Journal of Parkinson’s Disease 7 (2017) 471–479 471

DOI 10.3233/JPD-171131
IOS Press

Research Report

Gastrointestinal Transit Time in Parkinson’s

Disease Using a Magnetic Tracking System
Karoline Knudsena,∗ , Anne-Mette Haaseb , Tatyana D. Fedorovaa , Anne Charlotte Bekkera ,
Karen Østergaardc , Klaus Kroghb and Per Borghammera
a Department of Nuclear Medicine and PET Centre, Aarhus University Hospital, Denmark
b Department of Hepatology and Gastroenterology, Aarhus University Hospital, Denmark
c Department of Neurology, Aarhus University Hospital, Denmark

Accepted 21 June 2017

Abstract.
Background: Symptoms from the gastrointestinal tract are highly prevalent in Parkinson’s disease (PD), but knowledge of
the underlying pathology is incomplete and valid objective markers on regional gastrointestinal function are limited.
Objective: The aims were to evaluate gastrointestinal transit time and motility in PD patients and controls.
Methods: Twenty-two PD patients and 15 controls were included. Gastric-, small intestinal-, and caecum-ascending colonic
transit times as well as colonic motility, defined as mass- and fast movements, were performed using the ambulatory 3D-Transit
system. Gastrointestinal transit time with radio opaque markers, gastric emptying scintigraphy, and subjective non-motor
symptoms were also evaluated.
Results: Using the 3D-Transit system, the patient group displayed significantly longer small intestinal- and caecum-ascending
transit times (p = 0.030 and p = 0.0063). No between-group difference was seen in gastric transit time (p = 0.91). Time to
first mass- and fast colonic movement were significantly increased in PD (p = 0.023 and p = 0.006). Radio opaque marker
gastrointestinal transit time was significantly increased in the patient group (p < 0.0001), whereas no difference was seen in
scintigraphic gastric emptying time (p = 0.68). Prevalence of constipation symptoms on the NMSQuest was 41% in PD and
7% in controls.
Conclusions: Significantly increased small intestinal- and caecum-ascending 3D-Transit times were detected in PD patients.
Also, time to first propagating colonic movement was increased. Radio opaque marker gastrointestinal transit time was
significantly delayed, but no difference was seen in gastric transit time and gastric emptying time. The present findings
highlight widespread intestinal involvement in PD increasing throughout the gastrointestinal tract.

Keywords: Constipation, gastrointestinal, non-motor symptom, Parkinson’s disease, transit time

