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Effect of mild cognitive impairment on balance
Journal of the Neurological Sciences 305 (2011) 121–125
Contents lists available at ScienceDirect
Journal of the Neurological Sciences j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / j n s
Effect of mild cognitive impairment on balance Bo Mi Shin a, Soo Jeong Han a,b,⁎, Ji Hyang Jung c, Jung Eun Kim c, Felipe Fregni b,d a
Department of Rehabilitation Medicine, School of Medicine, Ewha Womans University, Seoul, Republic of Korea Laboratory of Neuromodulation, Spaulding Rehabilitation Hospital, Harvard Medical School, Boston, MA, USA c Department of Neurology, School of Medicine, Ewha Womans University, Seoul, Republic of Korea d Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA b
a r t i c l e
i n f o
Article history: Received 30 November 2010 Received in revised form 18 February 2011 Accepted 22 February 2011 Available online 21 March 2011 Keywords: Mild cognitive impairment Balance Posturography Aging
a b s t r a c t Objective: To investigate the effect of mild cognitive impairment (MCI) on balance. Methods: 87 subjects with subjective memory impairment were enrolled, and subdivided into two groups, MCI and non-MCI, according to diagnostic criteria of amnestic subtype of MCI according to the 1999 MCI international panel (Current Concepts in Mild Cognitive Impairment). These two groups were matched for age and gender. Posturography was used to assess balance by measuring the mediolateral and anteroposterial sway speed and distance in the standing position, with both opened and closed eyes. Results: The mediolateral sway speed and distance were higher in the MCI group than the non-MCI group, with both opened and closed eyes (p b 0.05). However, there was no significant difference between the MCI group and non-MCI in anteroposterior sway speed and distance. These results were confirmed in a multivariate model adjusting for gender, age, weight, height, foot size, and education. The mediolateral, and anteroposterior sway speed and distance values were higher on eye closing status than on eye opening status in both the MCI and control groups (p b 0.00). Conclusion: The falling risk is assumed to be higher in MCI subjects than in non-MCI subjects, especially due to decreased mediolateral balance, as shown in our adjusted analysis. These findings underscore the importance of specific balance exercise in which mediolateral balance is measured and visual compensation training programs for MCI subjects in order to prevent fall and related fracture, as well as the importance of programs for improvement of cognitive function. © 2011 Elsevier B.V. All rights reserved.
1. Introduction The common understanding until a few decades ago was that forgetfulness in the elderly is a physiological phenomenon. But in the 1960s, Kral described ‘benign senescent forgetfulness’ as pathological state between normal state and dementia [1] and in the 1980s and 1990s, other studies had suggested various terms in order to describe the commonly observed mild memory impairment, which was regarded as different from dementia [2,3]. Petersen et al. first proposed the diagnostic criteria for mild cognitive impairment (MCI) in 1997 [4]. It is based on the presence of subjective memory impairment, as assessed by subjective symptoms and objective cognitive assessments showing preserved general intellectual function, intact ability to perform daily living activities, and absence of dementia [5–10]. One important issue in older adults with cognitive problems is the higher risk of fall due to decreased motor function and balance [11–13]. A growing number of neuroimaging studies have shown that motor ⁎ Corresponding author at: Department of Rehabilitation Medicine, Ewha Womans University, School of Medicine, 911-1 Mok-Dong, Yangcheon-Gu, Seoul, South Korea. Tel.: +82 2 2650 5035; fax: +82 2 2650 5145. E-mail addresses: [email protected], [email protected] (S.J. Han). 0022-510X/$ – see front matter © 2011 Elsevier B.V. All rights reserved. doi:10.1016/j.jns.2011.02.031
function decline is associated with age-related white matter change. So-called leukoaraiosis and marked periventricular white matter change appeared as the strongest magnetic resonance brain correlate of mobility decline in older people with MCI [14]. Older adults with cognitive impairment have at least twice as high of a risk of fall as normal older adults. Furthermore, the consequence of fall in this population is more serious than in normal older people [15]. MCI patients need more help to transfer or gait than healthy people and have more secondary falling risk [16,17]. The purpose of this study was to ascertain the effect of MCI on balance as compared to subjects with memory complaint and no MCI. In addition, this study intended to investigate whether any other factors influence this effect. This investigation is critical to the exploration of specific balance dysfunction in MCI subjects in order to plan future rehabilitation programs that prevent falls in MCI. 2. Materials and methods 2.1. Subjects Subjects with subjective memory impairment were invited to participate in this study. Among the subjects with normal range of
