Abstract
INTRODUCTION:
Older adults with cognitive impairment, including those with Alzheimer’s disease and related dementias, are particularly at risk for hospitalization and hospital-associated disability. Understanding of key risk factors for hospital-associated disability is limited. Sarcopenia, age-related declines in muscle mass and strength, is common in older adults with cognitive impairment and may be an important risk factor for hospital-associated disability.
METHODS:
Using data from the Health ABC Study, we examined associations of pre-hospitalization appendicular lean mass (ALM), and grip strength with the development of new activity of daily living (ADL) disability at the next annual assessment after hospitalization.
RESULTS:
Grip strength, but not ALM, was negatively associated with increased risk of hospital-associated ADL disability, and this association was greater among those with cognitive impairment compared to those without.
DISCUSSION:
Lower grip strength may be an important risk factor for hospital-associated ADL disability in older adults, particularly those with cognitive impairment.
1. BACKGROUND
Inability to independently perform activities of daily living (ADL), known as ADL disability, is common among older adults with cognitive impairment and is a hallmark of Alzheimer’s disease and Alzheimer’s disease related dementias (AD/ADRD) 1. Approximately 5.5 million Americans, most of whom are older than age 65, have AD/ADRD, and that number is projected to rise to 14 million by 2050 2. Therefore, ADL disability among older adults with cognitive impairment represents an increasingly urgent public health dilemma. Importantly, half of all physical disability, including ADL disability, among older adults arises in the setting of hospitalization, and this disability is commonly referred to as hospital-associated ADL disability 3, 4. Older adults with cognitive impairment are particularly at risk for both hospitalization and hospital-associated ADL disability 5. However, understanding of which individuals with cognitive impairment are at greatest risk for hospital-associated ADL disability is limited. Identification of key risk factors for hospital-associated ADL disability among those with cognitive impairment would advance understanding of pathogenesis of this important source of disability and could facilitate the development of novel strategies to prevent it.
Sarcopenia refers to age-related declines in muscle mass and strength, and measures of sarcopenia in older adults often include assessment of grip strength and appendicular lean mass 6, 7. In the general population of older adults, low grip strength and low appendicular lean mass are known to be important predictors of long-term poor functional outcomes, including mobility impairment, institutionalization, and mortality 6–8. Older adults with cognitive impairment are at increased risk of both hospital-associated ADL disability and sarcopenia 9. Moreover, sarcopenia, and in particular grip lower grip strength, may be associated with risk of cognitive impairment10, 11. However, it is not known if sarcopenia is an important risk factor for the development of hospital-associated ADL disability in older adults with cognitive impairment.
The aim of this study is to evaluate whether grip strength and appendicular lean mass, key components of sarcopenia, are risk factors for the development of hospital-associated ADL disability in those with cognitive impairment.
2. METHODS
2.1. Sample
The sample for the present study derives from the Health, Aging and Body composition (Health ABC) study. The Health ABC study cohort consists of 3,075 black and white men and women aged 70-79 who reported no difficulty walking one-quarter mile, climbing 10 steps, or performing basic ADLs at enrollment in whom appendicular lean mass, grip strength, and ADL function were assessed annually. Baseline study data were collected in 1997 and 1998 12. Individuals from Health ABC who were hospitalized during the first 5 years of follow-up, when measures of appendicular lean mass and grip strength were collected every year, were eligible for the present study. Only individuals’ first hospitalization (index hospitalization) during this follow-up period was analyzed to focus on incident hospital-associated ADL disability and avoid potential confounding resulting from prior hospitalizations. History of mild to moderate cognitive impairment prior to hospitalization was defined as a Modified Mini-Mental State Examination (3MS) score less than 78 and greater than 48 13, 14. 3MS was conducted in Health ABC study years 1, 3, and 5. The most recent 3MS score prior to the index hospitalization was used to ascertain cognitive impairment status.
Individuals were excluded who were already unable to perform independently all 3 ADL activities (bathing, dressing, and transferring) prior to hospitalization (n=4), were missing ADL outcome data and did not die within one year of last ADL assessment (n=692), or were missing appendicular lean mass data (n=25), grip strength data (n=72), or both (n=175) within 2 years before first hospitalization. In addition, those with severe cognitive impairment, defined as 3MS score ≤ 48, (n=12 were excluded because inability to perform ADLs independently in these individuals is likely largely determined by degree of cognitive impairment. The final sample for the present study was comprised of a total of 1712 individuals (Supplementary Figure 1). Supplementary Table 1 compares baseline characteristics between those included in the present study and those excluded due to missing outcome data.
