Association Between Sarcopenia and Quality of Life in Patients with Early Dementia and Mild Cognitive Impairment

Abstract

Background:

Cognitive impairment is linked to decreased quality of life (QOL), but few studies have investigated the impact of comorbid sarcopenia.

Objective:

The aim of this study was to elucidate the association of sarcopenia with QOL in patients with early dementia and mild cognitive impairment.

Methods:

Individuals with a Clinical Dementia Rating of 0.5 or 1 and a Mini-Mental State Examination score of 20–30 underwent a battery of neuropsychological assessments administered by a group of well-trained clinical psychologists. The EQ-5D was completed by both the patients and their main caregivers. EQ-5D utility and visual analog scale scores were measured. Sarcopenia was defined according to the criteria published in the 2019 consensus update by the Asian Working Group for Sarcopenia.

Results:

Patients with sarcopenia had significantly lower scores on the Digit Symbol Substitution Test and Trail Making Test Part A. There was a significant negative association between sarcopenia and both self- and proxy-rated EQ-5D utility scores independent of potential confounding factors. However, there was no association between QOL visual analog scale scores and sarcopenia.

Conclusion:

Given that sarcopenia is often found in individuals with cognitive impairment, early detection by timely screening and effective intervention may help to maintain or improve QOL in this population. However, this study could not determine whether reduced QOL is a direct consequence of sarcopenia.

Keywords

Cognitive dysfunction gait speed grip sarcopenia

INTRODUCTION

Diminished quality of life (QOL) has been reported in individuals with cognitive impairment, even if cognitive decline is mild [1]. Given that there is still no disease-modifying treatment available for dementia, optimizing QOL is a priority in persons with cognitive impairment. Several factors have been linked to reduced QOL in individuals with early dementia or mild cognitive impairment (MCI). Depressive mood was reported to be associated with decreased QOL in Korean elderly with MCI [2]. Both frailty and neuropsychiatric symptoms were found to be determinants of QOL in individuals with a Mini-Mental State Examination (MMSE) score of more than 21 [3]. However, sufficient research data have not been accumulated.

Sarcopenia, which is an age-related decline of muscle mass and power, has been reported to be associated with cognitive impairment [4]. The prevalence of sarcopenia has been found to be higher in individuals with dementia than in those without dementia [5].

With the increasing research interest in sarcopenia, accumulating evidence has led to revision of the diagnostic criteria for sarcopenia in the Asian population [6]. According to the revised diagnostic criteria in the 2019 consensus update by the Asian Working Group for Sarcopenia (AWGS), sarcopenia is now defined as low muscle mass, muscle weakness (handgrip), or lower physical performance (e.g., gait speed) [6]. While several studies have suggested that sarcopenia is also associated with a decline in QOL in the general older population [7 –11], there has been little research on the association of sarcopenia with QOL and cognitive function in the cognitively impaired population. Because sarcopenia is a condition frequently found in the cognitively impaired population and is also potentially treatable, the effects of sarcopenia on QOL and cognition in this population should be investigated.

The aim of this study was to investigate the association of sarcopenia with QOL and cognitive function in individuals with early dementia and MCI.

MATERIALS AND METHODS

Participants

This study involved Japanese patients who attended the memory clinic at a university hospital in Japan and had a Clinical Dementia Rating (CDR) [12] of 0.5 (questionable dementia) or 1 (mild dementia) and an MMSE score of 20–30. Participants with CDR of 0 (no dementia) were not included. MMSE score ≥20 was set to include only participants who could reliably assess their own QOL. All participants were community-dwellers and not living in institutions or nursing homes. Exclusion criteria were a current serious medical or psychiatric disorder or a history of symptomatic cerebrovascular disease. Comorbidities of ischemic heart disease, congestive heart failure, cerebrovascular disease, diabetes mellitus, dementia, cancer, neurodegenerative disorders (including Parkinson’s disease) and other diseases were considered in the Charlson Comorbidity Index [13], which represents the sum of weighted indices taking into account the number and severity of pre-existing comorbid conditions.

