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A.T. Olagunju1,2,3, J.A. Morgan2, A. Aftab4, J.R. Gatchel5, P. Chen6, A. Dols7,8, M. Sajatovic6, W.T. Regenold9


1. Department of Psychiatry and Behavioral Neurosciences, McMaster University/St Joseph’s Healthcare Hamilton, Hamilton, ON, Canada; 2. Discipline of Psychiatry, The University of Adelaide, Adelaide, SA, Australia; 3. Department of Psychiatry, College of Medicine, University of Lagos, Lagos, Nigeria; 4. Department of Psychiatry, University of California, San Diego, CA, USA; 5. Division of Geriatric Psychiatry, McLean Hospital, Harvard Medical School, Boston, MA, USA; 6. Departments of Psychiatry & Neurology, Case Western Reserve University School of Medicine, University Hospitals Cleveland Medical Centre, Cleveland, OH, USA; 7. GGZ inGeest Specialized Mental Health Care, Department of Old Age Psychiatry, 1081 HJ, Amsterdam, The Netherlands; 8. Amsterdam UMC, Vrije Universiteit Amsterdam, Psychiatry, Amsterdam Public Health research institute and Neuroscience Amsterdam, 1081 HV, Amsterdam, The Netherlands; 9. Noninvasive Neuromodulation Unit, Experimental Therapeutics and Pathophysiology Branch, Division of Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA.
Corresponding author: Andrew T. Olagunju, Department of Psychiatry and Behavioral Neurosciences, McMaster University/St Joseph’s Healthcare Hamilton, 100 West 5th Street, Hamilton, ON, L8N 3K7 Canada, Email:olagunja@mcmaster.ca

J Frailty Aging 2020;in press
Published online December 9, 2020, http://dx.doi.org/10.14283/jfa.2020.64


Objectives: To better understand the role of nutrition in older adults (aged 50 years or older) with bipolar disorders (OABD), we conducted a systematic review of the literature and appraise existing evidence. Methods: Following PRISMA guidelines, we searched databases including Medline/PubMed, PsychINFO, EMBASE, CINAHL, Scopus, Web of Science, Cochrane Register, FDA website, and clinical trial registries through 2019 for eligible reports. The search string combined MeSH terms for bipolar disorder, nutrition and older adults. This was supplemented by snowball searching of references in relevant studies and authors were contacted to request their work where necessary. All included studies were rated with the National Institutes of Health Study Quality Assessment Tools based on study designs. Results: Of 2280 papers screened, ten studies including eight observational and two interventional studies. The topic foci of the papers examined several nutrients, (including vitamin B12, vitamin D, coenzyme Q10, homocysteine, and folate), nutritional deficiencies and biochemical correlates. The prevalence rates of deficiencies varied with specific nutrients (3.7% to 71.6% for Vitamin B12 and 34.6% for Vitamin D), and between inpatient versus outpatient populations. While nutritional interventions appeared to be associated with improvement in both affective and cognitive outcomes, the sample sizes of OABD varied and were generally small. Conclusion: While there is evidence for the benefits of nutritional interventions on affective, cognitive and overall outcome in OABD, the quality of the evidence is limited. Our findings underscore the need for high quality studies to inform evidence-based guidelines for nutritional assessment and supplemention in OABD.

Key words: Bipolar disorder, depression, geriatrics, nutrition, older adults, mania.



Recent international collaborative research indicates that suboptimal diet contributes significantly to the global burden of diseases with 11 million deaths and loss of 255 million disability-adjusted life-years attributable to dietary risk factors in 2017 (1-3). Despite the evidence linking poor nutrition to disease, nutrition and nutritional supplements are often overlooked in the assessment and treatment of patients generally, and in individuals with bipolar disorder (BD) in particular.
Older adults with bipolar disorder (OABD) may be especially prone to nutritional deficiencies due to various age-related factors that can diminish nutrient intake and absorption. Reduced dietary intake of nutrients may occur due to decreased sensory function, decreased appetite and dysphagia with advanced age (4). Causes of decreased nutrient absorption that are more common in older adults include: age related changes in the gut or atrophic gastritis; peptic ulcer disease with Helicobacter pylori infection; gastric and intestinal resections and taking medications that can interfere with nutrient absorption. Many of these interfering medications are commonly prescribed and include inhibitors of gastric acid secretion such as proton pump inhibitors and histamine-2 receptor antagonists; anti-epileptics, metformin, methotrexate, triamterene and trimethoprim (5, 6). Importantly, nutritional status, particularly vitamin levels, can influence cognitive function and affective symptoms in older adults with mood disorders, including BD (7-10).
In addition to the lack of awareness of diet and nutritional deficiencies in the care of OABD, clinicians are often unaware of the increasing use of nutritional supplements by their patients. Herbal and nutritional compounds are used widely by older adults and have been reported to be taken by nearly one in three older adults with bipolar disorder or major depression (11). Most individuals who use these supplements do not mention this to their clinicians, putting them at risk for potential drug-supplement interactions with adverse health effects.
Given the clinical importance of nutritional deficiencies and nutritional supplement use, a working group within the International Society for Bipolar Disorders (ISBD) (12) OABD taskforce undertook a systematic review with the following objectives in mind: 1) to synthesize literature evidence on nutritional deficiencies and supplements in OABD; 2) to review the quality of research evidence on nutritional deficiencies and supplements in relation to the epidemiology, pathophysiology, clinical treatment, outcome and wellbeing of OABD, and 3) to make recommendations regarding further research that will promote evidence-based assessment and management of OABD.



Eligibility criteria

We followed the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines in conducting the literature search in this review (13, 14). All literature for all years through 2019 was searched. The age cut-off for OABD for eligible studies in this review is 50 years and older based on the knowledge that around 50 years adults already have decreased absorption of nutrients, which is a primary age-related cause of nutritional deficiency (15, 16). Screening for nutrient deficiencies has been recommended in people aged 50 years and older in the United States and elsewhere in the world (15-18). We included all study designs including retrospective, observational, cross-sectional, and intervention trial but excluded case reports. Other inclusion criteria were availability of study full-text in the English language,19 and a clearly described representation of OABD among the study participants.

Information sources

We searched databases including Medline/PubMed, PsychINFO, EMBASE, Web of Science, Cochrane Register, the Food and Drug Administration (FDA) website, and international clinical trial registries for all years through 2019 for eligible reports. The bibliographies of included studies and relevant reviews were snow-ball searched for additional studies. Study authors were also contacted to request their work where necessary.

Search strategy

We used a search strategy addressing the following key terms in various permutations: nutrition, older adults, and bipolar disorder combined with OR and AND. Search strings included “diet* OR Diet, Food, and Nutrition OR food OR nutrition* OR “nutritional status” OR “nutritional physiological phenomenon” OR micronutrient* vitamin* OR multivitamin* OR vitamin B OR folate OR B6 OR B12 OR niacin OR vitamin C OR vitamin D OR vitamin E OR calcium OR chromium OR iron OR magnesium OR zinc OR artemisin OR caffeine OR dehydroepiandrosterone OR DHEA OR echinacea OR fish oil OR GABA OR gamma-amino butyric acid OR garlic OR ginkgo OR glucosamine OR karaela OR melatonin OR methylsulfonylmethane OR primrose oil OR probiotics OR S-adenosylmethionine OR St. Johns wort OR tryptophan OR tyrosine OR valerian AND “old age” OR aged OR elder* OR geriatric* OR geriatric psychiatry OR older OR aging OR ageing AND “bipolar disorder” OR manic depressi* OR bipolar depression. Search strings were performed in titles, abstracts, major topic/subject headings, and MeSH headings.

Study selection

Study selection, review of included studies and data extraction were conducted by Andrew T. Olagunju (ATO), Julie A. Morgan (JAM), Awais Aftab (AA), and supervised by William T. Regenold (WTR). Titles and abstracts were screened independently by at least two authors to shortlist studies for further review. The full texts of the shortlisted studies were reviewed by at least two authors independently according to the inclusion criteria. Inconsistencies about inclusion or exclusion of studies were resolved by discussion between authors or in consultation with WTR or other members of the task force to reach consensus.

Quality/bias assessment

As studies with different designs and representation of older adults were eligible, the Study Quality Assessment Tools of the National Institutes of Health (NIH) for the assessment of Observational Cohort and Cross-Sectional Studies, Case-Control, and Controlled Intervention Studies were used to assess the quality of included studies.20 We rated individual studies on a range of 12-14 items depending on their designs to produce a comprehensive overview of the risk of bias in individual studies and highlighted relevant overall quality limitations.

Data collection process

Data items collected from eligible reports included study characteristics, nutrients, main findings and implications for OABD (Table 1). In total, we screened 2280 titles and abstracts to produce a shortlist of 92 potential reports for full-text review. Of these 92 reports, 10 studies were selected for inclusion in the final review. (See Figure 1)

Table 1
Studies included in the review examining nutrition in older adults with bipolar disorder

Legend: BD- bipolar disorders, BCAA- branched-chain amino acid, C-cross-sectional, CC-case control, MTHFR- Methylene tetrahydrofolate reductase, N-total number of sample, NR-not reported, OABD- Older adults with bipolar disorders, R-retrospective chart review, RCT-randomized controlled clinical trial, YMRS- Young Mania Rating Scale

Figure 1
Flow of studies through the systematic review



Study characteristics

Ten studies were included in the review (5, 7, 8, 10, 11, 21-24, 25). The publication dates of these reports spanned three decades from 1990 to 2015. Of the ten studies, six were retrospective chart reviews, two were cross-sectional studies, and the remaining two were clinical trials. Considering the study participants, in two studies all participants were adults diagnosed with BD with a representation of OABD, (21, 22) while in the remaining studies (n=8), participants with BD represented a subset of the total sample. In general, the topic foci in the included studies addressed different aspects of nutrition and nutritional deficiencies, including biochemical, epidemiological and clinical factors, and nutritional supplements in OABD. All were able to specify the sample sizes of OABD in the included studies aged 50 years or older, ranging from 3-50. Follow-up was limited as the majority of the studies reported cross-sectional observations. (See table 1)

Biochemical, clinical and epidemiological findings on nutrients

Table 2 presents findings on specific nutrients and nutritional supplements covered in the ten studies included in this review. In total, four classes of nutrients including vitamins, minerals, and dietary herbs and nutritional supplements are covered in the studies and described below.

Table 2
Quality assessment with NIH scale-tool based on study design

1-14 are quality assessment items/criteria; CCS- case-controlled studies; CD- cannot determine; CIS- controlled intervention studies, NIH- National Institute of Health; NA- not applicable; NR-not reported; OCCSS- observational cohort and cross-sectional studies; OR-overall rating; SD-study design.



Five retrospective chart reviews (5, 7, 8, 10, 23) focused on vitamin B12 and/or folate. Importantly, several reports looked at vitamin B12 deficiency in mixed populations of older adults including patients with BD. The prevalence rates of Vitamin B12 deficiency ranged from 3.7%8 to 71.6%.10 Lower levels of vitamin B12 correlated strongly with memory loss and poor cognitive performance in psychotic depression (8). Approximately one quarter of geriatric clinic outpatients with B12 deficiency had neuropsychiatric symptoms with behavioural disturbance, memory loss and sensorimotor disorders being most common (10). Folate deficiency was reported to be 1.3% in acute geropsychiatric inpatients (7). One study concluded that the biochemically interrelated vitamins, B12 and folate, may exert both separate and concomitant influences on affect and cognition and that poorer vitamin status may contribute to certain geropsychiatric disorders that have later life onset and lack a familial predisposition (7).
Another study investigated the relationships between Vitamin B12 and folate levels as well as homocysteine (HCY) levels on brain volume changes and brain white matter disease in geriatric patients with psychiatric disorders (23). These authors found that, low serum concentrations of folate, but not of B12, were associated with magnetic resonance imaging (MRI) evidence of brain white-matter disease and smaller hippocampus and amygdala brain-volume measures. Elevated HCY, which can result from folate deficiency, was also associated with MRI evidence of brain white matter disease (23). Finally, one study found that among older adult psychiatric inpatients, B12 serum levels and percentages of probable and possible B12 deficiency did not differ significantly between cognitive disorder patients and non-cognitive disorder patients, including OABD, suggesting that it was reasonable to routinely screen older adult psychiatric inpatients for B12 deficiency whether or not cognitive disorder symptoms were present (5). One retrospective chart review study (24) and cross-sectional study(25) addressed vitamin D in OABD. Vitamin D deficiency prevalence rates ranged from 3.7 % to 34.6%. Vitamin D insufficiency (less severe and defined as levels <30 ng/mL) was reported in approximately 75% of psychiatric inpatients in two cross sectional assessments (25). However, no associations were found between vitamin d levels and a screen of global cognitive function or psychiatric diagnoses (24, 25).

Dietary, Herbs and Nutritional Supplements

In one cross sectional study of OABD and older adults with major depression (11), herbs and nutraceutical (HNC) products were ingested by 30% of individuals. About 40% incorrectly believed that HNC products were FDA-regulated at that time. The majority (64%) had not discussed the use of HNC with treating physicians and some preferred to take HNC compared to physician-prescribed psychotropic medications (14-20%). The use of HNC was more common in those with BD (44%) than those with unipolar major depression (16%).
Two open label trials (21, 22) reported significant reduction in the severity of depressive symptoms with high-dose CoEnzyme Q10 in OABD (21). These findings could support a role of therapy targeted at mitochondrial function in affective disorders (22).

Study Quality Assessment

Quality assessment of all included studies (n = 10) was rated fair (n=8) and good (n=2) with risk of bias items included in the tool. The limited representation of OABD represented a risk of bias. Notwithstanding the limitations in the quality of the studies, the reported outcomes on nutritional deficiencies and supplements in OABD were considered the best available evidence for the recommendations made. (See table 2)



Clinical implications

Most of the studies reviewed—seven of ten studies (70%) focused on three vitamins—vitamin B12, vitamin D and folate and the consequences of their deficiencies. These studies support a relationship between vitamin B12 deficiency and both affective symptoms and cognitive impairment in OABD (7, 8). They also provide evidence for associations between folate levels and hippocampus and amygdala volumes and brain MRI white matter hyper- intensities (WMHs) in older adult psychiatric patients (23). Vitamin D deficiency was reported to be common in older adult psychiatric patients. Generally, vitamin deficiencies did not differ across psychiatric disorders, indicating that screening for these deficiencies in older adults should not be limited to particular diagnostic groups such as cognitive disorders. Evidence for a therapeutic role for vitamin supplementation was limited. There is some evidence for a benefit from folate supplementation for OABD taking lithium.
Tissue levels of homocysteine can be elevated due to vitamin B12 or folate deficiencies. Four studies examined the relationships among vitamin B12, folate and homocysteine levels and their associations with psychiatric symptoms or evidence of brain disease (23). These studies support an inverse relationship between B12 and folate blood levels on one hand and homocysteine blood levels on the other in individuals with bipolar depression. They also suggest that HCY blood levels are elevated in individuals with BD and support an association between elevated levels and impairment in executive function and in the extent of brain WMHs. These studies provide evidence for measuring HCY blood levels along with vitamin B12 and folate levels in OABD.
Studies of diet and nutritional supplements revealed that supplement use is very common among OABD (11). Furthermore, supplement use was typically not discussed with health providers (11).
Clinical trials of adjunctive nutritional supplements found preliminary evidence for a benefit from Coenzyme Q10 on depressive symptoms in OABD (21, 22). The positive results in these supplement studies require replication in a larger group of OABD prior to their consideration for routine clinical use in OABD.