2.2. Primary measures
The primary predictors for the present study are appendicular lean mass (ALM) to body mass index (BMI) ratio (ALMBMI) and grip strength measured at the annual assessment prior to hospitalization. ALMBMI was determined from total body scans using fan-beam dual energy X-ray absorptiometry (Hologic QDR 4500A; Hologic, Bedford, MA). Low ALMBMI was defined as <0.789 for men and <0.512 for women 15. Grip strength (kg) was measured via hand-held dynamometer (Jamar, TEC, Clifton, NJ) according to a standardized procedure in which two trials were conducted in each hand and the maximum grip strength recorded in any single trial was used as the value for grip strength16. A pre-specified secondary analysis examined ALM to height ratio, defined as ALM/(height^2). Low grip strength was defined as <26kg for men and <16kg for women 6. The primary outcome for the present study is new ADL disability at the next annual assessment after hospitalization. New ADL disability was defined as newly being unable or needing help to bathe, dress, or transfer 17. ADL disability was determined by self-report or proxy report if needed. Use of an assistive device such as a walker or cane was not considered as being disabled. A secondary outcome examined is death by the next annual assessment after hospitalization.
2.3. Other Measures
Sociodemographic characteristics and smoking status were assessed at study entry in Health ABC. Baseline medical comorbidities (history of falls, diabetes, non-skin cancer, arthritis, pulmonary disease, cardiac disease, stroke, or depression), modified mini mental status exam (3MS) score, physical activity (self-report of kCals of walking per week) were assessed annually according to a standardized protocol in Health ABC 18.
2.4. Statistical analysis
Analyses were stratified by cognitive impairment status. First, separate logistic regression models assessed the association of 1) ALMBMI and 2) grip strength measures prior to hospitalization with the risk of death at the next annual assessment after hospitalization with and without adjusting for covariates. Then, only among those individuals who survived to the next annual assessment after hospitalization, separate logistic regression models assessed the association of 1) ALMBMI and 2) grip strength measures prior to hospitalization with the risk of new ADL disability at the next annual assessment with and without adjusting for covariates. This analytic approach, which focuses on survivors of hospitalization, was used in order to address the clinically relevant question of how best to prevent ADL disability among those with cognitive impairment who are recovering from a hospitalization. Tests of interaction determined whether the association of pre-hospitalization ALMBMI or grip strength measures with risk of ADL disability after hospitalization differed between those with and without cognitive impairment. All models were adjusted for age, race, study site, baseline 3MS score, baseline physical activity, smoking status, baseline medical comorbidities, number of days from hospital discharge to outcome (new ADL disability or death) assessment, and number of days from pre-hospitalization ALMBMI or grip strength assessment to start of hospitalization. Grip strength models were also adjusted for BMI. Additional sensitivity models 1) to account for time between 3MS measurement and index hospitalization or 2) to stratify by sex were also conducted.
3. RESULTS
Baseline participant characteristics grouped by cognitive impairment status are shown in Table 1. 201 individuals (12%) were classified with baseline mild to moderate cognitive impairment. The mean ± standard deviation number of days from assessment of 3MS to index hospitalization for all participants was 237 ± 234. Among those with cognitive impairment, 79 individuals (39%) were female and 156 individuals (78%) were Black. Among all participants, the most prevalent comorbidities were arthritis (n=1004, 59%) and heart disease (n=500, 29%); and low ALMBMI (n=301, 18%) was more common than low grip strength (n=178, 10%).
Table 1.
Participant baseline characteristics
| Cognitive Impairment N=201 (12%) |
No Cognitive Impairment N=1510 (88%) |
p-value3 | Total N=1711 |
|
|---|---|---|---|---|
| Age (mean ± std dev) | 74.1 ± 3.1 | 73.7 ± 2.9 | 0.07 | 73.7 ± 2.9 |
| Female, n (%) | 79 (39%) | 723 (48%) | 0.02 | 802 (47%) |
| Black Race, n (%) | 156 (78%) | 560 (37%) | <0.001 | 716 (42%) |
| Memphis HABC Study Site, n (%) | 122 (61%) | 703 (47%) | 0.0002 | 825 (48%) |
| Pittsburgh, HABC Study Site, n (%) | 79 (39%) | 807 (53%) | 886 (52%) | |
| 3MS (mean ± std dev) | 75.0 ± 9.3 | 91.9 ± 5.3 | <0.001 | 90.0 ± 8.1 |
| Smoking status2, n (%) | ||||
| Never | 79 (39%) | 596 (39%) | <0.001 | 675 (39%) |
| Former | 79 (39%) | 754 (50%) | 833 (49%) | |