INTRODUCTION (NMS) from the gastrointestinal (GI) tract including

Parkinson’s disease (PD) is now known to be a
multi-system disorder involving not only the cen-
tral nervous system (CNS), but also the peripheral
and enteric nervous systems. The majority of PD
patients experience autonomic non-motor symptoms
∗ Correspondence
to: Karoline Knudsen, BMLT MMDI,
Department of Nuclear Medicine and PET Centre, Noerrebrogade
44, building 10G, 6. Floor, DK-8000 Aarhus C, Denmark. Tel.:
+45 78462240; Fax: +45 78462260; E-mail: karoknud@rm.dk.
ISSN 1877-7171/17/$35.00 © 2017 – IOS Press and the authors. All rights reserved
constipation. These symptoms are often present at
an early prodromal stage, which lends support to the
hypothesis that PD pathology may initiate in the GI
tract, and subsequently spread to the CNS via auto-
nomic nerves [1, 2].
Symptoms from the upper and lower GI tract
can overlap and be difficult to distinguish. Differ-
ent objective methods are available for obtaining
data on GI transit time and motility, although
often restricted by lack of standardization, radiation
472 K. Knudsen et al. / Intestinal Transit Time in Parkinson’s Disease
exposure, cost, and invasiveness [3]. Furthermore,
the small intestine is not very accessible to exami-
nation. However, improved objective markers of GI
function may be essential to study small-intestinal
medication absorption and to obtain knowledge of
the underlying gut pathology and involvement in
PD. Gastric emptying time (GET) and total GI tran-
sit time (GITT) have previously been studied in
PD, but detailed data on regional intestinal tran-
sit and dysmotility are lacking, and specifically
the small intestine has received very little attention
[4, 5].
The 3D-Transit system is a novel method for
assessing GI regional transit times and motility pat-
terns based on the position of an ingested wireless
electromagnetic capsule. This ambulatory system
allows safe and well-tolerated GI examination under
near-normal physiological conditions in the patient’s
home environment [6]. The system provides unique
data on segmental transit times throughout the GI
canal, and can also assess certain colonic motility pat-
terns. It has been validated in healthy controls (HC)
and trialed in patients with various gastrointestinal
disorders [6–8]. However, no data on PD patients
have yet been published.
The study aims were to evaluate GI transit time and
motility in a group of PD patients and control subjects
using the novel 3D-Transit magnetic system.
METHODS
Ethics statement
The study was approved by the Central Den-
mark Region Committee on Health Research Ethics
and Danish Health and Medicines Authority (No.
1-10-72-255-14 and 2014112300). All participants
provided written informed consent.
Subjects
Twenty-two PD patients and 15 age- and sex-
matched controls without neurological disorders
were included. Gastric emptying scintigraphy was
performed in a subset of subjects (19 PD, 14
HC). All participants were unselected according to
presence or degree of constipation symptoms. Par-
ticipants were excluded if meeting the following
criteria: prior gastrointestinal surgery, gastrointesti-
nal disorders besides constipation (i.e. malignancy,
inflammatory bowel disorders, coeliac disease), sig-
nificant systemic disorders or medical conditions,
diabetes, endocrine disorders, psychiatric disease,
substance abuse, and pregnancy.
All PD patients were diagnosed according to the
UK Brain Bank criteria by movement disorder spe-
cialists [9]. All PD patients were on dopaminergic
medication. Median levodopa equivalent daily dose
(LEDD) was 626 mg (range 180–1750 mg). Specific
details on medication are provided in the online Sup-
plementary Table 1. Four patients were treated with
laxatives before and during the study (Psyllium, Mag-
nesium citrate, Macrogol 3350). Intake of proton
pump inhibitors were prohibited >3 days prior to
examinations.
Unified Parkinson’s Disease Rating Scale part III
(UPDRS-III) was performed in all patients after
>12 hours withdrawal of parkinsonian medication.
All other testing and questionnaires were performed
in the “on” state. Eleven patients had a previous
dopamine transporter SPECT (all pathological).
3D-Transit
The ambulatory 3D-Transit system (Motilis Med-
ica SA, Lausanne, Switzerland) includes a portable
detector, an ingestible wireless electronic capsule,
and analysis software (Fig. 1). An electromagnet and
a battery (lifetime ∼60 hours at 10 Hz sampling rate
or 120 hours at 5 Hz) are incorporated in each capsule
(21 mm × 8 mm). The electromagnetic field emitted
from the capsule is monitored by four sensors placed
in the portable detector and stored on a memory card.
By using an iterative algorithm, the electromagnetic
field is converted to space-time coordinates (position:
x, y, z; orientation angles: , θ). This allows evalua-
tion of capsule position in the gut as well as contractile
GI activity and progression dynamics. A thoracic res-
piratory belt and an accelerometer inside the detector
record artifacts due to breathing and posture change
[3, 6].
Transit time in each GI segment is determined by
changes in contraction frequency as follows: gastric
transit time (GTT): time from ingestion until fre-
quency change from 3 contractions per minute (cpm)
to 9–12 cpm; small intestinal transit time (SITT):
time from pyloric to ileocaecal passage (frequency
change from 6 to 3 cpm); caecum-ascending transit
time (CATT): time from ileocaecal entry to passage
of the hepatic flexure; colorectal transit time (CRTT):
time from ileocaecal passage until capsule exit coin-
cident with a bowel movement [6, 10]. Also, 2D
spatial information obtained by the continuous posi-
tion and orientation triangulation of the capsule was
 K. Knudsen et al. / Intestinal Transit Time in Parkinson’s Disease 473

Table 1
Demographic and clinical data of patients with Parkinson’s disease (PD) and control subjects
PD patients Controls P
Gender, male/female 15/7 11/4 1.0
Age, years 65.4 ± 6.9 64.4 ± 6 0.67
BMI 26.3 ± 2.5 27.7 ± 3.6 0.21
Disease duration, years 5.8 ± 4.1 – –
MDS-UPDRS (motor), off 21 (9–35) – –
Hoehn & Yahr stage I/II/III, off 1/19/2 – –
NMSQuest
Total score 13 (2–20) 1 (0–5) <0.0001
Constipation 9/22 (41%) 1/15 (7%) 0.028
Odor identification score 7 (1–11) 12 (7–15) <0.0001
MMSE score 29 (24–30) 29 (25–30) 0.55
3D-Transit time, min.
Stomach 165 (12–363) 161 (77–305) 0.91
Small intestine 400 (199–802) 295 (159–696) 0.030
Caecum-ascending colon in 24 h 821 (16–1076) 324 (1–1072) 0.0063
Total colon – 1128 (205–2835) –
Gastric emptying, min.**
T 1/2 50.1 ± 11.1 48.32 ± 13.9 0.68
Emptying rate >90% 166.5 ± 36.9 160.5 ± 46.2 0.68
Radio opaque markers, total number 31.7 ± 13.7 14.1 ± 8.4 <0.0001
Transit time, days 3.7 ± 1.4 1.9 ± 0.8 <0.0001
Data given as mean ± SD or median (range). *The “24 h” entry for controls reflects the caecum-ascending transit
time during the first 24 h recording. ∗∗ n = 19 PD and 14 controls. BMI, body mass index; MDS-UPDRS, Movement
Disorder Society-unified Parkinson’s disease rating scale; MMSE, Mini-Mental State Examination; NMSQuest,
Non-Motor Symptoms Questionnaire.

