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Journals of Gerontology: Medical Sciences

cite as: J Gerontol A Biol Sci Med Sci, 2018, Vol. 73, No. 9, 1238–1243
doi:10.1093/gerona/glx261
Advance Access publication 16 January 2018

Research Article

Association Between  Timed Up and Go Test and Future


Dementia Onset

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Ji Eun Lee, MD, MPH,1 Dong Wook Shin, MD, DrPH, MBA,2,3 Su-Min Jeong, MD,1
Ki Young Son, MD, MPH, PhD,1 Belong Cho, MD, MPH, PhD,1 Jong Lull Yoon, MD, MPH, PhD,4
Byung Joo Park, MD, MPH, PhD,5 In Soon Kwon, MD, PhD,6 Jinkook Lee, PhD,7 and
SangYun Kim, MD, PhD8
Department of Family Medicine, Seoul National University Hospital, Republic of Korea. 2Department of Family Medicine & Supportive
1

Care Center, Samsung Medical Center, Seoul, Republic of Korea. 3Department of Digital Health, SAIHST, Sungkyunkwan University,
Seoul, Republic of Korea. 4Department of Family Medicine, Hallym University Medical Center, Seoul, Republic of Korea. 5Department of
Preventive Medicine, Seoul National University College of Medicine, Republic of Korea. 6Department of Internal Medicine, Inje University
Seoul Paik Hospital, Republic of Korea. 7Department of Economics & Center for Economic & Social Research, University of Southern
California, Los Angeles, & RAND Corporation, Santa Monica. 8Department of Neurology, Seoul National University Bundang Hospital &
Seoul National University College of Medicine, Seongnam, Republic of Korea.

Address correspondence to: Dong Wook Shin, MD, DrPH, MBA, Department of Family Medicine, Samsung Medical Center Supportive Care
Center, Samsung Comprehensive Cancer Hospital, Seoul, Korea, 81 Irwon-Ro, Gangnam-gu, Seoul, Korea. E-mail: dwshin.md@gmail.com

Received: August 24, 2017; Editorial Decision Date: December 19, 2017

Decision Editor: Anne Newman, MD, MPH

Abstract
Background:  This study evaluated whether baseline results of the Timed Up and Go (TUG) test is associated with future dementia occurrence.
Methods:  Using the Korean National Health Insurance Service-National Health Screening Cohort database, we identified 49,283 subjects
without a dementia diagnosis who participated in the National Screening Program for Transitional Ages at 66 years of age during 2007–2012.
Gait impairment was defined as taking longer than 10 seconds to perform the TUG test. Dementia occurrence was defined by the first
prescription for acetylcholinesterase inhibitors or N-Methyl-D-Aspartate receptor antagonist with an International Classification of Diseases
10th Revision (ICD-10) code for dementia (F00, F01, F02, F03, G30, F051, or G311) during 2007–2013. Cox proportional hazard regression
models were used to assess the hazard ratios for dementia occurrence according to baseline TUG test results.
Results:  Mean follow-up period was 3.8 years. Incidence rates of dementia were 4.6 and 6.8 cases per 1,000 person-years in the normal and
impaired TUG groups, respectively. The impaired TUG group showed a higher risk of total dementia incidence (adjusted hazard ratio [aHR],
1.34; 95% confidence interval [95% CI], 1.14–1.57). Subtype analysis showed that the impaired TUG group had a higher risk of Alzheimer’s
disease (aHR, 1.26; 95% CI, 1.06–1.51) and vascular dementia (aHR, 1.65; 95% CI, 1.19–2.30).
Conclusions:  The TUG test result was associated with future dementia occurrence. More vigilant follow-up and early intervention to prevent
dementia would benefit elderly people with impaired TUG test result.
Keywords: Frailty, Functional Performance, Gait, National insurance data, Successful Aging

