C. Loecker, M. Schmaderer, L. Zimmerman
University of Nebraska Medical Center, College of Nursing, Omaha, NE, USA
Corresponding Author: Courtney Loecker, MSN, APRN-NP, AGACNP-BC, 985330 Nebraska Medical Center, Omaha, NE, USA, firstname.lastname@example.org, 402-559-6571 phone, 402-472-7345 fax
J Frailty Aging 2021;in press
Published online April 14, 2021, http://dx.doi.org/10.14283/jfa.2021.14
Background: Frailty is a public health priority resulting in poor health outcomes and early mortality in older adults. Early identification, management, and prevention of frailty may reduce frailty trajectory into later life. However, little is known about frailty in younger adults.
Objective: Describe frailty prevalence, definitions, study designs, and components contributing to multidimensional frailty in 18 to 65-year-olds and impart guidance for future research, practice, and policies with potential to positively impact frail individuals.
Methods: Integrative review approach was selected to explore frailty allowing for inclusion of diverse methodologies and varied persepectives while maintaining rigor and applicability to evidence-based practice initiatives. CINAHL, Embase, PsycInfo, PubMed databases were searched for studies describing frailty in adults age 18 to 65. Articles were excluded if published prior to 2010, not in English, lacked frailty focus, or non-Western culture.
Results: Twelve descriptive correlational studies were included. No intervention or qualitative studies were identified. No standard conceptual definition of frailty was discovered. Studied in participants with health disparities (n=3) and chronic conditions (n=8); HIV was most common (n=4). Frailty prevalence ranged from 3.9% (313 of 8095) to 63% (24 of 38). Many factors associated with frailty were identified among physical (18) and social (14), and fewer among psychological (11) domains.
Conclusions: Universal frailty definition and multidimensional assessment tool is needed to generate generalizable results in future studies describing frailty in young and middle-aged adults. Early frailty identification by clinicians has potential to facilitate development and implementation of targeted interventions to prevent or mitigate frailty progression, but additional research is needed because risk factors in younger populations may be different than older adults.
Key words: Frail, medical frailty, disability, middle age, young adult.
Frailty, a physiologic decline that heightens vulneraiblity to stressors, is a public health priority according to the World Health Organization (1, 2). Frailty doubles the seven-year mortality rate in older adults, and up to 5% of deaths could be delayed if frailty was prevented (3, 4). Associated with increased risk for falls, disability, hospitalizations, increased costs, and early mortality (2, 4, 5), frailty is traditionally described in the elderly emphasizing functional decline seen with aging (4, 6). However, recent literature describes frailty as multifactorial inclusive not only of physical, but also social and psychological constructs, occurring on a continuum regardless of age (7, 9). A life-course approach has prompted researchers to explore frailty in younger adults with potentially modifiable risk factors that persist into older age (10, 12). Younger adults with comorbidities and lower psychosocial health demonstrate high frailty trajectory into older age (10, 11), but frailty and associated risk factors in earlier life are not well understood because most frailty research targets older adults (4, 8)..
Frailty identification is predominantly based on a physical phenotype (2) or accumulation of deficits approach (6), although both have been criticized for clinical impracticality (13, 14). Inconsistent definitions and myriad frailty tools complicate the arduous but seemingly beneficial task of frailty identification (8, 13-14). Helping to guide clinical decision-making or care planning around elective surgeries or procedures, frailty assessments have utility in clinical settings where biologic age can be a poor prognostic indicator (5, 15-16).
Adult Medicaid expansion represents an arena in which frailty assessment is especially important among younger adults (19 to 64-year-olds whose income is at or below 138% of the federal poverty level) (17). Individual states are required to define medical frailty intended to protect benefits for those with complex health care needs who do not qualify based on a disability. Improper determination could have dire consequences in a group of socioeconomically disadvantaged adults likely to have higher than average frailty rates (18). Failure to identify medical frailty could result in unmet needs or deprivation of key benefits succumbing to worse outcomes and higher costs. On the other hand, over-identification may result in wasted resources and excess expenditures.