| Current | 43 (21%) | 160 (12%) | 203 (12%) | |
| Walking Activity (kCal/kg/week) (mean ± std dev) | 5.6 ± 9.8 | 8.2 ± 20.3 | 0.003 | 7.9 ± 19.4 |
| Body mass index (BMI) | 27.6 ± 5.4 | 27.4 ± 4.5 | 0.74 | 27.5 ± 4.7 |
| Prevalent Health Conditions2, n (%) | ||||
| Cancer | 29 (14%) | 359 (24%) | 0.003 | 388 (23%) |
| Lung Disease | 30 (15%) | 214 (14%) | 0.77 | 244 (14%) |
| Heart Disease | 55 (27%) | 445 (29%) | 0.54 | 500 (29%) |
| Stroke | 19 (9.5%) | 127 (8.4%) | 0.62 | 146 (8.5%) |
| Diabetes Mellitus | 49 (24%) | 246 (16%) | 0.004 | 295 (17%) |
| Falls | 38 (19%) | 334 (22%) | 0.30 | 372 (22%) |
| Arthritis | 115 (57%) | 888 (59%) | 0.67 | 1003 (59%) |
| Depression | 10 (5.0%) | 152 (10%) | 0.02 | 162 (9.5%) |
| ALMBMI (mean ± std dev) | 0.8 ± 0.2 | 0.7 ± 0.2 | <0.001 | 0.7 ± 0.2 |
| Grip strength, kg (mean ± std dev) | 29.6 ± 9.7 | 29.0 ± 9.8 | 0.42 | 29.1 ± 9.8 |
| # of days from ALM or grip strength measurement to index hosp. (mean ± std dev) | 320 ± 221 | 302 ± 232 | 0.32 | 304 ± 230 |
| Low ALMBMI1, n (%) | 28 (14%) | 272 (18%) | 0.15 | 300 (18%) |
| Low grip Strength1, n (%) | 26 (13%) | 152 (10%) | 0.21 | 178 (10%) |
| Days from index hosp. to outcome (mean ± std dev) | 179 ± 122 | 179 ± 120 | 0.97 | 179 ± 120 |
| ADL Disability Prior to Index Hosp, n(%) | 12 (6.0%) | 29 (1.9%) | 0.0004 | 41 (2.4%) |
ALM: appendicular lean mass
3MS: Modified mini-mental status exam score (range 0-100)
ADL: activity of daily living
Low ALMBMI: men <0.789, women <0.512; low grip strength men <26kg, women <16kg (McLean RR, Shardell MD, et al. Criteria for clinically relevant weakness and low lean mass and their longitudinal association with incident mobility impairment and mortality: the foundation for the National Institutes of Health (FNIH) sarcopenia project. J Gerontol A Biol Sci Med Sci. 2014;69(5):576-83
Smoking status and prevalent health conditions defined per Visser M, Goodpaster BH, et al. Muscle mass, muscle strength, and muscle fat infiltration as predictors of incident mobility limitations in well-functioning older persons. J Gerontol A Biol Sci Med Sci. 2005; 60A(3): 324-333
p-value comparing those with and without cognitive impairment
Table 2 depicts index hospitalization characteristics. Among all participants, the mean length of stay was approximately 6 days and 97% of individuals were alive at the time of discharge from the index hospitalization. The most common reasons for hospitalization were angina or myocardial infarction (13%), circulatory disease (11%), and gastrointestinal conditions (11%).
Table 2.
Participant index hospitalization characteristics
| Cognitive Impairment N=201 (12%) |
No Cognitive Impairment N=1510 (88%) |
p-value1 | Total N=1711 |
|
|---|---|---|---|---|
| Length of Stay for index hospitalization, days | 7.1 ± 9.1 | 5.6 ± 6.5 | 0.03 | 5.8 ± 6.9 |
| Admitted to ICU for index hospitalization (y/n) | 26 (13%) | 171 (11%) | 0.50 | 197 (12%) |
| Alive at discharge from index hospitalization (y/n) | 193 (96%) | 1465 (97%) | 0.44 | 1658 (97%) |
| Index Hosp. Primary Diagnosis Category | 0.0004 | |||
| Angina/Myocardial infarction | 16 (8%) | 201 (13%) | 217 (13%) | |
| Circulatory disease | 21 (10%) | 164 (11%) | 185 (11%) | |
| Gastrointestinal conditions | 24 (12%) | 160 (11%) | 184 (11%) | |
| Cancer | 18 (9.0%) | 154 (10%) | 172 (10%) | |
| Musculoskeletal conditions | 16 (8.0%) | 160 (11%) | 176 (10%) | |
| Other | 21 (10%) | 142 (9.4%) | 163 (10%) | |
| Cerebrovascular disease | 11 (5.5%) | 108 (7.2%) | 119 (7.0%) | |
| Trauma/Injury | 16 (8.0%) | 87 (5.8%) | 103 (6.0%) | |
| Genitourinary conditions | 11 (5.5%) | 79 (5.2%) | 90 (5.3%) | |
| Pneumonia | 5 (2.5%) | 64 (4.2%) | 69 (4.0%) | |
| Congestive heart failure | 12 (6.0%) | 45 (3.0%) | 57 (3.3%) | |
| COPD/Asthma | 7 (3.5%) | 40 (2.7%) | 47 (2.8%) | |
| Endocrine conditions | 6 (3.0%) | 30 (2.0%) | 36 (2.1%) | |
| Neurologic | 8 (4.0%) | 28 (1.9%) | 36 (2.1%) | |
| Pulmonary | 1 (0.5%) | 22 (1.5%) | 23 (1.3%) | |
| Dermatologic | 2 (1.0%) | 14 (0.9%) | 16 (0.9%) | |
| Infection | 2 (1.0%) | 10 (0.7%) | 12 (0.7%) | |
| Dementia | 3 (1.5%) | 0 | 3 (0.2%) | |
| Hematologic | 1 (0.5%) | 2 (0.1%) | 3 (0.2%) | |
| # of Hospitalizations within 365 days of index hosp. (including index hosp) | 1.6 ± 1.1 | 1.5 ± 0.9 | 0.12 | 1.5 ± 0.9 |
| Total # of days hospitalized within 365 days of index hosp. (including LOS for index hosp) | 11.7 ± 13.4 | 8.8 ± 10.9 | 0.001 | 9.1 ± 11.2 |
p-value comparing those with and without cognitive impairment
A total of 174 individuals (10%), 26 (13%) among those with cognitive impairment and 148 (10%) among those without cognitive impairment, died (Table 3). Among individuals who survived until the next annual assessment following hospitalization, 12 individuals (6.9%) with cognitive impairment developed new ADL disability, compared to 50 individuals (3.7%) without cognitive impairment.
