Author(s): Marielisa Lopez, MD
Originally published: December 27, 2012 Last updated: April 20, 2022
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Disease/Disorder

Definition

Frailty is a multisystem dysregulation leading to decreased physiologic reserve and increased vulnerability to stressors. This geriatric syndrome is associated with increased risk of adverse health outcomes such as falls, hospitalizations, institutionalization and death.1

There aretwo concepts for frailty, one that describes physical frailty with signs and symptoms also called phenotypic frailty and another called index frailty which takes into account cumulative comorbidities.

There are multiple definitions and outcome measures of frailty.2 The Cardiovascular Health Study (CHS) which included over 5000 men and women aged 65 years or older, defines frailty if three or more of the following five criteria are met:3

  • Unintentional weight loss (> 10 pounds in 1 year or ≥5% in year)
  • Exhaustion (positive response to questions regarding effort required for activity)
  • Weakness (decreased grip strength)
  • Slow walking speed (> 6 to 7 seconds for 15 feet)
  • Decreased physical activity (males <383 kilocalories, kcals); females <270 kcals)

Pre-frailty is when 1-2 of these characteristics are met while one is classified as robust if none are present.

Another common measure used is the Study of Osteoporotic Fractures (SOF) index which defines frailty as the presence of at least two of the following three components:4

  • Weight loss of ≥ 5 percent in last year (irrespective of intent to lose weight)
  • Inability to rise from a chair five times without the use of arms
  • A “no” response to the question, “Do you feel full of energy?”

Those having one component were considered to be prefrail, and those with no component present classified as robust. The end stage of the continuum of frailty could be considered as failure to thrive.

Etiology

Primary frailty is multifactorial, with sarcopenia (loss of skeletal muscle mass and strength) being a central component. Frailty occurs due to alterations in neuromuscular, metabolic and immune systems causing a homeostatic decline.

Secondary frailty is a similar dysregulation that develops due to the core wasting processes of inflammatory and immune diseases.

Differential diagnoses can include depression, malignancy, neurologic disease and rheumatologic disease among others.

Epidemiology including risk factors and primary prevention

Frailty increases with age. Of the overall population, 30% meet frailty criteria by age 90. According to the Cardiovascular Health Study, 7% of community dwellers are frail.3 The Women’s Health Initiative Observational Study, using the CHS criteria in 40,000 women age 65 to 70, found that frailty was present in 16.3%.5 In 6,000 community-dwelling men older than age 65, according to the CHS criteria 4% met criteria for frailty and 40% for pre-frailty.  In this study, frailty was found to be more common in African Americans and Asians than among Hispanics and Caucasians. Mortality is doubled among frail men.

Patho-anatomy/physiology

In frailty, the balance between the normal reaction to stressors — apoptosis and senescence — or the acceleration of either, changes mainly in these three systems:6-9

Musculoskeletal: Sarcopenia (loss of muscle mass and function), VO2 max, strength and exercise tolerance, thermoregulation, energy expenditure, resting metabolic rate and muscle innervation.

Immune: There is a decrease in immunoglobulin G (IgG), IgA, interleukin 2 (IL-2) and mitogen response. There is an increase in IL-6, IL-10 and C-reactive protein (CRP). A recent meta-analysis showed that frailty and pre-frailty are associated with higher inflammatory parameters in particular CRP and IL-6. There is also a demonstrated association between frailty and clotting markers that could represent triggering of the clotting cascade by immune system activation10.

Neuroendocrine: decrease in growth hormone, insulin-like growth factor 1, vitamin D, estrogen and testosterone (DHEA-S). Increase in insulin resistance, cholecystokinin, sympathetic tone and steroid dysregulation.

Disease progression including natural history, disease phases or stages, disease trajectory (clinical features and presentation over time)

  1. New onset/acute: Although a gradual decline in function with activities of daily living (ADLs) and transfers occurs, frail elderly persons often present acutely with muscle weakness, falls, balance and gait deficits, decreased vision with acuity, depth perception and contrast sensitivity and orthostatic hypotension.
  2. Pre-frailty as defined above is the subacute presentation of frailty.
  3. Chronic/stable: Disease progression. Social and environmental factors determine the stability and progression.
  4. Pre-terminal: At its extreme, frailty ends in a failure to thrive that presages death.

Specific secondary or associated conditions and complications

Both acute illnesses and decompensation from long-standing chronic diseases can trigger or perpetuate the syndrome of frailty.