The aging of populations worldwide has led to a marked increase in dementia are enormous (2) and family members suffer the burden of
chronic, disabling diseases; specifically, the prevalence of dementia caring for dementia patients over a long period of time (3).
is steadily increasing. The worldwide prevalence of dementia is esti- Despite extensive research efforts, a cure for dementia has yet to
mated to be 5%–7% for the people ≥ 60 years old and is reported to be developed. Until now, the best practice has been to identify indi-
be 80% for people ≥ 90 years old (1). In addition, worldwide costs of viduals who are at a high risk of developing dementia and provide

© The Author(s) 2018. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved.
1238
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Journals of Gerontology: MEDICAL SCIENCES, 2018, Vol. 73, No. 9 1239

preventive strategies. Therefore, predicting the risk of dementia has Screening Cohort (NHIS-HEALS) database, which comprises 515
been regarded as a research priority, although our prediction meth- 000 people. This figure represents 10% of a random selection from
ods are still lacking (4). the total Korean population aged 40–79  years who participated
In this regard, the association between physical frailty and cog- in the NHSP at least once during the 2002–2003 index year. The
nitive decline is attracting attention. Some previous studies have NHIS-HEALS contains demographic factors such as age, sex, death
suggested that physical frailty is a risk factor of cognitive decline date, and results of the NHSP as well as information on the utiliza-
(5). The recently developed concept of “cognitive frailty” includes tion of medical facilities, including the International Classification
the presence of both physical frailty and cognitive impairment (6). of Diseases 10th Revision (ICD-10) codes and prescribed medicines
Because of potential for reversibility of frailty, cognitive frailty is from outpatient clinics and hospitalization. As NHI is mandatory
attracting attention as an important target of prevention of demen- social insurance in Korea, attrition from this cohort occurs only by
tia (7). emigration, which is not common at the age over 65.

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As to association between physical frailty and cognitive de- For this study, the people at 66  years old who participated in
cline, some recent studies have investigated the relationship be- the NSPTA program during 2007–2012 were selected. The initial
tween gait impairment, which is an important indicator of physical population was 53,000 subjects. Subjects who were diagnosed with
frailty, and future cognitive decline (8–11). In one prospective co- dementia or prescribed acetylcholinesterase inhibitors or N-Methyl-
hort study with 10,308 participants in England, decline in physical D-Aspartate (NMDA) receptor antagonist before the screening day
activity was observed since 9  years before dementia diagnosis (8). (n  =  1,004) and the subjects with missing records involving the
In another study with 1,265 elderly people in France, baseline gait TUG test or other covariables (n = 2,713) were excluded (Figure 1).
speed independently predicted dementia occurrence after 12  years Ultimately, 49,283 subjects were included in the analysis.
of follow-up (9). These studies suggested possibility of gait speed as This study was approved by the institutional review board of
predictor of dementia occurrence. However, in these studies, phys- Seoul National University Hospital (IRB No. E-1611-061-807).
ical performance was assessed with a questionnaire which entails a Consent from individual subjects was waived because we used pub-
risk of memory bias, or 6-m walk test which is not commonly used licly open, anonymous data.
in clinical setting at least until now (9,10). One study suggested that
the Timed Up and Go (TUG) test, which is a simple marker of gait Variables
impairment, could predict cognitive decline (11); however, the study Independent variable
focused on cognitive decline rather than clinical dementia occur- The TUG test was conducted on the examination day of NSPTA pro-
rence. That study also had a small sample population (n = 111) and gram at community hospitals. Subjects were timed while they rose
a short follow-up period (3 years). Therefore, it is necessary to deter- from a chair, walked at a comfortable pace to a line on the floor 3 m
mine whether the TUG test can serve as a simple predictive marker away, turned and walked back to the chair, and sat down again. The
of dementia occurrence in a larger study population over a longer person wore regular footwear and used his/her customary walking
follow-up period. aid. Gait impairment was defined as taking longer than 10 seconds
In this large, nationwide study using health insurance claims to perform the TUG test (18).
data, we investigated the association between baseline TUG test
results and future dementia occurrence. Our underlying hypothesis
Outcome Variable
was that the TUG test could be used as a simple predictive marker
Dementia occurrence was defined by the first prescription of acetyl-
of dementia occurrence.
cholinesterase inhibitors (donepezil, galantamine, rivastigmine)
or NMDA receptor antagonist (memantine) (19) with an ICD-10
dementia code (F00, F01, F02, F03, G30, F051, or G311) after the
Methods NSPTA examination (20). We also considered subtypes of demen-
Study Setting tia; Alzheimer’s disease and vascular dementia. Alzheimer’s disease
The Korean National Health Insurance (KNHI) service is a man-
datory public health insurance system, which provides universal
health coverage to all Koreans (12). The KNHI service offers a
biennial National Health Screening Program (NHSP) to all mem-
bers over 40 years of age. The NHSP includes a questionnaire (past
medical history, health behavior), anthropometric exam (body mass
index, blood pressure), and laboratory test (blood sugar, cholesterol,
etc) (13). For all people of 66 years old, KNHI provides a special
health screening program called the National Screening Program
for Transitional Ages (NSPTA) (14). Besides the routine items of
NHSP, NSPTA also includes a questionnaire regarding cognitive
function and depression screening, as well as some tests including
TUG test that covers common problems of the elderly people such
as frailty (14).
Figure 1.  Flow chart of study population selection process. aInitial population:
People who participated in the National Screening Program for Transitional
Data Source and Study Population
Ages (NSPTA) during 2007–2012 were extracted from the Korean National
The KNHI database has been widely used in various epidemio- Health Insurance Service-National Health Screening Cohort (NHIS-HEALS)
logical studies (15) and is described in detail elsewhere (16,17). This database. bMissing value in variables: Timed Up and Go test results, smoking,
study used the National Health Insurance Service-National Health depressive symptom, or baseline cognitive function.
1240 Journals of Gerontology: MEDICAL SCIENCES, 2018, Vol. 73, No. 9