Table 3.
Number and proportion of participants who died and, among survivors, who developed new ADL disability by the next annual Health ABC assessment*
| Cognitive Impairment N=201 (12%) |
No Cognitive Impairment N=1510 (88%) |
p-value1 | Total N=1711 |
|
|---|---|---|---|---|
| Death | 26 (13%) | 147 (10%) | 0.16 | 173 (10%) |
| ADL Disability* | ||||
| Any ADL | 12 (6.9%) | 50 (3.7%) | 0.04 | 62 (4.0%) |
| Transferring | 4 (2.3%) | 22 (1.6%) | 0.52 | 26 (1.7%) |
| Bathing | 6 (3.4%) | 32 (2.4%) | 0.39 | 38 (2.5%) |
| Dressing | 7 (4.0%) | 25 (1.8%) | 0.06 | 32 (2.1%) |
Activity of Daily Living (ADL) disability defined as newly being unable or needing help to bathe, dress, or transfer.
p-value comparing those with and without cognitive impairment
Neither baseline ALMBMI nor baseline low ALMBMI was associated with death at the next annual assessment (Table 4a). Grip strength was negatively associated with death among those without cognitive impairment such that for each standard deviation decrement in baseline grip strength the adjusted odds of death at the next annual assessment was 1.36 (95% CI 1.00, 1.84). Among all participants, a similar relationship was observed, but it did not reach statistical significance (adjusted odds ratio expressed per standard deviation decrement in baseline grip strength of 1.28 (95% CI (0.98, 1.68). Baseline grip strength was not significantly associated with death among those with cognitive impairment (adjusted odds ratio 0.77 (95% CI (0.38, 1.57).
Table 4a:
Odds ratios and 95% confidence intervals for the association of pre-hospitalization sarcopenia measures with death among older adults in Health ABC
| All Subjects | Cognitive Impairment | No Cognitive Impairment | |||||||
|---|---|---|---|---|---|---|---|---|---|
| n | Unadjusted | Adjusted1 | n | Unadjusted | Adjusted1 | n | Unadjusted | Adjusted1 | |
| ALMBMI1 | 1711 | 0.79 (0.68, 0.93) | 0.91 (0.66, 1.26) | 201 | 0.97 (0.66, 1.44) | 0.89 (0.38, 2.08) | 1510 | 0.77 (0.65, 0.92) | 0.91 (0.64, 1.31) |
| Low ALMBMI2 | 1711 | 0.93 (0.61, 1.42) | 1.03 (0.63, 1.68) | 201 | 1.14 (0.36, 3.61) | 1.74 (0.37, 8.14) | 1510 | 0.91 (0.58, 1.44) | 0.98 (0.57, 1.67) |
| (mean) Grip strength1 | 1711 | 0.94 (0.81, 1.10) | 1.29 (0.98, 1.69) | 201 | 1.02 (0.67, 1.54) | 0.80 (0.39, 1.64) | 1510 | 0.93 (0.79, 1.10) | 1.37 (1.01, 1.85) |
| Low (mean) grip strength2 | 1711 | 1.36 (0.85, 2.17) | 1.46 (0.83, 2.55) | 201 | 1.75 (0.60, 5.12) | 0.90 (0.21, 3.90) | 1510 | 1.27 (0.75, 2.15) | 1.46 (0.78, 2.74) |
Adjusted models control for age, sex, race, study site, baseline MMSE score, baseline physical activity (walking/week), smoking status, history of falls, history of diabetes, history of cancer, history of arthritis, history of pulmonary disease, history of cardiac disease, history of stroke, history of depression, number of days from hospital discharge to ADL/death, number of days from sarcopenia (grip or lean mass) measurement to first hospitalization, and whether they had any ADLs prior to the first hospitalization. Grip strength models are also adjusted for baseline BMI. Odds ratios are per unit decrease in standard deviation for the ALM/grip strength measure
Adjusted models control for all of the above in 1 except for sex.
p-value for all interaction terms >0.1.
