BRIEF REPORT

Objectives: To investigate whether the Timed Up and

Timed Up and Go Test and the Go test is associated with PD.
Risk of Parkinson’s Disease: A Methods: We included 1,196,614 participants at
66 years of age who underwent the National Screen-
Nation-wide Retrospective ing Program for Transitional Ages for Koreans
Cohort Study between 2009 and 2014. Timed Up and Go test times
were classified into <10 and ≥ 10 seconds. Incidence
of PD was defined using claims data.
Jung Eun Yoo, MD,1 Wooyoung Jang, MD, PhD,2 Results: During the median follow-up period of
Dong Wook Shin, MD, DrPH, MBA,3,4* 3.5 years, participants with slow Timed Up and Go
Su-Min Jeong, MD,5,6,7 Hee-Won Jung, MD, PhD,8 test time had significantly increased risk of developing
Jinyoung Youn, MD, PhD,9,10 Kyungdo Han, PhD,11 and PD compared with those with normal Timed Up and
Bongseong Kim, BS11 Go test time (adjusted hazard ratio: 1.28; 95% confi-
dence interval: 1.20–1.37). Furthermore, participants
with an abnormal Timed Up and Go test result,
1
Department of Family Medicine, Healthcare System Gangnam defined as ≥ 20 seconds, had a significantly increased
Center, Seoul National University Hospital, Seoul, Republic of risk of PD compared with those with a normal Timed
Korea 2Department of Neurology, Gangneung Asan Hospital, Up and Go test result (adjusted hazard ratio: 2.18;
University of Ulsan College of Medicine, Gangneung, Republic of 95% confidence interval: 1.63–2.92).
Korea 3Department of Family Medicine, Samsung Medical Center, Conclusion: An indicator of subtle motor deficits, the
Sungkyunkwan University School of Medicine, Seoul, Republic of
Timed Up and Go test could be a prodromal marker
Korea 4Department of Clinical Research Design & Evaluation,
for the risk of PD development. © 2020 International
SAIHST, Sungkyunkwan University, Seoul, Republic of Korea
5
Department of Family Medicine, Seoul Metropolitan Government- Parkinson and Movement Disorder Society
Seoul National University Boramae Medical Center, Seoul, Republic
of Korea 6Department of Family Medicine, Seoul National University Key Words: mild parkinsonian signs; Parkinson’s
Health Service Center, Seoul, Republic of Korea 7Department of disease; prodromal Parkinson’s disease; Timed Up and
Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, Go test
USA 8Department of Internal Medicine, Seoul National University
Hospital, Seoul, Republic of Korea 9Department of Neurology,
Samsung Medical Center, Sungkyunkwan University School of
Medicine, Seoul, Republic of Korea 10Neuroscience Center,
Samsung Medical Center, Seoul, Republic of Korea 11Department
of Statistics and Actuarial Science, Soongsil University, Seoul,
Republic of Korea
Parkinson’s disease (PD) is identified by clinical diag-
nostic criteria that encompass various motor symptoms.1
Slight motor deficits precede clinical PD in prodromal
A B S T R A C T : Background: If mild parkinsonian PD patients and are very mild and therefore insufficient
signs can be a marker for Parkinson’s disease (PD)
to make a diagnosis for clinical PD. These subtle motor
development, an impaired Timed Up and Go test
(TUG) should also be a marker for prodromal PD. deficits, which have been termed mild parkinsonian signs
(MPSs), could be associated with the risk of PD.2,3
The Timed Up and Go test (TUG) is used to assess
-*Correspondence
- - - - - - - - - - - - - - -to:- - Dr.
- - - Dong
- - - - -Wook
- - - - -Shin,
- - - - Department
- - - - - - - - - -of- -Family
---------- physical performance and correlates with functional
mobility and gait speed.4 TUG could be significantly
Medicine/Supportive Care Center, Samsung Medical Center, Depart-
ment of Clinical Research Design & Evaluation, SAIHST, Sungkyunkwan associated with functional impairment and UPDRS
University, 81 Irwon-Ro, Gangnam-gu, Seoul 06351, South Korea; scores in PD patients.5 MPSs are defined by the pres-
E-mail: dwshin.md@gmail.com
ence of any UPDRS item scored as 1 or higher, and
Dr. Jung Eun Yoo and Dr. Wooyoung Jang contributed equally to the most patients with MPSs show symptoms in the posture
manuscript as co-first authors.
and gait domains,3 so an impaired TUG could be a
Relevant conflicts of interest/financial disclosures: Nothing to
report. plausible substitute for an MPS evaluation.
Full financial disclosures and author roles may be found in the online
Therefore, if MPS can be a marker for PD develop-
version of this article. ment, an impaired TUG should also be a marker for
Received: 14 January 2020; Revised: 19 March 2020; Accepted: 23 prodromal PD. In the present retrospective cohort
March 2020 study, the association between an impaired TUG with
Published online 00 Month 2020 in Wiley Online Library
the future risk of developing PD was investigated using
(wileyonlinelibrary.com). DOI: 10.1002/mds.28055 a large, population-based database.