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B.M. Shin et al. / Journal of the Neurological Sciences 305 (2011) 121–125
Korean version of Mini-Mental State Examination (K-MMSE) score, the subjects were included if they showed normal cognitive function on short version of literacy independent cognitive assessment by trained clinician after the written consent. And subjects with any history of dementia, memory impairment secondary to other degenerative problems like Parkinson's disease, stroke, severe cardiovascular disease, major surgery due to spinal or arthrogenic problem, fall or medication affecting balance such as benzodiazepine were excluded. We enrolled a total of 87 subjects to participate in this study. In order to adjust our results with important covariates, we measured subjects' weight, height, foot size, and level of education, measured as period of education. Patients were enrolled after having given written informed consent for the study which was approved by the institutional review board of Ewha Womans University Medical Center. 2.2. Clinical criteria for MCI Mild cognitive impairment is classified as the stage between cognition of normal aging and mild dementia. We therefore classified subjects with subjective memory complaint in MCI and non-MCI. Here it should be noted that we chose the non-MCI comparison group with subjects with subjective memory complaint (without MCI) as to control for this variable (subjective memory complaint) in our analysis. The criteria of MCI were defined according to the panel/consensus meeting with MCI experts from around the world that took place in 1999 and published in 2004 [18]. According to this document, the suggested criteria (used in this study) — we decided to focus on the most common MCI subtype, the amnestic subtype, also the most accepted one — is the following: (1) memory complaint, preferably corroborated by an informant, (2) objective memory impairment for age and education, (3) largely normal general cognitive function, (4) essentially intact activities of daily living and (5) not demented. We therefore determined MCI status in our sample based on neuropsychological and clinical testing, as defined by Seoul Neuropsychological Screening Battery (SNSB) Dementia Version [19]. In summary, all subjects complained of consistent memory impairment,
Fig. 1. Balance test using posturography. The figure shows that subjects were performing the balance test through posturography. The posturography consists of a force platform, amplifier and software program. Subjects were positioned with both hands above their umbilicus, eyes staring straight ahead.
but this impairment had minimal to no impact on activities of daily living. And episodic memory was assessed by sub-test like Seoul Verbal Learning Test (SVLT) in SNSB in order to fulfill the diagnostic criteria for amnestic MCI. In addition, subjects had no history of dementia, stroke, or medical diseases associated with cognitive impairment, and the total K-MMSE [20] score, after correcting for age and education level, was over the mean value minus two standard deviations. Subjects were also included if their Clinical Dementia Rating scale score (CDR) was 0.5, and Global Deterioration Scale score (GDS) was 2 or 3 [7].
2.3. Posturography For measuring balance, we used the Good Balance® posturography (Jyväskylä, Finland). It consists of a force platform, amplifier, and software program. The platform measures 80 cm and is shaped like an equilateral triangle. This platform is connected to an amplifier with 3 channels. The center of pressure is analyzed based on vertical force while the subject is standing on the platform. The balance test was conducted in a closed space. Subjects were asked to take off their shoes, and then their feet were positioned parallel with a 20 centimeter distance between them. Subjects were positioned with both hands above their umbilicus, eyes staring straight ahead. Neither communication nor motion was permitted during the test (Fig. 1). We conducted the test twice, once in an eye opening state and once in an eye closing state, in 5 second intervals, and measured the mean score. Anteroposterior and mediolateral sway speed and distance were analyzed (Fig. 2).
Fig. 2. Postural sway pattern. The balance test was consisted with eye opening state and eye closing state with 5 second interval. A. Anteroposterior sway speed and distance. B. Mediolateral sway speed and distance were analyzed.
B.M. Shin et al. / Journal of the Neurological Sciences 305 (2011) 121–125 Table 1 Demographics of subjects. Factor
MCI
Control
p value
Sexa (M:F) Age⁎ (years) Weight⁎ (kg) Height⁎ (cm) Foot size⁎ (mm) K-MMSE⁎ (score) Education⁎ (years)
12:19 72.1 ± 4.1 56.4 ± 9.8 155.2 ± 8.3 239.6 ± 17.0 24.2 ± 4.1 6.6 ± 5.7
26:32 71.5 ± 3.7 58.4 ± 9.2 156.1 ± 7.3 243.8 ± 14.1 26.4 ± 2.7 6.5 ± 4.6
0.767 0.798 0.426 0.501 0.474 0.458 0.615
K-MMSE: Korean Version of Mini Mental Status Examination. ⁎ Values are mean ± standard deviation. a Values are numbers.