occurrence was defined by the first prescription of an acetylcholin- comorbid conditions (stroke, hypertension, diabetes mellitus, and
esterase inhibitor or NMDA receptor antagonist with an ICD-10 hypercholesterolemia) was obtained from the questionnaire admin-
code for Alzheimer’s disease (F00, G30); vascular dementia occur- istered on the screening day. Depressive symptom was assessed with
rence was defined by the first prescription of the same medication a three-item questionnaire extracted from the Geriatric Depression
with an ICD-10 code for vascular dementia (19,21). Scale (GDS), including items 2, 17, and 22 that relate to loss of
To file expense claims in Korea, the National Health Insurance interest, feelings of uselessness, and feelings of hopelessness, respect-
Reimbursement Criteria must be fulfilled. When prescribing acetyl- ively (23). A  negative response to any of the three items was con-
cholinesterase inhibitors or NMDA receptor antagonist, physicians sidered evidence of depressive symptom. Baseline cognitive function
need to document evidence of cognitive dysfunction according to was assessed with the Prescreening Korean Dementia Screening
relatively strict criteria: a Mini-Mental State Examination (MMSE) Questionnaire (KDSQ-P), which has a score ranging from 0 to 10;
≤ 26 and either a Clinical Dementia Rating (CDR) ≥ 1 or a Global a higher KDSQ-P score indicates more severe cognitive decline (24).

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Deterioration Scale (GDS) ≥ 3. Thus, all the elderly people of this The KDSQ-P has shown a significant correlation with the Korean
study who were prescribed the medication were considered to meet version of the MMSE with high validity and reliability (24). Patients
these criteria. A similar definition of dementia occurrence has been with total scores ≥ 4 are expected to receive further evaluation for
used in other studies that collected data from administrative data- cognitive function.
bases (22).