Movement Disorders, 2020 1

Y O O E T A L

Materials and Methods
Study Setting
The National Health Insurance Service (NHIS) is a
single insurer in Korea. The NHIS database contains
information regarding patients’ use of medical facilities,
including International Classification of Diseases, Tenth
Revision (ICD-10) codes and prescribed medications
from outpatient clinics and hospitalizations. These data
are widely used in epidemiological studies.6 In addition,
the NHIS provides a free health screening program for
all beneficiaries aged >40 years and all employees
regardless of age, and the programs consist of a self-
questionnaire on health behavior, anthropometric mea-
surements, and laboratory testing.7 The National
Screening Program for Transitional Ages (NSPTA) is
offered to all beneficiaries and employees at 66 years of
age and includes geriatric assessments, such as TUG
and screening for depression and dementia.8
Study Population
The present study initially included 1,497,093 sub-
jects who were aged 66 years and participated in the
NSPTA between 2009 and 2014. Subjects who were
diagnosed with PD (n = 5,422) or parkinsonism
(n = 496) before the screening date were excluded; in
addition, subjects with other neurological diseases
TABLE 1. Baseline characteristics of the study population
which might affect TUG results (n = 69,148). In addi-
tion, subjects with end-stage renal disease (n = 11,087)
or any registered disabilities (n = 169,047), including
physical disabilities (e.g., spinal cord injury, limb ampu-
tation), brain impairment (cerebral palsy, stroke with
significant sequelae), communication impairment
(visual, hearing, and linguistic problems), and missing
at least one variable (n = 47,399), were excluded.
Finally, 1,196,614 eligible subjects were included for
analysis. The cohort was followed from baseline to the
date of incident PD or until the end of the study period
(December 31, 2016), whichever came first (Supporting
Information Fig. S1).
This study was approved by the Institutional Review
Board (IRB) of Samsung Medical Center (IRB File
No. SMC 2018-03-135). The IRB waived requirement for
written informed consent from patients because the data are
public and anonymized under confidentiality guidelines.
Exposure: TUG
As part of the NSPTA, TUG was conducted on the
examination day at each community clinic or hospital.9
For primary analysis, TUG results were classified into
binary responses (<10 and ≥ 10 seconds). Results were also
categorized as <10, 10 to 20, and ≥ 20 seconds for second-
ary analysis to confirm the dose-response relationship.
Although many different cutoffs for TUG times were

TUG Time

Total <10 sec ≥10 sec

(N = 1,196,614) (n = 888,438) (n = 308,176)