Among individuals who survived to the next annual assessment, neither baseline ALMBMI nor baseline low ALMBMI was associated with ADL disability at the next annual assessment (Table 4b). However, baseline grip strength was associated with development new ADL disability at the next annual assessment. The adjusted odds ratio for development new ADL disability expressed per standard deviation decrement in baseline grip strength was 1.77 (95% CI 1.17, 2.70) among all individuals, 3.82 (95% CI 1.06, 13.7) among those with cognitive impairment, and 1.60 (95% CI 0.998, 2.55) among those without cognitive impairment. The p-value for the test of interaction to determine whether the association of baseline grip strength with development of new ADL disability differed between those with and without cognitive impairment was 0.07. In addition, among all participants baseline low grip strength, compared to not low grip strength (as a dichotomous variable), was associated with development of new ADL disability at the next annual assessment. The adjusted odds ratio for development of new ADL disability in those with baseline low grip strength, compared to those without baseline low grip strength was 2.07 (95% CI 1.04, 4.13).
Table 4b:
Among those who survived to follow-up, odds ratios and 95% confidence intervals for the association of pre-hospitalization sarcopenia measures with new ADL disability among older adults in Health ABC
| All Subjects | Cognitive Impairment | No Cognitive Impairment | |||||||
|---|---|---|---|---|---|---|---|---|---|
| n | Unadjusted | Adjusted1 | n | Unadjusted | Adjusted1 | n | Unadjusted | Adjusted1 | |
| ALMBMI1 | 1538 | 1.32 (1.01, 1.72) | 1.23 (0.75, 2.00) | 175 | 2.18 (1.16, 4.10) | 2.58 (0.67, 9.94) | 1363 | 1.20 (0.89, 1.62) | 1.11 (0.64, 1.92) |
| Low ALMBMI2 | 1538 | 1.00 (0.52, 1.95) | 0.94 (0.47, 1.87) | 175 | 0.55 (0.07, 4.49) | 0.28 (0.02, 3.20) | 1363 | 1.13 (0.56, 2.29) | 1.09 (0.52, 2.29) |
| (mean) Grip strength1 | 1538 | 1.55 (1.17, 2.05) | 1.69 (1.11, 2.59) | 175 | 2.92 (1.41, 6.06) | 5.16 (1.30, 20.5) | 1363 | 1.36 (1.01, 1.84) | 1.52 (0.95, 2.43) |
| Low (mean) grip strength2 | 1538 | 2.24 (1.17, 4.30) | 1.94 (0.96, 3.90) | 175 | 2.69 (0.67, 10.8) | 4.60 (0.68, 30.9) | 1363 | 2.09 (0.99, 4.39) | 1.87 (0.84, 4.16) |
Adjusted models control for age, sex, race, study site, baseline MMSE score, baseline physical activity (walking/week), smoking status, history of falls, history of diabetes, history of cancer, history of arthritis, history of pulmonary disease, history of cardiac disease, history of stroke, history of depression, number of days from hospital discharge to ADL/death, number of days from sarcopenia (grip or lean mass) measurement to first hospitalization and whether they had any ADLs prior to the first hospitalization. Grip strength models are also adjusted for baseline BMI. Odds ratios are per unit decrease in standard deviation for the ALM/grip strength measure
Adjusted models control for all of the above in 1 except for sex.
p-value for the interaction of grip strength (continuous measure) and cognitive impairment=0.07, p-values for all other interaction terms >0.1.
Baseline appendicular lean mass to height ratio, ALM/(height^2), was not significantly associated with new ADL disability among those who survived to the next annual assessment (Supplementary Table 2). However, baseline ALM/(height^2) was associated with death at the next annual assessment. The adjusted odds ratio for death expressed per standard deviation decrement in ALM/(height^2) was 1.43 (95% CI 1.11, 1.84) among all individuals, 2.43 (95% CI 1.15, 5.14) among those with cognitive impairment, and 1.32 (95% CI 1.01,1.73) among those without cognitive impairment. The p-value for the test of interaction to determine whether the association of baseline ALM/(height^2) with death differed between those with and without cognitive impairment was 0.1.
In all sensitivity analyses, both those accounting for whether or not 3MS measurement was done within 1 year of the index hospitalization and those stratified by sex, the overall trends for the associations of lean mass and grip strength measures with ADL disability were largely unchanged. The point estimates for these associations were all in the same direction as in the primary analyses (Supplementary Tables 3–5).
4. DISCUSSION
We found that, among older adult survivors of hospitalization in Health ABC, baseline weaker grip strength prior to hospitalization may be an important risk factor for the development of new hospital-associated ADL disability. Moreover, baseline weaker grip strength may be a particularly significant risk factor for hospital-associated ADL disability in older adults with cognitive impairment prior to hospitalization compared to those without cognitive impairment. Baseline differences in appendicular lean mass (ALMBMI) were not associated with the risk of hospital-associated ADL disability in our cohort. These findings suggest that weaker muscle strength, a key component of sarcopenia, may be a useful tool in identifying individuals with cognitive impairment most at risk for hospital-associated ADL disability and may contribute to the likelihood of developing ADL disability in this vulnerable patient population.