Co-occurrences of multiple diseases, primarily the following nine co-morbidities, increase the patient’s risk of becoming frail: myocardial infarction, angina, congestive heart failure, claudication, arthritis, cancer, diabetes, hypertension, chronic obstructive pulmonary disease.

Essentials of Assessment

History

History based on geriatric syndromes, and Comprehensive Geriatric Assessment:11, 12

  • Functional Status: assess the level of need of assistance/independence
    • ADL
    • IADL
    • Falls
  • Physical Health
    • General: Weight changes, adequacy of sleep
    • HEENT: vision, hearing deficits, dentition status
    • Cardiopulmonary: shortness of breath, chest pain
    • GI: constipation, fecal incontinence
    • GU: Urinary incontinence, prostate enlargement
    • MSK: joint pains, weakness, sensation changes, muscle wasting, fractures
    • Neuro: tremors, imbalance, dizziness
  • Cognitive/psychiatric function: signs and symptoms of
    • Cognitive impairment/ dementia
    • Delirium
    • Mood disorders
  • Medical history
    • Comorbidities
    • Medication (presence of polypharmacy)
  • Socioeconomic / environmental issues
    • Care-giver availability
    • Environmental assessment: home accessibility, home safety (e.g., bathroom equipment, clutter), transportation
    • Savings, income, housing
  • Legal and ethical: advanced directives, care preference documentation, life sustaining treatment decisions and end-of-life preferences, decision capacity.

Physical examination

Routine general systems exam and focused exam of the following:

  1. Neurologic: The Mini Mental State Examination (MMSE) evaluates cognitive function, with scores of 26 or less being abnormal. The clock drawing test assesses executive control and visual spatial skills, which are incompletely tested by the MMSE. When combined with the 3-item recall, it constitutes the Mini-Cog Test, which takes about 3 minutes to administer and is relatively less influenced by the level of education or language differences than is the MMSE. Check for truncal ataxia, proprioception.
  2. Psychiatric: The best question to ask is, “Do you often feel sad or depressed?” If the answer is affirmative, perform the Geriatric Depression Scale, a 15-item scale with scores of 6 or more indicating depression.
  3. Vision: Test acuity or ask the patient to read the headline and the fine print of a newspaper.
    Hearing: Ask the patient to repeat words whispered by the examiner at 2 feet.
  4. Nutrition: Signs of malnutrition, height and weight. Weight loss greater than 10 lb in 6 months, low BMI (< 20 kg/m2) needs further evaluation.
  5. Muscle strength: proximally (e.g., hip flexors) and distally (e.g., grip).
  6. Range of motion: especially shoulders, hips and knees.

Functional assessment

  1. Timed Up-and-Go (TUG) test: The patient gets up from an armchair, walks 10 ft (3 m) in a line, turns around, walks back to the chair, and sits down. The time required to complete this is normally 10 seconds or less. Impaired balance and mobility is likely if it takes the patient longer than 20 seconds, predicting future disability.
  2. Postural stability, step height, stride length and sway are measured.
  3. Balance is tested by asking the patient to stand first with feet side by side, then in semi-tandem position, followed by tandem position. Difficulty with this predicts fall risk.

Laboratory studies

The initial workup should include

  1. Complete blood count (CBC)
  2. Comprehensive metabolic panel (CMP) for kidney or liver dysfunction, albumin and total cholesterol
  3. Inflammatory markers, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR).
  4. 25 hydroxide (OH) Vitamin D
  5. Vitamin B12 and folate levels
  6. Thyroid-stimulating hormone (TSH)
  7. Other tests for the diagnosis and management of multisystem effects of frailty.

Efforts should be made to differentiate between frailty and reversible causes of chronic inflammation (e.g., infections).

Imaging

The role of imaging is limited to diagnosing and managing secondary causes of frailty and their effects on the body’s reserve. Examples: Chest X-ray to assess tuberculosis or malignancy and electrocardiogram to detect myocardial infarction.

Supplemental assessment tools

There are several screening tools available that will assist clinicians in identifying patients that require more extensive assessments (i.e., Comprehensive Geriatric Assessment), these include the FRAIL and the Clinical Frailty Scale.

Cognitive Status: Mini Mental Status Examination

Affective Status: Yesavage Geriatric Depression Scale (GDS), Geriatric Depression Scale

Mobility: Tinetti Performance-Oriented Mobility Assessment (POMA)

Functional Status: The Katz daily living scale, which scores bathing, dressing, toileting, transferring, continence and feeding. Range, 0 to 6 points. 0: lowest functional level/very dependent. 6: Independent.