Study limitations

There are several study limitations of this review. The included studies were not homogenous nor entirely focused on OABD. Of the ten articles included in the review, only two reported study results exclusively from a sample or population of OABD. By expanding our inclusion criteria to capture studies with some significant number of OABD participants, we were able to report a more comprehensive review of studies. The majority of these studies were retrospective chart reviews and cross-sectional studies, while the number of RCTs was limited. Consequently, inferences on causal relationships between the nutrients studied and the pathophysiology or treatment of OABD is limited. Furthermore, none of the included studies (n=10) looked at the potential contributions of gender and the type of bipolar disorder (I and II) to their study findings despite the clinical importance of these two factors (26).



Scientific literature on nutrition and nutritional supplements in OABD exists but is limited in both quantity and quality. However, we can draw several conclusions from this review. First, because older adults are prone to nutritional deficits and suffer from several vitamin deficiencies that influence cognition and affective symptoms, there should be consideration given to better research to develop clinical guidelines for routine screening for deficiencies of vitamin B12, folate and vitamin D in OABD. Second, screening for elevated blood levels of HCY that result from vitamin deficiencies should also be considered. Notably there is need for well-designed and powered clinical trials to examine the effects of nutritional interventions including dietary questionnaires, vitamin deficiency screening, HCY blood level screening, and adjunctive nutrient supplementation in OABD.


• Nutrition is critical to physical health and general well-being of older adults with bipolar disoder (OABD), however nutritional deficiencies are common albeit varies for specific nutrients.
• While there is evidence for the benefits of nutritional interventions on affective, cognitive and overall outcome in OABD, the quality of the evidence is limited.
• Findings in this review underscore the need for high quality studies for development of evidence-based guideline for assessing and supplementing nutrition in OABD.


Acknowledgements: The authors thank the International Society for Bipolar Disorders executives, and staff for their support for this task force. Our gratitude also goes to Ms Maureen Bell of the University of Adelaide library for her support and advice.
Conflicts of interest: The authors declare no conflicts of interest to the content of the manuscript.
Disclosure information: Financial Disclosure information for Martha Sajatovic MD are stated below: Research grants within past 3 years: Otsuka, Alkermes, Janssen, International Society for Bipolar Disorders, Reuter Foundation, Woodruff Foundation, Reinberger Foundation, National Institutes of Health (NIH), Centers for Disease Control and Prevention (CDC); Consultant: Alkermes, Bracket, Otsuka, Janssen, Neurocrine, Health Analytics; Royalties: Springer Press, Johns Hopkins University Press, Oxford Press, UpToDate; CME activities: American Physician’s Institute, MCM Education, CMEology, Potomac Center for Medical Education, Global Medical Education, Creative Educational Concepts
Financial Disclosure information: Dr. Gatchel reports other relevant financial activities from Merck, grants from Alzheimer’s Association, grants from BrightFocus Foundation, outside the submitted work.



1. GBD 2017 Diet Collaborators. Health effects of dietary risks in 195 countries, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet (London, England). 2019;393(10184):1958-72.
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6. Langan RC, Goodbred AJ. Vitamin B12 Deficiency: Recognition and Management. Am Fam Physician. 2017;96(6):384-9.
7. Bell IR, Edman JS, Marby DW, Satlin A, Dreier T, Liptzin B, et al. Vitamin B12 and folate status in acute geropsychiatric inpatients: affective and cognitive characteristics of a vitamin nondeficient population. Biol Psychiatry. 1990;27(2):125-37.
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S. Crosignani1, C. Sedini1, R. Calvani2, E. Marzetti2, M. Cesari3

1. Fellowship in Geriatrics and Gerontology, University of Milan, Milan, Italy; 2. Fondazione Policlinico Universitario “Agostino Gemelli” IRCCS, Catholic University of the Sacred Heart Rome, Italy; 3. IRCCS Istituti Clinici Scientifici Maugeri, University of Milan, Milan, Italy
Corresponding author: Silvia Crosignani, MD, Email: silvia.crosignani@unimi.it

J Frailty Aging 2020;in press
Published online December 7, 2020, http://dx.doi.org/10.14283/jfa.2020.63


Detection of sarcopenia in primary care is a first and essential step in community-dwelling older adults before implementing preventive interventions against the onset of disabling conditions. In fact, leaving this condition undiagnosed and untreated can impact on the individual’s quality of life and function, as well as on healthcare costs. This article summarizes the many instruments today available for promoting an earlier and prompter detection of sarcopenia in primary care, combining insights about its clinical management. Primary care physicians may indeed play a crucial role in the identification of individuals exposed to the risk of sarcopenia or already presenting this condition. To confirm the suspected diagnosis, several possible techniques may be advocated, but it is important that strategies are specifically calibrated to the needs, priorities and resources of the setting where the evaluation is conducted. To tackle sarcopenia, nutritional counselling and physical activity programs are today the two main interventions to be proposed. Multicomponent and personalized exercise programs can (and should) be prescribed by primary care physicians, taking advantage of validated programs ad hoc designed for this purpose (e.g., the Vivifrail protocol). It is possible that, in the next future, new pharmacological treatments may become available for tackling the skeletal muscle decline. These will probably find application in those individuals non-responding to lifestyle interventions.

Key words: Skeletal muscle, aging, geriatrics, physical function, muscle strength.



“Sarcopenia” is a term referred to the progressive loss of skeletal muscle mass typically occurring with advancing age, as defined by Irwin Rosenberg in 1989 (1). Since then, the term has been used to more broadly embrace the age-related skeletal muscle decline, including both decrease in mass as well as reduction in strength and performance. To date, several definitions of sarcopenia have been proposed in the literature, and different consensus articles have tried to operationally frame this condition. Unfortunately, despite the fact that sarcopenia has even received a specific ICD-10 code in October 2016 (2), there is still no agreement in the scientific community about the gold standard definition to adopt for capturing this condition (3). Table 1 presents the most widely used definitions of sarcopenia currently available in the literature.

Table 1
Main definitions of sarcopenia


Sarcopenia still represents an underdiagnosed condition in daily practice, leaving untreated many cases amenable of interventions. Given the aging of the population, it is important that primary care physicians become familiar with the management of this condition for multiple reasons:
1) Detecting sarcopenia should be part of the routine visit due to the simplicity of the necessary tools and for the limited time required;
2) Sarcopenia is considered a reversible condition and can be contrasted by correct nutrition advices and personalized physical activity programs (4, 5);
3) Interventions directed against geriatric conditions, such as sarcopenia, are usually developed with long-term objectives (6), thus likely to involve the co-management by the primary care physician;
4) The management of a clinical condition, especially at advanced age, is strongly facilitated when the primary care physician (the one who best knows the clinical characteristics and behaviours of the patient) plays an active role;
5) Tackling sarcopenia is of primary importance in the community, where the vicious cycle of disability may still be amenable of reversion;
6) Recognizing sarcopenia in primary care may improve the design of the optimal care plan for the older person.

The present article is aimed at summarizing available evidence about the diagnosis and therapeutic process that can be activated for sarcopenia in primary care. The available diagnostic tools to recognize and quantify sarcopenia will be critically discussed. In particular, it will be considered that the operational definition of sarcopenia in primary care should be balanced to the limited availability of resources and time in this specific setting.


Prevalence, clinical relevance and costs

According to the World Health Organization (WHO), in 2050 there will be at least 2 billion persons aged 65 years or older, compared to the current 600 million. The increasing life expectancy is a worldwide demographic phenomenon, parallel to the growing number of persons affected by age-related chronic conditions (including sarcopenia).
In the absence of a gold standard for capturing sarcopenia, the estimate of its prevalence remains quite variable. Furthermore, the prevalence of sarcopenia is also highly influenced by the studied population and the setting where the condition is looked for, thus limiting the availability of single and reliable estimates. Nevertheless, a relatively robust evaluation of the phenomenon sets the prevalence of sarcopenia to be between 8.4% and 27.6% in community-dwelling older persons (7, 8), 14-33% in long-term care residents and 10% in acute hospital care population (9).
Sarcopenia is more likely to be present in men than in women and tends to increase with advancing age. Asians, persons with low body mass index, and those with low education represent other groups of people at higher risk of sarcopenia (7).
Sarcopenia has been associated with many negative health-related outcomes, including disability, poor physical function, falls, fractures, loss of independence, hospitalizations, institutionalization, and mortality. In patients with several comorbidities and clinical conditions (e.g., patients with cancer or undergoing surgery), sarcopenia has shown to represent a negative prognostic factor (10, 11).
Analyses conducted on Third National Health and Nutrition Examination Survey (NHANES III) database have calculated the direct costs of sarcopenia. Sarcopenia was found to cost about$18,5 billion ($10.8 billion in men, $7.7 billion in women) per year in the United States, and it represented about 1.5% of total direct health care costs calculated in the year 2000 (12). Reducing the prevalence of sarcopenia by 10% would result in about $1.1 billion savings per year. And this without considering the indirect costs of sarcopenia, such as the loss of productivity for the individual as well as for the eventual caregivers(12).Another example of how burdensome is sarcopenia for public health is brought by a Portuguese study showing that sarcopenia is independently related to hospitalization costs, independently of age. Sarcopenia was responsible for adding €884 per patient (95% confidence interval [95%CI] €295-€1,476) to hospital care costs, that represents a 58.5% increase. Again, these figures are likely underestimating the economic burden of sarcopenia because not taking into account the indirect costs (13).
In order to adequately tackle sarcopenia and prevent its detrimental consequences (for both the individual and the healthcare system), it is mandatory to design and implement an effective plan of action. In fact, it is important to preventively track sarcopenia when it is still reversible, and before its vicious cycle might cause the onset of frailty and disability.In this context, it is noteworthy that not everyone with sarcopenia is disable, but the condition substantially increases the risk of disability (14). Not surprisingly, sarcopenia is frequently considered as a condition to target for avoiding the most negative consequences of the disabling process. At the same time, the positioning of sarcopenia at the initial phases of physical dysfunction automatically indicates this as a condition of special interest for primary care professionals. In other words, the detection of sarcopenia (or, at least, the suspicion of it) in primary care might promote the implementation of successful interventions when the person is still independently living in the community.



It is recommended that adults aged 65 years and older should be screened annually for sarcopenia, or after the occurrence of major health events (falls, hospitalization).
It is also advisable screening older adults on the occasion of the first consultation or, for instance, at annual health check-up or flu vaccination appointments (15).
For the screening of sarcopenia in primary care, several instruments and methodologies have been developed over the years. It is generally recommended that the presence of sarcopenia should be suspected in every individual aged 65 years or older, presenting signs or symptoms suggestive of skeletal muscle impairment (3). A recent consensus paper promoting the identification and management of sarcopenia in primary care has proposed the so-called “Red Flag Method”(3) (Table 2). The purpose of this method is to generate alerts about those physical manifestations typically caused by sarcopenia that can be 1) reported by the subject, or 2) evaluated by the physician during the clinical assessment. In other words, the Red Flag Method may represent a sort of checklist for supporting the physician at the identification of several neglected signs, symptoms and conditions behind which sarcopenia might be hidden(3). The pedagogical value of the method should also be acknowledged. In fact, healthcare professionals may find in it a way for being trained at the clinical manifestation of sarcopenia, becoming more familiar with it, and introducing the process in the daily routine.

Table 2
The“red flag” method, SARC-F, and other instruments for the assessment of sarcopenia in the primary care setting

BIA: Body Impedance Analysis; DXA: Dual-energy X-ray Absorptiometry; CT: computed tomography; MRI: magnetic resonance imaging; SPPB test: Short Physical Performance Battery test; TUG: Time Up and Go.


Alternatives to formal/structured assessments might also be found in actions made by the individual during the clinical contact. For example, hints about the possible presence of sarcopenia might be provided by the strength of the individual’s handshake, his/her walking speed from the waiting room to the office, or observing how the person sits down and stands up from the chair.
If the Red Flag Method is based on a relatively long list of items to consider in the identification of possible sarcopenia, John Morley recently developed an ad hoc instrument (i.e., the SARC-F questionnaire) for a more rapid screening of the condition(16). SARC-F is the acronym of Strength, Assistance in walking, Rise from a chair, Climb stairs, and Falls. Each of these items receives a score ranging between 0 (absence of the sign) and 2 (inability or severe issue). A total score equal to or higher than 4 points is predictive of sarcopenia and poor health-related outcomes. The SARC-F can be used to identify individuals in the need of a more detailed and careful assessment of sarcopenia, and potentially lead to a more in-depth analysis of the case through the comprehensive geriatric assessment. Interestingly, in the revised version of the European recommendations for the definition and diagnosis of sarcopenia, designed by the European Working Group on Sarcopenia in Older People (EWGSOP), the use of SARC-F is suggested for the early identification of individuals amenable of further evaluation (17). This choice is motivated by the low sensitivity and high specificity of the instrument (17, 18).
Another opportunity for promoting the inclusion of the sarcopenia assessment in primary care can be found in a wider use of anthropometry. Although they would be useful to assess the body composition, the most commonly considered imaging methods might be unfeasible in primary care. Anthropometry (i.e., the measurement of body mass index, waist circumference, calf circumference, mid-upper arm circumference, and/or skinfold thickness) may provide easily applicable, inexpensive, and non-invasive techniques for identifying individuals at risk of presenting low muscle mass (19, 20). Recently, the Yubi-Wakka (finger-ring)test has also been proposed in this context. This is a simple self-screening method to quickly assess sarcopenia, comparing the calf circumference with the ring generated by the individual’s fingers (21).Table 2 lists several methods to be considered for the screening of sarcopenia in primary care.