TUG time, sec 8.3  2.8 7.2  1.5 11.5  3.2

Sex, male 536,928 (44.9) 413,329 (46.5) 123,599 (40.1)
BMI, kg/m2 24.2  3.0 24.2  2.9 24.4  3.1
<18.5 24,763 (2.1) 18,160 (2.0) 6,603 (2.1)
18.5 to 23.0 385,230 (32.2) 290,425 (32.7) 94,805 (30.8)
23 to 25 337,725 (28.2) 253,488 (28.5) 84,237 (27.3)
25 to 30 407,734 (34.1) 298,237 (33.6) 109,497 (35.5)
≥ 30 41,162 (3.4) 28,128 (3.2) 13,034 (4.2)
Smoking status
Never 838,965 (70.1) 613,524 (69.1) 225,441 (73.2)
Former 207,703 (17.4) 162,440 (18.3) 45,263 (14.7)
Current 149,946 (12.5) 112,474 (12.7) 37,472 (12.2)
Alcohol consumption
None 856,226 (71.6) 628,217 (70.8) 228,009 (74.0)
Moderate (<30 g/d) 284,034 (23.7) 217,590 (24.5) 66,444 (21.6)
Heavy (≥30 g/d) 56,354 (4.7) 42,631 (4.8) 13,723 (4.5)
Regular physical activity, yes 303,655 (25.4) 232,052 (26.1) 71,603 (23.2)
Income, lowest quintile 277,655 (23.2) 203,840 (22.9) 73,815 (24.0)
Cognitive function, abnormal 158,067 (13.2) 113,571 (12.8) 44,496 (14.4)
Depressive mood 220,594 (18.4) 157,085 (17.7) 63,509 (20.6)
Diabetes mellitus, yes 231,850 (19.4) 168,352 (19.0) 63,498 (20.6)
Hypertension, yes 628,890 (52.6) 459,935 (51.8) 168,955 (54.8)
Dyslipidemia, yes 446,641 (37.3) 328,197 (36.9) 118,444 (38.4)
CKD, yes 127,434 (10.7) 91,595 (10.3) 35,839 (11.6)

Data are expressed as means  SD or n (%).

CKD, chronic kidney disease.

2 Movement Disorders, 2020

 T I M E D U P A N D G O T E S T A N D P A R K I N S O N ’ S D I S E A S E

suggested in previous studies (e.g., 13.5,10 15,11 and 20 sec-

1.28 (1.20, 1.37)

1.31 (1.18, 1.46)

1.26 (1.15, 1.37)

onds12), in the Korean NSPTA, TUG results are classified

Model 5

1.00

1.00

1.00
normal (<10 seconds), borderline (10–20 seconds), and
abnormal (≥20 seconds) according to expert consensus,
which were the same criteria used in previous studies.13

Study Outcome: PD Case Ascertainment

1.30 (1.22, 1.40)

1.33 (1.20, 1.48)

1.28 (1.17, 1.40)

The primary endpoint was newly diagnosed PD during

Model 4

1.00

1.00

1.00
the follow-up period. PD was defined based on ICD-10
code for PD (G20) and the registration code for PD
(V124), which was implemented by the NHIS in 2006 to
enhance the health coverage for rare intractable diseases
(RIDs), including PD, as used in previous studies.14 To

1.31 (1.23, 1.41)

1.34 (1.20, 1.49)

1.30 (1.19, 1.41)

HR (95% CI)
receive copayment reduction for PD-related medical care,

Model 3
physicians need to approve whether patient clinical con-

1.00

1.00

1.00
ditions are appropriate to be diagnosed as PD.

Covariates
Potential confounders were sex, income level, body

1.31 (1.23, 1.41)

1.34 (1.20, 1.49)

1.30 (1.19, 1.42)

TABLE 2. Risk of PD based on baseline TUG time
mass index (BMI), lifestyle factors, mental health, and

Model 2

1.00

1.00

1.00
comorbidities (Supporting Information).