Once identified, earlier targeted interventions have potential to prevent or mitigate frailty progression. Earlier health promotion or targeted population approaches in younger vulnerable adults may confer greater impact than directing strategies toward frailer older adults (12, 19-20). In a study that aimed to quantify frailty risk factors in over 6,000 middle-aged adults, unhealthy behaviors accounted for 30% of the socioeconomic gradient. Smoking, alcohol, activity, and diet have been identified as potentially modifiable frailty risk factors, but how and why risk factors develop in early adulthood remains unknown (10, 11). Another large cohort study observed age 65 as the turning point; frailty increased twice as fast after age 65 suggesting interventions may be more effective before old age (21). Evidence points toward opportunity to intervene early, but we need a better understanding of frailty in younger adults to help explain risk factors and their relationships. Therefore, the purpose of this integrative review is to synthesize literature to describe frailty prevalence, definitions, study designs, and components contributing to multidimensional frailty (physical, psychological, social) in 18 to 65-year-olds and impart guidance for future research, practice, and policies that has potential to positively impact frail individuals. This exploratory work also intends to support future inquiries surrounding medical frailty among Medicaid adult expansion beneficiaries in pursuit of a more cohesive characterization of frail young and middle-age adults.
An integrative review approach was selected to explore the phenomenon of frailty in lieu of other review types (e.g., systematic, meta-analysis) because it allows for inclusion of diverse methodologies (e.g., experimental and non-experimental, quantitative and qualitative) while employing rigorous methods to explore a broad topic from many viewpoints rather than focusing on a specific clinical question (22). Findings from integrative reviews enhance holistic understanding of complex topics like frailty and can be applied to clinical practice and health care policy (22). Whittemore & Knafl’s (22) integrative review methodology was thus utilized to conduct a comprehensive search following steps of the PRISMA checklist (23). A sentinel frailty model expanding the concept to include tripartite domains of frailty and determinants of health was published in 2010 (7), followed by acknowledgement of frailty as a public health priority (1) thus prompting a search of articles from inception (February 2020) dating back to January 2010.
Databases CINAHL, Embase, PsycInfo, and PubMed were searched using subject search terms “frail*” or «medically frail» or «medical frailty,» and full text search terms «young old» or «young adult» or «middle old» or «middle age.» In addition, “psychological frailty» or «social frailty” or “physical frailty” as described in the theoretical Frailty Framework among Vulnerable Populations (FFVP) (9) were used as full text search terms individually and combined with aforementioned terms. The FFVP is a theoretical framework derived from extant frailty and vulnerability frameworks, empirical literature, and expert consultation recognizing multidimensional constructs of frailty (physical, psychological, social) among vulnerable populations regardless of age . Adult Medicaid expansion beneficiaries represent young and middle-aged adults who may lack resources rendering them vulnerable, or at increased risk for frailty, and similar frailty domains may be evident among that population. Bibliographies of relevant articles were further hand searched. Efforts were thus made to include all articles addressing frailty specifically in 18 to 65-year-olds.
Articles were included in the review if they were published in English dating back to 2010 and described frailty in adults age 18 to 65 years. Age range representing Medicaid adult expansion beneficiaries (19 to 64 years) was expanded to include 18 and 65-year-olds because multiple studies would have been otherwise excluded. Qualitative and quantitative research was included as part of the integrative methodology. Western cultures were a criterion based on the knowledge that frail Medicaid adult expansion beneficiaries are recipients of traditional Western medicine favored in the United States and reflective of Western culture (e.g., evidence-based diagnosis and guideline-driven treatment recommendations based on symptom recognition, physical exam, and diagnostic confirmation) (24). Articles were excluded if they were dissertations, theses, abstracts, editorials, lacked a frailty focus (e.g., if frailty was not a variable or outcome but merely mentioned in text), if the study included “frail elderly” with “elderly” defined as greater than 65 years, or if the aim of this review was not addressed. Studies inclusive of those > 65 were intentionally omitted because it was felt including the elderly would misdirect the purpose of the review.
Study design, setting, country, sample size, baseline/defining participant characteristics, and physical, psychological, and social factors associated with frailty were abstracted. Frailty definitions, measurement tools, and prevalence of frailty and/or prefrailty were also gleaned from each study.
A total of 569 records were identified, 42 duplicates were removed, and 527 records were screened for eligibility through title and abstract review. Of those screened, 137 records, plus one record identified from a hand search of relevant articles’ bibliographies, totaling 138 underwent full-text review (see Figure 1). Of those 138 studies, 12 met criteria and were included in the review. A flowchart of the search strategy and selection criteria is depicted in Figure 1. Studies included in the review are summarized in Appendix A.
