Introduction

The Frailty Syndrome is one of several geriatric syndromes that has received recent attention.  The Frailty Syndrome reduces one’s response to stress thereby enhancing the risk of dying.  Importantly, the Frailty Syndrome is potentially modifiable.  Although an official consensus definition of Frailty Syndrome does not exist, it is generally defined as “a clinical syndrome that leads to a progressive, multisystem decline in function and physiologic reserve, and increased vulnerability to adverse outcomes” (Park and Ko, 2021).

Identification Protocols of the Frailty Syndrome

One of two protocols have generally been used to identify the Frailty Syndrome.  The first is the Fried’s Frailty Phenotype.  It characterizes frailty with the  use of 5 criteria.  They are 1) unintentional weight loss ((≥5 percent of body weight in the past year), 2) self-reported exhaustion, 3) low grip strength, 4) slow walking speed  and 5) low physical activity.  Individuals diagnosed with 3 or more of the  5 conditions are considered frail and at risk of a 2 fold increase in morbidity and death.  However, expression of one or two criteria is deemed pre-frail and predicts an enhanced risk of progression to greater frailty.  Older adults without any of the above characteristics are non-frail or robust.

The second protocol is the Frailty Index.  The Frailty Index seeks to assess vulnerability based on a wide range of age changes to include disabilities, disease states, functional and cognitive deficits and psychosocial factors.  Some 30-40 factors may be assessed.  The Index is derived by counting the number of deficits and dividing by the total possible.  The higher the frailty index number, the greater the accumulation of deficits and the greater the degree of frailty.  This relates to an increase in negative outcomes, such as falls, surgical complications, institutionalizations, or worse, disability and death.

A systematic review of community dwelling individuals (65 years and old) indicated that the prevalence of frailty ranges from 4-59.7% depending on the frailty criteria used (Collard et al., 2012).  Although frailty increases with age and is a burden on healthcare costs, there are interventions validated by clinical trials that can prevent and/or ameliorate frailty.

Origins of Frailty Syndrome

Several organ systems contribute to frailty.  A major contributor is the significant changes that occur in the endocrine system with age.  These changes include a major decline in levels of hormones e.g. growth hormone, insulin-like growth factor-1 (a growth hormone assistant) and some adrenal steroids such as DHEA (dehydroepiandrosterone).  In contrast, another adrenal steroid, cortisol, increases (see Blog 19). These hormones play key roles in muscle maintenance and coupled with an absence of resistance exercises, permit loss of muscle mass and strength (see Blog 2,3). 

Another factor is inflammaging, a condition of low grade inflammation, identified with increased blood levels of pro-inflammatory factors such as ” interleukin 6, c-reactive protein, increased numbers of neutrophils and macrophages and activation of markers of clotting cascade” (Park and Ko, 2021).  One of the hallmarks of aging (epigenetic alterations, see Blog 26) fosters inflammaging, a condition of continual organ/tissue degradation.

Interventions for the Frailty Syndrome

Multidisciplinary Intervention – How to modify

There have been many interventional studies seeking to reduce/prevent frailty.  One of the earliest clinical trials to address this goal was the Frailty Intervention Trial (FIT) (Cameron et al., 2013).  This study found that frailty can be successfully treated with an interdisciplinary multifaceted treatment program.  Specifically, 216 participants with frailty (Fried’s Phenotype), average age of 83 years were randomized to receive either multidisciplinary intervention or standard health care for one year.  The multidisciplinary interventions were tailored to the individual depending on the frailty characteristics.  They consisted of, for example, nutritional evaluation and home-delivered meals for weight loss and home-based physiotherapy sessions and home exercise program for weakness, slowness or low energy expenditure.  The trial results showed individualized interventions clearly reduced frailty and increased mobility.

Effective Exercises Modify the Frailty Syndrome

In an assessment of multiple trials, a systematic review of frailty interventions from 46 primary care studies, world-wide concluded that “interventions with both strength training and protein supplementation consistently placed highest in terms of relative effectiveness and ease of implementation” (Travers et al., 2019).  Effective exercises ranged from mild-intensity mixed exercises (e.g. aerobics, resistance) or singular exercises such as walking or tai-chi.  Interventions targeting behavioral changes were easy to implement but of low value.  Home visits, comprehensive geriatric assessment, administration of hormones (testosterone, DHEA) were difficult to implement and also of low efficacy.  Approximately 65% of these studies employed more than one intervention.

Another earlier comprehensive review (12 randomized controlled trials and 2 cohort studies) with the goal of preventing or reducing frailty found interventions that significantly reduced the greatest number of frailty markers were physical exercises (all types and combinations) (Puts et al., 2017).

Specific Physical Activity Modify the Frailty Syndrome

Travers et al., proposes the following physical activity for frailty intervention: “20–25 minutes of activity, 4 days per week at home, comprising 15 exercises: three for strengthening arms, seven for strengthening legs, and five for balance and coordination. Each exercise is repeated 10 times per minute, progressively reaching 15 times after 2–3 months, with a rest of half a minute between each set”. 

Finally, early intervention is highly desirable.  A twenty year longitudinal study of over 6000 adults reported that healthy habits started at a younger age  (age 50) reduce the risk of frailty later in life.  Those habits included 1) not smoking, 2) moderate alcohol consumption, 3) physical activity of at least 2.5 hours per week, and 4)  consuming fruits and vegetables at least twice daily.  Following all 4 yields a 70% reduction in frailty risk.

Conclusions

The Frailty Syndrome is a preventable decline in organ function summating in seriously reduced response to inevitable stresses.  Expert analysis of over 50 clinical studies indicate that a program of physical activity is key in ameliorating frailty.  Where possible an individualized program addressing each frailty component is ideal.

References (pubmed)

Aas SN et al., Strength training and protein supplementation improve muscle mass, strength, and function in mobility-limited older adults: a randomized controlled trial. Aging Clin Exp Res. 32(4):  605-616, 2020.

Cameron ID et al.,  A multifactorial interdisciplinary intervention reduces frailty in older people: randomized trial.  BMC Med. 11:  65, 2013.

Collard RM et al., Prevalence of frailty in community-dwelling older persons: a systematic review. J Am Geriatr Soc . 60(8):  1487-92, 2012.

Fried LP et al.,  Frailty in older adults: evidence for a phenotype. The journals of gerontology Series A, Biological sciences and medical sciences. 56(3):  M146–56, 2001.

Gil-salcedo A et al., Healthy behaviors at age 50 years and frailty at older ages in a 20-year follow-up of the UK Whitehall II cohort: A longitudinal study. PLoS Med. 17(7):   e1003147, 2020.

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Park C, Ko FC.  The Science of Frailty: Sex differences. Clin Geriatr Med. 37(4):  625–638, 2021.

Puts MTE et al., Interventions to prevent or reduce the level of frailty in community-dwelling older adults: a scoping review of the literature and international policies. Age Ageing. 46(3):  383-392, 2017.

Rockwood K, Mitnitski A.  Frailty in relation to the accumulation of deficits. J Gerontol A Biol Sci Med Sci .  62(7):  722-7, 2007.

Rockwood K, Mitnitski A. Frailty defined by deficit accumulation and geriatric medicine defined by frailty. Clin Geriatr Med. 27(1):  17–26, 2011.

Roschel H.  et al., Supplement-based nutritional strategies to tackle frailty: A multifactorial, double-blind, randomized placebo-controlled trial Clin Nutr  40(8):  4849-4858, 2021.

Travers J et al., Delaying and reversing frailty: a systematic review of primary care interventions Br J Gen Pract. 9(678):  e61–e69, 2019.