The combination of physical and cognitive deficits in individuals with both weaker grip strength and cognitive impairment may particularly predispose them to hospital-associated ADL disability compared to individuals with either one deficit or the other. Weaker grip strength may be an important risk factor for developing new hospital-associated ADL disability in those with cognitive impairment for various reasons. However, we hypothesize that older adults with cognitive impairment, compared to those without, may be particularly vulnerable to the negative effects of sarcopenia on ADL function because their concomitant cognitive impairment also predisposes them to ADL impairment. Previous studies on the development of physical disability in those with cognitive impairment have similarly observed a combined deleterious effect of baseline physical and cognitive deficits on the risk of future functional declines 19–21. Our observation that weaker grip strength may be especially associated with hospital-associated ADL disability in those with cognitive impairment is consistent with these prior observations of a combined deleterious effect of baseline physical and cognitive impairment on the risk of subsequent ADL disability and provides the additional insight that muscle weakness may be a key risk factor specifically for ADL disability arising after hospitalization in older adults with baseline cognitive impairment.
Baseline lean mass, unlike baseline grip strength, was not associated with either death or ADL disability in our cohort. These findings corroborate prior studies in which muscle strength, and in particular grip strength, is more closely associated with functional declines in older adults than is lean mass 22–24. There are various explanations for why baseline lean mass, compared to baseline muscle strength, may be less associated with functional outcomes of hospitalization in older adults. First, muscle strength may be more closely related than is muscle mass to an individual’s ability to perform ADL tasks, and therefore strength may be more closely related to development ADL impairment. Alternatively, the observed lack of association could reflect limitations of the DXA-based approximation of muscle mass. DXA directly measures fat and bone mass but not muscle mass. Lean mass is calculated as total body mass minus bone and fat mass, and it is an approximation of muscle mass 25. However, lean mass also includes water and connective tissue. This inherent limitation of using DXA to quantify muscle mass could lead to measurement error that would tend to bias results towards the null. Future studies, including those evaluating novel methods of directly assessing muscle mass in older adults, may help determine potential relationships between muscle mass and hospital-associated ADL disability in older adults with and without cognitive impairment. Lastly, consistent with prior observations that lean mass corrected for height (ALM/(height^2)) is associated with mortality but not with incident functional limitations in older adults26, we found that ALM/(height^2) was associated with death following hospitalization but not with hospital-associated ADL disability.
These findings may have important implications for both the clinical care of hospitalized older adults with cognitive impairment and development of novel strategies to prevent hospital-associated ADL disability these individuals. Our findings suggest that grip strength, a key component of sarcopenia, may be a useful and practical tool to identify older adults with cognitive impairment who are at particularly increased risk of developing hospital-associated ADL disability. As a less complex motor task compared to other common performance measures such as gait speed and chair stands, grip strength may be a particularly useful assessment in those with cognitive impairment 27. In addition, individuals with cognitive impairment and weaker grip strength may be the most likely to benefit from existing interventions, such as interdisciplinary inpatient care teams and early physical therapy, to prevent hospital-associated disability. Though we acknowledge that this population may be difficult to reach with existing interventions. Lastly, the identification of weaker grip strength as a potentially important risk factor for hospital-associated ADL disability in those with cognitive impairment, may also advance understanding of the pathogenesis of hospital-associated disability in these patients by suggesting a contribution of baseline body composition and muscle strength. Future studies, including prospective cohorts of hospitalized older adults, will need to directly examine each of these hypotheses.
The prevalence of low ALMBMI and low grip strength in our cohort of hospitalized older adults in Health ABC did not statistically significantly differ between those with and those with cognitive impairment (Table 1). Unlike prior studies that have suggested a positive association between sarcopenia and cognitive impairment 9, 11, our study was limited to hospitalized older adults in whom the potential relationship between sarcopenia measures and cognitive impairment may be different. In addition, most prior studies define sarcopenia as the presence of both low muscle mass and low muscle strength, whereas in our study we examine the relationships of ALMBMI and grip strength with hospital-associated ADL disability separately.