Appraisal of Study Quality
Study appraisal was conducted using Joanna Briggs Institute (JBI) critical appraisal checklist (25) independently and agreed upon by a second author. The 8-item checklist was utilized for critical appraisal across all studies with a uniform approach to allow for comparison. The tool was felt to be appropriate because all studies contained primarily cross-sectional descriptive data. Initially designed for appraising cross-sectional analytical studies in systematic reviews, the tool is also used for appraising more broad topics such as those described in an integrative review (25). The appraisal results and JBI checklist are detailed in Appendix B and C, respectively. Percentage “yes” responses were calculated, omitting any “non-applicable” responses, and results ranged from 42% (26) to 100% (27). Criteria deemed “unclear” were similar among studies and may be attributed to heterogeneity of frailty tools and lack of ‘gold standard.’ Most studies did not clearly report reliability and validity for tool(s) (n=10) data (27- 36). In general, studies were considered of moderate to high quality evidence; all meeting nearly half (at least 42%), and majority meeting more than half (57%) of JBI criteria (27-33, 35-37). All articles were thus included in the review.
Defining Characteristics of Studies
Studies were primarily descriptive correlational (n=12) (26-37). Variations among these study designs included a prospective cohort of participants that attended a maximum of eight study visits every six months (29). Another included a prospective subset of participants that attended a follow-up visit approximately 3.5 years after baseline (36). Two authors described longitudinal associations of participants at baseline and one time point, six years and nine years, respectively (26, 32). A descriptive pilot study was included (36). Matched cohorts were compared in four descriptive correlational studies (26, 28-29, 32), and the remainder were single cohort cross-sectional (27, 30-31, 33-37).
Half of studies (n=6) included participants that were part of larger cohort studies, (28, 32-35, 37), and two samples were part of the same larger study involving adults infected with human immunodeficiency virus (HIV) (28, 34). Most studies were conducted in the continental United States (n=9) located in urban areas of the Midwest (26, 32, 36), Maryland (37) and California (27-29, 34). International study settings were the United Kingdom (35), Austria (31), and Turkey . Sample sizes ranged widely from 38 to 8,095 participants. Age of participants ranged from 18 to 65 years at the time of baseline data collection. Mean age was reported by nine authors and ranged from 38.9 to 58.7 years. A study sample comprised only of women had the youngest mean age (38.9 years) of all studies (27). Follow-up periods in the two studies reporting prospective and longitudinal outcomes ranged from six months to nine years, respectively. Loss to follow-up was reported in studies that assessed mortality in relation to frailty; seven of 222 and 42 of 2541 participants (26, 37).
A standard conceptualization of frailty was not recognized, but similarities suggested frailty is a multisystem (29, 34-36) age-related (29, 32-35, 37) syndrome (27, 30, 33, 37) characterized by vulnerability (28-29,32,34) to stressors (26, 28) that increases risk for adverse health outcomes (26-28, 30, 34, 37) and mortality (27, 32, 37). Physical attributes of Fried’s criteria are described as characterizing frailty by two authors (32-33). Accumulation of health deficits was an alternate approach to defining frailty (36). Physical, psychological, and social domains were specifically named by two authors (27, 36), and each domain was defined separately in one of the two articles (27). Prefrailty is simply described as “an early stage of frailty” (31) or “prodromal frailty” (37).
Fried’s criteria was utilized most often (n=9) (28-30, 32, 33, 35, 36). Also referred to as Fried’s Frailty Phenotype or Fried’s Frailty Index, Fried’s criteria defines frailty as the presence of at least three of the following criteria; weakness, slowness, shrinking (unintended weight loss), low activity level, and exhaustion. Prefrailty is the presence of at least two of the five criteria (2). Of the nine studies that operationalized frailty citing Fried’s criteria, five adapted criteria to meet the purpose or needs of the study or population (28, 29, 32, 33, 35). For example, “low lean muscle mass” was calculated using x-ray absorptiometry in childhood cancer survivors and a benchmark served as “unintended weight loss,” defined by Fried (2) as self-reported weight loss of 10 pounds or more in the past 12 months (32). Another study involving men with and without HIV categorized participants as frail if any one of Fried’s criteria was met (28). In a sample of English general practice patients, Fried’s criteria was adapted into a questionnaire and data was collected via mailed correspondence (35). The Frailty Instrument for Primary Care of the Survey of Health, Ageing and Retirement in Europe (SHARE-FI), a tool based on Fried’s criteria plus a sex-specific calculation, was used to operationalize frailty in a sample of patients with rheumatoid arthritis (31).