Model 3: adjusted for model 2 plus BMI, household income, smoking status, alcohol consumption, and regular physical activity.
Statistical Analysis

Model 4: adjusted for model 3 plus comorbidities (diabetes mellitus, hypertension, dyslipidemia, and chronic kidney disease).
Baseline characteristics based on TUG were examined
using a t test or chi-square test. A Cox proportional

1.32 (1.23, 1.41)

1.34 (1.20, 1.49)

1.30 (1.19, 1.42)

hazard regression analysis was conducted to estimate the
Model 1

1.00

1.00

1.00
hazard ratio (HR) and 95% confidence interval
(95% CI) values for PD development that were associ-
ated with TUG. Model 1 was unadjusted, whereas model
2 was adjusted for sex. Model 3 was further adjusted for
BMI, household income, and lifestyle variables. Model
0.8
1.1

0.8
1.1

0.8
1.1
IR

4 was further adjusted for the presence of comorbidities.

Finally, model 5 was further adjusted for mental health
status. All statistical analyses were performed using SAS
Follow-up Duration (PYs)

software (version 9.4; SAS Institute Inc., Cary, NC).

Model 5: adjusted for model 4 plus cognitive function and depressive mood.
465,717.8

713,196.7
3,203,505.9
1,178,914.5

1,477,987.9

1,725,518.1

Data Availability Statement

The data set analyzed in this study is not publicly
available because of restricted access, but further infor-
mation about the data set is available from the
corresponding author on reasonable request.
493

784
Events (n)

2,585
1,277

1,149

1,436

Results
IR indicates events per 1,000 person-years.

Baseline Characteristics of the Study

PYs, person-years; IR, incidence rate.

Population
Subjects (n)

30,8176
888,438

413,329
123,599

475,109
184,577

Characteristics of participants based on TUG are sum-

Model 2: adjusted for sex.

marized in Table 1. Mean TUG time was 8.3 seconds.

Among the participants, 74.2% had TUG <10 seconds
Model 1: unadjusted.

and 25.8% had TUG ≥10 seconds. Baseline TUG times

TUG Time (sec)