2.4. Statistical analysis Analyses were performed with STATA® statistical software (version 11.0; STATA, Cary, NC). Based on our sample size of 87 subjects, we considered adequate to use regression models based on the central limit theorem. Also with this sample we could add up to 8/9 variables in the model. We therefore built a linear regression model to compare mediolateral, and anteroposterior sway distances, as well as speeds between the MCI and non-MCI groups, and between eye closed and eye opened status in all subjects. Because subjects were selected based on the presence of MCI, we performed a multivariate analysis in order to investigate the presence of potential confounding factors including age, gender, weight, height, foot size, and education level. Statistical significance refers to a p-value of less than 0.05. 3. Results 3.1. General characteristics The subjects comprised of 30 MCI patients and 57 control subjects. The mean age according to the group was 72.1±4.1 and 71.5±3.7 years old, respectively. In Table 1 we report values for sex, weight, height, foot size, and years of education in the MCI group and control group. All of these factors were not significantly different between the two stimulation groups (pN 0.10) and there was no correlation with the value measured during posturography (pN 0.05, Tables 2 and 3). As expected, there was no significant difference in MMSE average between the two groups (the mean MMSE score was 24.2±4.1 in MCI, and 26.4±2.7 in the control group). 3.2. Posturography Tables 2, 3, and 4 show the results for posturography. The univariate analysis showed a significant difference in mediolateral sway speed and distance values in the MCI group as compared with the control group for the eyes opened and closed condition (p b 0.05).
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However, there was no significant difference when performing the same analysis for anteroposterial sway speed and distance (p N 0.05). Finally we conducted a multivariate analysis including all the demographic characteristics (sex, age, weight, height, foot size, and educational level) as covariates, to determine whether our results were being confounded by one of these factors, though univariate analysis was not significant for these variables. Our results showed that adjusting for all these factors, the results remained the same: there was a significant difference in mediolateral sway speed and distance values between the two groups (see Table 3). As expected, when comparing eye status, the mediolateral, anteroposterior sway speed, and distance values were significantly higher with closed eyes than with opened eyes in all subjects (p b 0.05, Table 4); however there was no interaction effect between eye status and group (p N 0.7 for all the analyses); suggesting no worse compensation (when eyes are closed) in the MCI group as compared to control group. 4. Discussion Since the 1960s, many attempts have been made to define the earliest stage of dementia and its impact on different health-related domains. Many terms have been proposed to explain the transitional state between the cognitive changes of normal aging and dementia, but the most common is MCI [2,21,22]. Several clinical studies have explored the various mechanisms of MCI but there is no unified theory. Clinical evidence shows that a central cholinergic deficit is thought to be present in amnestic MCI, related to the loss of neurons in the nucleus basalis of Meynert [11,23]. The findings of a Religious Order Study indicated that cerebrovascular involvement in MCI is intermediate between that observed in aging and early Alzheimer's disease [24]. The role of amyloid deposition and neurofibrillary tangle formation in MCI has not yet been studied extensively, though Mitchell et al. established that pathological findings of neurofibrillary tangles in the mesial temproral structures do indeed correlate with MCI [25]. Furthermore, Mufson et al. demonstrated amyloid deposition in the mesial temporal lobes [23]. In the context of anatomical and functional changes in MCI, the balance system needs to be carefully evaluated as there is a complex system in place to control balance, composed of an afferent pathway of visual, auditory, somatosensory, and proprioceptive senses as well as an efferent pathway through the cerebral cortex, cerebellar cortex, subcortical area, and spinal cord. Balance usually declines as an individual ages, and the decline is even more pronounced in individuals with MCI [11,12,15,26–29]. Previous neuroimaging studies have shown that the worsening of motor function is associated with age-related white matter changes and, more specifically, marked periventricular white matter change, which appeared as the strongest magnetic resonance correlate of declined mobility in older people with MCI [14,30–32].
Table 2 Univariate analysis of balance with demographic factors. Factors
ML sway speed
ML sway distance
EO
Sex Age Weight Height Foot size Education Group
EC
EO
EC
Coef.
SE
p value
Adj R2
Coef.
SE
p value
Adj R2
Coef.
SE
p value
Adj R2
Coef.
SE
p value
Adj R2
0.292 −0.003 −0.026 −0.004 0.007 0.005 −1.476
0.451 0.065 0.024 0.030 0.015 0.045 0.444
0.519 0.967 0.283 0.892 0.640 0.911 0.001⁎
−0.007 −0.012 0.002 −0.012 −0.009 −0.011 0.105
−0.749 0.005 −0.020 0.028 0.028 0.029 −1.450
0.685 0.099 0.037 0.046 0.023 0.070 0.702
0.277 0.957 0.583 0.550 0.232 0.683 0.037⁎
0.002 −0.012 −0.008 −0.008 0.005 −0.010 0.048
8.766 −0.083 −0.784 −0.123 0.213 0.156 −44.252
13.532 1.956 0.726 0.904 0.455 1.376 13.317
0.519 0.966 0.283 0.892 0.640 0.910 0.001⁎
−0.007 −0.012 0.002 −0.012 −0.009 −0.012 0.105
−22.488 0.162 −0.613 0.824 0.830 0.862 −43.488
20.533 2.981 1.112 1.376 0.688 2.101 21.055
0.277 0.957 0.583 0.551 0.231 0.683 0.042⁎
0.002 −0.012 −0.008 −0.008 0.005 −0.010 0.037
ML: mediolateral, EO: eye opening, EC: eye closing. Coef.: correlation efficient, SE: standard error, Adj R2: adjusted R-squared. ⁎ p b 0.05.