The second most common tools to measure frailty were the Frailty Index, a calculation of accumulated health deficits (n=2) (26, 36), and the FRAIL scale (n=2) (26, 37) which consists of self-reported fatigue, resistance (ability to climb 10 stairs), ambulation (ability to walk a quarter mile), number of illnesses, and loss of weight. One author adapted ‘loss of weight’ criteria to an inquiry about appetite (37).
Another study operationalized frailty using the 15-item Tilburg Frailty Indicator to assess specific domains of physical, psychological, and social frailty (27). The Study of Osteoporotic Fractures (SOF) scale (26) and the Comprehensive Frailty Assessment Instrument (CFAI) were also used to measure frailty (36).
Most studies measured frailty using only one tool (n=10) (27-29, 30, 31-34, 37); however, another study measured frailty using four tools (FRAIL, SOF, Fried’s criteria, and Frailty Index) (25). One study used two tools (CFAI and Fried’s Criteria) and created seven evidence-based questions (36). Measuring frailty using different tools in the same study sample of adults seeking care at free clinics yielded different results; 24 of 38 participants were determined frail using the CFAI versus 4 of 38 according to Fried’s criteria (36).
To operationalize prefrailty, Fried’s criteria was used most often (n=3) (28, 32, 35), but the CFAI (n=1)  and SHARE-FI (n=1) (31) were also utilized. Measuring prefrailty using different tools in a single sample also yielded different results; the CFAI determined only eight of 38 participants prefrail, but Fried’s criteria determined 21 of 38 participants prefrail (32).
Measurement data were gleaned from medical records and collected during study visits, mailed questionnaires (35), and home-based assessments (25).
Prevalence of Frailty
Frailty prevalence varied depending on the population, tool(s), and criteria used. Of those studies that reported frailty and prefrailty, prevalence ranged from 3.9% (313 of 8095) to 63% (24 of 38) (n=8) and 11% (125 of 1122) to 55% (21 of 38) (n=7), respectively (28, 30-33, 35-37). The table in Appendix D outlines each study’s author, publication year, purpose, frailty and prefrailty prevalence (if reported), and tool(s) used to measure frailty.
Some authors alternatively compared frailty among matched cohorts (n=3) (26,29,34). The proportion of “men who have sex with men” that converted to a positive frailty phenotype was 12% of HIV infected men versus 9% of HIV non-infected men (29). Mean frailty index scores were higher in a cohort of middle-aged African American diabetics compared to non- diabetics (26). A stepwise pattern of frailty index scores from more frail to less frail was described among three cohorts of comorbid HIV positive methamphetamine users, non-users, and a control group (34). One author quantified frailty with subscales of physical, psychological, and social frailty in homeless, formerly incarcerated women (27).
Factors Associated with Frailty
Factors associated with frailty were identified among nearly all studies and divided among physical, psychological, and social frailty domains (see Appendix A) guided by the FFVP (9). One descriptive study did not perform correlational statistics, so the strength or direction of variables were not described (36).
Physical domain. The most common factor identified was age (n=6) (27, 29, 30, 32, 33, 37), followed by HIV infection (n=3) (28, 29, 34), pain (n=2) (27, 31), diabetes (n=2) (26, 29), and higher BMI (n=2) (32, 36). Other factors were polypharmacy (37), functional limitations (26), comorbidities (34), kidney disease (29), hepatitis C infection (29), higher rheumatoid arthritis disease activity and longer duration (31), female gender (37), lower BMI (32), and prior radiation (32). Elevated cytokines (26) and laboratory abnormalities including decreased serum vitamin D, hemoglobin, and albumin levels in the setting of chronic kidney disease (26).