This study has certain limitations. First, the study is limited by the timing of data collection in the parent Heath ABC Study, which was not designed to examine functional outcomes of hospitalization. Measures of muscle mass and strength and ADL functioning were collected annually in Health ABC. Thus, the time between assessment of baseline muscle mass and strength and hospitalization and between hospitalization and assessment of ADL function varies between patients. Second, given that our analytic approach is limited to individuals who survived to the next annual Health ABC study visit after hospitalization, our conclusions on potential relationships between baseline grip strength and hospital-associated ADL disability are limited to those who survived several months after their hospitalization and may or may not generalize to individuals with shorter post-hospitalization survival. Third, the sample includes only black and white older adults, and therefore may or may not be generalizable to other racial or ethnic groups. Fourth, individuals excluded from analysis due missing outcome data were more likely to be female, never smokers, and had a lower prevalence of medical comorbidities; which could affect our findings and their generalizability. Fifth, cognitive impairment defined by 3MS score does not correlate exactly with a clinical diagnosis of dementia. Sixth, ADL status after hospitalization could not be ascertained in individuals who died between hospitalization and the next annual assessment. While most older adults pass through a period of ADL disability prior to death, this inability to assess ADL status in those who died before the next planned annual assessment would likely tend to result in underestimation of incident ADL disability and of the associated between grip strength and the development of hospital-associated ADL disability. Despite these limitations, our study has several strengths. The study includes a relatively large sample of older adults with and without cognitive impairment. The measures of muscle mass and muscle strength used are well-established and standardized in the literature. The study also leverages data from the Health ABC Study which was specifically designed to examine longitudinal relationships between body composition, muscle strength, and ADL functioning in older adults.
In conclusion, weaker grip strength appears to be significantly associated with development of hospital-associated ADL disability in older adults with cognitive impairment. Thus, grip strength may be an important risk factor for hospital-associated ADL disability in older adults with cognitive impairment, and it may be a practical screening tool to assist in the identification of individuals most at risk for hospital-associated ADL disability.
Supplementary Material
ACKNOWLEDGEMENTS
This research was supported by National Institute of Aging (NIA) grants K23AG058756 and R03AG063168 to Dr. Andrews. In addition, this research was supported by NIA Contracts N01-AG-6-2101; N01-AG-6-2103; N01-AG-6-2106; NIA grant R01-AG028050, and NINR grant R01-NR012459. Lastly, this research was funded in part by the Intramural Research Program of the NIH, National Institute on Aging.
Financial Support:
This research was supported by National Institute of Aging (NIA) grants K23AG058756 and R03AG063168 to Dr. Andrews. Part of Dr. Gold’s effort was supported by NIA grant K23AG058756. In addition, this research was supported by NIA Contracts N01-AG-6-2101; N01-AG-6-2103; N01-AG-6-2106; NIA grant R01-AG028050, and NINR grant R01-NR012459. Lastly, this research was funded in part by the Intramural Research Program of the NIH, National Institute on Aging.
Financial Conflicts of Interest:
Dr. Abay has nothing to disclose. Dr. Andrews is PI on NIA awards K23AG058756 and R03AG063168 and an investigator-initiated award from Grifols. All payments were made to the University of Washington. Dr. Andrews has received a speaker’s honorarium from the Northwest Rheumatism Society ($250). Dr. Gold has received support from the University of Washington for travel expenses to attend the North American Cystic Fibrosis Conference. Dr. Cawthon is PI on NIH awards R01AG066671, R21AG070804, R56AG061085. All payments were made to the California Pacific Medical Center Research Institute. Dr. Cawthon has received support from the University of Melbourne for travel expenses.
REFERENCES
- 1.Alzheimer’s Disease Fact Sheet Bethesda: National Institute of Aging; 2016. [cited 2020, September 8]. Available from: https://http://www.nia.nih.gov/health/alzheimers-disease-fact-sheet. [Google Scholar]
- 2.Hebert LE, Weuve J, Scherr PA, Evans DA. Alzheimer disease in the United States (2010-2050) estimated using the 2010 census. Neurology. 2013;80:1778–83. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Gill TM, Allore HG, Gahbauer EA, Murphy TE. Change in disability after hospitalization or restricted activity in older persons. JAMA. 2010;304:1919–28. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Covinsky KE, Pierluissi E, Johnston CB. Hospitalization-associated disability: “She was probably able to ambulate, but I’m not sure”. JAMA. 2011;306:1782–93. [DOI] [PubMed] [Google Scholar]
- 5.Mukadam N, Sampson EL. A systematic review of the prevalence, associations and outcomes of dementia in older general hospital inpatients. Int Psychogeriatr. 2011;23:344–55. [DOI] [PubMed] [Google Scholar]