Functional Status: The Lawton IADL scale: Identifies independent living skills: ability to use a telephone, shopping, food preparation, housekeeping, laundry, mode of transportation, responsibility for own medications and ability to handle finances. Scores: 0 to 8. Score 0: needs assistance. score 8: independent.

Nutritional Adequacy: Mini Nutrition Assessment (MNA)

Frailty Screening Tool for Hospitalized Patients (MFST-HP)

Pain Assessment

Driving

Decisional Capacity

Early predictions of outcomes

The preserved ability to walk despite of frailty status can translate into better outcomes.13

Frailty scores of 4 to 5, with low cholesterol and albumin, indicate high short-term and surgical mortality.  Frailty can also predict disability, hospitalization and hip fractures after adjusting for comorbidities.5

End stage frailty is poorly responsive to treatment and associated with high rates of pressure sores, infection and decreased cell-mediated immunity, with disability and dependency in the final year of life.

Frailty with HIV/AIDS is a predictor of a lower therapeutic response and a worse prognosis than AIDS alone.

Environmental

Environmental barriers include financial resources, socioeconomic factors, cultural factors and physical barriers such as transportation. These should be made available, along with continuity of care and provision of appropriate durable medical equipment (DME).

Professional Issues

The guiding principles of autonomy, nonmaleficence, beneficence and justice should be practiced, with consideration to cultural differences. Specific tests for decisional capacity must be used in the context of the individual patient. The last most competent decision is often the most relevant.

Rehabilitation Management and Treatments

Available or current treatment guidelines

  • Pharmacotherapy in frailty:
    • Avoid polypharmacy, anticholinergics and sedating antihistamines.
    • Insomnia: Non-pharmacological treatments are preferred as first line and these can include sleep hygiene education, Cognitive Behavioral Therapy for Insomnia and relaxation techniques. When a pharmacological approach is required, antidepressants Doxepin and Mirtazapine improve sleep parameters with less side effects, with recent recommendations of avoiding trazodone as harms outweight benefits. Melatonin receptor agonist Ramelteon is FDA approved as well. Benzodiazepines and Nonbenzodiazepine Sedatives (i.e., zolpidem, zopiclone) should be avoided due to increased risk with chronic use and use of melatonin requires further research.14
    • Depression: Use serotonin reuptake inhibitors (SSRIs) rather than tricyclic antidepressants (TCADs). If TCADs must be used, nortriptyline and desipramine are preferred. Psychostimulants, such as methylphenidate improve the symptoms of depression rapidly, but must be titrated against their adverse effects.
    • Chronic pain: Acetaminophen is first line, followed by NSAIDs if pain is not controlled effectively. NSAIDs should be given for a short period of time during flares due to their established renal, gastrointestinal and cardiovascular side effects. Other options include topical medications like topical NSAIDs, capsaicin and topical lidocaine. Opioids are reserved for severe pain that has failed other treatments and is titrated for lowest effective dose with extra caution due to increased half-life in this population. For neuropathic pain anticonvulsants (i.e., carbamazepine, gabapentin, pregabalin) are useful with dose adjustments required for renal impairment, serotonin-norepinephrine reuptake inhibitors (duloxetine) are generally well tolerated and tricyclic antidepressants are avoided due to side effects.  Cannabinoids have shown reduction in pain with minimal side effects but long term effects are not yet established.15
    • Weight loss: Nutritional supplements between meals and protein and calories with meals. Correct macronutrient and vitamin deficiencies. When cognition is affected, enteral feeding does not affect survival in 24 months compared to caregiver assisted feeding at meal times. Appetite stimulants are not recommended routinely and should be used with caution due to side effects. Megestrol can worsen congestive heart failure (CHF) and increase the risk of deep vein thrombosis (DVT). Dronabinol has significant central nervous system (CNS) side effects. Also consider whether depression or occult malignancy are contributory factors.
    • Vitamin D deficiency: Evaluate and supplement. There is evidence that Vitamin D preserves muscle strength and prevents falls.16
    • Anabolic agents: growth hormone, testosterone (patch or gel) and oxandrolone need to be studied further.
  • Exercise:17, 18
    • Evidence shows that exercise has beneficial effects in frail older persons improving overall physical function resulting in improved Quality of Life and ability to perform Activities of Daily Living.
    • Intensity and duration should be low for highly deconditioned older adults and progression should be individualized to individual’s tolerance and preferences.
    • Pre-Frail older adults: Minimum activity to achieve health benefits should be 150 minutes of moderate-intensity aerobic activity and two or more days of resistance training per week or 75 minutes of vigorous aerobic activity plus muscle strengthening at least two days.
    • Frail adults: Muscle strengthening and balance training preceding aerobic training. It can include unstructured activities, beginning with those the patient can actually perform with goals of increasing activity time followed by intensity.
    • Resistance training: Preserves muscle strength and physical functioning in adults.
    • Flexibility training: improves and maintains joint range of movement in older adults. Should be performed at least two days per week.
    • Balance training: Can improve or maintain physical function and reduce falls in older adults at risk. It is recommended for three or more days per week.
    • Specific medical conditions should be taken into account when prescribing an exercise program.

