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Timed Up and Go, Cognitive, and Quality of Life

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Article in Archives of physical medicine and rehabilitation · January 2013

DOI: 10.1016/j.apmr.2013.10.031

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journal homepage: www.archives-pmr.org
Archives of Physical Medicine and Rehabilitation 2014;95:649-55

ORIGINAL ARTICLE

Timed Up and Go, Cognitive, and Quality-of-Life

Correlates in Parkinson’s Disease
Elizabeth L. Stegemöller, PhD,a,b Joe Nocera, PhD,c,d Irene Malaty, MD,e
Mack Shelley, PhD,f Michael S. Okun, MD,e Chris J. Hass, PhD,a and the NPF Quality
Improvement Initiative Investigators
From the aDepartment of Applied Physiology and Kinesiology, University of Florida, Gainesville, FL; bDepartment of Kinesiology, Iowa State
University, Ames, IA; cVA Rehabilitation R&D Center of Excellence, Atlanta VA Medical Center, Atlanta, GA; dDepartment of Neurology, Emory
University, Atlanta, GA; eDepartment of Neurology, Center for Movement Disorders & Neurorestoration, University of Florida, Gainesville, FL;
and fDepartments of Statistics and Political Science, Iowa State University, Ames, IA.

Abstract
Objective: To examine the relationship between Timed Up and Go (TUG) performance, verbal executive function (EF) performance, and quality-
of-life (QOL) measures in Parkinson’s disease (PD).
Design: Cross-sectional.
Setting: Sixteen movement disorder centers from across the United States.
Participants: Patients with PD (NZ1964).
Interventions: Not applicable.
Main Outcome Measures: TUG test, immediate and delayed 5-word recall, verbal fluency, PD QOL Questionnaire.
Results: TUG performance and verbal EF performance were significantly associated with, and predictors of, QOL measures, having the greatest
association and predictability with the mobility domain of the QOL measures.
Conclusions: The TUG test and verbal EF tests have QOL correlates, making the combined evaluation of mobility, cognitive, and QOL decline a
potential examination tool to evaluate the sequelae of PD.
Archives of Physical Medicine and Rehabilitation 2014;95:649-55
ª 2014 by the American Congress of Rehabilitation Medicine

Parkinson’s disease (PD) affects physical, mental, and psychoso-
cial health. There remains a need to better understand how all 3
areas interrelate and affect quality of life (QOL) in individuals
with PD. QOL is the individual’s self-perceived life function
resulting from the impact of a disease.1 Motor symptoms, such as
rigidity, bradykinesia, gait and postural instability, in combination
with nonmotor symptoms, such as depression, cognitive dysfunc-
tion, and sleep problems, can considerably affect the QOL for
individuals with PD.2,3 In addition, self-care limitations and dis-
ease duration have been associated with poor QOL in individuals
with PD.3 Many studies4-7 are incorporating subjective QOL
Supported by the National Parkinson Foundation.
No commercial party having a direct financial interest in the results of the research supporting
this article has conferred or will confer a benefit on the authors or on any organization with which
the authors are associated.
measures to understand how treatment interventions affect QOL
in individuals with PD. Yet, to better understand how physical and
mental capacities, and QOL are changing because of a treatment
intervention, it is important to first understand the existing rela-
tionship between these factors. Moreover, as cognitive impair-
ments progress, a patient-reported evaluation of QOL may not be
as reliable.2 Examining the relationships between quantifiable
measures readily available to clinicians with QOL measures may
prove beneficial to the clinical evaluation of individuals with PD
and provide further insight into how mobility, cognition, and QOL
are interrelated. Thus, the purpose of this study was to examine
the relationship between the combined objective and quantifiable
measures of mobility and cognitive performance, and QOL in
individuals with PD.
There is currently little research examining the relationship be-
tween quantifiable measures of mobility and cognitive performance

