2%) iRBD
patient developed PD, whereas 14 (32%) met the MCI criteria. The iRBD patients had
a 2.2-fold increased risk of developing MCI or PD over non-RBD patients [41]. In this
study, however, subjects with iRBD developed a cognitive disorder far more
frequently than a movement disorder, demonstrating the importance of performing
neuropsychological assessments to detect cognitive changes or MCI in iRBD patients.

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The core of the dysfunction in RBD is at the brainstem level, where it involves
the neuronal pontomedullary nuclei and networks, such as the locus coeruleus and
magnocellularis nucleus. The lesions of these networks result in REM sleep without
atonia and involve different neurochemical transmissions, such as cholinergic,
glutamatergic, glycine and GABAergic systems [42, 43]. Several brainstem structures

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that are impaired in RBD or PD project to the cerebral cortex and modulate its neural
activity. Cognitive deficits in iRBD may reflect dysfunctions of the associated cortex,

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which were found to correlate with neurophysiological and neuroimaging measures.
The presence of marked EEG slowing on spectral analysis may be indicative of the

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short-term development of MCI in iRBD [44]. iRBD patients with MCI showed EEG

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abnormalities, which were mainly characterized by slowing in the posterior cortical
regions. These findings are similar to those reported in DLB and PD [45]. Short-latency
afferent inhibition (SAI) of the motor cortex was significantly reduced in RBD

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patients compared with that in control subjects, which is thought to reflect the state of
subcortical cholinergic function, with SAI values being found to correlate with
deficits in verbal memory and executive function [46]. The mean SAI was also
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significantly reduced in PD with RBD patients compared with that in PD without
RBD patients and controls and correlated positively with neuropsychological tests [47].
Single-photon emission computed tomography indicated that cortical hypoperfusion
in the occipital, temporal, and parietal regions in patients with RBD and MCI were
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similar to that in patients with PDD or DLB [48]. Positron emission tomography (PET)
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studies have also found that glucose hypometabolism was mostly confined to the
primary visual cortex in patients with iRBD that did not convert to probable DLB,
whereas glucose hypometabolism involved the parietal and lateral occipital regions in
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patients with disease that converted [49]. Patients with iRBD exhibited decreased
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cortical thickness in the frontal cortex, lingual gyrus, and fusiform gyrus, as well as
reduced gray matter volume in the superior frontal sulcus [50]. Further BOLD-MRI
demonstrated altered nigrostriatal and nigrocortical correlations in patients with iRBD
[51]
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. These studies observed changes in cortical function that were consistent with
cognitive dysfunction.
There were some limitations to our study. First, the findings must be interpreted
with caution because of the small size of our sample. Second, although our
neuropsychological battery was relatively extensive, the patients were not selected
from the community but from clinics, which may have resulted in bias.
In summary, impaired verbal memory was readily observed in Chinese iRBD
patients. The MoCA could detect the cognitive abnormalities and serve as a screening
scale. The present study further confirmed that cognitive deficits in patients with
iRBD could serve as an early clinical marker in the prodromal stage of
synucleinopathy.

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Table 1 Demographic and cognitive results in iRBD patients and controls

Items iRBD Normal control t/ p
(n=23) (n=23)
Age (years) 72.48±6.78 72.52±6.72 -0.022 0.983
Gender 19/4 19/4 0 1.000

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(male/female)
Education 14.22±2.56 14.22±2.52 0 1.000

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(years)
RBD duration 6.98±8.10 4.133 ＜0.001*

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(years)

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MMSE 28.20±1.70 28.64±0.90 -1.051 0.300
MoCA 24.90±3.08 26.91±1.51 -2.646 0.013*
Digit Span 7.96±0.77 7.83±1.15 0.451 0.654

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Forward
Trail Making 59.04±32.47 51.70±22.20 0.896 0.375
Test A
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(seconds)
Stroop Color 16.45±6.09 16.61±5.03 -0.093 0.927
Word Test Part
A (seconds)
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Digit Symbol 35.19±10.94 41.50±10.17 -1.960 0.057

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Trail Making 125.18±55.74 97.95±45.04 1.782 0.082

Test B
(seconds)
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Stroop Color 30.09±11.93 29.30±6.14 0.280 0.781

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Word Test Part

C (seconds)
Digit Span 4.87±1.58 4.96±1.02 -0.222 0.087
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Backward
sum of trials 1 36.87±9.29 42.48±9.56 -2.018 0.050
to 5 of RAVLT
immediate 7.61±2.86 10.74±2.28 -4.107 ＜0.001**
recall of
RAVLT
delayed recall 6.39±3.17 9.74±2.49 -3.981 ＜0.001**
of RAVLT
recognition of 13.04±2.25 13.73±1.42 -1.214 0.231
RAVLT
false 1.22±1.45 0.14±0.35 3.483 0.002**
recognition of
RAVLT
Immediate 18.80±8.26 25.26±5.75 -3.078 0.004*
recall of
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complex figure
delayed recall 18.20±7.73 24.54±5.56 -3.197 0.003*
of
Rey-Osterrieth
complex figure

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Semantic 10.95±3.29 12.83±2.48 -1.653 0.106
Category-fruit

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Semantic 13.71±4.11 14.61±4.21 -0.712 0.480
Category-

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vegetable

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Semantic 18.53±5.28 19.26±4.26 -0.485 0.630
Category-
supermarket

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Semantic 16.87±5.45 20.13±3.28 -2.460 0.019*
Category-
animal
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Boston 24.71±2.39 24.47±2.97 0.256 0.799
Naming Test
copy of the 32.87±3.05 34.96±1.15 -3.072 0.005*
Rey-Osterrieth
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Complex
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Figure
Block Design 29.62±6.51 32.09±6.90 -1.217 0.230
Clock Drawing 9.22±1.57 9.83±0.49 -1.779 0.087
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Test-comment
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Clock Drawing 9.82±0.53 9.82±0.41 0.029 0.977

Test-copy
**statistically significant applying the Bonferroni correction (p<0.0022); *
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statistically significant (p<0 05).

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Highlights

Cognitive abnormalities were investigated in Chinese patients with iRBD.

MoCA could detect cognitive abnormalities and serve as a screening scale.
The iRBD patients performed poorly on verbal memory tests.

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The visual memory and visuospatial abilities were also impaired in iRBD patients,
although no difference was found after Bonferroni correction.

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Cognitive deficits were an early clinical marker in the prodromal stage of
synucleinopathy.

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