Fig. 1. 3D-Transit system. (A) Sensors in the detector plate register electromagnetic signals from the ingested capsule. A chest worn respiration
belt registers artifacts due to respiration. (B) Graphs displaying position (x, y, z) and orientation (, θ) of the capsule when passing the GI
tract. Upper left window shows capsule position in x-y direction according to the external monitor. Arrows mark the contraction frequency
of 3 per minute, characteristic of the stomach. Vertical line marks the shift in capsule position from stomach to small intestine. Yellow line
marks respiration. Green line marks accelerometer.

used to support the definition of segmental transit
times (Fig. 1B).
Mass movements in the colon and rectum, also
known as high-amplitude propagated contractions
(HAPCs) [11], was defined with the 3D-Transit
methodology as movements covering one or more
colorectal segments in ≤2 minutes (Fig. 3C) [10]. We
also defined a subtype of fast movements as appar-
ent propagating contractions covering less than one
colorectal segment in ≤2 minutes. Both categories of
movements were manually counted and registered for
each participant. The reader was blinded to clinical
category.
Gastrointestinal transit times
Gastric emptying time (GET) and total gastroin-
testinal transit time (GITT) were evaluated using
474 K. Knudsen et al. / Intestinal Transit Time in Parkinson’s Disease
scintigraphy and the radio opaque marker (ROM)
techniques, as described previously [12]. In short,
exponential gastric half-emptying time (T1/2 ) and
time to emptying rate >90% (T90 ) were calculated
from 1 min. abdominal scintigraphic images at 0,
30, 60, 90, 120, 150 and 180 min. after finishing
a standardized solid meal containing 19–37 MBq
99m Tc-labelled colloid [13]. Semi-automatic analy-
sis was performed using dedicated software (Hermes
Medical Solutions, Stockholm, Sweden).
GITT was defined as number of retained ROM on
a CT scan performed on day seven, after ingestion of
one capsule containing 10 ROM every morning for
six consecutive days. GITT was calculated using the
validated equation: GITT = (total ROM + 5)/10 [14].
A subset of the GET and GITT data was published
previously [12].
Clinical assessment
Clinical disease stage and motor function were
evaluated using the Hoehn and Yahr scale (H&Y) [15]
and UPDRS-III [16]. Subjective NMS were assessed
by the NMS questionnaire (NMSQuest), defining
constipation as presence of <3 bowel movements per
week and/or straining during the past month [17].
Olfactory function was tested with Sniffin’ Sticks 16-
item identification test (Burghart, Wedel, Germany)
[18] and cognitive function evaluated by the mini
mental state examination (MMSE) [19].
Protocol
To maximize valid comparison of methods, 3D
recordings were started immediately after the CT
scan and simultaneous to gastric scintigraphy. The
3D monitor is worn throughout the day and night,
which gives rise to some discomfort. This is particu-
larly true for PD patients with a poor quality of sleep.
Moreover, many PD patients have severely prolonged
total GITT, and would need to wear the monitor for up
to one week to obtain complete data sets. For this rea-
son, the present pilot study was restricted to a 24-hour
(range 22–26.5 h) recording period in the PD group.
The main objective was to assess the tolerability of
the system in PD, obtain data on small intestine tran-
sit time, and get preliminary data on perturbations in
colonic mass movements. In the control group record-
ings were performed until exit of the capsule from the
body. The participants were instructed not to eat or
drink for six hours after capsule ingestion to prevent
prolonged gastric emptying.
All participants kept a diary on defecation time,
time of food ingestion, sleep, and daily activities.
Time of meals were restricted to 8 a.m., 2 p.m.,
and 6.30 p.m., and intake of coffee, alcohol, and
soft drinks were prohibited throughout the recording
period. Also, sports and hard physical work were not
allowed. The detector was only removed for a short
period each day to allow the participants to shower.
Statistics
Statistical analyses were performed using Prism
6 (GraphPad Software, La Jolla California, USA).
Clinical and demographic data were interrogated
using unpaired two-way t-tests or equivalent non-
parametric tests as appropriate. Between-group
differences in segmental GI transit times were ana-
lyzed by unpaired Mann-Whitney test. The time
period from capsule entry into the colon to the first
mass movement/fast movement was analyzed using
Log-rank (Mantel-Cox) tests. In all subjects the cap-
sule had travelled at least to the ascending colon in
24 hours. We therefore performed a post hoc dichoto-
mous comparison of the location of the capsule after
exactly 24 hours using Fisher’s exact test, i.e. by con-
trasting “capsule in ascending colon” with “capsule
in more distal colon” in PD and controls, respectively.
Spearman rank correlation analyses were performed
as appropriate to evaluate associations between 3D-
Transit and scintigraphic GET.
RESULTS
Demographic and clinical data are listed in Table 1.
PD patients and controls were matched on gender,
age, and body mass index (BMI). No significant dif-
ference was seen in cognitive performance between
groups. The patients showed significantly lower
olfaction scores and significantly higher levels of sub-
jective constipation symptoms. A positive correlation
was seen between 3D GTT and scintigraphic GET in
the control group (p = 0.018) but not in the PD patients
(p = 0.34) (Supplementary Figure 1).
3D-Transit
3D-Transit examinations were well tolerated
without side effects. The patient group displayed
significantly longer SITT and CATT compared to
controls (Fig. 2). No between-group difference was
seen in GTT.
 K. Knudsen et al. / Intestinal Transit Time in Parkinson’s Disease 475