were significantly impaired in participants with incident

PD (mean, 8.9 seconds; standard deviation [SD]: 3.8)
Female
< 10

< 10

< 10
≥ 10

≥ 10

≥ 10

compared with those obtained for patients without PD

Total

Male

(mean, 8.3 seconds; SD, 2.9; Supporting Information

Movement Disorders, 2020 3

Y O O E T A L
Table S1). With a cut-off point of 10 seconds, the sensi-
tivity, specificity, and positive likelihood ratios of TUG
at predicting PD were 0.33, 0.74, and 1.29, respectively.
Incidence of PD Based on TUG Time
There were 3,862 new PD cases (0.3%) during a
median follow-up of 3.5 years in the entire cohort. An
incrementally higher risk of PD was observed in the
slow TUG group compared to the normal TUG group
in all models. In model 5, the association between TUG
time and PD remained significant (adjusted HR [aHR]:
1.28; 95% CI: 1.20–1.37). Results were consistent
when stratified based on sex (Table 2).
Secondary analysis showed a significant dose-response
relationship between TUG time and PD; TUG time 10 to
20 seconds (aHR, 1.26; 95% CI: 1.18–1.35), and TUG
time ≥ 20 seconds (aHR, 2.18; 95% CI: 1.63–2.92;
Supporting Information Table S2).
Discussion
To the best of our knowledge, this is the first study in
which the association between TUG and risk of PD was
investigated in a large-scale study population. Subjects
with impaired TUG (≥10 seconds) had 28% higher risk
of PD compared to subjects with normal TUG. The asso-
ciation was robust in individuals with abnormal TUG
(≥20 seconds), who showed more than twice the risk of
PD compared to subjects with normal TUG.
TUG has been extensively used in healthy and frail
older adults as part of a comprehensive geriatric assess-
ment.15 This test shows promise for identifying early PD
because it consists of a sequence of sit-to-stand, walking,
turning, and stand-to-sit tasks, each of which is eventu-
ally affected by PD, especially when performed in a
sequence.16 Thompson and colleagues reported that
TUG can identify functional limitations in PD patients
and also emphasized its correlation with H & Y stages.17
Nocera and colleagues suggested using TUG as a predic-
tor of falling in PD patients.4 Therefore, TUG may serve
as a surrogate marker for motor impairment that results
from prodromal or clinical PD. However, as described in
another report, the traditional TUG was not able to dif-
ferentiate between untreated PD patients without obvious
clinical signs and control participants.16 Thus, because
TUG assesses mobility and balance, and UPDRS scoring
includes a gait component, a delayed TUG time could
simply be regarded as a subtle motor deficit, which is
insufficient for the diagnosis of PD, such as mild MPSs.
MPSs have been defined variably between studies, and
estimates of their prevalence rates have ranged from
15% to 95% according to applicable criteria.3 Recently,
Chu and colleagues reported that patients with minimal
motor deficits showed significant reductions in both
dopaminergic neuron and phosphorylated alpha-
4 Movement Disorders, 2020
synuclein inclusion in the SN, which is compatible with
findings in PD patients.18 Considering that the definition
of a minimal motor deficit in Chu and colleagues’ series
required a score of more than 1 point for any parkinso-
nian motor feature or any type of MPS, a delayed TUG
could also result from dopaminergic dysfunction.
Our finding that a slow TUG suggested that the patient
had an increasing tendency for developing overt PD could
be interpreted as an indication of subthreshold parkinson-
ism or abnormal quantitative motor testing followed by a
clinical diagnosis of PD, as proposed in the International
Parkinson and Movement Disorder Society’s research
criteria for prodromal PD; each component imposed a
10 or 3.5 likelihood ratio to calculate the probability of
prodromal PD, respectively.19 Therefore, the present study
supports the plausibility of an association between a slow
TUG and the future risk of developing PD.
The present study had several limitations. First, because
claims data were used, undetected, overestimated, or mis-
diagnosed PD was possible. However, the RID registra-
tion code for PD was also used to ensure that the
definition of PD would be highly accurate. Second,
reverse causality could have existed. Although subjects
with a previous diagnosis of PD before the health screen-
ing date were excluded to minimize the possible effects of
reverse causality, early-stage PD symptoms may already
be present when TUG time increases. Third, whether the
conditions affecting TUG were adequately controlled is
unclear. This may be partially overcome by excluding
various neurological diseases and comorbidities, which
might affect TUG results, to minimize the risk of influ-
ence from other relevant characteristics. Fourth, the
follow-up was relatively short (mean, 3.7 years; up to
5.1 years). PD has a long prodromal phase, and results
from the present study might be more pronounced if the
follow-up period was longer. Last, because TUG was
only administered in patients who were aged 66 years,
there might be difficulties in generalizing these findings to
a patient population of another age group.
In conclusion, in this nation-wide population-based
cohort study, slow TUG was associated with an
increased risk of PD incidence. The results support
TUG as an indicator of subtle motor deficit and could
be a prodromal marker for risk of PD development.
Acknowledgements: This study was performed using the database
from the National Health Insurance System (NHIS-2018-1-255), and the
results do not necessarily represent the opinion of the National Health
Insurance Corporation.
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Supporting Data
Additional Supporting Information may be found in
the online version of this article at the publisher’s
web-site.

Movement Disorders, 2020 5

 SGML and CITI Use Only
DO NOT PRINT

Author Roles
(1) Research Project: A. Conception and Design; B. Acquisition of Data; C. Analysis and Interpretation of Data;
(2) Manuscript: A. Writing of the First Draft, B. Review and Critique; (3) Other: A. Statistical Analysis; B. Drafting
of the Tables.
J.E.Y.: 1A, 1C, 2A, 2B, 3B
W.J.: 1A, 1C, 2A, 2B, 3B
D.W.S.: 1A, 1B, 1C, 2A, 2B
S.-M.J.: 2B
H.-W.J.: 2B
J.Y.: 2B
K.H.: 1B, 1C, 2B, 3A
B.K.: 1B, 1C, 2B, 3A

Financial Disclosures
Nothing to report.