0003-9993/14/$36 - see front matter ª 2014 by the American Congress of Rehabilitation Medicine
http://dx.doi.org/10.1016/j.apmr.2013.10.031
650
and QOL in individuals with PD. The Timed Up and Go (TUG)
test, consisting of a sequence of sit-to-stand, walking, turning, and
stand-to-sit tasks, is advocated as a useful and reliable tool to
quantify mobility performance in persons with PD8 and is
commonly used as a measure of functional mobility in many
pharmacologic, surgical, and rehabilitative intervention studies
in PD.9,10 Longer TUG times are associated with decreased
mobility11 and have been shown to be a predictor of falls in in-
dividuals with PD off medication.12 Yet, the relationship between
TUG test performance and the full spectrum of QOL in individuals
with PD is lacking. Likewise, research examining the relationship
between cognition and QOL is lacking, with most research
comparing individuals with PD who have dementia with those who
do not have dementia.13-16 Individuals with dementia demonstrated
poorer QOL.14,15 However, individuals with PD typically progress
to dementia during the later stages of the disease.1 Only 1 study1
has demonstrated a significant association between attention/
memory and executive function (EF) measures and QOL in in-
dividuals with PD without dementia. Moreover, research exam-
ining relationships between both functional mobility and cognitive
function, and QOL in individuals with PD is also lacking.
To further examine the relationship between mobility and EF
performance and QOL, correlation and regression analyses were
completed between TUG test performance, EF performance, and
QOL measures by using the Parkinson’s Disease Questionnaire-39
(PDQ-39). Because previous research has shown that functional
mobility17 and EF18 (when tested independently from each other)
are significant predictors of QOL in individuals with PD, TUG test
performance and EF performance were designated as
the independent variables, and the PDQ-39 was designated as the
dependent variable. Further analyses were completed to examine
the relationship between TUG test performance and EF perfor-
mance, and each PDQ-39 domain score. We hypothesized that (1)
TUG test performance and EF performance would be significantly
associated with QOL measures; and (2) TUG test performance and
EF performance would be most predictive of the mobility and
cognitive QOL domains of the PDQ-39, respectively.
Methods
A cross-sectional study design was completed from data drawn
from the National Parkinson Foundation’s Quality Improvement
Initiative (NPF-QII) Clinical Study, which included 16 partici-
pating National Parkinson Foundation (NPF) Centers of Excel-
lence from within the United States. A total of 2985 baseline
records from patients registered in NPF-QII between 2009 and
2010 were available. Of the 2985 patients, 1021 were excluded
because of a lack of crucial information, such as age, diagnosis,
disease duration, TUG test scores, PDQ-39 scores, or EF test
List of abbreviations:
EF executive function
H&Y Hoehn and Yahr
NPF National Parkinson Foundation
NPF-QII National Parkinson Foundation’s Quality Improvement
Initiative
PD Parkinson’s disease
PDQ-39 Parkinson’s Disease Questionnaire-39
PDQ-SI Parkinson’s Disease Questionnaire–Summary Index
QOL quality of life
TUG Timed Up and Go
E.L. Stegemöller et al
scores. Patients who had deep brain surgery and those patients
who were unable to complete the TUG test without assistance
were also excluded from the study. These exclusions resulted in a
total of 1964 patients. This study was in accordance with the
Declaration of Helsinki, and all patients signed an
informed consent.
All evaluations were completed in the “on” medication state,
which was confirmed by the patient before completing further
tests. Site neurologists and coordinators were provided scripted
instructions for each test. Disease severity was rated using Hoehn
and Yahr (H&Y) staging,19 and disease duration was determined
from the date of diagnosis until the date of study examination.
The TUG test was administered as a measure of mobility and
has been shown to have excellent test-retest and interrater reli-
ability in patients with PD.20,21 Patients were timed in seconds as
they stood up from an armchair, walked forward at a comfortable
and safe pace for 3m, turned and walked back to the chair, and sat
down.17,22,23 Total time measured was from the command “go”
until the patient made contact sitting in the chair. Patients were
allowed, if needed, to complete the task using their hands to push
off from the chair.
For a measure of QOL, the PDQ-39 was administered during the
office visit and completed by the patient or patient and caregiver.
The PDQ-39 has been shown to have excellent validity, test-retest
and interrater reliability.24 Scores for each domain were recorded as
the sums of items 1 to 10 for mobility, items 11 to 16 for activities
of daily living, items 17 to 22 for emotional well-being, items 23 to
26 for stigma, items 27 to 29 for social support, items 30 to 33 for
cognition, items 34 to 36 for communication, and items 37 to 39 for
pain. Scores were then expressed as a percentage (100 indicating
greater disruption/dissatisfaction within a domain). The total
Parkinson’s Disease Questionnaire–Summary Index (PDQ-SI) score
was computed by summing the 8 domain scores and dividing by the
total number of domains (ie, 8).25
Immediate 5-word recall, delayed 5-word recall (verbal
working memory), and verbal fluency were completed to assess
verbal EF performance. All tests have been shown to be valid tests
of verbal EF performance.26,27 For immediate word recall, patients
were presented with 5 words (face, velvet, church, daisy, red)
slowly and distinctly 1 time and were instructed to verbally repeat
the 5 words immediately. For delayed word recall, patients were
asked to recall as many of the same 5 words as possible after
performing a distracting task that lasted approximately 1.5 mi-
nutes. Patients were not prompted, and the number of correct re-
sponses was recorded for both immediate and delayed word recall.
For verbal fluency, patients named as many animals as possible in
1 minute. All living creatures that were not plants were counted
and recorded.
Statistical analysis
Mean and SD were computed for the disease duration, H&Y, TUG
score, immediate 5-word recall, delayed 5-word recall, verbal
fluency, PDQ-SI, and each PDQ-39 domain score. Because
bivariate Pearson correlation analyses revealed significant asso-
ciations between the verbal EF measures and differences in range
(0e5 for word recall and 0e46 for verbal fluency), z scores were
calculated using the mean and SD from each variable and aver-
aged across each subject to obtain a mean verbal EF z score.
Lower z scores indicate fewer responses and worse performance.
The distribution of all data was checked for normality, and data
www.archives-pmr.org
Timed Up and Go, cognition, and quality of life in Parkinson’s disease 651