As mentioned, a gold standard definition to diagnose sarcopenia is today not yet available. In general, the available recommendations coming from different panels of experts and task forces tend to indicate the need of combining a quantitative dimension (capturing the skeletal muscle mass) and a qualitative one (assessing the skeletal muscle function). Whereas the assessments of skeletal muscle strength and/or physical performance are relatively easy to be conducted, the body composition evaluation might be challenging in the primary care setting. In fact, general practitioners may not have easy/immediate access to the suggested methodologies for measuring the skeletal muscle mass, or (at best) may have to rely on suboptimal techniques. For this reason, the accurate diagnosis of sarcopenia is likely to require the referral to specialized centres, where the dual energy X-ray absorptiometry (DXA) or other (more sophisticated) techniques (e.g., magnetic resonance imaging or computerized tomography) are available. At best, the quantification of the skeletal muscle mass in primary care might be estimated using the bioelectrical impedance analysis (BIA). This technique is inexpensive, easy to use, and readily reproducible, although its results might be inaccurate, especially in the presence of certain clinical conditions (e.g., in the presence of fluid retention).
Nevertheless, a lot can still be done in primary care to detect the sarcopenia condition. The identification of individuals with sarcopenia might also start by measuring some neglected signs or symptoms of muscular poor health, for example by formally and routinely testing muscle strength/performance. In this context, the routine adoption of the handgrip strength is widely recommended and relatively easy to implement in primary care and represents a cornerstone parameter for the diagnosis of sarcopenia (22–24). In case a dynamometer is not available, the Chair Stand Test can be a valid and reliable alternative for measuring the muscle strength (17).
It is likely that, in the next future, novel methodologies will be developed for supporting Physician to diagnose sarcopenia. One of themost promising ones is represented by the deuterated creatine (D3-creatine) dilution method, which is able to provide a direct quantification of the individual’s muscle mass via the ingestion of deuterium-marked creatine and is the only technique providing a direct and unbiased estimate of muscle mass.
Although its use is currently limited to the research setting(19), this method has relevant potential for diffusion in primary care because 1) based on the simple administration of a pill and a urine analysis (to be performed after 24-48 hours), and 2) overcoming the need of the above-mentioned diagnostic tools for body composition assessment.



Primary care physicians may play a crucial role in the identification of individuals exposed to the risk of sarcopenia or already presenting this condition. They may preventively act providing recommendations for managing reversible risk factors (e.g., sedentary behavior, unhealthy diet) and eventually referring them to specialists for further evaluation.
To date, no pharmacological agent is available for the treatment of sarcopenia, but several molecules (at different stages of development) are in the pipelines of pharmaceutical industries. Thus, physical activity and nutritional interventions currently represent the basis of the clinical management of sarcopenia(25,26). Unfortunately, there is still a general lack of knowledge among healthcare professionals for correctly prescribing personalized interventions of physical activity and/or healthy diet.

Physical activity

The design ofa person-tailored physical activity program for tackling sarcopenia is not easy, especially if considering 1) the clinical complexity of older persons presenting this condition, and 2) the lack of adequate training that healthcare professionals may receive for this task during the curriculum of traditional study. Nevertheless, the beneficial effects that a physical exercise program may exert in frail and/or sarcopenic individuals is very well documented (27).
In general, multicomponent/combined exercise programs including aerobic activities, resistance training, and flexibility exercises are recommended. These should be proposed by primary care physicians to frail and/or sedentary community-dwelling persons as part of clinical routine (15). In this context, the material produced by VIVIFRAIL project is important to be mentioned (28). VIVIFRAIL was designed to provide support to primary care physicians in the prescription of personalized programs of physical activity. The program is based on a preliminary assessment of the individual’s physical performance, muscle strength, balance, and risk of falls. The results of such evaluation are then used to design an intervention that is tailored to the individual’s capacities and deficits. Importantly, VIVIFRAIL is designed for empowering the individual at monitoring his/her progresses (29). The VIVIFRAIL material is available at the project website (www.vivifrail.eu), and an app has also been developed for supporting the individual and the healthcare professionals.
Another project to be mentioned for its potential of reshaping the management of sarcopenia is “The Sarcopenia and Physical fRailty IN older people: multi-componenT Treatment strategies” (SPRINTT) study(30). This project, funded by the Innovative Medicines Initiative (IMI), is aimed to developing an operational definition of sarcopenia that might be acceptable by regulatory agencies. The project includes a randomized control trial designed to test the effects of a multidomain lifestyle intervention (mainly based on physical activity and nutritional counselling) on a condition combining physical frailty and sarcopenia. Interestingly, the target condition was theoretically framed in order to mirror the nosological conditions that are traditionally object of observation by regulatory agencies. The developed operational definition has been preliminarily endorsed by the European Medicines Agency before the beginning of the SPRINTT randomized controlled trial. At the end of the trial, investigators will be in the position of 1) estimating the prevalence of the novel condition in the general population, 2) ascertain the reversibility of the condition after implementation of lifestyle changes promoting healthy ageing, and 3) identify a subgroup of individuals resistant to the beneficial effects of physical activity and healthy diet. In particular, this latter point is of special interest because paving the way towards the profiling of future candidates to pharmacological interventions against sarcopenia (31).


Malnutrition is a condition due to a protein or other nutrient imbalance, responsible for negative effects on body composition, physical function, and clinical outcome. It plays a key role in the pathogenesis of sarcopenia and fragility. It is necessary to recognize malnutrition early in older adults to plan nutritional programs aimed at improving the outcome (32).
In hospital settings Nutrition Risk Screening-2002 (NRS-2002) or Malnutrition Universal Screening Tool (MUST) are used for the screening of malnutrition whereas Mini Nutritional Assessment (MNA) is considered the gold standard for the older adults hospitalized or in an outpatient setting. In the subject at risk of malnutrition, the evaluation of the nutritional status must be carried out.
These screening tools help to have a patient-centered approach, provide adequate nutritional advice, and monitoring nutritional status over time (33, 34).
An example of malnutrition prevention is the “Health Enhancement Program (HEP)”, a randomized trial with robust results. After an initial assessment conducted by a trained staff of each participant’s health and functional status, a personalized plan was carried out to counteract disability risk factors. The program consists in motivational strategies to promote behavioral changes in depression, poor nutrition, and a sedentary lifestyle. At one year follow up, compared with enrollment, a reduction of risk factors was registered (35).
An attempt of intervention in frail older adults in a clinical setting is the program of the Geriatric Frailty Clinic (G. F. C.) at the Gerontopole of Toulouse. Older adults, considered as frail by their General Practitioner, underwent a multidisciplinary evaluation at the G.F.C where the team members proposed a Personalized Prevention Plan (PPP); in case of malnutrition, detected by the MNA, a nutritionist was asked for improve dietary intake with specific recommendations. A follow-up, consisted of a nurse call after one month and three months, was organized to determine the intervention’s efficacy. After one year the Geriatrician reassessed the patient’s improvements with a multidisciplinary evaluation (36).
Recently, two consensus papers (promoted by the European Society for Clinical Nutrition and Metabolism and the PROT-AGE study group) agreed that people aged 65 years or older require a higher intake of proteins compared to what usually recommended for activating muscle protein synthesis and maintaining muscle health. Therefore, both groups recommended the assumption of at least 1–1.2 g of proteins/kg/day in older persons, pushing even higher this minimum threshold in the presence of catabolic or muscle wasting conditions (37, 38).
About the quality of proteins, essential amino acids (EAAs; in particular leucine) are recognized as providing an important anabolic stimulus. In fact, leucine is able to increase muscle protein synthesis in older people, as also confirmed in a recent meta-analysis. In fact, its consumption has been found to be directly correlated with muscle mass in healthy older people (39).
β-hydroxy β-methylbutyrate (HMB) is one of the metabolites of leucine that is able to exert anabolic effects. HMB is frequently used by athletes to improve their physical performance and has also showed promising results in improving muscle mass and strength in older adults. When applied to bed resting older people, HMB stimulated muscle mass preservation. HBM supplementation combined with exercise seems to promote the regenerative capacity of skeletal muscles (25).
For what concerns vitamin D, its supplementation is surely useful for correcting states of insufficiency or deficiency (40, 41). Nevertheless, no evidence supports its use in individuals with normal vitamin D concentrations for improving muscle health.


No drugs are currently registered for use in the treatment of sarcopenia, and no pharmacological intervention can be accepted as first-line therapy of sarcopenia (15). However, several new molecules are currently under study at various stages of development. It is noteworthy the special interest devoted by regulatory agencies in this field. Both the Food and Drugs Administration and the European Medicines Agency are paving the way for structuring pharmacological research on this topic.
Despite the urgency of the problem, the development of pharmaceutical therapies for sarcopenia and frailty has lagged, in part because of the lack of consensus definitions for the two conditions. In 2015,an experts’ group gathered during the International Conference on Frailty and Sarcopenia Research (ICSFR) to discuss challenges related to drugs designed to the target the biology of frailty and sarcopenia (8).
Based on the available evidence, myostatin antagonists, like Bimagrumab, may be promising candidates to treat people with low lean muscle mass, in particular people older than 70 years. Bimagrumab is a monoclonal antibody that blocks the binding of myostatin to activin, thus blocking its negative regulation of muscle growth (42). Young men treated with a single dose of Bimagrumab may experience an increase in muscle mass similar to that induced by 12 week of high-intensity resistance training(43,44), while sedentary adults may receive a benefit equivalent to 9 months of jogging 12-20 miles per week (45).
Researchers are also focused on selective androgen receptor modulators (SARMs). These are a class of androgen receptor ligands that increase low lean muscle mass by binding to the androgen receptor in muscles. Different molecules have already undergone phase I, II and III trials, but at the moment longer studies are required to demonstrate the long-term safety and the efficacy of these drugs (8).
Inflammatory modulators, such as those acting on the tumour necrosis factor-α (TNFα) and interleukin-1 (IL1), are also under study. Systemic inflammation and the increasing of TNFα and IL1 in blood lead to muscle atrophy (46). Inflammatory modulators could limit the reduction of skeletal muscle by reducing pro-inflammatory cytokines.



Sarcopenia is the age-related progressive decline of skeletal muscle. It is a common age-related condition, and has a relevant impact on the person’s quality of life and functioning, as well as on healthcare costs.
Primary care physicians may play a pivotal role in the identification of the risk of sarcopenia in the aged population. Indeed, the primary care physician may detect the early manifestations of this condition and lead to its fast diagnosis and care. In this framework, multiple instruments have been developed for promoting the detection of sarcopenia in primary care. Once sarcopenia is identified, a comprehensive assessment of the individual may lead to person-tailored interventions based on nutritional counselling and physical activity programs. In the next future, the availability of pharmacological therapies could be able to prevent the skeletal muscle decline in those individuals resistant to the benefits of healthy lifestyle prescriptions.


Conflicts of Interest: Matteo Cesari received honoraria from Nestlé for presentations at scientific meetings and as member of scientific advisory boards. No other conflict of interest declared by the Authors.



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E. Wool1, J.L. Shotwell1, J. Slaboda3, A. Kozikowski1,2, K.L. Smith1,2, K. Abrashkin1,2, K.V. Rhodes1,2, G.J. Norman3, R. Pekmezaris1,2


1. Office of Population Health Management, Northwell Health, Manhasset, NY, United States; 2. Donald and Barbara Zucker School of Medicine at Hofstra/Northwell , Hempstead, NY, United States; 3. West Health Institute, La Jolla, CA, United States.
Corresponding author: Eve Wool, 600 Community Drive, Suite 400, Manhasset, NY 11030, Tel: (914)-438-1203 eve.wool@nyu.edu
J Frailty Aging 2019;8(4)210-214
Published online June 26, 2019, http://dx.doi.org/10.14283/jfa.2019.19



Background: Home-based primary care (HBPC) provides team-based clinical care for homebound patients who have difficulty accessing typical outpatient care. Interdisciplinary team members also provide social and emotional support and serve as a resource for family caregivers, who often experience significant emotional stress. Objectives: This qualitative study explores the impact of HBPC on family caregivers to identify aspects of the program that caregivers find most helpful and meaningful as well as areas for improvement. Design: Semi structured recorded interviews were conducted with family caregivers of frail, elderly homebound patients. Interviews included the following topics: overall program satisfaction and suggestions for improvement. Setting: A HBPC program serving patients in Queens, Nassau and Suffolk counties in New York. Participants: Nineteen family caregivers: 13 women, 6 men; 10 were adult children; 6 were spouses, and 3 were other family members of patients in a HBPC program. Measurements: Thematic coding of all recorded transcribed interviews was prepared by 3 qualitative coders. Interrater reliability was conducted to ensure reliability across coders before themes were disseminated and discussed until consensus was achieved with the larger group of investigators. Results: Three main themes were identified: the importance of staff emotional support; the burden of caring for homebound patients; and the need for a broader range of home-based services. Multiple family members noted that the program not only had saved their loved one’s life, but had also metaphorically saved their own. Conclusions: Family caregivers value the communication and accessibility of HBPC and report that the program has a positive impact on their stress and mental health. Results can inform key aspects that need to be retained or enhanced with the expansion in HBPC programs.

Key words: Caregiver stress, home based primary care, geriatrics, value-based care.




The number of people living 65 years or older is predicted to double from 2000 to 2030 and average life expectancy is nearing 80 (1). As life expectancy increases, the number of older people needing long-term care in the home, has also increased (1, 2).  Last year, an estimated 34.2 million Americans, usually family members, provided unpaid care to an adult 50 or older (3). Given these dynamics, caregiver physical and emotional health has become a burgeoning public health issue (3, 4). Caregiving is a risk factor for caregiver mortality, and strained caregivers have significantly higher levels of depressive symptoms, anxiety, and lower perceived levels of health (5).  Caregiver health is vitally important for patients, as the largest risk of institutionalization of the older adult is not their own health decline, but a decline in the health of a family caregiver (3). Protective factors, such as social and emotional support are important, as they are associated with decreased stress in family caregivers of older adult, chronically ill and home bound patients (6-8).
Home Based Primary Care (HBPC) is a longitudinal interdisciplinary medical model for homebound patients shown to improve patient outcomes while reducing unnecessary health care utilization and alleviating caregiver burden (7, 9). Studies of HBPC have found that patients and caregivers alike value access to around-the-clock, team-based care, as well as providers with strong interpersonal skills (10).
With support from national demonstration projects such as Independence at Home and Program of All Inclusive Care for the Elderly (11), as well as innovation in the private sector (12), evidence for comprehensive home-based models for frail older adults, is growing (13, 14). This has led to a rapid expansion of for-profit and not-for-profit home-based models. In this period of tremendous growth due to alternative payment models, it is important to identify and maintain the aspects of HBPC that most contribute to the quality of care. While generally positively received (10), less work has been done to identify the key elements of HBPC that are most valuable to caregivers. The aim of this qualitative study is to understand the impact of HBPC on family caregivers and identify aspects of the model that are particularly valuable, as well as areas for improvement.