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Table 3 Multivariate analysis of balance with demographic factors. Factors
ML sway speed
ML sway distance
EO
Sex Age Weight Height Foot size Education Group
EC
EO
EC
Coef
SE
p value
Coef
SE
p value
Coef
SE
p value
Coef
SE
p value
0.729 −0.035 −0.039 0.011 0.036 0.014 −1.522
0.554 0.067 0.030 0.042 0.020 0.049 0.459
0.192 0.600 0.200 0.800 0.095 0.769 0.001⁎
−0.326 −0.045 −0.063 0.039 0.086 0.003 −1.592
0.878 0.106 0.048 0.066 0.033 0.077 0.728
0.712 0.673 0.191 0.554 0.246 0.965 0.032⁎
21.850 −1.052 −1.175 0.318 1.074 0.432 −45.633
16.606 1.998 0.909 1.252 0.617 1.457 13.775
0.192 0.600 0.200 0.800 0.086 0.768 0.001⁎
−9.784 −1.339 −1.901 1.177 1.144 0.103 −47.735
26.323 3.167 1.441 1.984 0.979 2.310 21.835
0.711 0.674 0.191 0.555 0.246 0.965 0.032⁎
ML: mediolateral, EO: eye opening, EC: eye closing. Coef: correlation efficient, SE: standard error. ⁎ p b 0.05.
Most of the previous studies that evaluated balance in older patients were conducted in patients with dementia. However it is more cost-effective to address balance in older adults with MCI. This was the goal of our study: to address balance decline in the MCI group via posturography. One interesting finding is that balance was not associated with sex, age, foot size, weight, or level of education. Although a previous study found an association between age and balance [12,26], one potential explanation for the lack of significance for the age factor is that we selected patients within a relatively narrow age range. In addition, despite the fact that factors such as foot size and height are associated with the center of pressure on a platform, they were not correlated to balance performance in this study probably because they are stable factors that subjects learn how to adapt throughout their lifetime. An expected finding that we confirmed in this study is that eyes status was significantly associated with mediolateral and anteroposterior balance. However, this factor was not associated with group. In other words, the amount of compensation when subjects close their eyes is similar in both groups. This was an interesting finding that supports training program for MCI patients to improve balance as the compensatory system seems to be relatively intact. One interesting point that is worth mention is the mechanism of decreased balance in MCI patients. Although balance is controlled mainly by subcortical nuclei and tracts, there is an intense cortical involvement, especially during compensation. For instance, a previous Transcranial Magnetic Stimulation (TMS) study illustrated that the Motor Evoked Potential (MEP) in the soleus muscle was facilitated during the voluntary heel-raise movement, as a part of anticipatory postural control [33]. Therefore, one question that needs to be addressed is whether degeneration in cortico-subcortical networks delays compensatory movements, though we did not see a differential effect of eye status in our results. Further studies with TMS might provide additional insights into the cortical mechanisms of balance in MCI. Table 4 Comparison of balance ability between EO and EC for each group. Factors
MCI Coef
Control SE
p value R
1.229 0.116 0.000⁎
ML sway speed (mm/s) ML sway distance 1.229 0.116 0.000⁎ (mm) AP sway speed 1.211 0.202 0.000⁎ (mm/s) AP sway distance 1.211 0.202 0.000⁎ (mm)
2
Coef
SE
p value R2
0.801 1.264 0.188 0.000⁎
0.450
0.801 1.264 0.188 0.000⁎
0.450
0.563 1.389 0.208 0.000⁎
0.448
0.563 1.388 0.208 0.000⁎
0.448
ML: mediolateral, AP: anteroposterior, EO: eye opening, EC: eye closing. Coef: correlation coefficient, SE: standard error. ⁎ p b 0.05.
In summary, mediolateral sway speed and distance were significantly higher in the MCI group than in the non-MCI group. There was no significant difference between the MCI group and the control group in the anteroposterial sway speed and distance. These results point to a specific deficit in balance control in MCI patients compared with controls, and encourages a specific combined balance exercise program with visual compensation training for improvement of cognitive function, in order to prevent fall and related fracture.
