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E. Patrizio1, R. Calvani2, E. Marzetti2,3, M. Cesari4

1. Azienda di Servizi alla Persona Istituti Milanesi Martinitt e Stelline e Pio Albergo Trivulzio, Milan, Italy; 2. Fondazione Policlinico Universitario «Agostino Gemelli» IRCCS, Rome, Italy; 3. Università Cattolica del Sacro Cuore, Institute of Internal Medicine and Geriatrics, Rome, Italy; 4. Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.
Corresponding author: Enrica Patrizio, Azienda di Servizi alla Persona Istituti Milanesi Martinitt e Stelline e Pio Albergo Trivulzio, Milan, Italy, Email: patrizio.enrica@gmail.com

J Frailty Aging 2020;in press
Published online November 24, 2020, http://dx.doi.org/10.14283/jfa.2020.61



The evaluation of the physical domain represents a critical part of the assessment of the older person, both in the clinical as well as the research setting. To measure physical function, clinicians and researchers have traditionally relied on instruments focusing on the capacity of the individual to accomplish specific functional tasks (e.g., the Activities of Daily Living [ADL] or the Instrumental ADL scales). However, a growing number of physical performance and muscle strength tests has been developed in parallel over the past three decades. These measures are specifically designed to: 1) provide objective results (not surprisingly, they are frequently timed tests) taken in standardized conditions, whereas the traditional physical function scales are generally self- or proxy-reported measures; 2) be more sensitive to changes; 3) capture the real biology of the function through the assessment of standardized tasks mirroring specific functional subdomains; and 4) mirror the quality of specific mechanisms underlying more complex and multidomain functions. Among the most commonly used instruments, the usual gait speed test, the Short Physical Performance Battery, the handgrip strength, the Timed Up-and-Go test, the 6-minute walk test, and the 400-meter walk test are widely adopted by clinicians and researchers. The clinical and research importance of all these instruments has been demonstrated by their predictive capacity for negative health-related outcomes (i.e., hospitalization, falls, institutionalization, disability, mortality). Moreover, they have shown to be associated with subclinical and clinical conditions that are also not directly related to the physical domain (e.g., inflammation, oxidative stress, overall mortality). For this reason, they have been repeatedly indicated as markers of wellbeing linked to the burden of multiple chronic conditions rather than mere parameters of mobility or strength. In this work protocols of the main tests for the objective assessment of physical function in older adults are presented.

Key words: Physical function, physical performance, gait speed, muscular strength, comprehensive geriatric assessment, older adults.



The aging of the global population is accompanied by an epidemiological transition from infectious and communicable diseases to a growing burden of chronic diseases. Health status in older persons is determined by the complex interaction of multiple factors (multiple chronic diseases, psychological, social, and environmental factors), that is not captured by traditional paradigms based on the concept of standalone diseases. The most common manifestation of poor health status in this population is represented by the loss of functioning, decrease in the autonomy of mobility and activities of daily living (ADLs), till the onset of disability and dependence (1, 2).
The Comprehensive Geriatric Assessment (CGA), evaluating not only the presence of diseases, but also the individual’s functions (intended both as physical and cognitive abilities), psychological factors, and social aspects, is a diagnostic and therapeutic process able to objectively define the health status of the frail older individual and support the design of tailored plans of intervention (3).
Loss of muscle strength and decline of physical performance are critical elements to consider in the detection of important age-related conditions. The definition of physical frailty usually includes measurements of handgrip strength and gait speed. Consistently, physical performance measures, as gait speed, Timed Up-and-Go (TUG) test, and the Short Physical Performance Battery (SPPB) are useful instruments for the screening of frailty in the general population (4). The European Working Group On Sarcopenia In Older People (EWGSOP2) recently published the updated diagnostic criteria for sarcopenia, that include poor muscle strength, and reduced physical performance to define the presence of sarcopenia and quantify its severity, respectively (5–7).
A recent position paper of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) working group on frailty and sarcopenia proposed a standardization of the clinical assessment of muscle function and physical performance in order to promote the diagnosis of these conditions and facilitate the design of care programs (8). Muscle strength was defined as “the amount of force a muscle can produce with a single maximal effort”. Physical performance, on the other side, is considered a rather multidimensional concept, a function of the whole body, resulting from the functioning of multiple organs and systems (e.g., musculoskeletal, cardiovascular, respiratory, central and peripheral nervous systems). Hence, poor physical performance can be considered an early marker of frailty and subclinical diseases. Muscular strength and physical performance measures are related to pathophysiological conditions (i.e., atherosclerosis, inflammation, reduction of aerobic capacities), and are proved to predict the risk of healthcare use (i.e., hospitalizations, institutionalization) and adverse events (i.e., falls, cognitive decline, disability, death) (9–12). At the same time, these measures may represent a target and marker of efficacy for preventive interventions, such as rehabilitative and physical activity programs, being sensitive to changes of the health status. Such predictive capacity is confirmed across large and different populations. Furthermore, being these tests very clinical-friendly, they have been gradually embraced in the daily routine by different disciplines and settings, from the primary care to oncology, from cardiology to surgery, in order to support the diagnostic and therapeutic process (13–16).
In the last years, a number of measures and tools have been developed for the assessment of physical function. The aim of this paper is to describe standard procedures guiding the administration of the most important measures of strength and physical performance. In particular, we here present how to administer the handgrip strength test, the gait speed test, and the 400-meters walking test (17–19). Other important and well-established instruments, as the SPPB and the TUG test are not object of the present work as detailed instructions and video tutorials are already available (https://sppbguide.com/, and https://youtu.be/BA7Y_oLElGY respectively) (20, 21).