We conducted qualitative interviews with family caregivers of patients enrolled in “House Calls”, a HBPC program serving approximately 1,400 homebound, older adults, or chronically ill patients in Queens, Nassau and Suffolk counties in New York. House Calls provides an interdisciplinary team who design care around the goals of patients and families. House Calls patients have access to primary care providers (PCPs) (MD, DO or NP), RNs and Social Workers for both routine primary care and urgent visits. House Calls also provides afterhours  access to a 24/7 nurse-run clinical call center with direct access to on-call PCPs and  the ability to send community paramedics to the home for acute care issues. Patients are assigned to one of three clinical acuity levels: Advanced; the highest risk of decompensation; Complex; still at risk for decompensation, but with fewer acute events, and Chronic; stable, but chronically ill. The number and type of home visits are based on level of acuity.
The interviews analyzed in this study were conducted as one aim of a larger study which was designed to evaluate the care delivered by the House Calls program with the goal of improving efficiency and scale while maintaining quality. During this phase of the study, we conducted interviews with patients, family caregivers, and formal caregivers of the program. This paper specifically focuses on the responses of family caregivers. The Northwell IRB determined the qualitative study to be a quality improvement activity, and therefore exempt from full board review. All subjects signed written informed consent for audiotaping. Semi-structured interviews were conducted with caregivers, including questions about: overall program satisfaction, suggestions for improvement, and preferences for communication. The interview guide can be found in the appendix.
We purposively sampled 19 family caregivers, by selecting caregivers of patients from 8 of the 10 PCP’s in the program, and from each level of patient acuity, and with a variety of relationships to the patient (Table 1). Staff on the program produced lists of caregivers who fit these criteria and the first author contacted them to ascertain their interest. Any caregiver that agreed to participate was interviewed, and if the patient had two caregivers, both were interviewed (this happened twice, for a total of 4 caregivers).  Since the interviews conducted addressed program satisfaction, as well as areas for improvement, selecting caregivers that had a variety of primary care providers, as well as, cared for patients with varying degrees of clinical severity helped create a diverse sample of participants. Family caregiver relationships were defined as children, spouses, siblings (and in-laws), and parents of patients.
Interviews were conducted between May and July 2017 inside the patient’s home. Before the interviews were conducted, the authors conducting interviews (EW, JLS, AK) shadowed staff on the program to better understand the services provided. Interviews were conducted until theme saturation was attained, which was determined by discussions between interviewers and a determination that they were not identifying new information. The interviews spanned from 6 to 48 minutes, with a mean of 22 minutes.

Table 1 Demographics of Caregivers and Patients

Table 1
Demographics of Caregivers and Patients

*The total number of patients in this section is 17, however we interviewed 19 caregivers, because for 2 patients we interviewed 2 caregivers.


Interviews were audio recorded and professionally transcribed. Transcripts were entered into NVIVO 11 software (QSR International, Burlington, MA). Qualitative data was analyzed using thematic analysis and coded by the 3 interviewer authors (EW, JLS, AK), who independently read and reviewed the transcriptions and developed lists of themes and a standardized group of codes. Field notes were recorded on the interview guide and were integrated into code creation. The 3 authors then independently coded all transcriptions and edited the codes for redundancy. Based on discussion among the authors, the codes were edited and all transcriptions were coded a second time. Inter-rater reliability with Cohen’s kappa was conducted with a minimum rate of 75% reliability. Coding was then deemed complete and the most pertinent themes were determined by consensus among all of the authors.



During the interview process, family caregivers were asked open ended questions, including: Overall, what was your experience with the House Calls program? What about House Calls do you find most beneficial/meaningful/comforting? What about House Calls do you like most? What are its strengths? What about House Calls do you not like? What are its weaknesses; What would you change to make House Calls better? Did you experience any barriers to fully benefitting from House Calls? How do you feel about interacting with House Calls staff? What was particularly beneficial/meaningful/comforting? What was not so beneficial/meaningful/comforting? In response to these questions, caregivers cited both valuable aspects of the program as well as suggestions for improvement. Three main themes related to these questions were identified: staff emotional support, the challenges of caring for homebound patients, and need for additional services.
Theme 1: Staff providing emotional support. 13 out of 19 participants cited the emotional support that the staff provided. Due to support and communication provided by House Calls staff, family caregivers reported increased confidence, ability to manage stress, and decreased anxiety, along with greater understanding of their family member’s condition. One family member noted that the ability to contact house calls alleviates their anxiety. “It’s comforting to the caregiver because sometimes, of course, I don’t know what’s going on…And they can talk me down off that shelf in seconds.” Here, a family caregiver describes being talked off a metaphorical “ledge” of emotional turmoil, through the reassurance of their family member’s doctor.   Additionally, there was mention that the house calls program provided comfort to family caregivers, because of the trust family members have in their decisions and medical care. “They’ve definitely given me that comfort level …feeling confident in their care and making decisions.”  Caregivers also felt that the trust was reciprocal and the house calls providers had trust in them as well and understood their concerns, and validated their understanding of their family member’s condition. “He [the doctor] trusts my judgment… he knows I’m not an alarmist, nor am I gonna… just say, oh, it’s nothing.” The reciprocal trust that family members and providers have in one another and the emotional support these services provide were so significant, that caregivers frequently reported the program had metaphorically saved their life. “I would say without the services, my God… I would die to be honest.” “I told you they saved my life.” Here, a family member is describing that the relief she felt from the support of the program has eased her stress so significantly due to the burden she experienced before receiving the House Calls program that she felt that she herself would’ve died without their help. The continuous access to support, emerged as a theme that provided great emotional relief to the caregivers. “Then they sent somebody to look at him and that was – it was great because …Sometimes I’m here alone at night.  And …I can call up …  They get on the phone, right then and there, so … I feel a sense of relief…”
Theme 2: When asked questions specifically about the program’s benefits, 13 out of 19 participants remarked on caregiver burden, and how the program alleviated the burden. Family caregivers reported that moving homebound patients to and from doctors’ offices and hospitals was stressful, difficult physically, and caused deterioration of the patient. Several aspects of the program allowing family caregivers to keep their homebound family member at home, were sources of stress relief, including the 24/7 accessibility of the program. «To be honest with you, I feel like with House Call 24/7 saved [First Name 1]’s life so many times that be honest with you, I’m so grateful.” Family members strongly felt that the access to care in the home, helped them avoid long and stressful outings with their homebound family members, potentially saving their family member’s life. “If he needs a doctor right away, I don’t have to get him ready to go out, which can be a two to three-hour process.  If really needed, they’re here, so the access is really helpful, whether it’s in person or over the phone.” The ability to access care in the home also meant that family caregivers did not have to continually bring a sick patient to the hospital which they mentioned contributed to the health of the patient. “He’s had infection after infection.  And I mean, he would have been living in the hospital.” “…when you’re unsure of something, you can call them…don’t always wanna visit the emergency room…every time…she goes it’s a setback.“ “But it’s been critically important, and I’m sure that that’s a key to her longevity, is that she can be seen here.” This feedback demonstrated that services provided in the home provided great physical relief to the caregiver because they could avoid moving a homebound patient. Caregivers also voiced recognition that not going to the hospital allowed the patient to avoid some of the negative impacts of hospitalization, such as hospital-acquired infections t.
Theme 3: Additional need for home-based services. When asked about additional services that House Calls could provide to improve the services, 22 suggestions overall were made. Most notably, family members suggested the program could be strengthened by additional home-based services including, mental health counseling, greater access to sub-specialists and non-medical care.  Particularly, there were suggestions of the need to access specialists other than primary care providers. “do they offer let’s say ophthalmology visits other than just regular M.D. visits…?  Because that also would be helpful.” Additionally, family members reported the need for more caregiver mental health support. “I asked for a therapist…you don’t have it in your program, but you could request it through… my insurance.  And I asked for it and I never got it.” Additionally, one family caregiver commented that if house calls could not provide additional services they could provide a list of home based resources. “a network of things, of just reaching out and saying, well, this patient used this doc, this dentist, this might help you…Even though they’re not affiliated with you guys, but to have like a bowl of resources.” When the HBPC program did provide additional home-based services, it seemed to have a positive impact on the stress levels of caregivers. “ the lab comes every three weeks to draw up her blood…I don’t have to take her out for that any longer…also, the foot doctor comes to the house.  We even had a dentist come to the house.  We’ve had all kinds of people come and give her services here, which I didn’t even think was possible.”



There is significant evidence that caring for older adults is stressful and burdensome, increasing physical health problems and mortality for family caregivers (5).  Protective factors for caregivers are associated with better physical health for the caregiver and reduced patient hospitalizations and institutionalizations (6, 15, 16).  This study suggests that high quality HBPC decreases stress and burden experienced by caregivers, by providing meaningful emotional support and decreasing the burden of caring for homebound patients. Easy access to medical support in the home, kindness provided by the staff, and a reduction in logistical stressors were identified as key elements of HBPC that may reduce caregiver stress (8).
Family caregivers cited enormous burden associated with caring for older family members and clearly stated that HBPC provided both medical support services and emotional relief. Keeping a loved one home while avoiding strenuous and emotionally taxing doctors’ visits and hospitalizations, were highly valued aspects of HBPC that decreased caregiver burden. Family caregivers also reported increased understanding of their loved one’s medical condition, increasing confidence in their own abilities as a caregiver. In fact, family members felt so strongly about the support that the program provides, that several cited the program as “life-saving” for themselves as well as for their family member. HBPC providers’ purposeful attention to caregiver social and emotional needs can positively impact caregiver stress and their ability to care for homebound patients. Finally, HBPC program staff must listen to caregivers about what additional services are needed, and design solutions to address these unmet needs.
This study has several limitations typical of qualitative studies. There were many caregivers who were not interviewed, and thus results may not be fully representative of caregiver perspectives across the House Calls program. Likewise, findings may or may not be generalizable to other HBPC programs. However, this study highlights valuable aspects of these unique programs which should be maintained during this period of rapid growth in HBPC models that serve this vulnerable population. In a ‘high touch’ program such as House Calls, it is vital to retain factors that are valuable to caregivers, so that HBPC can continue to be a life saver for caregivers and patients, and achieve outcomes needed to expand these much needed services across the United States.
In summary, this qualitative study interviewed caregivers of patients in a HBPC program and identified three main themes: the importance of staff emotional support; the burden of caring for homebound patients; and of the need for an even broader range of home-based services. Qualitative limitations notwithstanding, we found that family caregivers value the communication and accessibility of home-based primary care and feel that the program has a positive impact on reducing their stress and improving their mental health. Results can inform key aspects that need to be retained, enhanced, tracked and further evaluated with the expansion in home-based primary care programs.


Funding: This research was supported with funding from the Gary and Mary West Health Institute.  The research was initiated as a collaborative research study conducted by Northwell Health and the West Health Institute. The sponsors helped design the study, interpret the data and prepare and approve the manuscript, as part of the collaborative research study.
Acknowledgments: The authors would like to acknowledge Joyce Racanelli, LCSW and Asantewaa Poku, MPH for their help and guidance on this project. Finally, we want to thank all of the providers and team members for their kind, thoughtful, and diligent care of House Calls’ patients and families.
Conflict of Interest Disclosure: Eve Wool has nothing to disclose. Jillian Shotwell has nothing to disclose. Dr. Slaboda is employed at the Gary and Mary West Health Institute, this research was supported with funding from the Gary and Mary West Health Institute.  The research was initiated as a collaborative research study conducted by Northwell Health and the West Health Institute. Dr. Kozikowski has nothing to disclose. Dr. Norman is employed at the Gary and Mary West Health Institute, this research was supported with funding from the Gary and Mary West Health Institute.  The research was initiated as a collaborative research study conducted by Northwell Health and the West Health Institute. Dr. Smith has nothing to disclose. Dr. Abrashkin has nothing to disclose. Dr. Rhodes has nothing to disclose. Dr. Pekmezaris has nothing to disclose.



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R. McGrath1, K. M. Erlandson2, B.M. Vincent3, K.J. Hackney1, S.D. Herrmann4, B.C. Clark5,6,7


1. Department of Health, Nutrition, and Exercise Sciences, North Dakota State University, Fargo, ND, USA; 2. Department of Medicine, Divisions of Infectious Diseases and Geriatric Medicine, University of Colorado-Anschutz Medical Campus, Aurora, CO, USA; 3. Center for Clinical Management Research, VA Ann Arbor Healthcare System, Ann Arbor, MI, USA; 4. Sanford Research, Sioux Falls, SD, USA; 5. Ohio Musculoskeletal and Neurological Institute, Ohio University, Athens, OH, USA; 6. Department of Biomedical Sciences, Ohio University, Athens, OH, USA; 7. Department of Geriatric Medicine, Ohio University, Athens, OH, USA.
Corresponding author: Ryan McGrath, PhD, Department of Health, Nutrition, and Exercise Sciences, North Dakota State University, NDSU Dept. 2620, PO Box 6050, Fargo, ND 58108-6050, Email: ryan.mcgrath@ndsu.edu
J Frailty Aging 2019;in press
Published online December 28, 2018, http://dx.doi.org/10.14283/jfa.2018.47



Objectives: The primary purpose of this study was to determine the time-varying associations between decreased handgrip strength (HGS) and individual instrumental activities of daily living (IADL) impairments for a nationally-representative sample of aging adults in the United States. Design: Longitudinal-Panel. Setting: Detailed interviews were completed in person and core interviews were typically completed over the telephone. Participants: A total of 15,336 participants aged at least 50 years who participated in the 2006 wave of the Health and Retirement Study were followed biennially for 8-years. Measurements: A hand-held dynamometer assessed HGS and performance in IADLs were self-reported. Results: Every 5-kilogram decrease in HGS was associated with an increased odds ratio for the following IADL impairments: 1.11 (95% confidence interval (CI): 1.09, 1.13) for using a map, 1.10 (CI: 1.07, 1.12) for grocery shopping, 1.09 (CI: 1.05, 1.14) for taking medications, 1.07 (CI: 1.05, 1.09) for preparing hot meals, 1.06 (CI: 1.04, 1.08) for managing money, and 1.05 (CI: 1.02, 1.09) for using a telephone. Conclusions: Decreased HGS was associated with each IADL impairment, and slightly different associations were observed in individual IADL tasks for aging adults in the United States. Our findings suggest that decreased HGS, which is reflective of reduced function of the neuromuscular system, is associated with diminished performance in autonomous living tasks during aging. Losses in HGS may lead to the development of an IADL impairment. Therefore, health-care providers working with aging adults should utilize measures of HGS as a screening tool for identifying future deficits in neuromuscular functioning. Interventions designed to preserve IADLs in aging adults should also include measures of HGS for detecting early changes in IADL capacity, and intervening at the onset of HGS declines may help aging adults retain their ability to live autonomously.

Key words: Cognition, geriatrics, motor skills, muscle strength, muscle weakness



Handgrip strength (HGS) is commonly used for clinical and population screenings of overall muscle strength in aging adults (1). While decreased HGS is typically ascribed to reductions in muscle mass, there is evidence that suggests declines in HGS are sensitive to the integrity of the nervous system centers that mediate the control of coordinated movement (2). For example, the force generated during a maximum voluntary grip force task is around half of what would be expected if the skeletal musculature itself were fully activated by the nervous system (3, 4), due to reduced neural drive to the muscles (5). Moreover, deficits in cognitive and motor performance coexist during aging, and are important mechanisms for accelerating the disabling process (6). Therefore, it is plausible that decreased HGS is associated with tasks that require higher neuropsychological functioning and relatively little muscular force production, such as several instrumental activities of daily living (IADL).
Assessments of IADLs examine a person’s ability to perform tasks that are necessary for independent living, and the ability to perform IADLs are dependent on cognitive, motor, and perceptual capabilities (7). Given that age-related weakness, as measured by HGS, is reflective of both decreased muscle strength and nervous system integrity, we suspect that measures of HGS may help to identify future deficits in IADLs for aging adults, including those that require low levels of muscle force generation. Accordingly, the primary purpose of this investigation was to determine the time-varying associations between decreased HGS and individual IADL impairments for a nationally-representative sample of aging adults in the United States. Additionally, we also sought to examine the role of cognitive functioning as an influential factor in these associations for a secondary purpose.