Fig. 2. (A) Median 3D-Transit data (minutes) in PD patients and healthy controls (HC). Note that the CATT in PD patients is markedly
underestimated (see main text). (B) Scatter plot of small intestine transit time in both groups. GTT = gastric transit time, SITT = small
intestinal transit time, CATT = caecum-ascending transit time. ∗ P = 0.030. ∗∗ P = 0.0063.

Fig. 3. (A) Time to first mass movement in PD patients and healthy controls (HC) during mean 14.6 hours recording in the colon. (B) Time
to first fast movement in PD patients and HC during mean 14.6 hours recording in the colon. (C) A mass movement in a control subject. The
capsule passes from the hepatic flexure (HF) through the transverse (T), splenic flexure (SF), descending (D), and sigmoid (S) segments to
the rectum (R) in ≤2 minutes. See inset for colon anatomy.

After 24 hours, the capsule had reached the colon
in all participants, and was present in the caecum-
ascending segment (17 PD, 2 HC), transverse (2 PD,
4 HC), descending (2 PD, 1 HC), and recto-sigmoid
segment (2 HC). The capsule had passed the total
GI tract in one PD and six HC. Thus, after 24-hour
monitoring, the capsule was situated in the caecum-
ascending segment in 17 PD and 2 HC and more
distally in 5 PD and 13 HC, amounting to a highly
significant difference (p = 0.0002; Fisher’s exact test).
Of note, since the capsule had not passed the ascend-
ing segment after 24 hours in 17 patients compared to
only two HC, the CATT listed in Table 1 is markedly
underestimated in the PD group.
The mean CATT in the PD patients during 24-
hour recording period was 14.6 hours. We therefore
restricted the analyses of time to first mass movement
and fast movement to the 14.6 hours colonic record-
ing period in both groups. During this period, the
time to first mass- and fast movement were signifi-
cantly increased in the patient group (p = 0.023 and
p = 0.006; Fig. 3).
The prevalence of subjective constipation symp-
toms was 41% in PD and 7% in controls (Table 1).
No significant difference was seen in SITT and CATT
between constipated and non-constipated patients
(see Table 2). Note that full CATT was only obtained
in five PD patients.
DISCUSSION
Using the ambulatory 3D-Transit system we report
exact SITT data in PD for the first time. The SITT was
476 K. Knudsen et al. / Intestinal Transit Time in Parkinson’s Disease
Table 2
3D-Transit and NMSQuest subjective constipation data in patients
with Parkinson’s disease
+ constipation – constipation
SITT 529 (199–802) 359 (267–761)
CATT 825 (294–1076) 817 (16–1058)
Data given in minutes as median (range). NMSQuest, non-motor
symptoms questionnaire; SITT, small intestinal transit time; CATT,
caecum-ascending transit time.
significantly increased compared to control subjects.
We also demonstrated a highly significant increase
in proximal colonic transit time, and a decrease in
colonic mass- and fast movements in the PD patients.
As previously reported, no difference was found in
gastric transit times with the 3D-Transit system or
emptying time with gold standard scintigraphy [20].
Most studies of early-to-moderate disease stage PD
patients support this finding of unaffected gastric
emptying when measured by scintigraphy, whereas
the 13 C breath test methodology tends to show a more
profound difference between early stage patients and
controls [4].
Transit times
Total and segmental transit times were generally
easily determined. Only minor interference on tran-
sit data was caused by body movements. This was
considered acceptable compared to the advantage of
ambulatory examination under near-normal physio-
logical conditions. Also, previously published data
showed acceptable day-to-day variation and inter-
observer agreement in determining segmental transit
times with the 3D-Transit system [6].
In support of our findings, a recent scintigraphy
study also reported significantly increased SITT in
PD patients compared to controls after ingestion
of an isotope filled capsule [21]. However, due to
methodological limitations and radiation exposure,
the capsule location on scintigraphic images were
determined only at a few time points precluding an
exact determination of SITT. In contrast, 3D-Transit
data allows a specific determination of the regional
transit in each GI segment. Also, Su and colleagues
recently reported delayed SITT in 20% of PD patients
measured by the wireless motility capsule, although
the study did not include control subjects for compar-
ison and CTT data was not published [22]. Overall,
delayed SITT in PD may have clinical implications