Informants who saw the participants at least once a week and played a major part in their care were provided the proxy rating of the EQ-5D. Participants who had both self- and proxy-rated QOL data available were included in the analysis.

The study protocol was approved by the Ethics Committee of the Graduate School of Medicine, Nagoya University (2015-04356977). Written informed consent was obtained from all participants.

Sarcopenia assessment

Sarcopenia was diagnosed using the criteria in the 2019 consensus update by the AWGS [6]. Muscle mass was measured by a bioelectrical impedance system (Inbody 430; Biospace, Seoul, Korea). Skeletal muscle index (SMI) was calculated by dividing muscle mass by height squared (kg/m²). The cut-off for low SMI was <7.0 kg/m² in men and <5.7 kg/m² in women. Body weight and height were measured by research nurses and used to calculate body mass index (BMI).

Handgrip strength was measured twice for each hand, and the maximum values were recorded. Gait speed was assessed in meters per second with a stopwatch as participants walked on a 6 m-long straight and flat path. Low muscle strength was defined as a handgrip strength of <28 kg for men and <18 kg for women. The criterion for low physical performance was a gait speed of <1.0 m/s.

Ability to perform basic activities of living (BADL) was assessed by research nurses using the Barthel index [14].

Health-related QOL

The EQ-5D is a generic and non-disease-specific instrument used to evaluate current health-related QOL. It consists of both a health index and a visual analog scale (QOL VAS) score [15]. The health index component consists of five dimensions (mobility, self-care, pain/discomfort, usual activities, and anxiety/depression). Each of these dimensions has five levels of severity (i.e., no problems, slight problems, moderate problems, serious problems, and extreme problems). The scores for these five dimensions are combined to obtain up to 3,125 possible health states, from which a single index (utility) score is computed. The EQ-5D was administered to both the participants (self-rating) and their main caregivers (proxy rating). The QOL VAS used in this study is a 100-point scale where 100 represents the best imaginable health state and 0 represents the worst imaginable health state [16].

Neuropsychological assessments

Well-trained clinical psychologists administered a battery of neuropsychological assessments including CDR Memory was assessed using the Logical Memory I and II subsets of the Wechsler Memory Scale-Revised [17]. The MMSE [18] and Alzheimer’s Disease Assessment Scale [19] were used to evaluate general cognitive ability. The Category Fluency (Animal Naming) Test and the Letter Fluency Test were used for verbal fluency and the Digit Span (forward and backward) subtest and Visual Memory Span (forward and backward) subtest of the Wechsler Memory Scale-Revised for working memory. The Digit Symbol subtest (DSS) of the Wechsler Adult Intelligence Scale-III [20] was used to assess processing speed and the Trail Making Test (TMT) Parts A and B [21] and Stroop test [22] were used for executive function. Depressive mood was assessed using the Geriatric Depression Scale-15 (GDS-15) [23].

Statistical analysis

Student’s t-test was used to compare continuous variables and the chi-square test was used to compare categorical values. The difference between self- and proxy-rated EQ-5D utility values was assessed by the paired t-test. Pearson’s correlation coefficient was calculated between self- and proxy-rated EQ-5D utility values. Multiple regression analysis was used to investigate the association of sarcopenia with cognitive function and QOL scores with adjustment for age, sex, BMI, education, ability to perform BADL, and depressive mood. Depressive mood was defined as a GDS-15 score of >6, low education level as no education beyond high school, low BMI as <18.5, and impaired ability to perform BADL as Barthel index score <100.

RESULTS

The background characteristics of the participants are summarized in Table 1. Seventy-four participants (mean age 80.1±5.4 years) and their caregiver informants were enrolled in the study; 66 (89.2%) of the participants had a CDR of 0.5. The distribution of the MMSE scores according to CDR rating (0.5 or 1) is shown in Supplementary Table 1. Many of the participants were independent in terms of BADL (mean Barthel index score: 98.5±4.0). 47% of the participants had sarcopenia; the participants with sarcopenia had lower BMI, lower SMI, and fewer years of education than those without sarcopenia. Proxy-rated utility values and VAS were significantly lower in sarcopenic participants. Comparisons of the raw scores for each of the five domains of the EQ-5D (mobility, self-care, pain/discomfort, usual activity, and anxiety/depression) are shown in Supplementary Table 2. Proxy-rated mobility and pain/discomfort domains and both self and proxy-rated anxiety/depression domains were significantly lower in sarcopenia. Examination of the relationship with informants revealed that most informants were a spouse (n = 35) or child (n = 25).