Psychological domain. Depressive symptoms (n=3) (27-29), illicit drug use (n=2) (27, 34), and smoking (n=2) (29, 32) were most commonly associated with frailty. Higher perceived stress (28), lower self-rated health (37), lower personal mastery, lower grit, lower optimism (28], emotional regulation difficulty, witnessed violence, and post-traumatic stress disorder symptoms (27] were also described as contributors to frailty.
Social domain. Unemployment (n=2) (31, 35) and lower education (n=2) (29,3 7) were most commonly associated with frailty in the social domain. Many other factors were reported; poverty (37), lower social support (28), black race (29), more likely to disclose HIV status to family (33), adverse employment outcomes, not coping at work, sick leave, health related job loss, homelessness, incarceration (27), negative interactions (28), and prior violence (27) were also associated with frailty.
This review aimed to synthesize literature to gain a better understanding of the current state of the science of frailty in young and middle-aged adults. We identified 12 studies that examined frailty in adults age 18 to 65 years. We expected to find frailty examined in vulnerable younger adult populations with comorbidities or disabilities, but frailty was also described in adults with health disparities (27, 36-37) underscoring the importance of considering socioeconomic contributions to frailty development in younger adults. Frailty prevalence ranged from 3.9% (313 of 8095) (35) to 63% (24 of 38) (36), proportions similarly reported in community-dwelling older adults (4% to 59%) depending on criteria and tool(s) utilized . One explanation for this may be the lack of a uniform frailty definition, measurement tool, and criteria being adapted to meet the needs of a study or population.
The large variation of prefrailty prevalence described in the same sample using different tools (55% using CFAI versus 11% using Fried’s criteria) (36) may be explained by literature confirming unidimensional versus multidimensional tools captures different components of frailty (39). These findings further support the need for a uniform frailty measurement to enable relative comparisons. Of the six studies that described prefrailty, the proportions of prefrail participants were described as higher than frail participants with the exception of a study examining frailty in hemodialysis patients (53% frail, 18% prefrail) (30). Younger adults with advanced kidney disease may especially benefit from early frailty identification and intervention.
No universal frailty definition was recognized, but similar themes suggested frailty is a multidimensional state of reduced adaptability associated with age resulting in health-related adverse outcomes. This finding is consistent with recent literature highlighting the absence of a universal frailty definition and emerging evidence to support multiple overlapping domains of frailty (8, 9). Most authors used Fried’s physical phenotype to operationalize frailty despite discovering a number of social and psychological factors associated with frailty. Frailty in young and middle-aged adults compared to elderly may conceivably look different and potentially require an alternative operational definition. For example, grip strength as a single frailty measure (40) may be of less utility in younger adults compared to elderly. However, authors of the original investigations included in this review frequently adapted measurement tools to suit their population which is also a routine practice among studies inclusive of older adults (13, 14, 41). Our findings suggest a comprehensive standardized tool may capture additional frailty attributes specific to younger adults and allow for comparison across studies. Modifications for specific clinical needs or settings may also be beneficial based on the proportion of studies that modified existing frailty measures. The lack of reported reliability and validity of tools used by authors suggest validation of frailty tools in younger populations is also needed.
Prefrailty was measured most often using the physical phenotype, and consistently lacked explanation or definition. Implications of prefrailty were difficult to extrapolate without a conceptual meaning behind the reason for measurement. Although logical interpretation of prefrailty suggests the concept is a worthy focus of future frailty prevention and/or progression to a frail state, particularly given its prevalence described in this review (29, 30, 32, 34, 36, 37). All authors examined some aspect what contributed to frailty, but few described traditional outcomes (2, 42) like falls (26), functional status (26), and mortality (26, 32, 37). We recommend additional longitudinal studies to examine outcomes of frailty in young adults.
Factors associated with frailty in physical, psychological, and social domains were identified similar to those described in the FFVP (9). HIV infection, diabetes, and chronic kidney disease are described as health-related risk factors owing to frailty (9) and may represent valid health concerns for non-geriatric adults in the form of opportunistic infections, neuropathy, heart disease, or poor bone health. Early identification of health-related risk factors can allow for self-management interventions. Chronic disease can parallel biological mechanisms thought to contribute to frailty and accelerated aging in the form of chronic inflammation or hormone dysregulation reflective of HIV infection (43) or type 2 diabetes (44). Keeping viral loads undetectable through medication adherence or optimal blood sugar control with lifestyle changes may prove beneficial earlier in life. Unemployment (31, 35) is a situational frailty risk factor in the FFVP (9) that has potential to affect physical and/or mental health. Depressive symptoms and behaviors including illicit drug use and smoking are described as frailty risk factors in both the FFVP and this review. Depressive symptoms may influence all three frailty domains (9). Additional research is needed to untangle relationships among frailty risk factors and discover opportunities to favorably intervene.