Covariates Statistical Analyses


Comorbid conditions, smoking, depressive symptom, and base- Data are summarized as numbers with percentages for categor-
line cognitive function were considered to be related to the future ical variables, and mean values with standard deviations (SD) for
development of dementia and were included as covariates in the continuous variables. For each clinical characteristic by TUG test
multivariate analysis. Information on smoking history and relevant results, we performed a group-wise comparison using a two-tailed

Table 1.  Study Population Characteristics according to Baseline Timed Up and Go Test Results

Timed Up and Go Test Resulta

Total Normal Impaired

n (%) (n = 49,283) (n = 42,460) (n = 6,823) p Valueb

Sex
 Male 24,392 (49.5) 21,499 (50.6) 2,893 (42.4) <.001
 Female 24,891 (50.5) 20,961 (49.4) 3,930 (57.6)
Smokingc
 Never 34,468 (69.9) 29,360 (69.2) 5,108 (74.9) <.001
 Former 8,656 (17.6) 7,731 (18.2) 925 (13.6)
 Current 6,159 (12.5) 5,369 (12.6) 790 (11.6)
Strokec
 No 41,059 (83.3) 35,850 (84.4) 5,209 (76.3) <.001
 Yes 8,224 (16.7) 6,610 (15.6) 1,614 (23.7)
Hypertensionc
 No 28,240 (57.3) 24,447 (57.6) 3,793 (55.6) .002
 Yes 21,043 (42.7) 18,013 (42.4) 3,030 (44.4)
Diabetes mellitusc
 No 36,910 (74.9) 32,166 (75.8) 4,744 (69.5) <.001
 Yes 12,373 (25.1) 10,294 (24.2) 2,079 (30.5)
Hypercholesterolemiac
 No 39,384 (79.9) 34,286 (80.8)f 5,098 (74.7) <.001
 Yes 9,899 (20.1) 8,174 (19.3) 1,725 (25.3)
Depressive symptomd
 No 37,725 (76.6)f 32,891 (77.5) 4,834 (70.9)f <.001
 Yes 11,558 (23.5) 9,569 (22.5) 1,989 (29.2)
Baseline Cognitive functione
  Mean ± SD 1.5 ± 2.0 1.5 ± 1.9 1.8 ± 2.1 <.001
 <4 40,518 (82.2) 35,152 (82.8) 5,366 (78.7)f <.001
 ≥4 8,765 (17.8) 7,308 (17.2) 1,457 (21.4)

Note: SD = Standard deviation, All the subjects were 66 years old at screening.
a
Taking longer than 10 seconds to perform the Timed Up and Go test was regarded as gait impairment. bComparison was performed by Student’s t test for con-
tinuous variables and Chi-squared test for categorical variables. cSmoking history, stroke, hypertension, diabetes mellitus, and hypercholesterolemia were asked
in the questionnaire. dDepressive symptom was defined by a negative answer to any of three screening questions extracted from the Geriatric Depression Scale.
e
Baseline cognitive function was assessed by the Prescreening Korean Dementia Screening Questionnaire (KDSQ-P); 0–10 points. Higher score indicates cognitive
decline. Further evaluation is recommended for subjects with scores > 4. fTotal percentages may not equal 100% because of rounding.
Journals of Gerontology: MEDICAL SCIENCES, 2018, Vol. 73, No. 9 1241

function. The associations between the TUG test results and future
dementia occurrence are represented as hazard ratios and 95% confi-
dence intervals. Further, considering death before dementia diagnosis
as competing risk of dementia occurrence, we performed compet-
ing risk analysis using Fine and Gray model adjusting for the same
covariates. From this analysis, adjusted subdistribution hazard ratios
were obtained. The same analyses were repeated for the subtypes
of dementia; Alzheimer’s disease and vascular dementia (Table  2).
In addition, using the same models, subgroup analyses were con-
ducted for the subjects who showed normal baseline cognitive func-
tion, as indicated by a KDSQ-P score less than 4 (Supplementary

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Table 1), and elderly people with no history of stroke or Parkinson’s
disease (25) (Supplementary Table  2). In Korea, acetylcholinester-
ase inhibitors and NMDA receptor antagonist are used for vascular
dementia (19,21), however this is not yet a unified practice globally.
So, additional analysis was performed using vascular dementia def-
inition only by the diagnosis with ICD-10 code, excluding medica-
tion prescription (Supplementary Table 3). STATA software (ver. 14.1;
STATA Corp., Houston, TX) was used for all statistical analyses.