Table 1

Background characteristics of the participants

	Total	Sarcopenia	Non-sarcopenia	p
Number	74	35 (47%)	39 (53%)
Age (y)	80.1±5.4	80.6±5.7	79.6±5.1	0.44
Male n (%)	34 (45.9)	20 (41.2)	14 (58.8)	0.33
BMI (kg/m²)	22±3.2	20.5±2.9	23.3±3.0	<0.01
BMI < 18.5 n (%)	14 (18.9)	11 (32.4)	3 (7.7)	0.009
SMI (kg/m²)	6.2±0.9	5.6±0.7	6.7±0.8	<0.01
SMI n (%) male <7.0 female <5.7	42 (56.8)	35 (100)	7 (17.9)	<0.01
Gait speed (m/s)	0.9±0.2	0.9±0.2	1.0±0.2	0.13
Gait speed <1.0 m/s (%)	46 (63.0)	27 (77.1)	19 (48.7)	0.005
Grip (kg)	20.1±6.4	17.2±5.6	22.8±6.1	<0.01
Male <28 kg or female <18 kg %	42 (57.5)	29 (82.9)	13 (34.2)	<0.01
CCI	2.1±2.1	2.3±2.5	2.0±1.7	0.49
BADL	98.5±4.0	98.0±4.2	98.9±3.9	0.37
BADL full (%)	61 (82.4)	26 (74.3)	35 (89.7)	0.081
QOL index score (self-rated)	0.91±0.11	0.89±0.14	0.93±0.08	0.09
QOL VAS (self-rated)	73.9±19.3	71.6±19.1	76.0±19.5	0.32
QOL index score (proxy-rated)	0.84±0.14	0.80±0.15	0.89±0.12	<0.01
QOL VAS (proxy-rated)	76.8±17.1	72.3±17.8	80.9±15.6	0.03
Education (high school and less) n(%)	42 (56.8)	24 (68.6)	18 (46.2)	0.103
Informant’s relationship
Spouse	35 (42.3%)	15 (42.9%)	20 (51.3%)	0.205
Son/daughter	25	10 (28.6)	15 (38.5)

Means±standard deviation are shown. BMI, body mass index; SMI, skeletal muscle index; CCI, Charlson Comorbidity Index; BADL, basic activities of daily living; QOL, quality of life; VAS, visual analog scale.

The results of the neurocognitive assessments are shown in Table 2. Participants with sarcopenia had significantly lower DSS and TMT Part A scores than their counterparts without sarcopenia; however, there were no significant between-group differences in the results of the other tests (Table 2). Utility values for QOL were significantly lower when proxy-rated than when self-rated; 38 participants (51.4%) self-rated a full score of 1 (Table 1). A scatter plot of the self- and proxy-related utility values are shown in Fig. 1. The correlation coefficient between self- and proxy-rated values was 0.427, and the correlation coefficient between utility and VAS scores was 0.431 for self-ratings and 0.434 for proxy rating.

