Relationship between family caregiver burden and physical frailty in older adults without dementia: a systematic review

Background Physical frailty is a prevalent syndrome in older adults that increases vulnerability for a range of adverse outcomes including increased dependency and death. Caregivers of older adults experience significant physical, emotional, and financial burden, which is associated with poor physical and mental health. While it is known that care recipients’ dementia is associated with burden, the literature regarding the impact of physical frailty on burden has yet to be synthesized. We conducted a systematic review to assess the state of the evidence regarding the relationship between these two prominent concepts in the geriatric literature. Method We used a structured search of databases to identify original English-language articles. Two researchers screened the titles and abstracts of all 1202 retrieved studies and then full-text versions of 265 retained studies. Screening was based on a priori inclusion criteria, which included discussion of physical frailty, caregiver burden, and a population of community-dwelling older adults without dementia. Nine included papers underwent data abstraction and critical appraisal using the Cochrane Risk of Bias Tool or the Newcastle-Ottawa Scale (for randomized controlled trials or cross-sectional studies, respectively). Heterogeneity of the included studies precluded meta-analysis. Results Five publications had the same author and drew from the same population; these were treated as a single study. Three of our studies were of limited value since they did not include a validated measure of frailty. While caregivers of frail older adults experience burden, the scarce available evidence and lack of studies comparing this population with normative values does not allow conclusions to be drawn about the strength or nature of the relationship. Judging from excluded studies, the term “frailty” is often used without reference to a clear definition or is treated as synonymous with functional impairment or advanced age. Conclusions Our review suggests that caregivers of frail older adults experience burden and that the degree of burden may differ from that of other caregiver populations. The limited evidence does not allow conclusions to be drawn or to inform clinical practice. Further research is needed, given the salience of physical frailty and burden. Systematic review registration PROSPERO CRD42015019198 Electronic supplementary material The online version of this article (doi:10.1186/s13643-017-0447-1) contains supplementary material, which is available to authorized users.


Background
Physical frailty has been defined as "a medical syndrome with multiple causes and contributors that is characterized by diminished strength, diminished endurance, and reduced physiologic function that increases vulnerability for developing increased dependency and/or death" [1]. A recent systematic review involving 15 studies with a total of 44,984 participants found an average pooled prevalence of 9.9% of physical frailty in communitydwelling older adults [2]. Physical frailty has been shown to be a strong predictor of higher mortality risk and reduced life expectancy, as well as increased depression, impairment in activities of daily living, and postoperative complications and hospital length of stay [3][4][5][6][7][8].
Family caregivers are relatives, partners, friends, or neighbors providing a broad range of assistance for a care recipient and may be primary or secondary caregivers and live with or independently from the recipient [9]. Given the substantial morbidity associated with physical frailty, family caregivers providing care for community-dwelling older adults experience substantial physical, financial, and psychosocial burden [10,11]. In addition, caregivers of the frail elderly experience financial and emotional strain associated with diminished health-related quality of life and life satisfaction [12].
While caregiver burden associated with communitydwelling older adults has been evidenced, the relationship between physical frailty and family caregiver burden has not been previously synthesized. We conducted a systematic review of the literature to determine whether community-dwelling older adult physical frailty is associated with increased family caregiver burden.

Methods
We developed and followed a protocol that used the standard systematic review framework [13]. A PRISMA 2009 Flow Diagram is provided as Fig. 1. A completed PRISMA checklist is included as an Additional file 1 with this publication [14].

Literature search
We conducted a systematic search using Ovid MEDLI-NE(R) (1946 to present), Embase (1974Embase ( to 2015, PsycINFO (1987PsycINFO ( to 2015, Cochrane Central Register of Controlled Trials, and CINAHL. The search was conducted by a . We also emailed three noted scholars in the fields of frailty and/or caregiver burden, who did not identify any additional studies.