The protocols here presented are routinely part of a standard geriatric evaluation and do not require any authorization by institutional human research ethics committees. All patients can undergo the following tests. Exclusion criteria are specified within each protocol.

Handgrip strength test

To perform the test, a regularly calibrated, handheld hydraulic dynamometer is recommended (the JAMAR dynamometer is considered the gold standard). Use the same chair for every measurement. Subjects reporting current flare-up of pain in the wrist or hand or has recently undergone to surgery of the hand or wrist should not be tested on the affected side.

1 Seat the participant in a standard chair. Instruct to place forearms resting on the arms of the chair, with wrist just above the end of the arm of the chair. Tell to keep the hand in a neutral position, with the thumb pointing upwards.
2 Show the subject how to use the dynamometer. Place your hand around the handle, putting the base with the thumb on one side, and the other four fingers on the other. Tell the participant that he/she will not feel the grips moving when squeezing but the device is working and measuring his/her strength. Demonstrate the subject that the tighter the grip, the better score is registered by the instrument. Caution the participant that the dynamometer is quite heavy.
3 Place the adjustable handle of the dynamometer in the second position from the inside, unlocking the clip located on the lower post and fitting the adjustable handle on the second space between the teeth of the post.
4 Give the dynamometer to the participant and make sure that the grip bars are at the correct distance (with the fixed handle resting in the middle of the palm and the movable part in the center of the four fingers). If the handle seems to be too large or narrow to allow the patient to squeeze comfortably, remove the dynamometer and adjust, widening or tightening the handle.
5 Support the base with the palm of the hand while the subject holds the dynamometer, being careful not to limit its movement. Allow the participant to try to squeeze to familiarize with the instrument.
6 Check that the peak needle is set to zero. If it is not, rotate counter-clockwise the small caster in the middle of the gauge to move it to zero.
7 Start the test with the right hand. Invite the participant to squeeze the handle as strongly as possible. Use standard encouragement to highly motivate the participant during the test (e.g. «Squeeze, squeeze, harder!»). Ensure the participant maintains the maximum isometric effort for at least 3-5 seconds. When the needle stops rising, invite the participant to stop squeezing.
8 Read grip strength in kilograms from the outside dial and record the result to the nearest 1 kg. After each reading, reset the peak needle to zero. Repeat the measurement at the left hand. Obtain three readings in total for each hand, alternating the sides. Allow 10 seconds rest between each measurement.
Note: the peak-hold needle automatically records the maximum result. The gauge presents two dials, the inner one registers the value in lb, the outside in kg.
9 The highest reading of the 6 measurements is reported as the final result. Ask for and report about the hand dominance (i.e. right, left or ambidextrous).
10 If the participant complains about pain, discontinue the test and repeat the assessment only on the other side. If pain appears at both hands, stop the test.

Gait speed

To perform the test, the subject should wear comfortable clothes and shoes (with low heels for women). Only a single straight cane may be used during the walk. If the person can walk a short distance without it, should be encouraged to do so. If a person is unable or uses a walker, he/she should be considered as presenting mobility disability. As such, although the test can still be conducted with the use of the device, the meaning of the results for this specific geriatric outcome might be of limited value.
1 To perform the test, get a stopwatch and mark a 4-meter track along a flat floor. Ensure that the walking course is devoid of obstacles and include at least an extra meter at each end (Figure 1).
2 Encourage the person to walk without using any assisting devices. During the test watch particularly closely participants who normally use them, to prevent falls.
3 Instruct the participant to stand with both feet touching the starting line, and to start walking at usual pace over the 4-meter course, after a verbal command (“Go”). The assessor will then show how to perform the test to the participant, again stressing the request of walking at usual pace without running.
Note: The individual should not be aware where the goal line is placed in order to avoid a possible reduction of the pace when approaching to it. However, the tape on the floor might provide an implicit goal to the participant. For this reason, the participant might be instructed at walking well past the line on the floor.
4 During the walk stay to the side and slightly behind the subject, outside of the participant’s visual field, in order not to set the pace, but remaining in a good position for the safety of the person.
5 Begin timing when the first foot starts to move across the starting line, and stop when the first foot crosses the 4-meter mark. Do not start the watch when saying the verbal command, but when the participant actually begins to move. Do not stop timing if the foot lands on the line but does not completely cross it.
6 Report the time of execution of the test and calculate the gait speed. Repeat the test a second time and use the fastest time as result.
Note: If there is a problem with the stopwatch or the examiner is not sure of the timing, the test should be repeated.