Table 2

Results of cognitive assessments

	Total	Sarcopenia	Non-sarcopenia	p
MMSE	24.3±2.6	24.3±2.4	24.4±2.7	0.80
Number with CDR of 0.5 (%)	66 (89.2)	29 (82.9)	37 (94.9)	0.095
ADAS-Jcog	12.2±4.5	13.1±4.5	11.3±4.3	0.10
10-word recall (immediate)	4.4±1.5	4.3±1.4	4.6±1.6	0.35
10-word recall (delayed)	2.8±2.6	3.1±2.6	2.5±2.7	0.33
Logical memory I	7.6±4.6	7.6±4.2	7.7±5.0	0.95
Logical memory II	2.0±2.4	2.2±2.5	1.9±2.4	0.60
Verbal fluency (category)	12.3±3.7	12.3±3.8	12.3±3.7	0.99
Verbal fluency (initial letters)	7.3±3.0	7.3±3.0	7.3±3.1	0.94
Clock-drawing test (quantitative)	7.3±1.6	7.0±1.6	7.6±1.6	0.14
Clock-drawing test (qualitative)	6.2±2.5	5.7±2.3	6.6±2.6	0.10
Digit Symbol Substitution Test	10±2.5	9.1±2.4	10.8±2.3	<0.01
Digit span	10.7±2.7	10.5±2.2	11.0±3.1	0.40
Stroop test (s)	22.9±17.4	27.1±23.2	19.4±9.1	0.06
TMT-Part A (s)	83.3±34.0	97.7±38.0	70.1±23.3	<0.01
TMT-Part B (s)	265.0±119.4	288.5±116.3	244.4±120.0	0.15
GDS-15	4.0±2.9	4.1±2.8	4.0±3.1	0.84
GDS-15 > 6 (%)	23 (31.1)	11 (31.4)	12 (30.1)	0.95

Means±standard deviation are shown. MMSE, Mini-Mental State Examination; ADAS-Jcog, Alzheimer’s Disease Assessment Scale-cognitive component-Japanese Version; CDR, Clinical Dementia Rating; TMT, Trail Making Test; GDS, Geriatric Depression Scale.

Fig. 1

Scatterplot of self- and proxy-rated utility scores.

Multiple regression analysis showed that the significantly lower DSS and TMT Part A scores in participants with sarcopenia were independent of educational level, BMI, and depressive mood (Table 3). A similar analysis for each domain of sarcopenia (low SMI, low hand grip strength, and low gait speed), rather than for a diagnosis of sarcopenia, is shown in Supplementary Table 3. Low SMI and grip strength were significantly associated with lower DSS and TMT Part A scores. Sarcopenia showed a significant negative association with both self- and proxy-rated EQ-5D utility values independent of potential confounding factors (Table 4). However, there was no association with the QOL VAS scores. Similar analysis using each domain of sarcopenia instead of sarcopenia diagnosis is shown in Supplementary Table 4. Low SMI was significantly associated with low proxy-rated utility value.

Table 3

Multiple regression analysis for cognitive tests and sarcopenia

	B	95% CI	p
DSS	−1.748	−2.831, −0.346	0.013
TMT-A	26.387	9.472, 42.498	0.003

Adjusted for age, sex, body mass index, education, ability to perform basic activities of daily living, and depressive mood. DSS, Digit Symbol Substitution Test; TMT, Trail Making Test.

Table 4

Multiple regression analysis for the association between quality of life and sarcopenia

	B	95% CI	p
Self-rated utility value	−0.062	−0.120, −0.004	0.036
Proxy-rated utility value	−0.103	−0.165, −0.041	0.002
Self-rated VAS	−4.953	−14.798, 4.891	0.318
Proxy-rated VAS	−7.600	−16.536, 1.335	0.094

Adjusted for age, sex, body mass index, education, ability to perform basic activities of daily living, and depressive mood. VAS, visual analogue scale.

DISCUSSION

This study found that sarcopenia was associated with decreased executive function and both self- and proxy-rated QOL. Our most important finding was the association of sarcopenia with low QOL. Unadjusted comparison between sarcopenia and non-sarcopenia showed that proxy-rated utility value and QOL VAS were significantly lower in sarcopenia as well as self-rated utility value, though these findings were not statistically significant. Multiple regression analysis with adjustment for potential confounding factors showed that sarcopenia was significantly associated with lower self- and proxy-rated utility values.