Study selection
Our inclusion criteria were defined a priori. We included English-language studies that included family caregivers of community-dwelling older adults and reported on caregiver burden. Experimental [randomized controlled trial (RCT), controlled trial, quasi-randomized trial, and quasi-experimental], observational (before/after study, prospective cohort study, retrospective cohort study, case-control study, analytic or descriptive cross-sectional study, case report, and case series), and qualitative studies were considered eligible. Systematic reviews addressing our research question were included to identify additional eligible studies. Book chapters, symposium and conference proceedings, essays, editorials, letters, commentaries, narrative reviews, and protocols were excluded.
We defined family caregivers as unpaid caregivers who are typically close relatives (e.g., spouses and children) and provide the bulk of the care and support received by a dependent older adult living in the community (not in a hospital, retirement community, nursing home, or any form of long-term care) [15]. Studies involving solely institutionalized older adults were excluded on the basis that caregiver burden has previously been explored extensively in this setting. Family caregiver burden was defined as any construct or variable representing the physical, psychological, and financial cost of providing care for a loved one [16]. Studies reporting caregiverrelated outcomes related to subjective burden (e.g., effects on emotional, social, financial, physical, and spiritual functioning), objective burden (e.g., amount of time spent on caregiving, the caregiving tasks that are performed, and possible financial problems), or both were considered eligible. Studies that employed qualitative measures and quantitative measures (e.g., Caregiver Assessment Tool, Caregiver Burden Screen, and Caregiver Stress Scale) were both included.
Care recipient frailty was defined as any property or syndrome that may relate to physical frailty. Examples of such properties included, but were not limited to, unintentional weight loss, self-reported exhaustion, weakness, slow walking speed, low physical activity, and loss of energy, physical ability, or health. Articles defining frailty solely as a limitation in functional activity were considered ineligible. Finally, studies of older adults with dementia were excluded.
We note that our registered protocol did not include this last exclusion criterion. However, early abstract screening revealed that a large number of studies of caregivers of older adults included only patients with dementia. Based on the known substantial positive association between dementia and caregiver burden and our interest in identifying to the extent possible the impact of physical frailty in particular, we elected to exclude such studies on the assumption that they would be highly confounded [17,18].

Study selection
Two investigators (TR, AA) independently screened every original title and abstract identified. Consensus was reached on decisions to advance studies to full text screening, with discrepancies resolved by discussion between the two reviewers and adjudication by a third reviewer (AAH) as necessary. Full text versions of eligible studies were subsequently retrieved for detailed review and were independently screened in duplicate (TR, AM), with discrepancies resolved by discussion and adjudication by a third reviewer (AAH) as necessary. The reference lists of review articles encountered during the full text screening process were examined by both reviewers (TR, AM) to identify additional potentially eligible studies. Title and abstract as well as full text screening were conducted on the DistillerSR platform using predesigned online forms piloted by a pair of reviewers (TR, AM) and refined to ensure usability.

Data abstraction and quality assessment
After determining article inclusion, two reviewers (TR, AM) extracted study data into extraction tables in duplicate using piloted and standardized extraction forms and reconciled conflicts by discussion with adjudication by a third reviewer (AAH) as necessary. The following information was extracted from every included study: study design, country, study objectives, general description of care recipient population, care recipient age, care recipient gender, other descriptive information about care recipients (e.g., mini-mental status examination score), general description of caregiver population including age, gender, and additional details (e.g., whether caregivers resided with the recipient; relationship to care recipient). Outcome data regarding how frailty was defined and measured, how family caregiver burden was defined and measured, and reported results regarding the relationship between caregiver burden and physical frailty were extracted into summary tables.
All included papers were critically appraised in duplicate by two reviewers (TR, AM) using piloted and standardized assessment forms, with discrepancies resolved by discussion and adjudication by a third reviewer (AAH) as necessary. Included RCTs were rated on sequence generation, allocation concealment, blinding of participants, personnel and outcome assessors, incomplete outcome data, selective outcome reporting, and other sources of potential bias as per the Cochrane Collaboration's tool for assessing risk of bias [19]. Included cross-sectional studies were appraised on sample selection, comparability, and outcome assessment based on a published adapted version of the Newcastle-Ottawa Scale [20]. As mentioned below, five papers reported on essentially the same study. However, each paper was appraised separately, since critical appraisal considers not just the analysis and design of a study but the manner in which its results are reported.
We note that our registered protocol had contemplated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to assess the level of evidence across studies, which posits a systematic and explicit approach to making judgments about the quality of evidence supporting clinical recommendations, such as a practice guideline statement about the effect of a particular intervention [21]. However, factors such as the heterogeneity of designs and outcomes among included studies, and the paucity of interventional studies, precluded the identification of any evidence-based recommendations (regardless of quality), thus rendering GRADE inapplicable.