and could contribute to malabsorption of parkin-
sonian medication and the development of small
intestinal bacterial overgrowth (SIBO) [23, 24].
In six of the current control subjects, the capsule
had passed the entire GI tract within 24 hours. This
was the case for only one PD patient. The study
p-value
showed generally delayed CATT in the PD group,
0.55 but we cannot comment on transit times in the trans-
0.69
verse, descending, and rectosigmoid colon, since only
24-hour recordings were performed in the patient
group. In the present study, 17/22 (77%) PD patients
and 2/15 (13%) controls, the 3D capsule was situ-
ated in the caecum-ascending colonic segment after
24 hours, but based on the present data it is not
possible to evaluate the transit time in the more dis-
tal colonic segments measured by the 3D-Transit
system. Nevertheless, recently published ROM data
suggested that transit times in the transverse and
rectosigmoid colon is even more delayed as com-
pared to the ascending colon in PD patients [12]. Put
together, these findings indicate that colonic function
in PD is universally affected. The present study also
demonstrated that total GITT measured with ROM
was significantly increased in the patient group (see
Table 1). Correlation analyses between 3D and ROM
data for total GITT were not possible in this study,
as total 3D colonic transit was not obtained in the
patients. However, a good correlation between ROM
and 3D-Transit total GITT has previously been pub-
lished in healthy controls [6].
Fast- and mass movements
The time to first fast- and mass movement during
the initial 14.6 hours of colonic recording was signif-
icantly longer in the PD group. Of note, the results
may be somewhat biased by the limited recording
period in the patient group. Nevertheless, it has been
shown that mass movements are most often initiated
in the caecum-ascending part of the colon [25, 26],
giving rise to movement of colonic content through-
out the more distal segments. This means that even if
the capsule was situated in a more distal part of the
colon in the control group, the registered mass move-
ments would most probably have started proximally.
Also, both fast- and mass movements in the present
study were registered for a comparable time period of
14.6 hours in both groups. Supporting these findings,
a previous study reported decreased colonic motility
in patients with slow transit constipation, possibly
due to parasympathetic denervation [27].
Contributing factors
The relatively wide GITT range in the present
control group signifies considerable physiological
 K. Knudsen et al. / Intestinal Transit Time in Parkinson’s Disease
variation in non-symptomatic healthy subjects. A
day-to-day variation in GI transit measured by 3D-
Transit of up to 45% was previously demonstrated
in healthy subjects [6]. Therefore, multiple cap-
sule monitoring or consecutive monitoring of the
PD patients would provide more exact and specific
GI transit data. Moreover, treatment with dopamin-
ergic drugs in PD may contribute to constipation
[28, 29]. We recently showed a positive correlation
between LEDD and colonic volume in a group of PD
patients, indicating an impact of dopaminergic treat-
ment on GI function [12]. In contrast, Krogh et al.
showed a decrease in unsuccessful attempts at defe-
cation in PD patients using levodopa compared to
patients not using it, measured by a constipation ques-
tionnaire [30]. Such discrepancies in the literature
can now be investigated further using this real-
time capsule system, and further studies are needed
in populations of de novo untreated PD patients,
as well as to study the impact of dopaminergic
medications.
Functional gradients
Interestingly, Fig. 2A indicates a gradient of
increasing GI dysfunction from the proximal to the
distal GI tract. Early and severe damage to the
parasympathetic nervous system is well characterized
in PD [31], and recently we demonstrated decreased
PET signal in the small intestine and particularly
the colon in newly diagnosed PD patients using
the acetylcholinesterase marker 11 C-donepezil [20,
32]. In other words, a similar gradient of patholog-
ical signal decrease was seen on this PET tracer,
which may be a marker of the parasympathetic ner-
vous system. These gradients are reversed compared
to published studies of pathological ␣-synuclein
deposition, which demonstrated the greatest num-
ber of pathological inclusions in the proximal GI
tract [33, 34]. The authors interpreted these histolog-