A literature review examining frailty in older adults reported the most common components across physical, psychological, and social frailty domains were mobility, balance, nutrition, and cognitive function (39). In this review, the most common factors associated with frailty across all three domains, aside from older age, an expected finding (27, 29, 30, 32, 33, 37), were; unemployment (31, 35) lower education (29, 37), depressive symptoms (26, 27, 28), HIV (28, 29, 34), pain (27, 31), diabetes (24, 25), and abnormal BMI (32, 37). As young adults age with diabetes or HIV, unemployment may contribute to the inability to pay for preventative care or treatment of acute illness. Living with a chronic disease and/or unemployment may trigger depressive symptoms and result in further detriment, disability, or frailty. Early detection of frailty risk factors in an individual who is likely to experience frailty progression into older age thus presents an opportunity to intervene.
Existing literature clearly demonstrates patterns of increased health care costs and utilization associated with frailty in aging adults (45-47). This review offers new insight into frailty prevalence and factors associated with frailty among adults age 18 to 65 years. Based on these results, we suggest consideration of early frailty screening in younger adults with health disparities or chronic conditions, especially those with advanced kidney disease, HIV, diabetes, depressive symptoms, chronic pain, or obesity. Our findings are complimented by existing literature suggesting earlier frailty identification may be beneficial to develop targeted interventions (3, 48-51).
Intervention and qualitative studies were not identified suggesting there is much work to be done. Exercise and nutrition interventions to slow or reverse frailty have been described in older adults with some success (20, 52). Frail older adults have relayed the importance of social support and spirituality to ward off frailty (53, 54), but few studies incorporate experiences according to frail individuals. Adult Medicaid expansion beneficiaries represent a population of vulnerable younger adults in which attention to frailty is especially needed. Determination of medically frail individuals is important to preserve benefits but overidentification could waste resources. Informing policy makers about frailty in this population could thus support guidelines for accurate determination. Development and testing of tailored interventions are also important to consider given the increasing population of aging adults with comorbid conditions, but additional research is needed.
There were limitations to the present review. An existing theoretical framework (9) was utilized to help provide key search terms which may have introduced bias. Use of extant literature may pose a challenge to realizing aspects of frailty outside the framework, and potential findings may not have been elucidated in this review. A theoretical framework can also link findings to existing literature when studying a broad and comprehensive concept like frailty (55). Few studies have examined frailty in non-geriatric populations suggesting this area of research is in early stages, so including only peer-reviewed articles may have omitted unpublished data currently in development. Limiting the age range of study participants may have omitted studies inclusive of both frail younger and older adults; however, our intent was to explore frailty in those consistent in age with Medicaid adult expansion beneficiaries. Excluding studies published prior to 2010 may have eliminated literature that could have possibly contributed additional facets of frailty recognized among younger adults. Finally, one-third of articles examined frailty in adults with HIV. Generalization may be limited owing to the disproportionate number of studies involving HIV positive adults.
Frailty prevalence in young and middle-aged adults was similar to community-dwelling older adults, although factors associated with frailty across domains may differ. Presence of many physical and social, and fewer psychological factors associated with frailty suggest a multidimensional problem, but frailty was most often measured using a physical phenotype. Heterogeneity of frailty definitions, criteria, and tools used to measure frailty among samples with various health conditions and disparities created challenges in making relative comparisons across studies.
A universal frailty definition and multidimensional assessment tool that can be feasibly implemented in a variety of young and middle-aged populations is needed to conduct studies that can generate generalizable results. A robust understanding of factors associated with frailty in young and middle-aged adults is needed to assist with early detection, proper determination of medical frailty, and development of targeted interventions to prevent and/or mitigate frailty progression.
Disclosure statement: We have no disclosures.
Ethical Standards: This article does not contain studies with human participants performed by any of the authors.
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