Previous studies have suggested that physical independence is an important factor for preservation of QOL in persons with dementia [24]. Sarcopenia is closely associated with decreased ability to perform BADL [25]. The participants in our study were independent in BADL (82% had a full score for BADL and the lowest Barthel index score was 80). Therefore, the association between sarcopenia and reduced QOL could not be attributed to decreased performance of ADL. Sarcopenia is reported to be associated with anxiety [26] and fatigue [27], which should be investigated further as potential factors in the mechanism underlying the association between sarcopenia and reduced QOL. Indeed, in the present study, we found lower raw scores in the anxiety/depression domain for both self- and proxy-ratings in sarcopenia. Utility and VAS scores were weakly but significantly correlated (R = 0.431 and R = 0.434, respectively). However, no significant association was observed between sarcopenia and VAS scores for either self- or proxy-ratings.

Many studies have explored the factors influencing QOL in persons with dementia but there few have focused only on early dementia. According to a systematic review by Jing et al. in 2016 [24], only five studies have identified factors associated with QOL in persons with early dementia, among which depression was the factor most frequently reported. An association between sarcopenia and depressive mood has also been reported [28]. In the present study, sarcopenia was associated with lower QOL independent of depressive mood as assessed by the GDS-15.

The EQ-5D is a well-established tool for assessing health-related QOL [29]. In this study, we measured QOL by both proxy rating and self-rating. The usefulness of both proxy-rated and self-rated EQ-5D scores for assessment of QOL has already been reported in persons with dementia [30, 31]. Many of previous reports have shown that QOL scores assessed on the EQ-5D are higher when self-rated than when proxy-rated [31], which was also the case in the present study. There is some evidence of a ceiling effect with self-rated health-related QOL [31]. We also found that about half of our participants self-rated a full score of 1, which suggests the presence of a ceiling effect. The correlation between self- and proxy-rated scores was not particularly high (R = 0.427), which was in accordance with previous studies [31]. However, our study also found a significant association between sarcopenia and both self- and proxy-rated health-related QOL.

The diagnostic criteria for sarcopenia have been revised in both Europe [40] and Asia [6] in response to the increasing interest in sarcopenia and accumulation of evidence. In this study, we used the updated definition for Asians [6]. According to this definition, about half of our participants (47.3%) had a diagnosis of sarcopenia. Cognitive function is known to decline in parallel with physical function [41]. Our study involved cognitively impaired older patients attending a geriatric outpatient clinic and found a relatively high prevalence of sarcopenia.

Sarcopenia is an age-related condition that can be reversed to some extent by appropriate intervention. Nutrition, particularly adequate protein intake, has been reported to improve sarcopenia [42]. Resistance training may also improve muscle mass and function [43, 44]

Given that sarcopenia is often found in cognitively impaired participants, early detection by timely screening and effective intervention may help to maintain or improve QOL in the cognitively impaired population, although we could not determine whether the reduced QOL found in our participants was the consequence of sarcopenia. It is possible that our participants with reduced QOL had a sedentary lifestyle, which could lead to sarcopenia [45, 46]. Future studies are warranted to elucidate the association of sarcopenia with reduced QOL in persons with MCI.

This study has several limitations. First, it has a single-center design and a relatively small sample size. Therefore, it is unclear whether the results are generalizable to other populations with different cultural and religious backgrounds. More studies are needed to clarify the association between sarcopenia and QOL in individuals with cognitive impairment. Second, the cross-sectional nature of the study means that it was not possible to identify a cause-and-effect relationship between QOL and sarcopenia. Prospective studies are needed to confirm whether intervention for sarcopenia can improve QOL. Third, we had little information on the caregivers who proxy-rated QOL in our participants. Therefore, we could not assess whether the informants had any background characteristics that may have influenced their QOL ratings. Fourth, we assessed only BADL, not instrumental ADL. Therefore, we could not explore the effects of decline in instrumental ADL on QOL.

In conclusion, we have found an association of sarcopenia with both self-rated and proxy-rated QOL in individuals with early dementia and MCI.

Footnotes

ACKNOWLEDGMENTS

The study was partly supported by the Organized Registration for the Assessment of Dementia of the Nationwide General Consortium toward Effective Treatment in Japan.

Authors’ disclosures available online ().

The supplementary material is available in the electronic version of this article: .

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