ical findings to mean that the proximal gut is most
severely affected by disease-specific pathology. How-
ever, the relative scarcity of pathological ␣-synuclein
inclusions in more distal segments of the gut could
also be caused by a “dying-back” phenomenon, i.e.
that the colon shows fewer pathological inclusions
because of severe parasympathetic terminal loss [35,
36]. Similar inverse gradients of terminal loss and ␣-
synuclein inclusion density have been reported in the
heart and skin in PD patients [37, 38]. For the moment
this hypothesis remains speculative and is very diffi-
cult to prove, due to the challenges of demonstrating
477
parasympathetic nerve terminal loss on a background
of intrinsic enteric neurons, which are also mainly
cholinergic.
Subjective symptoms
The patient group presented significantly more
subjective NMS compared to controls, and signifi-
cantly higher constipation prevalence. No correlation
was seen between constipation and SITT. Correla-
tions with colonic transit were not tested, because
only 24-hour monitoring was performed, but previ-
ous publications have reported only minor or absent
correlations between subjective and objective GI data
in PD [5, 12].
Limitations
Only 24-hour 3D-Transit data was obtained in the
patient group. Thus, total colonic transit is not avail-
able. However, the primary goal of this study was
to trial the tolerability of the capsule system in a
PD population, and specifically to quantify SITT
in PD and also obtain initial data on colonic dys-
motility patterns. Moreover, total ROM-GITT data
was recently published showing highly significant
increased colonic transit time in the patient group,
so it was deemed less important to obtain full colonic
data sets in the PD patients [12].
The intake of food and beverage was not standard-
ized, laxatives were not paused during the study, and
intake of coffee was prohibited. Also, the participants
were allowed to live their normal daily life, all of
which might have affected the results. However, the
purpose was to examine the near-normal everyday
GI function, which requires preservation of daily life
routines. Also, laxative intake results in faster GI tran-
sit time, and a restriction would only have further
prolonged the capsule GI passage, resulting in even
more significant group differences.
The current study participants were not tested for
SIBO, which theoretically could affect small intesti-
nal transit time. However, it is unclear whether SIBO
is caused by delayed transit or may induce delayed
transit [23, 24]. As such, studies are needed to
establish the causal relationship between SIBO and
delayed SITT.
Colonic motility measured by fast- and mass move-
ments were manually determined, as an automated
procedure is not presently available. This might
have biased the results. Thus, all colonic movements
were carefully analyzed in relation to accelerometer
478 K. Knudsen et al. / Intestinal Transit Time in Parkinson’s Disease
and respiratory belt data, discarding changes not
explicitly related to colonic movement. Also, the
data were analyzed by an expert in the 3D-Transit
system, blinded to subject categories. Furthermore,
the capsule measures motility dynamically in rela-
tion to intestinal content. Thus, we speculate that
the capsule may travel a shorter distance during
a movement, therefore being categorized as a fast
movement, although it may be part of a mass move-
ment. The different movements remain to be defined
more accurately. Nevertheless, time to first propagat-
ing movement was in every case prolonged in the
patient group.
CONCLUSION
Using an ambulatory GI-Transit system, PD
patients showed significantly prolonged transit times
in the small intestine and in the proximal colon. Fur-
thermore, time to both first mass- and fast movement
in the PD patients were significantly increased. No
between-group difference was seen in gastric transit
time obtained with the 3D-Transit system and with
solid meal scintigraphy.
In conclusion, these first published results on real-
time 24-hour GI transit times in PD patients suggest
widespread slow transit times, which exhibits an
increasing gradient of dysfunction most significant
in the proximal colon, while gastric transit time
appeared normal. Further studies are needed to evalu-
ate patients in earlier disease stages and the influence
of anti-parkinsonian medication on GI motility.
ACKNOWLEDGMENTS
This work is supported by the Parkinson’s disease
foundation, Denmark and the foundation of July 2,
1984, Denmark.
FINANCIAL DISCLOSURES
Karoline Knudsen, Anne-Mette Haase, Tatyana D.