with a skewness score of greater than 1 or 1 were log trans-

Table 2 Mean  SD and range for each measure
formed before entering the data for analysis. TUG, PDQ-39
stigma, and PDQ-39 social data were transformed. Bivariate Measure Mean  SD Range
Pearson correlation analyses were completed to compare the TUG 11.03.4 5e29
strength of the association between the TUG score, verbal EF Immediate word recall 4.40.9 0e5
score, and the PDQ-SI. To examine the relationship of the TUG Delayed word recall 3.01.4 0e5
score and verbal EF score with the PDQ-SI independent of disease Verbal fluency 19.16.4 1e72
progression, variables found to significantly correlate with the PDQ-SI 22.214.5 0e95
PDQ-SI (P<.05) were entered into a multiple regression model, PDQ-39 domains
controlling for disease duration and disease severity (H&Y score). Mobility 24.322.9 0e100
To examine the relationship between mobility and verbal EF ADL 26.320.9 0e100
performance and each domain of the PDQ-39, 8 separate multiple Emotion 22.318.7 0e100
regression models were completed for each PDQ-39 domain in Stigma 17.419.9 0e100
which only variables found to significantly correlate with each Social 10.115.6 0e100
corresponding PDQ-39 domain (P<.05) were entered into the Cognition 23.918.6 0e100
model. Statistical analyses were performed using SPSS statistics Communication 20.920.4 0e100
version 17.0,a and statistical significance was set at alpha<.05. Pain 31.923.3 0e100
Abbreviation: ADL, activities of daily living.