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Contents lists available at ScienceDirect
Journal of the Neurological Sciences j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / j n s
Effect of mild cognitive impairment on balance Bo Mi Shin a, Soo Jeong Han a,b,⁎, Ji Hyang Jung c, Jung Eun Kim c, Felipe Fregni b,d a
Department of Rehabilitation Medicine, School of Medicine, Ewha Womans University, Seoul, Republic of Korea Laboratory of Neuromodulation, Spaulding Rehabilitation Hospital, Harvard Medical School, Boston, MA, USA c Department of Neurology, School of Medicine, Ewha Womans University, Seoul, Republic of Korea d Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA b
a r t i c l e
i n f o
Article history: Received 30 November 2010 Received in revised form 18 February 2011 Accepted 22 February 2011 Available online 21 March 2011 Keywords: Mild cognitive impairment Balance Posturography Aging
a b s t r a c t Objective: To investigate the effect of mild cognitive impairment (MCI) on balance. Methods: 87 subjects with subjective memory impairment were enrolled, and subdivided into two groups, MCI and non-MCI, according to diagnostic criteria of amnestic subtype of MCI according to the 1999 MCI international panel (Current Concepts in Mild Cognitive Impairment). These two groups were matched for age and gender. Posturography was used to assess balance by measuring the mediolateral and anteroposterial sway speed and distance in the standing position, with both opened and closed eyes. Results: The mediolateral sway speed and distance were higher in the MCI group than the non-MCI group, with both opened and closed eyes (p b 0.05). However, there was no significant difference between the MCI group and non-MCI in anteroposterior sway speed and distance. These results were confirmed in a multivariate model adjusting for gender, age, weight, height, foot size, and education. The mediolateral, and anteroposterior sway speed and distance values were higher on eye closing status than on eye opening status in both the MCI and control groups (p b 0.00). Conclusion: The falling risk is assumed to be higher in MCI subjects than in non-MCI subjects, especially due to decreased mediolateral balance, as shown in our adjusted analysis. These findings underscore the importance of specific balance exercise in which mediolateral balance is measured and visual compensation training programs for MCI subjects in order to prevent fall and related fracture, as well as the importance of programs for improvement of cognitive function. © 2011 Elsevier B.V. All rights reserved.
1. Introduction The common understanding until a few decades ago was that forgetfulness in the elderly is a physiological phenomenon. But in the 1960s, Kral described ‘benign senescent forgetfulness’ as pathological state between normal state and dementia [1] and in the 1980s and 1990s, other studies had suggested various terms in order to describe the commonly observed mild memory impairment, which was regarded as different from dementia [2,3]. Petersen et al. first proposed the diagnostic criteria for mild cognitive impairment (MCI) in 1997 [4]. It is based on the presence of subjective memory impairment, as assessed by subjective symptoms and objective cognitive assessments showing preserved general intellectual function, intact ability to perform daily living activities, and absence of dementia [5–10]. One important issue in older adults with cognitive problems is the higher risk of fall due to decreased motor function and balance [11–13]. A growing number of neuroimaging studies have shown that motor ⁎ Corresponding author at: Department of Rehabilitation Medicine, Ewha Womans University, School of Medicine, 911-1 Mok-Dong, Yangcheon-Gu, Seoul, South Korea. Tel.: +82 2 2650 5035; fax: +82 2 2650 5145. E-mail addresses: [email protected], [email protected] (S.J. Han). 0022-510X/$ – see front matter © 2011 Elsevier B.V. All rights reserved. doi:10.1016/j.jns.2011.02.031
function decline is associated with age-related white matter change. So-called leukoaraiosis and marked periventricular white matter change appeared as the strongest magnetic resonance brain correlate of mobility decline in older people with MCI [14]. Older adults with cognitive impairment have at least twice as high of a risk of fall as normal older adults. Furthermore, the consequence of fall in this population is more serious than in normal older people [15]. MCI patients need more help to transfer or gait than healthy people and have more secondary falling risk [16,17]. The purpose of this study was to ascertain the effect of MCI on balance as compared to subjects with memory complaint and no MCI. In addition, this study intended to investigate whether any other factors influence this effect. This investigation is critical to the exploration of specific balance dysfunction in MCI subjects in order to plan future rehabilitation programs that prevent falls in MCI. 2. Materials and methods 2.1. Subjects Subjects with subjective memory impairment were invited to participate in this study. Among the subjects with normal range of