Fedorova, and Anne C. Bekker have nothing to dis-
close.
Karen Østergaard: Consultancies: Medtronic Inc.;
Honoraria: Medtronic Inc., UCB, Fertin Pharma
and AbbVie outside the submitted work; Grants:
Lundbeck Foundation. Danish Research council for
Independent Research. The Danish Parkinson Asso-
ciation.
Klaus Krogh: Advisory Boards: Coloplast, Den-
mark. Wellspect, Sweden. Nordic Lifesciences,
Canada. Almirall, Denmark.
Per Borghammer: Consultancies: F. Hoffman-La
Roche; Grants: Aarhus University PhD salaries.
SUPPLEMENTARY MATERIAL
The supplementary material is available in the
electronic version of this article: http://dx.doi.
org/10.3233/JPD-171131.
CONFLICT OF INTEREST
The authors have no conflict of interest to report.
REFERENCES
[1] Adams-Carr KL, Bestwick JP, Shribman S, Lees A, Schrag
A, & Noyce AJ (2016) Constipation preceding Parkinson’s
disease: A systematic review and meta-analysis. J Neurol
Neurosurg Psychiatr, 87, 710-716.
[2] Hawkes CH, Del Tredici K, & Braak HH (2007) Parkinson’s
disease: A dual-hit hypothesis. Neuropathol Appl Neuro-
biol, 33, 599-614.
[3] Grønlund D, Poulsen JL, Sandberg TH, Olesen AE, Madzak
A, Krogh K, Frøkjaer JB, & Drewes AM (2017) Established
and emerging methods for assessment of small and large
intestinal motility. Neurogastroenterol Motil, 29, e13008.
[4] Borghammer P, Knudsen K, & Brooks DJ (2016) Imaging
systemic dysfunction in Parkinson’s disease. Curr Neurol
Neurosci Rep, 16, 51.
[5] Knudsen K, Krogh K, Østergaard K, & Borghammer
P (2016) Constipation in parkinson’s disease: Subjective
symptoms, objective markers, and new perspectives. Mov
Disord, 32, 94-105.
[6] Haase AM, Gregersen T, Schlageter V, Scott MS, Demierre
M, Kucera P, Dahlerup JF, & Krogh K (2014) Pilot study
trialling a new ambulatory method for the clinical assess-
ment of regional gastrointestinal transit using multiple
electromagnetic capsules. Neurogastroenterol Motil, 26,
1783-1791.
[7] Haase AM, Gregersen T, Christensen LA, Agnholt J,
Dahlerup JF, Schlageter V, & Krogh K (2016) Regional
gastrointestinal transit times in severe ulcerative colitis.
Neurogastroenterol Motil, 28, 217-224.
[8] Gregersen T, Brock C, Haase A-M, Laurberg S, Drewes AM,
Grønbæk H, & Krogh K (2016) Rectal mechano-sensory
function in patients with carcinoid diarrhea. J Neurogas-
troenterol Motil, 22, 264-271.
[9] Hughes AJ, Daniel SE, & Lees AJ (2001) Improved accu-
racy of clinical diagnosis of Lewy body Parkinson’s disease.
Neurology, 57, 1497-1499.
[10] Gregersen T, Haase A-M, Schlageter V, Grønbæk H, &
Krogh K (2015) Regional gastrointestinal transit times in
patients with carcinoid diarrhea: Assessment with the novel
3D-transit system. J Neurogastroenterol Motil, 21, 423-432.
[11] Dinning PG, Smith TK, & Scott SM (2009) Patho-
physiology of colonic causes of chronic constipation.
Neurogastroenterol Motil, 21 (Suppl 2), 20-30.
 K. Knudsen et al. / Intestinal Transit Time in Parkinson’s Disease
[12] Knudsen K, Fedorova TD, Bekker AC, Iversen P, Østergaard
K, Krogh K, & Borghammer P (2017) Objective colonic
dysfunction is far more prevalent than subjective consti-
pation in Parkinson’s disease: A colon transit and volume
study. J Parkinsons Dis, 7, 359-367.
[13] Donohoe KJ, Maurer AH, Ziessman HA, Urbain JLC, Royal
HD, & Martin-Comin J (2009) Procedure guideline for adult
solid-meal gastric-emptying study 3.0. J Nucl Med Technol,
37, 196-200.
[14] Abrahamsson H, Antov S, & Bosaeus I (1988) Gastroin-
testinal and colonic segmental transit time evaluated by a
single abdominal x-ray in healthy subjects and constipated
patients. Scand J Gastroenterol, (Suppl 152), 72-80.
[15] Hoehn MM, & Yahr MD (1967) Parkinsonism: Onset, pro-
gression and mortality. Neurology, 17, 427-442.
[16] Goetz CG, Fahn S, Martinez-Martin P, Poewe W, Sampaio
C, Stebbins GT, Stern MB, Tilley BC, Dodel R, Dubois B,
Holloway R, Jankovic J, Kulisevsky J, Lang AE, Lees A,
Leurgans S, LeWitt PA, Nyenhuis D, Olanow CW, Ras-
col O, Schrag A, Teresi JA, van Hilten JJ, & LaPelle
N (2007) Movement Disorder Society-sponsored revision
of the Unified Parkinson’s Disease Rating Scale (MDS-
UPDRS): Process, format, and clinimetric testing plan. Mov
Disord, 22, 41-47.
[17] Chaudhuri KR, Martinez-Martin P, Schapira AHV, Stoc-
chi F, Sethi K, Odin P, Brown RG, Koller W, Barone P,
MacPhee G, Kelly L, Rabey M, MacMahon D, Thomas S,
Ondo W, Rye D, Forbes A, Tluk S, Dhawan V, Bowron
A, Williams AJ, & Olanow CW (2006) International multi-
center pilot study of the first comprehensive self-completed
nonmotor symptoms questionnaire for Parkinson’s disease:
