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Timed Up and Go, Cognitive, and Quality of Life


Correlates in Parkinson’s Disease

Article in Archives of physical medicine and rehabilitation · January 2013


DOI: 10.1016/j.apmr.2013.10.031

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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- measures to understand how treatment interventions affect QOL
cial health. There remains a need to better understand how all 3 in individuals with PD. Yet, to better understand how physical and
areas interrelate and affect quality of life (QOL) in individuals mental capacities, and QOL are changing because of a treatment
with PD. QOL is the individual’s self-perceived life function intervention, it is important to first understand the existing rela-
resulting from the impact of a disease.1 Motor symptoms, such as tionship between these factors. Moreover, as cognitive impair-
rigidity, bradykinesia, gait and postural instability, in combination ments progress, a patient-reported evaluation of QOL may not be
with nonmotor symptoms, such as depression, cognitive dysfunc- as reliable.2 Examining the relationships between quantifiable
tion, and sleep problems, can considerably affect the QOL for measures readily available to clinicians with QOL measures may
individuals with PD.2,3 In addition, self-care limitations and dis- prove beneficial to the clinical evaluation of individuals with PD
ease duration have been associated with poor QOL in individuals and provide further insight into how mobility, cognition, and QOL
with PD.3 Many studies4-7 are incorporating subjective 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
Supported by the National Parkinson Foundation. individuals with PD.
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
There is currently little research examining the relationship be-
the authors are associated. 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 E.L. Stegemöller et al

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

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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 correlation with the PDQ-39 mobility score, and verbal EF
performance in individuals with PD,23 and patients with increased performance showed the greatest correlation with the PDQ-39
difficulty in postural stability and gait show longer performance cognitive score. However, previous research has shown that the
times on the TUG test31 and greater cognitive impairment than 8 domains of the PDQ-39 may not represent the best grouping of
nonfallers.32 TUG performance has also been shown to be sig- items.39 It remains unknown whether the PDQ-39 cognitive domain
nificantly associated with, and predictive of, cognitive decline in score is merely a measure of perceived cognitive ability or whether
community-dwelling older adults.33,34 Taken together, results of it fully captures cognitive faculties. The PDQ-39 cognitive domain
this and previous studies would suggest that declines in mobility only includes 4 questions, 2 of which involve questions regarding
and cognitive performance are potentially related in individuals sleep. The remaining 2 questions cover concentration and memory.
with PD. Yet, there remains a need to further examine the origin of Thus, interpretation of these results demonstrating an association
the relationship between mobility and cognitive performance. between verbal EF performance and the PDQ-39 cognitive domain
Research has suggested that the ongoing monitoring and up- should be taken cautiously given the number of items in the PDQ-
dating of gait and balance as a result of changes in the environ- 39 cognitive domain related to verbal EF performance. Nonetheless,
ment require working memory and may explain the association our results suggest that further research regarding the relationship
between mobility and verbal working memory revealed in this between cognitive function and the PDQ-39 cognitive domain
study.23 Global changes in processing speed may also account for is needed.
associations between mobility and verbal EF performance.23 When comparing across regression models for each PDQ-39
Dirnberger et al35 have suggested that declines in EF perfor- domain, TUG and verbal EF performance accounted for the
mance are associated with failure to modulate prefrontal activa- greatest amount of variance in the PDQ mobility score (26%). In
tion. Interestingly, research has shown that the prefrontal cortex remaining models, <16% of the variance was accounted for by
and anterior cingulate cortex are also involved with self- these 2 measures. These results, in keeping with previous
awareness, a major component to the subjective evaluation of research,21 would indeed suggest that mobility QOL measures
QOL.36,37 Thus, one’s subjective evaluation of QOL may also be may be more sensitive to quantifiable changes in mobility and
influenced by changes in activation of these areas resulting from cognitive performance in individuals with PD. However, other
PD. Further research warrants investigation to assess whether the QOL domains, including the cognition, activities of daily living,
associations revealed in this study are due to changes in common communication, social, and emotion domains, were significantly
brain areas that are involved with mobility, EF, and self-awareness associated with (though not strong associations) and predicted
or are due to socioemotional changes that result from reduced by both TUG and verbal EF performance. This may imply that
mobility and cognitive decline. In either case, the combined patients with more advanced disease, who are more likely to
objective evaluation of mobility and EF performance may provide have TUG performance difficulty and a decline in EF perfor-
more insightful information, evaluation, and treatment of in- mance, are also more likely to have accumulated social distress.
dividuals with poor QOL. However, given that the population sample in this study was
Only 2 studies17,38 have examined the relationship between mainly those individuals with mild to moderate PD (68.7% with
physical function and QOL measures. Scalzo et al38 have shown H&Y of 2 or less in the medicated state), continued research is
that lower scores on the Berg balance test and 6-minute walk are needed to further determine the longitudinal relationship be-
associated with poorer QOL perception, particularly with PDQ-39 tween mobility, EF, and QOL in individuals with advanced PD.
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 Study limitations
the relationship between the combined objective evaluation of
both mobility and EF performance and each domain of QOL. Evaluations were completed on medication. Evaluation in the off-
This study is the first to examine the relationship between TUG medication state may provide greater information regarding the
and verbal EF performance and each PDQ-39 domain score. As relationship between TUG performance, cognitive and QOL
may be expected, TUG performance showed the greatest measures. However, most individuals with PD strive to remain in

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654 E.L. Stegemöller et al

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