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Korean version of Mini-Mental State Examination (K-MMSE) score, the subjects were included if they showed normal cognitive function on short version of literacy independent cognitive assessment by trained clinician after the written consent. And subjects with any history of dementia, memory impairment secondary to other degenerative problems like Parkinson's disease, stroke, severe cardiovascular disease, major surgery due to spinal or arthrogenic problem, fall or medication affecting balance such as benzodiazepine were excluded. We enrolled a total of 87 subjects to participate in this study. In order to adjust our results with important covariates, we measured subjects' weight, height, foot size, and level of education, measured as period of education. Patients were enrolled after having given written informed consent for the study which was approved by the institutional review board of Ewha Womans University Medical Center. 2.2. Clinical criteria for MCI Mild cognitive impairment is classified as the stage between cognition of normal aging and mild dementia. We therefore classified subjects with subjective memory complaint in MCI and non-MCI. Here it should be noted that we chose the non-MCI comparison group with subjects with subjective memory complaint (without MCI) as to control for this variable (subjective memory complaint) in our analysis. The criteria of MCI were defined according to the panel/consensus meeting with MCI experts from around the world that took place in 1999 and published in 2004 [18]. According to this document, the suggested criteria (used in this study) — we decided to focus on the most common MCI subtype, the amnestic subtype, also the most accepted one — is the following: (1) memory complaint, preferably corroborated by an informant, (2) objective memory impairment for age and education, (3) largely normal general cognitive function, (4) essentially intact activities of daily living and (5) not demented. We therefore determined MCI status in our sample based on neuropsychological and clinical testing, as defined by Seoul Neuropsychological Screening Battery (SNSB) Dementia Version [19]. In summary, all subjects complained of consistent memory impairment,
Fig. 1. Balance test using posturography. The figure shows that subjects were performing the balance test through posturography. The posturography consists of a force platform, amplifier and software program. Subjects were positioned with both hands above their umbilicus, eyes staring straight ahead.
but this impairment had minimal to no impact on activities of daily living. And episodic memory was assessed by sub-test like Seoul Verbal Learning Test (SVLT) in SNSB in order to fulfill the diagnostic criteria for amnestic MCI. In addition, subjects had no history of dementia, stroke, or medical diseases associated with cognitive impairment, and the total K-MMSE [20] score, after correcting for age and education level, was over the mean value minus two standard deviations. Subjects were also included if their Clinical Dementia Rating scale score (CDR) was 0.5, and Global Deterioration Scale score (GDS) was 2 or 3 [7].
2.3. Posturography For measuring balance, we used the Good Balance® posturography (Jyväskylä, Finland). It consists of a force platform, amplifier, and software program. The platform measures 80 cm and is shaped like an equilateral triangle. This platform is connected to an amplifier with 3 channels. The center of pressure is analyzed based on vertical force while the subject is standing on the platform. The balance test was conducted in a closed space. Subjects were asked to take off their shoes, and then their feet were positioned parallel with a 20 centimeter distance between them. Subjects were positioned with both hands above their umbilicus, eyes staring straight ahead. Neither communication nor motion was permitted during the test (Fig. 1). We conducted the test twice, once in an eye opening state and once in an eye closing state, in 5 second intervals, and measured the mean score. Anteroposterior and mediolateral sway speed and distance were analyzed (Fig. 2).
Fig. 2. Postural sway pattern. The balance test was consisted with eye opening state and eye closing state with 5 second interval. A. Anteroposterior sway speed and distance. B. Mediolateral sway speed and distance were analyzed.
B.M. Shin et al. / Journal of the Neurological Sciences 305 (2011) 121–125 Table 1 Demographics of subjects. Factor
MCI
Control
p value
Sexa (M:F) Age⁎ (years) Weight⁎ (kg) Height⁎ (cm) Foot size⁎ (mm) K-MMSE⁎ (score) Education⁎ (years)
12:19 72.1 ± 4.1 56.4 ± 9.8 155.2 ± 8.3 239.6 ± 17.0 24.2 ± 4.1 6.6 ± 5.7
26:32 71.5 ± 3.7 58.4 ± 9.2 156.1 ± 7.3 243.8 ± 14.1 26.4 ± 2.7 6.5 ± 4.6
0.767 0.798 0.426 0.501 0.474 0.458 0.615
K-MMSE: Korean Version of Mini Mental Status Examination. ⁎ Values are mean ± standard deviation. a Values are numbers.