Those aged 50 years and older who participated in the 2006 wave of the Health and Retirement Study (HRS) were followed biennially for 8-years (n=18,469). Beginning in the 2006 wave, half of the participants alternated completion of the core interviews and detailed face-to-face interviews. Sample weights are supplied to account for the multi-stage, area probability design and they were utilized in the analyses. Participants from the HRS provided written informed consent and study protocols were approved by the University’s Behavioral Sciences Committee Institutional Review Board. Details for the HRS have been previously published (8).

Outcome Variable

At each wave, participants reported their ability to perform the following IADLs: use a map, prepare hot meals, take medications, manage money, use a telephone, and shop for groceries. Those indicating difficulty or an inability to complete an IADL were regarded as impaired for that specific task.

Exposure Variable

A Smedley spring type hand-held dynamometer (Scandidact, Denmark) was used to measure maximal HGS. Details for the HGS test protocol are explained elsewhere (9). Data for HGS from either the 2006 and 2008 waves, or 2010 and 2012 waves were concatenated because HGS measurements were a part of the detailed face-to-face interviews.


Cognitive functioning was evaluated with a series of tests from the modified Telephone Interview of Cognitive Status questionnaire (10). A 27-point composite scale was used for those aged under 65-years and respondents with scores ≤11 were considered as having a cognitive impairment (11). For those aged at least 65-years, a 35-point composite scale was used and respondents with a score of ≤10 were considered as having a cognitive impairment (12). Proxy respondents were excluded (n=2,735) because the ability to perform certain IADLs were a part of the cognitive functioning assessments for proxies.
Morbidity was collected by self-report of health-care provider diagnosed hypertension, diabetes, cancer, lung disease, heart condition, stroke, psychiatric problems, and arthritis. A morbidity count of affirmative diagnoses was summed at each wave and included in the analyses. Participants also reported at each wave if they had ever smoked 100 cigarettes or more in their lifetime, and if they were currently smoking cigarettes. Mental health was assessed at each wave with the 8-item Center for the Epidemiologic Studies Depression (CES-D) scale. Continuous scores were used in the analyses. Participants rated their perceived health (“excellent”, “very good”, “good”, “fair”, “poor”) at each wave with a single-item measure. Age, sex, race and ethnicity (Black, Hispanic, White), height, and body mass were also self-reported. Body mass index (BMI) was calculated as body mass divided by height in meters-squared.

Statistical Analysis

Separate hierarchical logistic regression models evaluated the time-varying associations between decreased HGS and impairments in each IADL. Demographic variables including sex, race and ethnicity, and age were controlled for in the crude models. Morbidity-related variables including smoking history, current smoking status, CES-D scores, self-rated health, the number of diagnosed morbidities, and BMI were subsequently added to the crude models (partially-adjusted models). Then, cognitive impairments were added to the partially-adjusted models (fully-adjusted models). The fully-adjusted models were used for determining the associations between decreased HGS and impairments in each IADL. Covariates included in the models were determined a priori by investigators because they were viewed as being influential for our results, and the time-varying analyses were calculated between each wave (2006, 2008, 2010, 2012, and 2014 waves). Those with missing covariates for all waves were excluded (n=398).
A sensitivity analysis was performed to examine the potential confounding effect of sex. The fully-adjusted hierarchical logistic models were stratified by sex, and if the estimates for each IADL outcome in the sex stratified models changed by >10% compared to the non-sex stratified models, there was evidence of confounding for sex in the models (13). Likewise, an additional sensitivity analysis was performed to examine the potential confounding effect of age. The fully-adjusted hierarchical logit models were stratified by age (middle-aged: 50-64 years; older adult: ≥65 years), and the estimates of the age stratified models were compared to the non-age stratified models using the same >10% criteria (13).



Of the 15,336 participants included from the 2006 wave, the majorities were female (60.0%) and White (81.4%). At each wave, the highest percentage of participants had an IADL impairment in reading a map; whereas, an IADL impairment in taking medications had the lowest percentage. Additional participant characteristics are detailed in Table 1 and a flow chart of exclusions is presented in Appendix 1. To compare descriptive variables between waves, Appendix 2 provides the means and 95% confidence intervals (CI). The number of missing observations at each wave for variables included are shown in Appendix 3.

Table 1 Descriptive Characteristics of the Participants

Table 1
Descriptive Characteristics of the Participants

Note: Results are Presented as Median (Quartile 1, Quartile 3) or Frequency (Percentage) as Indicated. IADL=instrumental activities of daily living; kg=kilogram; kg/m2=kilograms per meters-squared.


Table 2 summarizes the results of the crude, partially-adjusted, and fully-adjusted hierarchical logit models for the time-varying associations between decreased HGS and individual IADL impairments. When adding cognitive impairments to the partially-adjusted models (fully-adjusted models), the odds ratios were attenuated by 0.03 for using a telephone, 0.02 for taking medications, and 0.01 for using a map, preparing hot meals, managing money, and grocery shopping.
The results of the fully-adjusted hierarchical logit models determined that every 5-kilogram decrease in HGS was associated with increased odds for each IADL impairment: 1.11 (CI: 1.09, 1.13) for using a map, 1.10 (CI: 1.07, 1.12) for grocery shopping, 1.09 (CI: 1.05, 1.14) for taking medications, 1.07 (CI: 1.05, 1.09) for preparing hot meals, 1.06 (CI: 1.04, 1.08) for managing money, and 1.05 (CI: 1.02, 1.09) for using a telephone. Complete results for the crude, partially-adjusted, and fully-adjusted models are presented in Appendices 4, 5, and 6, respectively. The estimates for both the sex and age stratified models did not change by >10% when comparing to the estimates of the non-sex and age stratified models, suggesting sex and age were not confounding (Appendices 7 and 8).

Table 2 Results for the Time-Varying Associations Between Decreased Handgrip Strength and Individual IADL Impairments

Table 2
Results for the Time-Varying Associations Between Decreased Handgrip Strength and Individual IADL Impairments

Note: Model 1 (crude models) controlled for sex, race and ethnicity, and age. Model 2 (partially-adjusted models) controlled for Model 1 + body mass index, morbidity, depression score, current smoking status, smoking history, and self-rated health. Model 3 (fully-adjusted models) controlled for Model 2 + cognitive impairments. CI=95% confidence interval; HGS=handgrip strength; IADL=instrumental activities of daily living; OR=odds ratio. 



This investigation revealed that decreased HGS was associated with increased odds for individual IADL impairments, and slightly different associations were seen in each IADL for aging adults in the United States. Including cognitive impairments in our models attenuated the estimates by 1-3%. These findings suggest that age-related declines in HGS may lead to impairments in tasks that require strong neuropsychological and motoric functioning, including IADLs that only require low levels of muscle force generation.
Age-related decreases in muscle mass and strength have been strongly linked to a range of health-related conditions (1, 14). The general understanding for findings of this nature have been that muscle weakness, from sarcopenia and dynapenia, impairs a person’s ability to perform activities that require higher amounts of muscle force generation (15, 16). Accordingly, HGS is commonly interpreted as a measure of skeletal muscle function. The interpretation of HGS as a simple measure of skeletal muscle function could be viewed as an oversimplification, as there is evidence that HGS is strongly determined by the function of the nervous system (2). For instance, the maximum force that can be produced by each finger decreases in proportion to the number of other fingers that are engaged simultaneously, such that when four fingers contribute to the grip task, the maximum force that can be generated by each digit is typically less than half that produced when engaged in isolation (i.e., force deficit) (4, 17). This HGS force deficit is larger in aging adults compared to younger adults (4, 18). As such, declines in HGS are sensitive to the integrity of the nervous system centers that mediate the control of coordinated movement.
As adults age, the cognitive demand for completing motor tasks increases (19), and declines in HGS may help to identify early cognitive and motor defects (2). Given that the ability to execute IADLs is dependent on cognitive and motor capabilities (7), this may explain why our findings demonstrate that decreased HGS was associated with impairments in tasks that require a low amount of muscular force output. We believe our results support the notion that declines in HGS should be considered as a measure that is reflective of diminished musculoskeletal, neuromuscular, and nervous system function (or at least the motoric system).
Our findings also demonstrate that decreased HGS was associated with IADLs that require larger muscle force generation such as grocery shopping. The ability to shop for groceries is mostly driven by physical abilities such as mobility, lifting, and carrying items (20). This result is compatible with the results of other investigations suggesting decreased HGS is associated with physically driven tasks such as individual ADLs and gait speed (21, 22). Therefore, having an IADL impairment for grocery shopping may place aging adults at greater risk for functional declines. Health-care providers with aging adult patients should consider using HGS measurements as a screening tool for identifying future declines in neuromuscular functioning. Future research should work toward expanding HGS methods while also developing innovative strategies for assessing the link between HGS and neural function.
Cognitive declines during aging may also influence performance in autonomous living tasks. Several of the tasks included in IADL assessments require higher neuropsychological functioning, and persons with cognitive impairments tend to experience IADL deficits (23). For example, IADLs are helpful for detecting early cognitive declines (7), and mild cognitive impairments often lead to dementia (24). After adding cognitive impairments to our models, the odds ratios for the association between decreased HGS and each IADL impairment declined by a small percentage. Although our results suggest that decreased HGS can be used to help identify reduced motor and neural system function, cognitive functioning factors into the associations between HGS and IADLs to a much lesser extent, likely because IADLs are already cognitively driven. Future investigations should consider how cognitive functioning factors into the associations between HGS and more physically driven tasks.
These findings provide continued support for the belief that muscle strengthening, motor coordination, and agility enhancing activities are critical for maintaining functional capacity during aging. Participation in muscle strengthening activities has demonstrated promise for preserving muscle strength, motor performance, cognitive functioning, and neural integrity (25). Interventions aiming to preserve IADLs should be multidisciplinary in nature, wherein factors for maintaining motor performance, including physical, social, and mental health activities are incorporated. Interestingly, engaging in muscle strengthening activities has shown potential for improving spatial awareness in older adults by also improving brain health (26). Specifically, muscle strengthening activities may prevent age-related atrophy of the temporal lobe, which is important for vision, sensory input, and comprehension (27). The increased blood flow and usage of nutrients in the blood from participating in muscle strengthening activities may lead to improved neurogenesis and neurotransmission, thereby ameliorating spatial awareness and brain health (26, 28, 29). Intervening at the onset of HGS declines may help to preserve muscle strength, cognitive functioning, motor performance, and the ability to live independently.
There are limitations of this work that should be mentioned. Self-report bias may have created underestimations for our results because respondents reported IADL performance.  Another limit of our study was the progressive reduction of the sample size over time due to people who dropped-out or died during the examination period. Participants in the 2006 wave were followed biennially for 8-years and if there were missing covariates for a particular wave, those data were excluded from the models for that wave. However, multilevel models can overcome intermittent missing data between waves and participant drop-out was <5% between waves (30). Although our sensitivity analyses revealed that sex was not confounding for our results, it is still important to consider the potential role of gender norms when evaluating IADLs in aging adults.



Decreased HGS was associated with each IADL impairment, and slightly different associations were observed for impairments in individual IADLs, including those that not only require a minimal amount of muscle force generation, but rather motor coordination and cognitive functioning. Adding cognitive impairments to our models reduced the magnitude of the association between decreased HGS and individual IADL impairments by a small amount. Our findings support the notion that decreased HGS should be considered a measure that is reflective of both reduced skeletal muscle and nervous system function.


Acknowledgements: BCC is supported, in part, by the National Institute on Aging (R01AG044424).
Conflicts of Interest: BCC has received research funding from the National Institutes of Health, Regeneron Pharmaceuticals, Astellas Pharma Global Development, Inc., RTI Health Solutions, Ohio Department of Higher Education, and the Osteopathic Heritage Foundations. In the past 5-years BCC has received consulting fees from Regeneron Pharmaceuticals, Abbott Laboratories, and the Gerson Lehrman Group. Additionally, BCC is co-founder with equity and scientific director of AEIOU Scientific, LLC. The other authors report no conflicts of interest.





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S.M.L.M.  Looijaard1, S.J. Oudbier1, E.M. Reijnierse2, G.J. Blauw3,4, C.G.M. Meskers5, A.B. Maier2,6


1. Department of Internal Medicine, Section of Gerontology and Geriatrics, VU University Medical Center, Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands;  2. Department of Medicine and Aged Care, @AgeMelbourne, The Royal Melbourne Hospital, University of Melbourne, 300 Grattan Street, Parkville, Victoria 3050, Melbourne, Australia;  3. Department of Gerontology and Geriatrics, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands;  4. Department of Geriatrics, Bronovo Hospital, Bronovolaan
5, 2597 AX, The Hague, The Netherlands; 5. Department of Rehabilitation Medicine, VU University Medical Center, Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands;
6. Department of Human Movement Sciences, @AgeAmsterdam, Faculty of Behavioral and Movement Sciences, Vrije Universiteit Amsterdam, Amsterdam Movement Sciences, van der Boechorststraat 7, 1081 BT, Amsterdam, The Netherlands.
Corresponding author: A.B. Maier, Department of Human Movement Sciences, @Age, Faculty of Behavioral and Movement Sciences, Vrije Universiteit Amsterdam, Amsterdam Movement Sciences, van der Boechorststraat 7, 1081 BT, Amsterdam, The Netherlands, Telephone number: 020-5982000 a.b.maier@vu.nl

J Frailty Aging 2018;in press
Published online August 1, 2018, http://dx.doi.org/10.14283/jfa.2018.19



Background: Sarcopenia is highly prevalent in the older population and is associated with several adverse health outcomes. Equipment to measure muscle mass and muscle strength to diagnose sarcopenia is often unavailable in clinical practice due to the related expenses while an easy physical performance measure to identify individuals who could potentially have sarcopenia is lacking. Objectives: This study aimed to assess the association between physical performance measures and definitions of sarcopenia in a clinically relevant population of geriatric outpatients. Design, setting and participants:  A cross-sectional study was conducted, consisting of 140 community-dwelling older adults that were referred to a geriatric outpatient clinic. No exclusion criteria were applied. Measurements: Physical performance measures included balance tests (side-by-side, semi-tandem and tandem test with eyes open and -closed), four-meter walk test, timed up and go test, chair stand test, handgrip strength and two subjective questions on mobility. Direct segmental multi-frequency bioelectrical impedance analysis was used to measure muscle mass. Five commonly used definitions of sarcopenia were applied. Diagnostic accuracy was determined by sensitivity, specificity and area under the curve.Results: Physical performance measures, i.e. side-by-side test, tandem test, chair stand test and handgrip strength, were associated with at least one definition of sarcopenia. Diagnostic accuracy of these physical performance measures was poor. Conclusions: Single physical performance measures could not identify older individuals with sarcopenia, according to five different definitions of sarcopenia.