Results
(P<.001), accounting for 19.1% (adjusted R2Z.191) of the vari-
Participants’ characteristics are shown in table 1. Mean, SD, and
ance in the PDQ-SI.
range for the TUG score, each verbal EF measure, PDQ-SI, and
Correlation coefficients and the results of the regression ana-
each PDQ-39 domain are shown in table 2. Significant correlations
lyses between each PDQ-39 domain score and TUG and verbal EF
were found between TUG and PDQ-SI (rZ.307, P<.001), verbal
are shown in table 3. TUG was significantly correlated with each
EF and PDQ-SI (rZ .201, P<.001), and TUG and verbal EF
domain (r>.09, P<.001), except for the PDQ-39 stigma domain
(rZ .281, P<.001) (fig 1). Disease duration and H&Y signifi-
(rZ.04, PZ.074). The highest correlations were revealed with
cantly correlated with all 3 measuresdTUG ([rZ.063, PZ.005]
PDQ-39 mobility (rZ.37), activities of daily living (rZ.27), and
and [rZ.288, P<.288], respectively), verbal EF ([rZ .130,
cognition (rZ.24). Verbal EF was significantly correlated with
P<.001] and [rZ .268, P<.001], respectively), and PDQ-SI
each domain (r> .07, P<.003), except for PDQ-39 stigma
([rZ.273, P<.001] and [rZ.318, P<.001], respectively)dand
(rZ.011, PZ.63) and pain (rZ .01, PZ.53). Verbal EF had the
were subsequently controlled for to allow for better interpretation of
highest correlation with PDQ-39 cognition (rZ .24) and
the associations between the variables of interest. Multiple regres-
mobility (rZ .22). Multiple regression analyses revealed that
sion analysis revealed that both TUG (bZ.23, P<.001) and verbal
TUG was a significant predictor of each domain except for PDQ-
EF (bZ .06, PZ.003) were significant predictors of the PDQ-SI
39 stigma, while verbal EF was a significant predictor of each
domain except for PDQ-39 stigma and pain. In total, TUG and
verbal EF accounted for 26% of the variance in the PDQ-39
Table 1 Group demographics and clinical data
mobility domain. Less than 16% of the variance was accounted
for by TUG and verbal EF across the remaining PDQ-39 domains
Characteristics Values (see table 3).
Age (y) 66.69.6 (26e91)
Sex (men) 1262 (64.2)
Disease duration (y) 8.45.6 (1e45) Discussion
1e5 509 (25.9)
6e10 764 (38.9) Results of this study revealed potentially important associations of
11e15 444 (22.6) TUG performance and verbal EF performance with QOL mea-
16e20 159 (8.1) sures in persons with PD. Moreover, TUG performance and verbal
21e25 57 (2.9) EF performance were associated with, and significant predictors
26e30 21 (1.0) of, many PDQ-39 domains. These results suggest that objectively
31e35 5 (0.3) evaluating mobility and cognitive performance with QOL may be
36e40 3 (0.2) a valuable tool to aid clinicians in the assessment and treatment
41e45 2 (0.1) of PD.
H&Y stage Results of this study revealed a negative correlation between
1 222 (11.3) TUG performance and verbal EF performance, suggesting that
1.5 46 (2.3) slower TUG performance (more time to complete the test) is
2 1083 (55.1) associated with worse verbal EF performance (fewer responsese
2.5 86 (4.3) lower z scores). This result is in keeping with previous research
3 473 (24.0) that has demonstrated relationships between cognitive and
4 54 (2.7) mobility impairment in individuals with PD. In particular, im-
NOTE. Values are mean  SD (range) or n (%).
pairments in EF have been shown to affect gait and mobility in
individuals with PD.28-30 Recent research has shown that working

www.archives-pmr.org
652 E.L. Stegemöller et al

Fig 1 (A) PDQ-SI data plotted against TUG data for all participants. (B) PDQ-SI data plotted against verbal EF (z scores) data for all partic-
ipants. (C) TUG data plotted against verbal EF (z scores) data for all participants.

www.archives-pmr.org
Timed Up and Go, cognition, and quality of life in Parkinson’s disease 653