2.4. Statistical analysis Analyses were performed with STATA® statistical software (version 11.0; STATA, Cary, NC). Based on our sample size of 87 subjects, we considered adequate to use regression models based on the central limit theorem. Also with this sample we could add up to 8/9 variables in the model. We therefore built a linear regression model to compare mediolateral, and anteroposterior sway distances, as well as speeds between the MCI and non-MCI groups, and between eye closed and eye opened status in all subjects. Because subjects were selected based on the presence of MCI, we performed a multivariate analysis in order to investigate the presence of potential confounding factors including age, gender, weight, height, foot size, and education level. Statistical significance refers to a p-value of less than 0.05. 3. Results 3.1. General characteristics The subjects comprised of 30 MCI patients and 57 control subjects. The mean age according to the group was 72.1±4.1 and 71.5±3.7 years old, respectively. In Table 1 we report values for sex, weight, height, foot size, and years of education in the MCI group and control group. All of these factors were not significantly different between the two stimulation groups (pN 0.10) and there was no correlation with the value measured during posturography (pN 0.05, Tables 2 and 3). As expected, there was no significant difference in MMSE average between the two groups (the mean MMSE score was 24.2±4.1 in MCI, and 26.4±2.7 in the control group). 3.2. Posturography Tables 2, 3, and 4 show the results for posturography. The univariate analysis showed a significant difference in mediolateral sway speed and distance values in the MCI group as compared with the control group for the eyes opened and closed condition (p b 0.05).
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However, there was no significant difference when performing the same analysis for anteroposterial sway speed and distance (p N 0.05). Finally we conducted a multivariate analysis including all the demographic characteristics (sex, age, weight, height, foot size, and educational level) as covariates, to determine whether our results were being confounded by one of these factors, though univariate analysis was not significant for these variables. Our results showed that adjusting for all these factors, the results remained the same: there was a significant difference in mediolateral sway speed and distance values between the two groups (see Table 3). As expected, when comparing eye status, the mediolateral, anteroposterior sway speed, and distance values were significantly higher with closed eyes than with opened eyes in all subjects (p b 0.05, Table 4); however there was no interaction effect between eye status and group (p N 0.7 for all the analyses); suggesting no worse compensation (when eyes are closed) in the MCI group as compared to control group. 4. Discussion Since the 1960s, many attempts have been made to define the earliest stage of dementia and its impact on different health-related domains. Many terms have been proposed to explain the transitional state between the cognitive changes of normal aging and dementia, but the most common is MCI [2,21,22]. Several clinical studies have explored the various mechanisms of MCI but there is no unified theory. Clinical evidence shows that a central cholinergic deficit is thought to be present in amnestic MCI, related to the loss of neurons in the nucleus basalis of Meynert [11,23]. The findings of a Religious Order Study indicated that cerebrovascular involvement in MCI is intermediate between that observed in aging and early Alzheimer's disease [24]. The role of amyloid deposition and neurofibrillary tangle formation in MCI has not yet been studied extensively, though Mitchell et al. established that pathological findings of neurofibrillary tangles in the mesial temproral structures do indeed correlate with MCI [25]. Furthermore, Mufson et al. demonstrated amyloid deposition in the mesial temporal lobes [23]. In the context of anatomical and functional changes in MCI, the balance system needs to be carefully evaluated as there is a complex system in place to control balance, composed of an afferent pathway of visual, auditory, somatosensory, and proprioceptive senses as well as an efferent pathway through the cerebral cortex, cerebellar cortex, subcortical area, and spinal cord. Balance usually declines as an individual ages, and the decline is even more pronounced in individuals with MCI [11,12,15,26–29]. Previous neuroimaging studies have shown that the worsening of motor function is associated with age-related white matter changes and, more specifically, marked periventricular white matter change, which appeared as the strongest magnetic resonance correlate of declined mobility in older people with MCI [14,30–32].
Table 2 Univariate analysis of balance with demographic factors. Factors
ML sway speed
ML sway distance
EO
Sex Age Weight Height Foot size Education Group
EC
EO
EC
Coef.
SE
p value
Adj R2
Coef.
SE
p value
Adj R2
Coef.
SE
p value
Adj R2
Coef.
SE
p value
Adj R2
0.292 −0.003 −0.026 −0.004 0.007 0.005 −1.476
0.451 0.065 0.024 0.030 0.015 0.045 0.444
0.519 0.967 0.283 0.892 0.640 0.911 0.001⁎
−0.007 −0.012 0.002 −0.012 −0.009 −0.011 0.105
−0.749 0.005 −0.020 0.028 0.028 0.029 −1.450
0.685 0.099 0.037 0.046 0.023 0.070 0.702
0.277 0.957 0.583 0.550 0.232 0.683 0.037⁎
0.002 −0.012 −0.008 −0.008 0.005 −0.010 0.048
8.766 −0.083 −0.784 −0.123 0.213 0.156 −44.252
13.532 1.956 0.726 0.904 0.455 1.376 13.317
0.519 0.966 0.283 0.892 0.640 0.910 0.001⁎
−0.007 −0.012 0.002 −0.012 −0.009 −0.012 0.105
−22.488 0.162 −0.613 0.824 0.830 0.862 −43.488
20.533 2.981 1.112 1.376 0.688 2.101 21.055
0.277 0.957 0.583 0.551 0.231 0.683 0.042⁎
0.002 −0.012 −0.008 −0.008 0.005 −0.010 0.037
ML: mediolateral, EO: eye opening, EC: eye closing. Coef.: correlation efficient, SE: standard error, Adj R2: adjusted R-squared. ⁎ p b 0.05.