Coordination of care

Optimal results are achieved by comprehensive, coordinated, geriatric assessment and management using an interdisciplinary and multidisciplinary approach enacted by a team of physicians, nurses, and social workers, along with physical, occupational and speech therapists, pharmacists and nutritionists who are well versed in geriatrics and rehabilitation. When appropriate, palliative care engagement might be useful to assist with quality of life improvement and establishing goals of care.

Patient & family education

Although family and caregivers risk finances and health while providing care to the frail older adult, they tend to minimize their sacrifices. Practical assistance should be provided.

Address substance abuse among caregivers.

Screen for elder abuse and neglect.

Discuss advanced directives as well as health and financial powers of attorney.

Address spiritual and existential concerns.

Emerging/unique interventions

Prehabilitation to reduce frailty in surgical patients. Patients with frailty have worse prognosis after surgeries than those without. Prehabilitation can be used to decrease length of hospital stay and fewer postsurgical complications though adherence and compliance to the program are often barriers. Home-based pre-operative exercise programs are under investigation19 and due to the Pandemic, Telehealth delivered prehabilitation programs that also incorporate nutritional and psychological counseling have been well received.20

Translation into practice: practice “pearls”/performance improvement in practice (PIPs)/changes in clinical practice behaviors and skills

  1. Measurement of weight, gait speed, grip strength should be done on follow-up and routine visits.
  2. Obese persons can also be frail if they manifest the physical decline and vulnerability characteristic of frailty.
  3. Vitamin D supplementation is effective for fall prevention and improving balance.
  4. Exercise is curative, gives symptom relief in pain and improves cognition and mood.
  5. Evidence based management strategies must factor in the person’s life expectancy along with the benefits and risks of intervention.
  6. Secondary prevention and disease management of comorbid conditions is key to managing frailty.
  7. Management should include symptom relief for pain in all stages and palliative strategies in the pre-terminal patient.

Cutting Edge/Emerging and Unique Concepts and Practice

Cutting edge concepts and practice

The universal and standardized prescription of exercise, including balance training is an emerging paradigm in the rehabilitation of fragility. Yoga and tai chi enhance balance and reduce falls when cognition is intact.

Standardized exercise prescriptions for the elderly and use of electronic medical records should be implemented.

Pharmacologic interventions under investigation include: myostatin antagonists (bimagrumab and humanized monoclonal antibody LY 2495655) to increase lean appendicular body mass and grip strength; selective androgen receptor modulators (SARM) such as GTx-024 (Enobosarm) to maximize anabolic effects on both muscle and bone without androgenic effects on other tissues; Ghrelin, a peptide in the stomach, stimulates growth hormone production, and increased muscle mass and appetite.21, 22

Frailty as a vital sign for older adults with comorbidities: Frailty is increasingly being recognized as a marker for prognosis for cardiovascular disease, oncology, and success from surgery. Routine screen for frailty to enhance perspectives of risks, decision-makings for treatments are being implemented.23

Gaps in the Evidence-Based Knowledge

Optimal exercise program in regards to frequency, type of exercise and duration is not yet known or if it results in improvements to Activities of Daily Living and Quality of Life.