Data synthesis
Given significant heterogeneity in study populations, outcomes, and measures across eligible studies, it was not possible to perform a meta-analysis. Accordingly, results were synthesized narratively, with summary tables presenting the key study characteristics, findings, and limitations, and risk of bias assessments associated with each study.

Role of the funding source
The Geriatric Education and Research in Aging Sciences (GERAS) Centre employed and provided partial funding for the work of two co-authors (AP, AAH) but did not play a role in the selection of the topic, conduct of the study, or interpretation or presentation of the results as an institution acting in a corporate capacity. The GERAS Centre has no financial interest in the outcome of the study.
Of the 256 articles excluded after full text review, a large majority (202, 78.9%) did not discuss physical frailty. Some of these studies employed a non-physical definition of frailty, e.g., with reference to Rockwood and colleagues' Clinical Frail Scale [31]. Other studies defined frailty in terms of impaired functioning, e.g., diminished capacity to perform activities of daily living. Some studies used "frailty" as synonymous with advanced age. In many cases, the term "frail" was used without an explicit definition or a validated tool measuring frailty.
Although our review identified nine papers, we have decided that it is most accurate to characterize our review as including five studies. Five of the papers [22][23][24][25][26] had the same principal investigator and involved the same population: caregivers of frail older adults who were enrolled in a RCT of a multifactorial interdisciplinary intervention aimed at reducing mobility-related disability. We note that the study reporting on this RCT was not captured by our database search and would not have met our review's criteria because the population of the RCT itself did not include caregivers [32]. In a recruitment exercise distinct from the RCT itself, caregivers designated by RCT participants were sent a set of questionnaires.
We contacted the principal investigator on these five publications in December 2016 to clarify the relationships between them. Each paper consists of a different cross-sectional analysis of the data collected through the above-referenced questionnaires. Two of the papers describe cross-sectional analyses conducted at an earlier point in the underlying RCT and involved the caregivers of 93 RCT participants. The remaining three papers describe cross-sectional analyses which were conducted at a later point and involved caregivers of 119 participants in the same RCT. Because each paper reflects a different analysis of essentially the same questionnaire responses from the same population, but was published separately, we have designated one paper as the index study for purposes of extraction and appraisal and refer to it hereinafter as "the Aggar study" [25] and term the remaining publications "the related papers" [22][23][24]26].

Care recipient and caregiver populations
The care recipient and caregiver populations included in each study were similar in terms of most descriptive *This publication represents the index study for a series of five papers by a single set of investigators [22][23][24][25][26]. An explanation of the relationship between these articles appears in the "Results" section of the manuscript ** Care recipient demographics were not reported in this paper [25]; these details were extracted from Aggar 2011b, which involves the same population [24]. ZBI CES-D HADS-A EQ-5D-VAS In this study of a multifactorial intervention to prevent falls in frail older adults, there was no significant difference between control and intervention groups in potential proxy measures of frailty (TUG or velocity). There was no significant difference in any CG burden measure (including anxiety, depression, and quality of life) between CGs of CRs in the two groups.
No direct measure of frailty. Small study population. Study did not control for cognitive impairment.
Study did not include any non-frail participants for comparison (i.e., all participants had FFS ≥2).

[30]
CGs in the "frail elderly" group reported that they were caring for someone who was "frail due to age." Frailty not otherwise defined.
Self-reported physical strain, emotional stress, and financial hardship as rated on a 5-point scale (1 = not at all; 5 = great deal/ very much). Self-reported amount of money spent on caregiving/mo. Compared to three other groups of CGs (for patients with cancer, diabetes, and dementia), CGs of CRs whom the CGs themselves described as "frail due to age" reported the least physical strain, emotional stress, and financial hardship.
Of the four groups of CGs, carers of frail older adults also spent the least of their own money on caring and less than half the average time on caregiving activities.
Cross-sectional study (single point in time).
Risk of survey bias.
No direct measure of frailty; relied on CGs' subjective impression of "frailty due to age," which may have no relationship with physical frailty.
*This publication represents the index study for a series of five papers by a single set of investigators [22][23][24][25][26]. An explanation of the relationship between these articles appears in the "Results" section of the manuscript characteristics. Of note, two studies only included care recipients who met certain minimums of cognitive function based on the Mini-Mental Status Examination (MMSE): >18 for the Aggar study [25] and >15 in the RCT [29]. One study only included patients with mild or worse cognitive impairment (MMSE <27) [28]. Among studies reporting on co-residence, approximately half of caregivers co-resided with their care recipient (57.1% [25] in the Aggar study; 47% (control) to 50% (intervention) in the RCT [29]).