Results
Study Population Characteristics
Among the 49,283 subjects who were initially included in the ana-
lysis, 6,823 showed gait impairment according to their baseline TUG
test. The percentage of women was higher in the impaired TUG group
compared with the normal TUG group (57.6% vs 49.4%). The rates
of stroke (23.7% vs 15.6%), hypertension (44.4% vs 42.4%), dia-
betes mellitus (30.5% vs 24.2%), and hypercholesterolemia (25.3%
vs 19.3%) were higher in the impaired TUG group than in the normal
TUG group. The mean cognitive impairment score, as assessed by the
screening questionnaire, was higher in the impaired TUG group (1.8
vs 1.5). The distribution of all the above factors showed significant
differences between the two groups (p < .05; Table 1).

Risk of Dementia Occurrence


The mean follow-up period was 3.8 years. Incidence rates of demen-
tia were 4.7 and 6.9 cases per 1,000 person-years in the normal
and impaired TUG groups, respectively. The impaired TUG group
showed a higher risk of total dementia occurrence than normal
TUG group (adjusted hazard ratio [aHR], 1.34; 95% confidence
interval [95% CI], 1.14–1.57). Dementia subtype analyses showed
that the impaired TUG group had a higher risk for Alzheimer’s dis-
ease (aHR, 1.26; 95% CI, 1.06–1.51) and vascular dementia (aHR,
Figure 2.  Dementia occurrence according to baseline timed up and go test 1.65; 95% CI, 1.19–2.30). The competing risk analysis showed
results. similar results (Table 2).
Also for the subjects with normal baseline cognitive function, the
Student’s t test for continuous variables and the chi-squared test for impaired TUG group showed a higher risk of total dementia occur-
categorical variables (Table  1). Statistical differences between the rence (aHR, 1.33; 95% CI, 1.10–1.62); it showed a marginally sig-
two groups are represented by p values. nificant increase in the risk of Alzheimer’s disease (aHR, 1.24; 95%
The patients were followed up from the day of screening of CI, 0.99–1.55) or vascular dementia (aHR, 1.51; 95% CI, 0.99–2.31)
the NSPTA program to the occurrence of dementia, death, or the (Supplementary Table  1). For the elderly people without a history
last follow-up day (December 31, 2013), whichever came first. of a disabling disease (stroke or Parkinson’s disease), the impaired
A  Kaplan–Meier curve was used to assess the relationship between TUG group showed a higher risk of total dementia incidence (aHR,
TUG test results and dementia occurrence (Figure 2). Statistical sig- 1.26; 95% CI, 1.05–1.50) but not a significant increased risk of
nificance of the Kaplan–Meier curve was tested using a log-rank Alzheimer’s disease (aHR, 1.22; 95% CI, 0.99–1.48) or vascular
test. Multivariate analysis was conducted using a Cox proportional dementia (aHR, 1.48; 95% CI, 1.00–2.18) (Supplementary Table 2).
hazard regression model with other possible risk factors of demen- When vascular dementia was defined only by ICD-code, impaired
tia, including sex, smoking, stroke, hypertension, diabetes mellitus, TUG group also showed a higher risk of vascular dementia occur-
hypercholesterolemia, depressive symptom, and baseline cognitive rence (aHR, 1.57; 95% CI, 1.22–2.01) (Supplementary Table 3).
1242 Journals of Gerontology: MEDICAL SCIENCES, 2018, Vol. 73, No. 9

Table 2.  Occurrence of Dementia According to Baseline Timed Up and Go Test Results (n = 49,283)

Person-years Number of Occurrence Rate (1/1,000) HR (95% CI) aHR (95% CI)a aSHR (95% CI)b

All dementiac 188,963.5 950 5.0


  Normal TUG 160,451.6 752 4.7 1.00 1.00 1.00
  Impaired TUG 28,511.9 198 6.9 1.40 (1.20–1.64) 1.34 (1.14–1.57) 1.33 (1.14–1.56)
Alzheimer’s diseased 189,247.9 777 4.1
  Normal TUG 160,667.9 622 3.9 1.00 1.00 1.00
  Impaired TUG 28,580.0 155 5.4 1.32 (1.11–1.58) 1.26 (1.06–1.51) 1.25 (1.05–1.49)
Vascular dementiae 190,185.8 193 1.0
  Normal TUG 161,404.6 146 0.9 1.00 1.00 1.00