- 6.McLean RR, Shardell MD, Alley DE, Cawthon PM, Fragala MS, Harris TB, et al. Criteria for clinically relevant weakness and low lean mass and their longitudinal association with incident mobility impairment and mortality: the foundation for the National Institutes of Health (FNIH) sarcopenia project. J Gerontol A Biol Sci Med Sci. 2014;69:576–83. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Brown JC, Harhay MO, Harhay MN. Sarcopenia and mortality among a population-based sample of community-dwelling older adults. J Cachexia Sarcopenia Muscle. 2016;7:290–8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Hirani V, Blyth F, Naganathan V, Le Couteur DG, Seibel MJ, Waite LM, et al. Sarcopenia Is Associated With Incident Disability, Institutionalization, and Mortality in Community-Dwelling Older Men: The Concord Health and Ageing in Men Project. J Am Med Dir Assoc. 2015;16:607–13. [DOI] [PubMed] [Google Scholar]
- 9.Chang KV, Hsu TH, Wu WT, Huang KC, Han DS. Association Between Sarcopenia and Cognitive Impairment: A Systematic Review and Meta-Analysis. J Am Med Dir Assoc. 2016;17:1164.e7–.e15. [DOI] [PubMed] [Google Scholar]
- 10.Beeri MS, Leugrans SE, Delbono O, Bennett DA, Buchman AS. Sarcopenia is associated with incident Alzheimer’s dementia, mild cognitive impairment, and cognitive decline. J Am Geriatr Soc. 2021;69:1826–35. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Peng TC, Chen WL, Wu LW, Chang YW, Kao TW. Sarcopenia and cognitive impairment: A systematic review and meta-analysis. Clin Nutr. 2020;39:2695–701. [DOI] [PubMed] [Google Scholar]
- 12.Alley DE, Koster A, Mackey D, Cawthon P, Ferrucci L, Simonsick EM, et al. Hospitalization and change in body composition and strength in a population-based cohort of older persons. J Am Geriatr Soc. 2010;58:2085–91. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Karan NS. Assessment of the cognitive status in diabetes mellitus. J Clin Diagn Res. 2012;6:1658–62. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Bland RC, Newman SC. Mild dementia or cognitive impairment: the Modified Mini-Mental State examination (3MS) as a screen for dementia. Can J Psychiatry. 2001;46:506–10. [DOI] [PubMed] [Google Scholar]
- 15.Cawthon PM, Peters KW, Shardell MD, McLean RR, Dam TT, Kenny AM, et al. Cutpoints for low appendicular lean mass that identify older adults with clinically significant weakness. J Gerontol A Biol Sci Med Sci. 2014;69:567–75. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Cawthon PM, Fox KM, Gandra SR, Delmonico MJ, Chiou CF, Anthony MS, et al. Do muscle mass, muscle density, strength, and physical function similarly influence risk of hospitalization in older adults? J Am Geriatr Soc. 2009;57:1411–9. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Lunney JR, Albert SM, Boudreau R, Ives D, Satterfield S, Newman AB, et al. Three Year Functional Trajectories Among Old Age Survivors and Decedents: Dying Eliminates a Racial Disparity. J Gen Intern Med. 2018;33:177–81. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Visser M, Goodpaster BH, Kritchevsky SB, Newman AB, Nevitt M, Rubin SM, et al. Muscle mass, muscle strength, and muscle fat infiltration as predictors of incident mobility limitations in well-functioning older persons. J Gerontol A Biol Sci Med Sci. 2005;60:324–33. [DOI] [PubMed] [Google Scholar]
- 19.Aliberti MJR, Cenzer IS, Smith AK, Lee SJ, Yaffe K, Covinsky KE. Assessing Risk for Adverse Outcomes in Older Adults: The Need to Include Both Physical Frailty and Cognition. J Am Geriatr Soc. 2019;67:477–83. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.van Rossum ME, Koek HL. Predictors of functional disability in mild cognitive impairment and dementia. Maturitas. 2016;90:31–6. [DOI] [PubMed] [Google Scholar]
- 21.Canevelli M, Cesari M, van Kan GA. Frailty and cognitive decline: how do they relate? Curr Opin Clin Nutr Metab Care. 2015;18:43–50. [DOI] [PubMed] [Google Scholar]
- 22.Cawthon PM, Blackwell T, Cummings SR, Orwoll ES, Duchowny KA, Kado DM, et al. Muscle Mass Assessed by the D3-Creatine Dilution Method and Incident Self-reported Disability and Mortality in a Prospective Observational Study of Community-Dwelling Older Men. J Gerontol A Biol Sci Med Sci. 2021;76:123–30. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Manini TM, Clark BC. Dynapenia and aging: an update. J Gerontol A Biol Sci Med Sci. 2012;67:28–40. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24.Schaap LA, Koster A, Visser M. Adiposity, muscle mass, and muscle strength in relation to functional decline in older persons. Epidemiol Rev. 2013;35:51–65. [DOI] [PubMed] [Google Scholar]
- 25.Cawthon PM. Assessment of Lean Mass and Physical Performance in Sarcopenia. J Clin Densitom. 2015;18:467–71. [DOI] [PubMed] [Google Scholar]
- 26.Cawthon PM, Blackwell TL, Cauley J, Kado DM, Barrett-Connor E, Lee CG, et al. Evaluation of the Usefulness of Consensus Definitions of Sarcopenia in Older Men: Results from the Observational Osteoporotic Fractures in Men Cohort Study. J Am Geriatr Soc. 2015;63:2247–59. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27.Wranker LS, Elmstahl S, Ekstrom H. Physical performance in relation to birth cohort: A comparison of 60 year old Swedish men and women born twelve years apart. Arch Gerontol Geriatr. 2019;82:22–7. [DOI] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.