Reporting of care recipient frailty
No study included physical frailty as one of its areas of focus. Only two studies [25,29] included participants deemed frail using a validated measure (Fried Frail Scale (FFS) [33]. Because they were recruited from an RCT involving a frailty intervention, all participants in the Aggar study were frail (FFS >2) as a criterion for inclusion [25]. These studies did not otherwise report on participants' frailty. All participants in the included RCT were drawn from a study population previously determined to be frail (FFS ≥2), so recipients' degree of frailty was not measured as part of the study [29].
Two studies neither explicitly defined or measured frailty qualitatively or quantitatively [27,28]. Each study, however, included variables that reviewers agreed could be considered potential proxy measures for components of the FFS, such as gait ataxia or extrapyramidal gait disorder [28] which could be considered proxy measures for one of the FFS criteria (slow gait speed), a surrogate indicator for decreased physiologic reserve [33]. Another study analyzed care recipients' "timed up and go", poor balance, and use of walking aid [27]. In one study, care recipients were deemed frail if their caregiver described them as "frail due to age" [30].

Reporting of caregiver burden
There was considerable heterogeneity in caregiver burden measures used across included studies. With one exception [30], all studies employed a standardized instrument used to assess caregiver burden. These included the Caregiver Reaction Assessment (CRA), Hospital Anxiety and Depression Scale (HADS), Caregiver Strain Index (CSI), and Relative Stress Scale. One study employed a total of four instruments [29]. Kim et al. asked participants to report their physical strain, emotional stress, and financial hardship on a 5-point scale (1 = not at all; 5 = great deal/very much) [30].

Burden experienced by caregivers of physically frail older adults
All included studies suggested that caregivers of physically frail older adults experienced negative reactions to caregiving, as well as anxiety and depression. No studies included normative data for purposes of comparison with non-frail populations.
The Aggar study found that caregivers of a population of physically frail older adult care recipients experienced negative reactions to caregiving as measured using the CRA [25]. However, 68% of caregivers found it rewarding to provide care [25].
One study, which directly compared caregivers of frail adults with those of other types of patients, found that caregivers of older adults whom the caregivers themselves described as "frail due to old age" experienced the least physical strain, emotional stress, and financial hardship when compared with caregivers of patients with cancer, diabetes, and dementia [30].
Finally, two studies found that indirect indicators of frailty such as timed up and go, ataxic gait, use of walking aid, poor balance, and weight loss were not associated such measures as caregiver strain, irritability, or tension [28,29].

Risk of bias
Risk of bias assessments for the four cross-sectional studies and one RCT are presented in Tables 3 and 4, respectively [19]. Summative risk of bias scores were not calculated for each study, as this practice is disfavoured [19]. The Aggar study drew on a narrow population of study participants from a small geographical region, raising concerns about sample representativeness [25]. Not all of the cross-sectional studies used validated instruments to measure caregiver distress. All included studies relied on self-reported measures of caregiver burden, although this is appropriate given the outcome of interest in these studies was subjective caregiver burden. In our estimation, the one included randomized controlled trial reported incomplete outcome data and did not adequately conceal allocation [29]. As previously discussed, an overall assessment of the quality of the evidence using a tool such as the GRADE approach was deemed inapplicable.