References

  1. Fedarko NS. The biology of aging and frailty. Clin Geriatr Med. 2011;27(1):27-37.
  2. Dent E, Kowal P, Hoogendijk EO. Frailty measurement in research and clinical practice: A review. Eur J Intern Med. 2016;31:3-10.
  3. Fried LP, Tangen CM, Walston J, et al. Frailty in older adults: Evidence for a phenotype. J Gerontol A Biol Sci Med Sci. 2001;56(3):M146-56.
  4. Ensrud KE, Ewing SK, Taylor BC, et al. Comparison of 2 frailty indexes for prediction of falls, disability, fractures, and death in older women. Arch Intern Med. 2008;168(4):382-389.
  5. Woods NF, LaCroix AZ, Gray SL, et al. Frailty: Emergence and consequences in women aged 65 and older in the women’s health initiative observational study. J Am Geriatr Soc. 2005;53(8):1321-1330.
  6. Soysal P, Stubbs B, Lucato P, et al. Inflammation and frailty in the elderly: A systematic review and meta-analysis. Ageing Res Rev. 2016;31:1-8.
  7. Shore WS, DeLateur BJ. Prevention and treatment of frailty in the postmenopausal woman. Phys Med Rehabil Clin N Am. 2007;18(3):609-21, xii.
  8. Ko FC. The clinical care of frail, older adults. Clin Geriatr Med. 2011;27(1):89-100.
  9. Yao X, Li H, Leng SX. Inflammation and immune system alterations in frailty. Clin Geriatr Med. 2011;27(1):79-87.
  10. Walston J, McBurnie MA, Newman A, et al. Frailty and activation of the inflammation and coagulation systems with and without clinical comorbidities: results from the Cardiovascular Health Study. Arch Intern Med. 2002;162(20):2333. 
  11. Elsawy B, Higgins KE. The geriatric assessment. Am Fam Physician. 2011;83(1):48-56.
  12. Stuck AE, Iliffe S. Comprehensive geriatric assessment for older adults. BMJ. 2011;343:d6799.
  13. Arjunan, A. Peel, N, Hubbard, R. Gait Speed and Frailty Status in Relation to Adverse Outcomes in Geriatric Rehabilitation. Arch Phys Med Rehabil 2019;100:859-64
  14. Patel D, Steinberg J, Patel P. Insomnia in the Elderly: A Review. J Clin Sleep Med. 2018;14(6):1017-1024. Published 2018 Jun 15. doi:10.5664/jcsm.7172
  15. Ali A, Arif AW, Bhan C, Kumar D, Malik MB, Sayyed Z, Akhtar KH, Ahmad MQ. Managing chronic pain in the elderly: an overview of the recent therapeutic advancements. Cureus. 2018 Sep 13;10(9).
  16. Montero-Odasso M, Duque G. Vitamin D in the aging musculoskeletal system: an authentic strength preserving hormone. Mol Aspects Med. 2005;26(3):203. 
  17. Campbell, E. Petermann-Rocha, F, Welsh, P, et al. The effect of exercise on quality of life and activities of daily life in frail older adults: A systematic review of randomized control trials. Experimental Gerontology 147 (2021) 111287.
  18. Lee PG, Jackson EA, Richardson CR. Exercise Prescriptions in Older Adults. Am Fam Physician. 2017 Apr 1;95(7):425-432. PMID: 28409595.
  19. Home-based Prehabilitation for Elderly Patients (TRAilty). ClinicalTrials.gov Identifier: NCT03964363
  20. Wu F, Rotimi O, Laza-Cagigas R, Rampal T. The Feasibility and Effects of a Telehealth-Delivered Home-Based Prehabilitation Program for Cancer Patients during the Pandemic. Curr Oncol. 2021 Jun 17;28(3):2248-2259. doi: 10.3390/curroncol28030207. PMID: 34204531; PMCID: PMC8293185.
  21. Morley JE. Pharmacologic options for the treatment of sarcopenia. Calcif Tissue Int. 2016;98(4):319-333.
  22. Angulo J, El Assar M, Rodriguez-Manas L. Frailty and sarcopenia as the basis for the phenotypic manifestation of chronic diseases in older adults. Mol Aspects Med. 2016;50:1-32.
  23. Forman DE, Alexander KP. Frailty: A vital sign for older adults with cardiovascular disease. Can J Cardiol. 2016;32(9):1082-1087.

Original Version of the Topic

Deepthi S. Saxena, MD. Geriatric Frailty. 12/27/2012

Previous Revision(s) of the Topic

Philippines Cabahug, MD, Mi Ran Shin, MD. Geriatric Frailty. 4/3/2017.

Author Disclosure

Marielisa Lopez, MD
Nothing to Disclose