Table 3 Correlation coefficients and regression model for each PDQ-39 domain
Correlation Coefficients Regression Model
TUG Score EF Score TUG Score EF Score
PDQ-39 Domains r P r P Adjusted R 2
b P b P
Mobility .37 <.001 .22 <.001 .26 .27 <.001 .06 .004
ADL .27 <.001 .19 <.001 .16 .19 <.001 .07 .001
Emotion .17 <.001 .10 <.001 .04 .14 <.001 .03 .141
Stigma .04 .074 .01 .631 Not entered Not entered Not entered
Social .09 <.001 .07 .003 .05 .05 .044 .01 .808
Cognition .24 <.001 .24 <.001 .11 .16 <.001 .16 <.001
Communication .20 <.001 .18 <.001 .13 .12 <.001 .08 <.001
Pain .16 <.001 .01 .534 .05 .13 <.001 Not entered
Abbreviation: ADL, activities of daily living.

memory and response generation were associated with TUG
performance in individuals with PD,23 and patients with increased
difficulty in postural stability and gait show longer performance
times on the TUG test31 and greater cognitive impairment than
nonfallers.32 TUG performance has also been shown to be sig-
nificantly associated with, and predictive of, cognitive decline in
community-dwelling older adults.33,34 Taken together, results of
this and previous studies would suggest that declines in mobility
and cognitive performance are potentially related in individuals
with PD. Yet, there remains a need to further examine the origin of
the relationship between mobility and cognitive performance.
Research has suggested that the ongoing monitoring and up-
dating of gait and balance as a result of changes in the environ-
ment require working memory and may explain the association
between mobility and verbal working memory revealed in this
study.23 Global changes in processing speed may also account for
associations between mobility and verbal EF performance.23
Dirnberger et al35 have suggested that declines in EF perfor-
mance are associated with failure to modulate prefrontal activa-
tion. Interestingly, research has shown that the prefrontal cortex
and anterior cingulate cortex are also involved with self-
awareness, a major component to the subjective evaluation of
QOL.36,37 Thus, one’s subjective evaluation of QOL may also be
influenced by changes in activation of these areas resulting from
PD. Further research warrants investigation to assess whether the
associations revealed in this study are due to changes in common
brain areas that are involved with mobility, EF, and self-awareness
or are due to socioemotional changes that result from reduced
mobility and cognitive decline. In either case, the combined
objective evaluation of mobility and EF performance may provide
more insightful information, evaluation, and treatment of in-
dividuals with poor QOL.
Only 2 studies17,38 have examined the relationship between
physical function and QOL measures. Scalzo et al38 have shown
that lower scores on the Berg balance test and 6-minute walk are
associated with poorer QOL perception, particularly with PDQ-39
mobility and activities of daily living scores. Similarly, Ellis
et al17 have shown a significant association between TUG per-
formance and the PDQ-39 mobility score. No study has examined
the relationship between the combined objective evaluation of
both mobility and EF performance and each domain of QOL.
This study is the first to examine the relationship between TUG
and verbal EF performance and each PDQ-39 domain score. As
may be expected, TUG performance showed the greatest
correlation with the PDQ-39 mobility score, and verbal EF
performance showed the greatest correlation with the PDQ-39
cognitive score. However, previous research has shown that the
8 domains of the PDQ-39 may not represent the best grouping of
items.39 It remains unknown whether the PDQ-39 cognitive domain
score is merely a measure of perceived cognitive ability or whether
it fully captures cognitive faculties. The PDQ-39 cognitive domain
only includes 4 questions, 2 of which involve questions regarding
sleep. The remaining 2 questions cover concentration and memory.
Thus, interpretation of these results demonstrating an association
between verbal EF performance and the PDQ-39 cognitive domain
should be taken cautiously given the number of items in the PDQ-
39 cognitive domain related to verbal EF performance. Nonetheless,
our results suggest that further research regarding the relationship
between cognitive function and the PDQ-39 cognitive domain
is needed.
When comparing across regression models for each PDQ-39
domain, TUG and verbal EF performance accounted for the
greatest amount of variance in the PDQ mobility score (26%). In
remaining models, <16% of the variance was accounted for by
these 2 measures. These results, in keeping with previous
research,21 would indeed suggest that mobility QOL measures
may be more sensitive to quantifiable changes in mobility and
cognitive performance in individuals with PD. However, other
QOL domains, including the cognition, activities of daily living,
communication, social, and emotion domains, were significantly
associated with (though not strong associations) and predicted
by both TUG and verbal EF performance. This may imply that
patients with more advanced disease, who are more likely to
have TUG performance difficulty and a decline in EF perfor-
mance, are also more likely to have accumulated social distress.
However, given that the population sample in this study was
mainly those individuals with mild to moderate PD (68.7% with
H&Y of 2 or less in the medicated state), continued research is
needed to further determine the longitudinal relationship be-
tween mobility, EF, and QOL in individuals with advanced PD.
Study limitations
Evaluations were completed on medication. Evaluation in the off-
medication state may provide greater information regarding the
relationship between TUG performance, cognitive and QOL
measures. However, most individuals with PD strive to remain in