Discussion
Research has explored associations between caregiver burden and several classic geriatric syndromes such as dementia, functional decline, multimorbidity, falls, and geriatric depression [17,[34][35][36][37]. Frailty is increasingly being recognized as a true "geriatric giant" in its own right. Yet, it differs from these syndromes in that it offers a highly complex framework for understanding the relationships between physiologic reserve and a wide range of outcomes. Its clinical applicability is also attracting greater attention.
While a purely physical understanding of frailty has conceptual limitations, even those who espouse a frailty  *This publication represents the index study for a series of five papers by a single set of investigators [22][23][24][25][26]. As appraisal concerns not just study design and execution but also the way results are presented, it is based on a composite of these five papers. An explanation of the relationship between these articles appears in the "Results" section of the manuscript. Statistical test (a) Test used to analyze data is clearly described is appropriate, and measurement of association is presented including confidence intervals & probability (*); (b) Test not appropriate, not described, or incomplete construct based on accumulated deficits and psychosocial factors recognize that strength, speed, and body mass are essential components of physiologic reserve [38]. Our review represents the first effort to synthesize evidence regarding the association between this clinically and academically significant phenomenon in community-dwelling older adults receiving care and degree of burden experienced by family caregivers. Our review suggests that caregivers of physically frail older adults experience depression, anxiety, and other negative effects of caregiving. Though not included in abstraction or appraisal for this review, it bears mention that several of the related papers by Aggar and colleagues also reported that caregivers experienced anxiety and depression, with as much as 15% experiencing borderline depression (HADS-D 8-10) and as much as 10% experiencing abnormal depression (HADS-D ≥11) [22]. Up to 24% experienced borderline anxiety (HADS-A 8-10), while 12% experienced abnormal anxiety (HADS-A ≥11) [22].
Another study also concluded that, compared with caregivers of other types of care recipients, caregivers of patients whom they subjectively believed were frail due to old age appeared to experience less burden on a number of dimensions, including hours spent caring and financial burden [30]. However, the absence of normative data in the included studies did not allow us to conclude whether prevalence of depression and anxiety is higher or lower than in the general population.
Finally, though not included for abstraction and appraisal, one of the related papers by Aggar and colleagues explicitly explored the association between frailty and caregiver burden, finding that caregivers of care recipients deemed severely frail (FFS >3) did not differ from caregivers of merely frail (FFS = 3) in terms of their responses regarding both negative aspects of caregiving (e.g., time demands) and positive aspects (e.g., self-esteem), though the significance of this relationship was not stated [24].
Although results were based on a small number of studies with some risk of bias, studies did surface findings of interest that emphasize a need for further research in this area. First, some caregivers of frail older adults find it rewarding to provide care [23,25]. Second, compared with caregivers of care recipients with morbid medical conditions, caregivers of patients who were frail due to old age appeared to experience less burden on a number of dimensions, including hours spent caring, and financial burden [30]. Both of these findings serve to underscore the importance of a nuanced understanding of the richness and complexity of the experience of caring for frail older adults in particular.
We note that while the manuscript was undergoing review, three of the authors (TR, AAH, and AP) published a cross-sectional study examining the relationship between caregiver burden and physical frailty, which found that frailty was independently associated with burden in a convenience sample of 45 community-dwelling caregiver-care recipient dyads [39].

Limitations
Our study used well-defined a priori criteria and a rigorous systematic methodology. We do note three potential limitations. First, non-English-language studies were excluded. Second, the relatively small number of included papers, and the fact that five publications consisted of different analyses of essentially the same data and were treated as papers related to a single index study, may impact generalizability of findings and speaks to a substantial gap in the evidence. Finally, the findings are limited by the paucity of normative comparisons in the included studies.

Conclusions
Our review suggests that few, if any, studies have yet evaluated the relationship between physical frailty and caregiver burden as their primary objective. Despite broad criteria for both frailty and burden, our review yielded a relatively small number of eligible studies. That being said, the diversity of research questions and approaches represented in our review reveals that a range of interesting opportunities exist at the interface of these two highly salient phenomena.
Our review of the evidence also identified numerous potential methodological improvements to inform future projects. First, measures and definitions of "frailty" were A -Did the allocation sequence involve a random component or minimization? B -Was allocation adequately concealed, e.g., through central allocation? C -Were participants and key study personnel reliably blinded and/or it was unlikely that outcome measurement would be influenced by lack of blinding? D -Was incomplete outcome data adequately addressed? E -Are reports of the study free of suggestions of selective reporting, e.g., the protocol is available and all outcomes were reported in a prespecified way? F -Was the study apparently free of other problems that could put it at a risk of bias?
heterogeneous among included and excluded studies. A large number defines it solely in functional terms, as synonymous with old age, or use it without any definition at all. This reflects a lack of consensus in the frailty literature generally [40]. Second, few studies specifically considered positive attributes of caregiving (emotional, spiritual, physical, or other) or the factors, such as psychological resilience, which allow certain caregivers to avoid the negative impacts of strain [41]. Further, none of the included studies examined outcomes representing the effect of increased burden on quality of care experienced by the patient population. Future studies, particularly those of an interventional nature, might benefit from addressing these limitations.