The NMSQuest study. Mov Disord, 21, 916-923.
[18] Hummel T, Sekinger B, Wolf SR, Pauli E, & Kobal G (1997)
‘Sniffin’ sticks’: Olfactory performance assessed by the
combined testing of odor identification, odor discrimination
and olfactory threshold. Chem Senses, 22, 39-52.
[19] Folstein MF, Folstein SE, & McHugh PR (1975) “Mini-
mental state”: A practical method for grading the cognitive
state of patients for the clinician. J Psychiatr Res, 12, 189-
198.
[20] Gjerloff T, Fedorova T, Knudsen K, Munk OL, Nahimi A,
Jacobsen S, Danielsen EH, Terkelsen AJ, Hansen J, Pavese
N, Brooks DJ, & Borghammer P (2015) Imaging acetyl-
cholinesterase density in peripheral organs in Parkinson’s
disease with 11C-donepezil PET. Brain, 138, 653-663.
[21] Dutkiewicz J, Szlufik S, Nieciecki M, Charzyńska I,
Królicki L, Smektała P, & Friedman A (2015) Small intes-
tine dysfunction in Parkinson’s disease. J Neural Transm,
122, 1659-1661.
[22] Su A, Gandhy R, Barlow C, & Triadafilopoulos G (2017)
Utility of the wireless motility capsule and lactulose breath
testing in the evaluation of patients with Parkinson’s disease
who present with functional gastrointestinal symptoms.
BMJ Open Gastroenterol, 4, e000132.
[23] Tan AH, Mahadeva S, Thalha AM, Gibson PR, Kiew CK,
Yeat CM, Ng SW, Ang SP, Chow SK, Tan CT, Yong HS,
Marras C, Fox SH, & Lim SY (2014) Small intestinal bacte-
rial overgrowth in Parkinson’s disease. Parkinsonism Relat
Disord, 20, 535-540.
[24] Gabrielli M, Bonazzi P, Scarpellini E, Bendia E, Lauritano
EC, Fasano A, Ceravolo MG, Capecci M, Bentivoglio AR,
479
Provinciali L, Tonali PA, & Gasbarrini A (2011) Preva-
lence of small intestinal bacterial overgrowth in Parkinson’s
disease. Mov Disord, 26, 889-892.
[25] Dinning PG, Wiklendt L, Maslen L, Gibbins I, Patton V,
Arkwright JW, Lubowski DZ, O’Grady G, Bampton PA,
Brookes SJ, & Costa M (2014) Quantification of in vivo
colonic motor patterns in healthy humans before and after
a meal revealed by high-resolution fiber-optic manometry.
Neurogastroenterol Motil, 26, 1443-1457.
[26] Bharucha AE (2012) High amplitude propagated contrac-
tions. Neurogastroenterol Motil, 24, 977-982.
[27] Dinning PG, Wiklendt L, Maslen L, Patton V, Lewis H,
Arkwright JW, Wattchow DA, Lubowski DZ, Costa M, &
Bampton PA (2015) Colonic motor abnormalities in slow
transit constipation defined by high resolution, fibre-optic
manometry. Neurogastroenterol Motil, 27, 379-388.
[28] Borovac JA (2016) Side effects of a dopamine agonist
therapy for Parkinson’s disease: A mini-review of clinical
pharmacology. Yale J Biol Med, 89, 37-47.
[29] Park A, & Stacy M (2011) Dopamine-induced nonmotor
symptoms of Parkinson’s disease. Parkinsons Dis, 2011,
485063.
[30] Krogh K, Ostergaard K, Sabroe S, & Laurberg S (2008)
Clinical aspects of bowel symptoms in Parkinson’s disease.
Acta Neurol Scand, 117, 60-64.
[31] Braak H, Del Tredici K, Rüb U, de Vos RAI, Jansen Steur
ENH, & Braak E (2003) Staging of brain pathology related
to sporadic Parkinson’s disease. Neurobiol Aging, 24, 197-
211.
[32] Fedorova TD, Seidelin LB, Knudsen K, Schacht AC, Geday
J, Pavese N, Brooks DJ, & Borghammer P (2017) Decreased
intestinal acetylcholinesterase in early Parkinson disease:
An (11)C-donepezil PET study. Neurology, 88, 775-781.
[33] Gelpi E, Navarro-Otano J, Tolosa E, Gaig C, Compta Y,
Rey MJ, Martí MJ, Hernández I, Valldeoriola F, Reñé R,
& Ribalta T (2014) Multiple organ involvement by alpha-
synuclein pathology in Lewy body disorders. Mov Disord,
29, 1010-1018.
[34] Beach TG, Adler CH, Sue LI, Vedders L, Lue L, White
CL III, Akiyama H, Caviness JN, Shill HA, Sabbagh MN,
& Walker DG (2010) Multi-organ distribution of phospho-
rylated ␣-synuclein histopathology in subjects with Lewy
body disorders. Acta Neuropathol, 119, 689-702.
[35] Parkkinen L, Pirttilä T, & Alafuzoff I (2008) Applicability of
current staging/categorization of alpha-synuclein pathology
and their clinical relevance. Acta Neuropathol, 115, 399-
407.
[36] Duda JE (2004) Pathology and neurotransmitter abnormal-
ities of dementia with Lewy bodies. Dement Geriatr Cogn
Disord, 17(Suppl 1), 3-14.
[37] Donadio V, Incensi A, Piccinini C, Cortelli P, Giannoccaro
MP, Baruzzi A, & Liguori R (2016) Skin nerve misfolded
␣-synuclein in pure autonomic failure and Parkinson dis-
ease. Ann Neurol, 79, 306-316.
[38] Orimo S, Uchihara T, Nakamura A, Mori F, Kakita A, Wak-
abayashi K, & Takahashi H (2008) Axonal alpha-synuclein
aggregates herald centripetal degeneration of cardiac sym-
pathetic nerve in Parkinson’s disease. Brain, 131, 642-650.