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  Impaired TUG 28,781.2 47 1.6 1.72 (1.23–2.38) 1.65 (1.19–2.30) 1.64 (1.18–2.28)

Note: aHR = Adjusted hazard ratio; aSHR = Adjusted subdistribution hazard ratio; HR = Hazard ratio, All the subjects were 66 years old at screening.
a
Multivariate model included sex, smoking status, and past medical history (stroke, hypertension, diabetes mellitus, hypercholesterolemia), depressive symptom,
and baseline cognitive function. bCompeting risk analysis regarding death as competitive risk of dementia occurrence. Multivariate model included sex, smoking
status, and past medical history (stroke, hypertension, diabetes mellitus, hypercholesterolemia), depression, and baseline cognitive function. cDementia was defined
as starting acetylcholinesterase inhibitors or N-Methyl-D-Aspartate receptor antagonist (donepezil, rivastigmine, galantamine, or memantine) with a diagnosis
code of dementia (F00, F01, F02, F03, G30, F051, or G311) by the International Classification of Diseases 10th Revision (ICD-10) after the health screening day.
d
Alzheimer’s disease was defined as starting acetylcholinesterase inhibitors or N-Methyl-D-Aspartate receptor antagonist (donepezil, rivastigmine, galantamine, or
memantine) with an ICD-10 diagnosis code of Alzheimer’s disease (F00 or G30) after the health screening day. eVascular dementia was defined as starting acetyl-
cholinesterase inhibitors or N-Methyl-D-Aspartate receptor antagonist (donepezil, rivastigmine, galantamine, or memantine) with an ICD-10 diagnosis code of
vascular dementia (F01) after the health screening day.

Discussion Our results are robust, as shown by consistent findings, regard-


less of the covariate adjustment and application of different exclu-
To the best of our knowledge, this is the first study that showed sion criteria. Especially, the subgroup analysis showed normal
gait impairment measured by TUG test could predict future clin- baseline cognitive function (defined as a KDSQ-P score < 4) with gait
ical dementia in the elderly population. Strengths of this study impairment in TUG test is a predictive marker of future dementia
include use of a large, nationally representative homogenous sam- occurrence (Supplementary Table 1). Furthermore, the self-reporting
ple of the elderly population in terms of age (66  years old), and questionnaire for activities of daily living did not significantly pre-
independent examination of dementia occurrence in a clinical set- dict dementia (HR, 1.22; 95% CI, 0.93–1.58 and aHR, 1.22; 95%
ting rather than in a research setting, eliminating potential bias CI, 0.93–1.59; not shown on tables). This result further emphasizes
from the investigator. Therefore, our study can be considered a the usefulness of the TUG test for predicting dementia.
confirmation of the findings from previous small-scale studies con- Impairment on TUG test result increased the risk of future demen-
ducted in research settings. tia by 1.34-fold. The risk was comparable or higher than other known
To date, many researchers are seeking simple ways to predict risk factors of dementia (female sex: aHR, 1.57; 95% CI, 1.31–1.87,
dementia occurrence. The TUG test is a simple, much studied test baseline cognitive function: aHR, 1.14; 95% CI, 1.11–1.17; not
(18,26), and the test protocol is well established. The TUG test takes shown on tables). This suggests that physicians should be more vigi-
less than a minute and only requires a 3-m distance and a normal lant in looking for signs of cognitive decline if a patient shows gait
chair. From previous studies, the TUG test predicted fall risks (27), impairment. If patients show impairment on TUG test results, the
deterioration in activities of daily living (28), and nursing home physician may perform cognitive tests regularly in order to detect
placement (29). The TUG test also predicted dementia occurrence in cognitive impairment earlier. This would be valuable for preventing
this large, longitudinal study. dementia and its adverse consequences, as early detection and man-
The mechanisms linking gait impairment and cognitive agement can delay the status of dependency (36). Physicians can also
decline are not well understood. One possibility is the sharing provide patients and family members with strategies for preventing
of common risk factors between gait impairment and cognitive dementia (37).
decline, especially cardiovascular risk factors, nutrition, and This study does have some limitations. First, our definition of
depressive symptom. Cardiovascular risk factors may contrib- dementia occurrence is not based on strict criteria using in-depth
ute to gait impairment through impaired blood flow to skeletal cognitive testing. Instead, we used a clinical diagnosis and medica-
muscles (30). It is also known that cardiovascular risk factors tion prescription from claims data; our method does, however, reflect
play an important role in developing both vascular dementia and real clinical practice and is free from the bias of nonblinding. Second,
Alzheimer’s disease (31). Regarding nutrition, adherence to a we could not include several well-known risk factors for dementia in
Mediterranean diet has been linked to both better physical per- the covariate analysis such as the presence of the APOE4 gene and
formance (32) and cognitive function (33). Depression is also a education level. However, it is unlikely that these factors significantly
well-established risk factor of both decreased physical perform- affect the association between gait impairment and dementia.
ance and cognitive decline (34). In addition, some recent studies In conclusion, impairment on TUG test result increased the risk
have suggested that brain pathophysiologies, such as neurofibril- of future dementia occurrence. This suggests that the TUG test might
lary tangles and plaques, are common mechanisms for physical be a useful predictive marker of dementia occurrence. More vigilant
frailty and Alzheimer’s disease (35). Such brain deposition might follow-up and early intervention to prevent cognitive decline would
result in gait impairment before clinical dementia occurs. benefit elderly people with signs of gait impairment.
Journals of Gerontology: MEDICAL SCIENCES, 2018, Vol. 73, No. 9 1243