www.archives-pmr.org
654
the on state during their normal activities of daily life, and it makes
sense to assess QOL and performance measures in the typically
medicated state. Other mediating factors could not be controlled
for, including dementia, freezing of gait, loss of postural reflexes,
cardiovascular disorders, symptomatic orthostatic hypertension, and
the interaction(s) of medication type(s) and dosages. Participants
were tested at NPF Centers of Excellence. While this afforded
collection of a large sample with a wide variety of ages, disease
durations, and educational levels, participants may have greater
optimization of treatment than some community-dwelling patients.
Moreover, a large portion of the original population was excluded
because of missing data and may bias the results. Comparison of
demographics revealed that the population entered into the model
was similar to the original population (mean age  SD,
67.510.1y; percentage of men, 61.3%; mean  SD disease
duration, 9.26.1y) (see table 1). Given the large sample, weak to
moderate correlations (between 0.2 and 0.4) were found to be
significant. Finally, this study was cross-sectional. It will be
useful in follow-up to see whether serial TUG examinations
prove important in tracking progression over time.
Conclusions
This study is the first to examine the relationship between TUG
and verbal EF performance and QOL measures in a large cohort of
patients with PD. The results provide initial evidence regarding
the relationships between objective and quantifiable measures of
mobility and cognitive performance and QOL in individuals with
PD. These results may be a valuable tool to aid clinicians in
screening, assessment, and treatment, as well as in the evaluation
of new treatment interventions. Confirmation of this notion will
require future longitudinal follow-up of these patients, which is
planned as part of the NPF-QII study.
Supplier
a. SPSS Inc, 233 S Wacker Dr, 11th Fl, Chicago, IL 60606.
Keywords
Cognition; Parkinson’s disease; Quality of life; Rehabilitation
Corresponding author
Chris Hass, PhD, PO Box 118205, University of Florida, Gain-
esville, FL. E-mail address: cjhass@hhp.ufl.edu.
Acknowledgments
NPF Quality Improvement Initiative Investigators include Melanie
Bransabur, MD, Bastiaan Bloem, MD, Catherine Cho, MD,
Anthony Santiago, MD, Tanya Gurevich, MD, Mark Guttman, MD,
Robert Hauser, MD, Jospeoh Jankovic, MD, Kelly Lyons, MD,
Zoltan Mari, MD, John Morgan, MD, John Nutt, MD, Sotirios
Parashos, MD, Andrew Siderowf, MD, Tanya Simuni, MD, Daniel
Tarsy, MD, Thomas Davis, MD, Janis Miyasaki, MD, Eric Cheng,
MD, Nir Giraldi, MD, Laura Marsh, MD, Eugene Nelson, MD, and
Jorge Zamundio, MD.
E.L. Stegemöller et al
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