Key words: Aged, geriatrics, physical performance, sarcopenia.



Prevalence rates of sarcopenia, defined as age-related low muscle mass and muscle strength, vary between 0% and 15% in healthy older individuals and between 2% and 34% in geriatric outpatients, depending on the applied definition (1). Sarcopenia is associated with decreased mobility, a higher risk of falls, dependency in activities of daily living, morbidity and mortality (2-4). Although there is no consensus yet on the definition of sarcopenia, the majority of definitions contain a measure of muscle mass and/or muscle strength (5-10).
Equipment to measure muscle mass and muscle strength is often unavailable in clinical practice due to the related expenses (11). Poor physical performance has been shown to be associated with sarcopenia (12-14). Recently, a prediction model was proposed to identify sarcopenia with the use of demographic parameters and physical performance measures (15). However, such a prediction model is time consuming due to its inclusion of multiple physical tests and complex calculations. Identifying individuals who could potentially have sarcopenia in clinical practice would be greatly facilitated when an easy to use physical performance measure could be applied to identify individuals with sarcopenia. This could lead to the identification of individuals who could potentially have sarcopenia, who could then be referred to diagnose sarcopenia.
This study aims to assess the association between physical performance measures and different definitions of sarcopenia in a clinically relevant population of geriatric outpatients.



Study design

This cross-sectional study consisted of 140 community-dwelling older adults who were referred to a geriatric outpatient clinic of a middle-sized teaching hospital (Bronovo, The Hague, The Netherlands) between March 2011 and January 2012. These older adults were referred because of mobility problems for a comprehensive geriatric assessment. The study originally consists of 299 older adults, but muscle mass measurements were only available in 140 older adults as these measurements were later added as part of clinical care. No exclusion criteria were applied; inclusion was based on referral. The study was approved by the Medical Ethical Committee of the Leiden University Medical Center (Leiden, the Netherlands). Informed consent was waived as this study was based on regular care.

Study population characteristics

Medical charts were used to retrieve information on age, sex and medical history. Medical history included information on the presence of: hypertension, myocardial infarction, chronic obstructive pulmonary disease, diabetes mellitus, rheumatoid- or osteoarthritis, Parkinson’s disease and malignancy. The presence of two or more of these diseases was defined as multimorbidity. Anthropometric measurements included height and body weight and were measured to the nearest 0.1 decimal. Cognitive functioning was measured by the Mini Mental State Examination (MMSE) resulting in a score ranging from 0 to 30 points, higher scores indicating better cognitive function (16).

Physical performance measures, objective

Physical performance measures included balance tests, four-meter walk test, timed up and go (TUG), chair stand test (CST) and handgrip strength (HGS).
Balance tests were performed in three different positions (side-by-side, semi-tandem and tandem) according to the protocol of the Short Physical Performance Battery (17), and were performed with eyes open and with eyes closed. Individuals were classified as unable to maintain for ten seconds (0) and able to maintain for ten seconds (1). Tandem balance test with eyes closed was excluded from the present analysis as the number of individuals who were able to maintain in the tandem position for ten seconds was less than five individuals.
Gait speed was obtained by a four-meter walk test where individuals were asked to walk at their usual pace (17). The best performance of two measurements was used and expressed in meters per second.
The TUG measures the time in seconds needed to stand up from a sitting position without using hands, walk three meters, walk around a cone, walk three meters back and return to sitting position without using hands, as fast as possible.
The CST measures the time in seconds needed to stand up five times from sitting position to a straight standing position and sit down again while keeping the arms crossed over the chest, as fast as possible (17).
HGS was measured using a hydraulic handheld dynamometer (Jamar, Sammons Preston, Inc., Bolingbrook, IL, USA). Individuals were asked to squeeze as hard as possible three times with the right and left hand side alternately. Maximal HGS of the three trials was used for analysis (18) and expressed in kilograms.
Higher gait speed and HGS implied a better physical performance while a higher TUG and CST time implied a lower physical performance. For all physical performance measures, all individuals who could not perform or finish the test or used hands to stand up from a sitting position, were given a time of 100 seconds.

Physical performance measures, subjective

In addition to the objective physical performance measures, two questions were asked: 1) Falls: “Did you fall in the past year?” (yes/no) and 2) Difficulty with walking: “Do you experience difficulty with walking?” (yes/no).

Sarcopenia definitions

Muscle mass was measured using direct segmental multi-frequency Bioelectrical Impedance Analysis (DSM-BIA; InBody 720, Biospace Co., Ltd, Seoul, Korea) (19). Five definitions of sarcopenia were used to examine the association between physical measures and sarcopenia: 1) Baumgartner et al. using appendicular lean mass (ALM) divided by height2 (5); 2) Janssen et al. using relative skeletal muscle mass (SM) (SM divided by body mass) (6); 3) European Working Group on Sarcopenia in Older Persons (EWGSOP) using an algorithm of gait speed, HGS and skeletal muscle index (SMI; SM divided by height2) (7); 4) Foundation for National Institutes of Health (FNIH) definition one using HGS and ALM divided by body mass index (BMI) (8) and 5) The International Working Group on Sarcopenia (IWGS) using gait speed and ALM divided by height2 (9).

Statistical analysis

Continuous variables were reported by mean ± standard deviation (SD) if data was normally distributed or median [interquartile range (IQR)] for skewed distributions. Associations between physical performance measures (independent variables) with definitions of sarcopenia (dependent variables) were analyzed with binary logistic regression analysis. Two models were used: the crude model and an adjusted model for sex and age. P-values of less than 0.05 were considered statistically significant.
For the statistically significant associations between physical performance measures and definitions of sarcopenia, sensitivity, specificity and the area under the curve (AUC) were calculated to determine the diagnostic accuracy. Sensitivity and specificity were defined as low <70%, moderate 70-90% and high >90%. AUC was defined as low <0.70, acceptable 0.70-0.80, excellent 0.80-0.90 and outstanding >0.90. To test diagnostic accuracy, CST and HGS were dichotomized: CST ≥13 seconds (14, 20), and HGS <20 kilograms for females and <30 kilograms for males were considered low (21). Statistical analyses were performed using Statistical Package for Social Sciences (SPSS Inc, Chicago, USA), version 22.



Table 1 shows the characteristics of the geriatric outpatients, with a mean age of 80.9 (7.1) years and 42% males. Table 2 shows the applied definitions of sarcopenia and the prevalence of sarcopenia. Prevalence of sarcopenia ranged from 3.6% to 23.6%, depending on the definition.

Table 1 Characteristics of geriatric outpatients (N=140)

Table 1
Characteristics of geriatric outpatients (N=140)

All results are given in number (percentage) unless indicated otherwise. SD: standard deviation; MMSE: Mini Mental State Examination, score 0-30; IQR: interquartile range; TUG: Timed Up and Go; CST: Chair Stand Test; HGS: Handgrip Strength; ALM: Appendicular Lean Mass; BMI: Body Mass Index; SMI: Skeletal Muscle Index; SM: Skeletal Muscle.

Table 2 Prevalence of sarcopenia in geriatric outpatients according to the applied definitions of sarcopenia

Table 2
Prevalence of sarcopenia in geriatric outpatients according to the applied definitions of sarcopenia

ALM: Appendicular Lean Mass; SM: Skeletal Muscle; EWGSOP: European Working Group on Sarcopenia in Older People; HGS: Handgrip Strength; SMI: Skeletal Muscle Index; IWGS: International Working Group on Sarcopenia; FNIH: Foundation for the National Institutes of Health; BMI: Body Mass Index


Table 3 shows the association between physical performance measures and sarcopenia according to the applied definitions. Out of all balance tests, the ability to perform the tandem stance with eyes open was most often associated with a decreased likelihood to have sarcopenia (Baumgartner et al., EWGSOP and IWGS). CST was associated with sarcopenia by use of the EWGSOP and IWGS definitions. HGS was associated with sarcopenia using the definition of Baumgartner et al. and IWGS. The other physical performance measures i.e. semi-tandem balance test with eyes open and eyes closed, gait speed, TUG and the subjective physical performance measures did not show an association with any of the definitions of sarcopenia.
Table 4 shows the diagnostic accuracy for physical performance measures significantly associated with sarcopenia. The tandem balance test with eyes open showed moderate sensitivity and low specificity and AUC for all three sarcopenia definitions. The side-by-side test with eyes closed showed low sensitivity, moderate specificity and low AUC for the EWGSOP definition. CST showed low sensitivity, specificity and AUC for the EWGSOP and IWGS definitions. HGS showed low sensitivity, moderate specificity and low AUC for the Baumgartner et al. and IWGS definitions.

Table 3 Physical performance measures and sarcopenia according to the applied definitions

Table 3
Physical performance measures and sarcopenia according to the applied definitions

OR: Odds Ratio; CI: Confidence interval; EWGSOP: European Working Group on Sarcopenia in Older People; IWGS: International Working Group on Sarcopenia; FNIH: Foundation for the National Institutes of Health; NA: Not Applicable; TUG: Timed Up and Go; CST: Chair Stand Test; HGS: Handgrip Strength. Adjusted model adjusted for sex and age. All results with a p-value < 0.05 are considered significant and are given in bold; *Balance tests were dichotomized into unable to maintain for ten seconds (0) and able to maintain for ten seconds (1).


Table 4 Diagnostic accuracy of physical performance measures according to the applied definitions of sarcopenia

Table 4
Diagnostic accuracy of physical performance measures according to the applied definitions of sarcopenia

Sensitivity and specificity are given in percentage; AUC is given with 95% confidence interval. EWGSOP: European Working Group on Sarcopenia in Older People; IWGS: International Working Group on Sarcopenia; FNIH: Foundation for the National Institutes of Health; NA: Not Applicable; AUC: Area under the curve; CST: Chair stand test; HGS: Handgrip strength. NA indicates non-significant results in logistic regression analyses for which no diagnostic accuracy was calculated. All results with a p-value < 0.05 are considered significant and are given in bold. *Balance tests were dichotomized into unable to maintain for ten seconds (0) and able to maintain for ten seconds (1).



Physical performance measures, i.e. side-by-side test, tandem test, CST and HGS, were associated with sarcopenia using several definitions, but diagnostic accuracy was poor.
Previous studies have shown that tandem balance test, gait speed, CST and HGS are valid and reliable measures to assess physical performance (22, 23). Moreover, gait speed, CST and HGS have proven to be associated with sarcopenia according to the EWGSOP definition in community dwelling older adults (20, 24, 25). Unfortunately, the results of this study in geriatric outpatients did not show a single suitable physical performance measure to identify older individuals with sarcopenia. For a test to be suitable to identify individuals with a high risk on sarcopenia, it needs to have a high sensitivity as especially false-negatives are undesirable. Sensitivity was low to moderate, which would mean that many individuals who could potentially have sarcopenia would be missed. Moreover, specificity and AUC were low and therefore single physical performance measures have poor diagnostic accuracy to identify individuals with sarcopenia.
Sarcopenia is associated with negative health outcomes and therefore an important diagnosis in clinical practice. Nutritional and physical interventions have proven to increase muscle mass, muscle strength and physical performance (26, 27). Improving physical performance measures might reduce the risk of sarcopenia and therewith its negative health outcomes. Early recognition of sarcopenia is necessary to initiate interventions. BMI is a measurement that is often used to identify individuals who are at risk of adverse health outcomes, however, BMI does not encompass the risk of sarcopenia (28) Another proposed screening tool to identify individuals with sarcopenia is the SARC-F, a simple five-item questionnaire (subjective measures of strength, assistance in walking, rise from a chair, climb stairs, falls). This is one of the screening instruments that is increasingly being used in community-dwelling middle-aged to older adults to identify individuals who could potentially have sarcopenia (29, 30).
Multimorbidity was high in this population of geriatric outpatients and this could be an explanation for the lack of diagnostic accuracy of physical performance measures to identify older individuals with sarcopenia because physical performance could also be inflicted by disease-specific mechanisms.
To the best of our knowledge, this is the first study outlining the association between various objective physical performance measures and several commonly used definitions of sarcopenia in a clinically relevant population of geriatric outpatients. Validated physical performance measures were used. Furthermore, the population is heterogeneous and no exclusion criteria were used which makes it a good representation of the actual older population visiting outpatient clinics. A limitation of this study could be that only BIA and not Dual Energy X-ray Absorptiometry (DEXA) was used to determine muscle mass parameters of sarcopenia. However, BIA and DEXA showed high agreement in a population of community-dwelling individuals (19).
Single physical performance measures could not identify older individuals with sarcopenia, according to five different definitions. Therefore, no easy and fast method to identify individuals with sarcopenia can be recommended. Future research should focus on developing and validating screening tools so that individuals with a high probability of having sarcopenia can be identified. Individuals who are considered to be at risk of sarcopenia should be referred to diagnose sarcopenia using the diagnostic criteria that are used in the definitions of sarcopenia.


Acknowledgements: We thank M. Stijntjes and J.H. Pasma for their contribution to the study.

Funding: This study was supported by the Dutch Technology Foundation STW, which is part of the Netherlands Organization for Scientific Research (NWO) and which is partly funded by the Ministry of Economic Affairs. Furthermore, this study was supported by the seventh framework program MYOAGE (HEALTH-2007-2.4.5-10) and 050-060-810 Netherlands Consortium for Healthy Aging (NCHA). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Statement of authorship: All authors have made substantial contributions to all of the following: 1) conception and design of the study, acquisition of data or analysis and interpretation of data; 2) drafting the article or revising it critically for important intellectual content; 3) final approval of the version to be submitted.
Conflict of Interest: S.M.L.M. Looijaard: none to declare. S.J. Oudbier: none to declare. E.M. Reijnierse: none to declare. G.J. Blauw: none to declare. C.G.M. Meskers: none to declare. A.B. Maier: none to declare.
Open Access: This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits use, duplication, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license and indicate if changes were made.