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Table 3 Multivariate analysis of balance with demographic factors. Factors
ML sway speed
ML sway distance
EO
Sex Age Weight Height Foot size Education Group
EC
EO
EC
Coef
SE
p value
Coef
SE
p value
Coef
SE
p value
Coef
SE
p value
0.729 −0.035 −0.039 0.011 0.036 0.014 −1.522
0.554 0.067 0.030 0.042 0.020 0.049 0.459
0.192 0.600 0.200 0.800 0.095 0.769 0.001⁎
−0.326 −0.045 −0.063 0.039 0.086 0.003 −1.592
0.878 0.106 0.048 0.066 0.033 0.077 0.728
0.712 0.673 0.191 0.554 0.246 0.965 0.032⁎
21.850 −1.052 −1.175 0.318 1.074 0.432 −45.633
16.606 1.998 0.909 1.252 0.617 1.457 13.775
0.192 0.600 0.200 0.800 0.086 0.768 0.001⁎
−9.784 −1.339 −1.901 1.177 1.144 0.103 −47.735
26.323 3.167 1.441 1.984 0.979 2.310 21.835
0.711 0.674 0.191 0.555 0.246 0.965 0.032⁎
ML: mediolateral, EO: eye opening, EC: eye closing. Coef: correlation efficient, SE: standard error. ⁎ p b 0.05.
Most of the previous studies that evaluated balance in older patients were conducted in patients with dementia. However it is more cost-effective to address balance in older adults with MCI. This was the goal of our study: to address balance decline in the MCI group via posturography. One interesting finding is that balance was not associated with sex, age, foot size, weight, or level of education. Although a previous study found an association between age and balance [12,26], one potential explanation for the lack of significance for the age factor is that we selected patients within a relatively narrow age range. In addition, despite the fact that factors such as foot size and height are associated with the center of pressure on a platform, they were not correlated to balance performance in this study probably because they are stable factors that subjects learn how to adapt throughout their lifetime. An expected finding that we confirmed in this study is that eyes status was significantly associated with mediolateral and anteroposterior balance. However, this factor was not associated with group. In other words, the amount of compensation when subjects close their eyes is similar in both groups. This was an interesting finding that supports training program for MCI patients to improve balance as the compensatory system seems to be relatively intact. One interesting point that is worth mention is the mechanism of decreased balance in MCI patients. Although balance is controlled mainly by subcortical nuclei and tracts, there is an intense cortical involvement, especially during compensation. For instance, a previous Transcranial Magnetic Stimulation (TMS) study illustrated that the Motor Evoked Potential (MEP) in the soleus muscle was facilitated during the voluntary heel-raise movement, as a part of anticipatory postural control [33]. Therefore, one question that needs to be addressed is whether degeneration in cortico-subcortical networks delays compensatory movements, though we did not see a differential effect of eye status in our results. Further studies with TMS might provide additional insights into the cortical mechanisms of balance in MCI. Table 4 Comparison of balance ability between EO and EC for each group. Factors
MCI Coef
Control SE
p value R
1.229 0.116 0.000⁎
ML sway speed (mm/s) ML sway distance 1.229 0.116 0.000⁎ (mm) AP sway speed 1.211 0.202 0.000⁎ (mm/s) AP sway distance 1.211 0.202 0.000⁎ (mm)
2
Coef
SE
p value R2
0.801 1.264 0.188 0.000⁎
0.450
0.801 1.264 0.188 0.000⁎
0.450
0.563 1.389 0.208 0.000⁎
0.448
0.563 1.388 0.208 0.000⁎
0.448
ML: mediolateral, AP: anteroposterior, EO: eye opening, EC: eye closing. Coef: correlation coefficient, SE: standard error. ⁎ p b 0.05.
In summary, mediolateral sway speed and distance were significantly higher in the MCI group than in the non-MCI group. There was no significant difference between the MCI group and the control group in the anteroposterial sway speed and distance. These results point to a specific deficit in balance control in MCI patients compared with controls, and encourages a specific combined balance exercise program with visual compensation training for improvement of cognitive function, in order to prevent fall and related fracture.
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