Supplementary Material screening of 557,648 community-dwelling older adults. Arch Gerontol


Geriatr. 2017;68:174–180. doi:10.1016/j.archger.2016.10.008
Supplementary data is available at The Journals of Gerontology, 16. Shin DW, Cho B, Guallar E. Korean National Health Insurance Database.
Series A: Biological Sciences and Medical Sciences online. JAMA Intern Med. 2016;176:138. doi:10.1001/jamainternmed.2015.7110
17. Cheol Seong S, Kim Y-Y, Khang Y-H, Heon Park J, Kang H-J, Lee H, et al. Data
Resource Profile: The National Health Information Database of the National
Funding Health Insurance Service in South Korea. Int J Epidemiol. 2016;46(3):
This study was supported by research grants from Hanmi Pharmaceutical 799–800. doi:10.1093/ije/dyw253
Co.Ltd (grant number NHIS-2016-2-267). 18. Podsiadlo D, Richardson S. The timed “Up & Go”: a test of basic functional
mobility for frail elderly persons. J Am Geriatr Soc. 1991;39:142–148.
19. Ungerleider N, Han C, Zhang J, Yao L, Wu T. TGFβ signaling confers
Acknowledgments sorafenib resistance via induction of multiple RTKs in hepatocellular car-

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cinoma cells. Mol Carcinog. 2017;56:1302–1311. doi:10.1002/mc.22592
The authors appreciate the advice and assistance of Functional Assessment
20. Park HY, Park JW, Song HJ, Sohn HS, Kwon JW. The association

Committee for Elderly (FACE) Committee, The Korean Geriatrics Society.
between polypharmacy and dementia: a nested case-control study based
on a 12-year longitudinal cohort database in South Korea. PLoS One.
2017;12:e0169463. doi:10.1371/journal.pone.0169463
Conflicts of Interest 21. Hahn S-J, Paik N-J. Pharmacological treatment of dementia. Brain &
None reported. Neurorehabilitation. 2015;8:19–23.
22. Kosteniuk JG, Morgan DG, O’Connell ME, et al. Incidence and prevalence
of dementia in linked administrative health data in Saskatchewan, Canada:
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