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20.    Nishimura T, Arima K, Okabe T, et al. Usefulness of chair stand time as a surrogate of gait speed in diagnosing sarcopenia. Geriatr Gerontol Int. 2017;17(4):659-61.
21.    Lauretani F, Russo CR, Bandinelli S, et al. Age-associated changes in skeletal muscles and their effect on mobility: an operational diagnosis of sarcopenia. J Appl Physiol. 2003;95(5):1851-60.
22.    Freiberger E, de Vreede P, Schoene D, et al. Performance-based physical function in older community-dwelling persons: a systematic review of instruments. Age Ageing. 2012;41(6):712-21.
23.    Stevens PJ, Syddall HE, Patel HP, Martin HJ, Cooper C, Aihie Sayer A. Is grip strength a good marker of physical performance among community-dwelling older people? J Nutr Health Aging. 2012;16(9):769-74.
24.    Sanchez-Rodriguez D, Marco E, Miralles R, et al. Does gait speed contribute to sarcopenia case-finding in a postacute rehabilitation setting? Arch Gerontol Geriatr. 2015;61(2):176-81.
25.    Stoever K, Heber A, Eichberg S, Brixius K. Sarcopenia and Predictors of Skeletal Muscle Mass in Elderly Men With and Without Obesity. Gerontol Geriatr Med. 2017;3:2333721417713637.
26.    Verlaan S, Maier AB, Bauer JM, et al. Sufficient levels of 25-hydroxyvitamin D and protein intake required to increase muscle mass in sarcopenic older adults – The PROVIDE study. Clin Nutr. 2018;37(2):551-7.
27.    Beaudart C, Dawson A, Shaw SC, et al. Nutrition and physical activity in the prevention and treatment of sarcopenia: systematic review. Osteoporosis Int. 2017;28(6):1817-33.
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29.    Malmstrom TK, Miller DK, Simonsick EM, Ferrucci L, Morley JE. SARC-F: a symptom score to predict persons with sarcopenia at risk for poor functional outcomes. J Cachexia, Sarcopenia Muscle. 2016;7(1):28-36.
30.    Rolland Y, Dupuy C, Abellan Van Kan G, et al. Sarcopenia Screened by the SARC-F Questionnaire and Physical Performances of Elderly Women: A Cross-Sectional Study. J Am Med Dir Assoc. 2017;18(10):848-52.



E. LEVINOFF1,2,3, A. TRY1, J. CHABOT1, L. LEE4,5, D. ZUKOR4,6, O. BEAUCHET1,2,3,7,8


1. Faculty of Medicine, Department of Geriatric Medicine, McGill University; Montreal, Quebec, Canada; 2. Department of Medicine, Division of Geriatric Medicine, Jewish General Hospital; Montreal, Quebec, Canada; 3. Lady Davis Institute for Medical Research, McGill University; Montreal, Quebec, Canada; 4. Department of Orthopedic Surgery, Jewish General Hospital; Montreal, Quebec, Canada; 5. Department of Nursing, Surgical Services, Jewish General Hospital; Montreal, Quebec, Canada; 6. McGill University, Faculty of Medicine, Department of Surgery; Montreal, Quebec, Canada; 7. Dr. Joseph Kaufmann Chair in Geriatric Medicine, Faculty of Medicine, McGill University; 8. Centre of Excellence on Aging and Chronic Diseases of McGill integrated University Health Network, Quebec, Canada.
Corresponding author: Dr. Elise Levinoff, MD, MSc; Department of Medicine, Division of Geriatric Medicine, Sir Mortimer B. Davis – Jewish General Hospital, McGill University, 3755 chemin de la Côte-Sainte-Catherine, Montréal, QC, H3T 1E2, Canada; E-mail: elise.levinoff@mcgill.ca Phone number (514) 340-7501, Fax Number (514) 340-7547.

J Frailty Aging 2018;7(1):34-39
Published online October 4, 2017, http://dx.doi.org/10.14283/jfa.2017.37



Background: Hip fractures precipitate several acute adverse outcomes in elderly people, thus leading to chronic adverse outcomes. Objectives: The objective of our study was to examine the clinical characteristics associated with incident delirium in community dwelling elderly individuals who have a hip fracture. Design: Retrospective observational cohort study. Setting: Data was collected from an academic tertiary hospital affiliated with McGill University. Participants: 114 elderly individuals who were above 65 years of age, who underwent surgery for a fractured hip. Measurements: The main outcome variable was incident delirium, which was assessed by chart reviews of notes and observations recorded by nurses and physicians when patients were admitted post operatively to the surgical unit. Covariates included age, sex, length of stay, delay to surgery, number of medical comorbidities, number of medications and hip fracture location, and were extracted from medical records. Baseline mobility and functional status, preoperative cognitive impairment, postoperative complications, regular psychotropic medications, psychotropic medications in hospital, and location of discharge were also assessed through chart review. Results: The results demonstrated that 17.5% of participants with a diagnosis of delirium had a longer length of hospitalization (p = 0.01), a lower baseline functional status (p = 0.03) and pre-operative cognitive impairment (p = 0.01). Patients receiving new psychotropic medications in hospital were more likely to have delirium (OR = 4.6, p = 0.01) which was independent of pre-operative cognitive impairment. Conclusion: We have shown that an association exists between psychotropic medication prescription and incident delirium in patients with hip fractures, even when adjusting for cognitive impairment. Hence, the prescription of psychotropic drugs should be judicious in these patients so as minimize the risk of adverse outcomes.

Key words: Geriatrics, delirium, dementia, hip fractures.




A hip fracture in a previously functional community dwelling elderly individual is usually the consequence of a fall. Approximately 30% of elderly individuals over the age of 70 will fall at least once per year. Community-dwelling elderly individuals are at high risk for falls because of polypharmacy, impaired vision and hearing, gait instability and cognitive impairment (1). Patients who fall also have comorbid dementia. In fact, the incidence of hip fractures in elderly patients with dementia is higher than in those who are cognitively intact (2-4).
The immediate and long-term outcomes of hip fractures in the elderly population are associated with adverse consequences, with the most common being delirium. The incidence of delirium in the post-operative period varies between 3-50% (5). A recent systematic review highlighted risk factors such as age, cognitive impairment, medical comorbidities, institutionalization, polypharmacy, body mass index and functional impairment as predictors of delirium. However, not all of these risk factors were statistically significant predictors of delirium in multivariate models (6).
The relationship between psychotropic medication use and falls in the elderly has been well documented (1). Psychotropic medications can cause adverse side effects such as drowsiness, syncope and delirium, particularly in the elderly. Although psychotropic medications are associated with precipitating delirium in the elderly (7), studies of prophylactic psychotropic medication use in hospitalized settings to prevent incident delirium have shown variable outcomes (8, 9). A meta-analysis showed that prophylactic antipsychotic treatment reduced the incidence, but not duration or severity of delirium in medical and surgical patients (7). Conversely, a prospective trial using haloperidol prophylaxis to reduce the incidence of delirium demonstrated that antipsychotic use in hospital decreased the severity and duration of delirium, but not necessarily the incidence (8). In a small prospective analysis, Sampson et al., were unable to demonstrate a benefit of donepezil at reducing the incidence of post-operative delirium in patients undergoing elective total hip replacements (10). The use of melatonin to treat delirium in patients with hip fracture has also been investigated. These results were inconclusive at suggesting an overall benefit of reducing the incidence of delirium (11).
All of the above studies were prospective analyses that examined the efficacy psychotropic medications at preventing delirium in the acutely hospitalized patient. However, the risk of delirium in patients who are prescribed new psychotropic medications during hospitalization for hip fracture has not been well documented. Furthermore, it is unclear whether the risk of delirium in patients using psychotropic medications differs between patients who are cognitively intact and those who are cognitively impaired. The purpose of this study was to identify which pre-hospital and which in-hospital clinical characteristics were associated with incident delirium in older inpatients admitted in surgery for post-fall hip fracture. Because psychotropic medication use has been shown to cause delirium and falls (12), and because patients with cognitive impairment are more likely to be taking psychotropic medications than those without cognitive impairment (13), we hypothesized that new psychotropic medications prescribed in hospital would be associated with delirium in this vulnerable population and that this would be more pronounced in patients with pre-fracture cognitive impairment.




This was a retrospective observational cohort study based on a chart review that was conducted at the Jewish General Hospital (JGH). The JGH is a tertiary care facility that is affiliated with McGill University in Montreal, Quebec, Canada. Approximately 350 patients are admitted to the JGH annually for surgical management of a hip fracture. Ethics approval was obtained by the Research Ethics Committee of the JGH to conduct this study in accordance with the ethical standards set forth in the Helsinki Declaration.
Names and unit numbers of all the patients who were admitted to the hospital for a hip fracture from July1st, 2014 to December 31st, 2014 were collected from admission and discharge records. Patients were included if they were 65 years of age or older, were living in the community prior to admission, and sustained a hip fracture following a fall from their own height. Exclusion criteria included transfer from another hospital with length of stay of less than five days, hardware revision, non-operative management, and the presence of metastatic cancer which may have directly precipitated the hip fracture. Data were collected from patients’ charts through the hospital database. The chart review was done by a geriatrician and two trained individuals.

Outcome variables

The main outcome measure selected for this study was incident delirium. Delirium was assessed by reading observational notes of nurses and physicians when patients were admitted to the surgical unit. Lack of orientation alone was not considered enough to classify a patient as delirious, since many patients demonstrated baseline cognitive impairment. Thus, we based our search on whether key words such as “delirium” or “delirious” and “confused” were present in patients’ charts. Whenever present, we also looked for documentation of the Confusion Assessment Method (CAM) criteria, which include the following characteristics 1) acute onset of confusion and fluctuating course and 2) inattention, plus one of either 3) disorganized thinking and 4) altered level of consciousness (14).
Covariates included age, sex, length of stay, delay to surgery, number of medical comorbidities and number of medications. In addition, location of hip fracture (femoral neck fracture, intertrochanteric fracture or subtrochanteric fracture) was classified as a nominal variable. Baseline mobility and functional status, preoperative cognitive impairment, postoperative delirium, postoperative complications, regular psychotropic medications, psychotropic medications in hospital, pre-operative vitamin D consumption, location of discharge, post-rehabilitation disposition and final disposition were all classified as binary variables.
Mobility status was recorded by extracting information from the post-operative physiotherapy consultation and multidisciplinary chart notes. Mobility was classified as walking with or without an aid. Preoperative cognitive impairment was ascertained from the chart based on notes from formal multidisciplinary assessments, where present, as well as from nursing notes, flowsheets and history obtained from family members. Similarly, functional status was recorded as independent for activities of daily living or dependent for activities of daily living. Functional status was also ascertained subjectively by reviewing nursing documents, the physiotherapy consultation and the occupational therapy consultation, if present. A patient was considered dependent if he/she required assistance or was dependent for more than half of the activities reported. If there was a supplemental specialist consultation (i.e. geriatrics consultation or occupational therapy assessment), additional information on a patient’s cognitive, mobility and functional status was recorded.
Post-operative complications included blood transfusions, congestive heart failure, wound infections, delirium and pneumonia. A urinary tract infection was not recorded as a post-operative complication. For psychotropic medication use in hospital, a minimum of four doses of one or more psychotropic drug(s) during the hospital stay was required. A patient was not classified as having taken a psychotropic medication prior to admission if he/she was using a medication to stabilize the progression of dementia (i.e. donepezil, rivastigmine and memantine).


Participants’ characteristics were summarized using either means +/- SD or frequencies and percentages where appropriate. Individuals were separated in two groups: those with and without delirium. Between groups comparison were performed using Pearson Chi-square tests or independent samples t-test as appropriate. Uni and multiple logistic regressions were performed to determine the association between delirium (dependent variable) and psychotropic medications, cognitive impairment or their combinations (independent variables) adjusted on participants’ characteristics. The global significance level was set at 0.05 and all tests were bilateral. All statistical analyses were done using SPSS 23 software.



A total of 164 patients underwent an operation for hip fracture between July and December, 2014. Fifty (30.5%) patients were excluded because they did not fit the criteria for the study (see Figure 1). Table 1 presents the baseline characteristics for 114 (69.5%) community-dwelling elderly individuals who had a hip fracture. The majority of patients were female (73.7%) and the mean age of patients was 83.8 years. The average length of stay was 14.7 days, with a mean delay to surgery of 3.3 days. Participants had an average of five medical comorbidities on admission, and they were taking an average of 6.7 medications on admission. The most common fracture types were femoral neck fracture (45.6%) and intertrochanteric fracture (46.5%), with subtrochanteric fractures consisting of 7.9% of fractures. At baseline, 57.9% of participants walked without any gait aids and 48.2% were independent for basic activities of daily living and instrumental activities of daily living. A total of 37/114, or 32.5% of the sample size had signs of cognitive impairment prior to their hip fracture. Seventeen of these patients (17/37), or 46% of patients with pre-operative cognitive impairment, were taking psychotropic medications prior to their admission. Within the entire sample, 17.5% of patients had evidence of postoperative delirium and 54.4% had postoperative complications. 35.1% of participants were taking some form of psychotropic medication prior to admission. Fourteen participants (12.3%) were given a psychotropic medication in the hospital that was not previously prescribed in the community. Five of these 14 participants (36%) who received psychotropic medication in hospital for the first time had a pre-operative diagnosis of cognitive impairment prior to their hip fracture. The most commonly prescribed medications included zopiclone, lorazepam and quetiapine. Patients with delirium had a longer length of hospitalization (p = 0.01), a lower baseline functional status (p = 0.03) and more frequently a pre-op cognitive impairment (p = 0.01) compared to those without delirium.


Figure 1 Flow diagram of included and excluded patients

Figure 1
Flow diagram of included and excluded patients

LOS = Length of stay

Table 1 Baseline characteristics, presence of iatrogenic factors and outcomes of all patients and of patients with and without postoperative delirium

Table 1
Baseline characteristics, presence of iatrogenic factors and outcomes of all patients and of patients with and without postoperative delirium

*Independent samples t-test, †Chi Square analysis


Table 2 depicts the results of unadjusted and adjusted odds ratios for delirium in patients with pre-operative cognitive impairment and in patients with new psychotropic medication use while in the hospital. Patients with pre-operative cognitive impairment were more likely to develop delirium in hospital (OR = 5.4; p < 0.001). When adjusted for age, length of stay, and baseline mobility and functional status, there was still a significant association of delirium in hip fracture patients with pre-operative cognitive impairment. There was a significant association between delirium and psychotropic use (OR = 4.6; p = 0.013), which remained significant when controlling for covariates such as age, length of stay, baseline mobility and functional status and pre-operative cognitive impairment.
We further classified patients according to their baseline cognitive status and whether or not they were prescribed psychotropic medications in hospital for the first time. Figure 2 depicts the unadjusted and adjusted odds ratios of delirium in patients, depending on whether they had pre-operative cognitive decline and whether they were prescribed psychotropic medications for the first time in the hospital. Patients who were prescribed antipsychotic medications during their hospitalization were at high risk for developing delirium, regardless of their pre-operative cognitive status. However, the association of delirium was the highest in patients who were cognitively intact, but prescribed new medications in hospital (unadjusted OR = 4.6; p = 0.013 adjusted for age and sex OR = 3.9; p < 0.001 See Figure 2).

Table 2 Unadjusted and adjusted odd ratios of patients with delirium

Table 2
Unadjusted and adjusted odd ratios of patients with delirium


Figure 2 Unadjusted and Adjusted Odds Ratios for Delirium in Patients With or Without Cognitive Impairment and Patients With or Without Psychotropic Medication Use in Hospital

Figure 2
Unadjusted and Adjusted Odds Ratios for Delirium in Patients With or Without Cognitive Impairment and Patients With or Without Psychotropic Medication Use in Hospital



The results from this study demonstrate that when adjusting for age, sex, baseline mobility and baseline functional status, both pre-operative cognitive impairment, as well as intake of psychotropic medications in hospital increases the odds that an elderly individual who is hospitalized for a hip fracture after a fall will have delirium over the course of his/her hospitalization. More importantly, this association is stronger even in patients who are cognitively intact but taking psychotropic medications in hospital for the first time. Our results are similar to those found in previous studies which suggest that polypharmacy is a risk factor for delirium in acutely hospitalized and surgical patients [6, 15, 16]. However, in contrast to other studies that have looked at the impact of polypharmacy on delirium, our study demonstrates a direct association between the use of psychotropic medication use in hospital and acute post-operative outcomes in patients with hip fractures. An independent association exists between falls and hip fractures in patients with dementia [4]. Moreover, patients with dementia are at increased risk of developing delirium in the acute hospital setting and they are more likely to take psychotropic medications prior to being admitted to the hospital for a hip fracture. However, our study suggests that regardless of pre-operative cognitive status, there is a strong association between psychotropic medications and delirium in hospital.
The pathophysiology of delirium in elderly individuals is multifactorial. Several hypotheses suggest that delirium is associated with an excess of dopamine, or a cholinergic deficit (17). The excess of dopamine in the brains of patients with delirium may account for the rationale of using antipsychotic medications as treatment options for delirium. Another pathophysiological hypothesis for delirium is a cholinergic deficiency. This hypothesis accounts for the idea that potent anticholinergic psychotropic medications can precipitate delirium in elderly people. Nonetheless, the pathophysiology of delirium is very non-specific, and closely interacts with other environmental and genetic risk factors. These include the underlying physiological stress of sustaining a hip fracture, the addition of sedating anesthetic agents that are used in the peri-operative period and the use of pain medications in the post-operative recovery period. Post-operative complications such as infections, congestive heart failure, and blood loss can independently precipitate delirium in the elderly population. Furthermore, a change in environment alone is sufficient to precipitate delirium in an elderly individual with cognitive impairment. However, some of these precipitants are directly avoidable and, their absence may limit the risk of delirium.

Previous studies have shown that prophylactic administration of antipsychotic medications may reduce the onset of delirium, as well as the severity and duration (7, 11, 18-20). That was not the case in this study. In fact, we demonstrated that the prescription of psychotropic medications for the first time in hospital was associated with incident post operative delirium. Furthermore, the strength of this association persists, even in patients without pre-existing cognitive impairment. One explanation to suggest why we found that patients who are cognitively intact develop delirium in the context of a prescription of psychotropic medication may be explained by the cognitive reserve hypothesis (21). It is possible that perhaps the patients in our study had cognitive impairment prior to their hospitalization, but that this remained undiagnosed because of intact functional abilities. However, once they were exposed to the catastrophic event of a fall and a hip fracture, these two precipitants were sufficient sources of stress to precipitate delirium, which subsequently may have been exacerbated by the use of psychotropic medication in hospital.
This study was a retrospective chart review which examined specific factors that impacted the acute post-operative course of elderly patients with hip fractures. Because a chart review was done, one of the major advantages of this study is that there are minimal data points missing from the analysis. Furthermore, the chart review enabled us to examine the multiple factors and etiologies that may have had a direct impact on delirium in elderly individuals with hip fractures after having a fall in the community. There were also several limitations of this study. The information extracted on pre-operative mobility and pre-operative functional status was done by trainees and a geriatrician. However, in many cases, there was no formal scale that was used to document baseline mobility, functional and cognitive status. The information extracted from patients’ charts was based on family reports and physiotherapy consults and, in some specific cases, occupational therapy assessments. Some patients had formal comprehensive geriatric evaluations, which included these assessments. As well, the diagnosis of delirium, in the majority of cases, was not formally made with an objective measure such as the CAM. The information was extracted by chart reviewers on the basis of nursing notes and observations. Additionally, a difficult challenge with a retrospective analysis that uses delirium as an outcome measure is determining the true timing of the onset of delirium. It is possible in this study, that many patients were confused prior to, as well as after their operation. Therefore, a direct causation towards one specific precipitant is difficult to make because it is unclear whether the stress of the surgery or other multifactorial pre- or post-operative changes may have precipitated delirium. This further complicates whether there was a cause and effect relationship between antipsychotic medication use in hospital and delirium. However, we have shown a direct association between the two. Future studies should determine prospectively whether such a cause and effect relationship exists. Finally, the severity and duration of delirium was unclear, making it difficult to determine the absolute direct association between psychotropic medication and delirium.
In conclusion, we have demonstrated that the odds of delirium in a patient who is hospitalized for a hip fracture is significantly higher in patients who are prescribed new psychotropic medications throughout the period of their hospitalization. This is independent of age, medical comorbidities, as well as pre-operative cognitive and functional status. The results of this study suggest that there is an association between the use of antipsychotic medication and delirium and as such, the use of these medications in the elderly patient in an acute care facility should be prescribed judiciously. Because delirium is associated with poor long-term outcomes (22-30) in elderly individuals, future studies should further examine the direct benefits of implementing a geriatric specialist in the care of these patients. This specialized care will be useful in identifying those patients who are at high risk for delirium in order to minimize adverse outcomes.


Acknowledgments: The authors would like to thank Dr. Ruby Friedman, Ms. Judy Bianco, Ms. Evgenia Liatsopolous, Ms. Sonia Halpern Bazaar, and Ms. Suzette Chung for their assistance with gathering data, input on the project design and feedback on the manuscript.
Funding: This study was funded by a salary stipend granted to Dr. Levinoff from the Department of Medicine at the Jewish General Hospital and from the Division of Geriatric Medicine at McGill University. The sponsors had no role in the design and conduct of the study; in the collection, analysis and interpretation of data; in the preparation of the manuscript; or in the review or approval of the manuscript.
Conflict of interest: None



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Published online October 4, 2017, http://dx.doi.org/10.14283/jfa.2017.37





1. Semillero de Neurociencias y envejecimiento, Facultad de Medicina, Pontificia Universidad Javeriana, Bogotá, Colombia; 2. Facultad de Medicina, Instituto de Envejecimiento, Pontificia Universidad Javeriana, Hospital Universitario San Ignacio, Bogotá, Colombia; 3. Unidad de Geriatria, Hospital Universitario San Ignacio, Bogotá, Colombia; 4. Department of epidemiologic research on Geriatrics, Nacional institute of geriatrics, Mexico DF, mx.
Corresponding author: Mario Ulises Perez-Zepeda, Department of epidemiologic research on Geriatrics, Nacional institute of geriatrics, Mexico DF, mx, ulises.perez@salud.gob.mx, Tel +52 5555738685

J Frailty Aging 2017;6(3):141-143
Published online May 31, 2017, http://dx.doi.org/10.14283/jfa.2017.17



Background and objective: Muscular dysfunction and cognitive impairment are both disabling states, affecting especially the elderly. Thus, are important subjects of research. Our goal is to describe the association between these two entities in the elderly. Methods: This is a secondary analysis from the SABE 2012 Bogota survey, which is a cross-sectional study. We define muscular dysfunction as an abnormal result in gait speed and/or handgrip strength tasks. Cognitive impairment was defined as an abnormal result in Mini Mental State Examination. Other independent variables were measured. Results: A total of 1,564 older adults were included in the analysis. Cognitive impairment showed statistically significant association with both low handgrip strength (OR: 2.25; CI 1.52 – 3.33) and low gait speed (OR: 2.76; CI 1.83 – 4.15) in the adjusted model. Conclusion: In older adults, muscular dysfunction is associated with cognitive impairment. New studies should address the causality and temporality of this relationship.

Key words: Cognitive disorders, muscular dysfunction, geriatrics, motor unit.




Muscular dysfunction (MD) in elderly leads to worse performance in activities of daily living (1). From now on MD is understood as a worst performance in Gait Speed (GS) task and Handgrip strength (HS) (2).
On the other hand, cognitive impairment (CogImp) is the measurable deficit in cognition areas, that leads or not to impairment in Activities of daily living. However, with early and proper identification, the disabling process can be halted in order to improve quality of life and function in affected older adults (3).
A study with Mexican-American older adults with a follow-up of up to 7 years found that a decrease in HS was related to CogImp (4). On the other hand, recent evidence from a Netherlands study, showed that lower HS predicted an accelerated decline in CI in 2-year follow-up (5).
The aim of this study is to describe the association between CI and MD in a group of community-dwelling older adults from Bogota, Colombia.



Sample and Design

We analyzed data from the SABE (Salud, Bienestar y Envejecimiento) 2012 Bogota survey, which was a cross-sectional study that included 2,000 subjects aged 60 years or more, living in rural and urban areas in the city of Bogota, Colombia. Sampling was probabilistic, made by clusters (housing segments) and block stratification, and representing 779,539 subjects aged 60 years and older; with 81.9% of eligible adults finally agreeing to participate in the study. The instrument used in the SABE 2012 Bogota study was derived from the international instrument designed for the original SABE study conducted in 5 Latin American capital cities between 1999 and 2000. However, it was modified and adapted to Colombian context. Further information about SABE study is available elsewhere (3).

Dependent Variable

Our dependent variable was cognitive function. We assessed it using the modified version of the Mini-mental State Examination (MMSE) validated in the initial SABE studies. The score ranges from 0-19 with a higher score representing better cognitive function –less than 12 minor o equal points was considered as cognitive decline (3).

Independent Variables

As part of the anthropometric evaluation of the study participants went through GS and HS testing. GS was measured by asking the subject to walk 3.4 meters starting from standing position, and the time taken to walk this path was registered. The best result of two tests was used for analysis. Four cut-off values were estimated for GS: according to height mean (mean or higher and lower than the mean) and sex, taking the lowest quintile for each subgroup (supplementary table 1). Mean height value was 1.62 and 1.49 meters (m) for men and women, respectively. A hand dynamometer standardized in kilograms was used to measure HS. The subject was asked to perform three trials, and the best result of the three was used. Cut-off values for HS were determined by the lowest quintile for each body mass index (BMI) quartile (Q) and sex group. Consequently, eight values were obtained (supplementary table 1).
Socio-demographic variables such as education, sex and age in years were included as confounding variables, as well as self-reported comorbidities.

Statistical analysis

Initially, we used univariate analyses to explore extreme values and normal distributions in order to adjust and categorize variables. Categorical variables are presented using frequencies and percentages. Afterwards, we analyzed data with bivariate models to determine association between independent variables and subjects with and without CogImp, using chi-square tests for categorical variables and t-test for continuous variables. Finally, we made a multivariate regression model to obtain the odds ratio (OR) with it’s corresponding 95% confidence intervals (CI), unadjusted and adjusted for confounding variables. The statistical level of significance was set at p < 0.05. Data was analyzed using STATA (12th version).



A total of 1,564 older adults were included with a frequency of women of 63,4%. Age mean was 71.17 years. 12.25% of individuals received 0 years of education, 55.55% individuals 1 – 5 years, 21.7% of individuals 6 – 11 and 10.50% received >= 12 years education. The incidence of CogImp was12.6% of older adults. The mean of BMI was 27.52 kg/m2 (Table 1). As shown in table 2 individuals with low HS, 38.22% had CogImp (p value < 0.0001). CogImp was also present in 56.03% (p value < 0.0001) of older adults with low GS.


Table 1 Sample characteristics (n=1,564) – SABE Bogota

Table 1
Sample characteristics (n=1,564) – SABE Bogota

SD: standard deviation.

CogImp showed statistically significant association with low HS in the unadjusted model (OR 2.76; 95% CI 2.01 – 3.80) and also after adjustment (OR: 2.25; 95% CI 1.52 – 3.33). Low GS also displayed association with CogImp both before (OR: 3.85; 95% CI: 2.10 – 5.49) and after adjustment (OR: 2.76; 95% CI 1.83 – 4.15) (table 2).


Table 2 Bivariate analysis: muscular dysfunction stratified by cognitive function and Multivariate analysis: based on dependent and independent variables of interest

Table 2
Bivariate analysis: muscular dysfunction stratified by cognitive function and Multivariate analysis: based on dependent and independent variables of interest

MMSE: Mini Mental State Examination; *Adjusted by sex, years of school, body mass index and age; OR = odds ratio. CI: confidence interval.



Particularly, this study focuses on assessing association between MD and CI. This association has never been established before in a Colombian older adults.
Results suggest older adults who had low HS and GS, had increased odds to suffer of CogImp, regardless of age, sex, schooling, or BMI. Our results could be explained by the description of the motor unit made by Sherrington and Liddell in 1929 (6), grounded on the main components, anterior horn cell, peripheral nerve, neuromuscular junction, and the muscle fibers, in where the model of CogImp affected Gamma Cortical neuron in the frontal motor cortex (7). Moreover, it is well know that the innervation ratio (IR) depends on the muscle used and complexity of the movement, for example the highly IR for the muscles of the eye varies between 3 to 10, on the other hand the IR for the muscles used for walking and balance is 2000 – that means that 1 axon innervates 2000 muscle fibers. With this in mind it is more likely that MD affects walking due to a disruption in this motor unit chain, even in the early stages of CogImp (8).
On the other hand, the MD it’s been associated with CogImp by two different processes. First strength impairment in patients reduces their activities of daily living, increasing their dependency (3) and second also reducing their social interaction, increasing in turn the CogImp (9). Moreover Cesari et al, reported that there is an inflammatory status with MD (10), caused by an increase in cytokines; which is a well-known factor involved in the genesis of neurodegenerative processes (11).
The association of cognitive impairment and sarcopenia or frailty is controversial as muscular mass has not been associated with an increased risk (13, 14) of CogImp; nevertheless, some authors claim that there is a mixed condition so-called «cognitive frailty» with features both of frailty and CogImp. Nevertheless, there is a need to establish the temporal relationship and associated factors on how MD appears in the neurodegenerative process or vice-versa; and the exact role that each factor plays.
Our study has strengths, for example SABE Bogotá is the first population-based study in adults over 60 in Colombia evaluating health and its determinants. Therefore, the association we described, could be generalized to Colombian older adults, and is in line with other recent research on this topic.
This study has the limitation to be a cross-sectional study where causation cannot be established. The cut-off points of the HS and GS could be affected by the height and the biotype of Colombian adults. Such as others population base studies, data are self-reported, so recall bias could affect our results.


Acknowledgements: We would like to thank the Semillero de Neurociencias y Envejecimiento at Pontificia Universidad Javeriana, group base of our researchers. Compliance with ethical standards
Funding: This study was supported by a grant from the Administrative Department of Science, Technology and Innovation—Colciencias in Colombia, Code 120354531692 and the Pontificia Universidad Javeriana.
Conflict of interest: The authors report no conflict of interest.



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