Figure 1
4-meter walking test. The walking course should be unobstructed. Timing begins when the first foot starts to move across the starting line, and should be stopped when the first foot crosses the 4-meter mark


400-meter walking test

To perform the test, the subject should wear comfortable clothes and shoes (with low heels for women). During testing, the use of walk assistive devices, other than a single straight cane, is not allowed. If the subject does not feel safe attempting the walking course without aids (i.e. walker, quad cane, crutch), do not administer the test.
The assessor must be completely familiar with the test procedures and practice before attempting to administer the test to a participant. Procedures should be clearly demonstrated to the participants before performing the test and they should be queried to ensure that they understand the instructions. To ensure reproducibility, it is imperative that all participants are given the same instructions and that quantitative measurements associated with the tests are made in a uniform manner.
1 Identify a 20-meter long track by marking it with small traffic cones. Make sure that the walking path is not obstructed and include at least an extra meter at each end. Get a stopwatch and position two standard chairs along the walking course in order to allow the subject to rest during the test, if necessary (Figure 2).
2 Conduct the subject to the starting line and instruct to stand in a still position behind the line. It is important to clarify the goal of the test to the participant, i.e. to complete the 400-meter course.
3 Before starting the test measure the radial pulse for 30 seconds and blood pressure.
4 Instruct the subject to walk at usual pace, without overexerting, back-and-forth the 20-meter track for ten times, in order to allow the participant to plan the activity and consequently organize the walking pace according to his/her own reserves.
5 When participant indicates to feel ready to begin, proceed with the test. Instruct the individual to start to walk down the corridor at the command “Go”, and turn around the traffic cones, generating a continuous loop. Start timing when the participant takes the first step.
6 Stay by the side and just behind the participant, outside the subject’s visual field, during the walk. Be close enough to be able to support the participant if manifests difficulty or risks to fall, but not so close to dictate the pace.
7 When the 4rth lap is completed, ask the participant to report the perceived exert, and record the corresponding score of the Borg index for dyspnea.
Note: The test should be conducted at usual pace and the final goal is to complete the 400-meter course and not to reach the maximal effort. The participant should not overexert, therefore, if the participant reports “hard” or “very hard” should be invited to reduce the effort. The measurement of vital signs (radial pulse and blood pressure) before starting and at the end of the test, as well as the administration of the Borg scale after 4 laps and at the end of the test provide additional information useful to guarantee the participant’s safety and provide insights about the undergoing aerobic stress.
8 At the end of each lap (20-meter back and forth), encourage the subject with standardized phrases and count the number of completed and remaining laps.
9 Provide the participant the cane if he/she asks for it during the test, or has the evident necessity to use it to complete the walk.
10 Allow the participant to stop the walk to rest at any time, but not to lean against the wall, other surface (desk, counter, etc.), or sit. After 30 seconds, ask the participant if he/she can continue walking. If it is possible, continue the test, otherwise another 30 seconds of rest, in standing position, are allowed. If the subject is unable to continue after a 60-second rest or needs to sit down, stop the test.
Note: There is no limit to the number of rest stops as long as they can complete the walk without sitting.
11 Stop the stop-watch when the participant completes 400 meters (10 laps, first foot touching the floor beyond the finish line) or after 15 minutes, even if the participant has not covered all the distance. Record the time or, in the second case, measure the accomplished distance.
12 Immediately stop the test if participant reports chest pain or tightness, dyspnea, feeling faint, dizzy, or lower limbs pain.
13 At the end of the test, record the Borg index score, the sitting radial pulse for 30 seconds and blood pressure. Record the number, timing, and reasons for the rest stops (fatigue, chest pain, feeling faint or dizzy, shortness of breath, or other).

Figure 2
400-meter walking test. A 20-meter long track should be identified by marking it with small traffic cones. The participant has to walk at usual pace back-and-forth the 20-meter track for ten times, turning around the traffic cones in a continuous loop. The two chairs should be positioned by the side of the walking course, in order to not obstruct the track, but close enough to be rapidly reached if the subject needs to rest and sit during the test


Importance and predictive value of the presented tests

Low grip strength was found to be associated with slow gait speed, incident dismobility, disability, functional dependence, cognitive impairment, depression, cardiovascular diseases, hospital admission, and mortality (all-cause mortality, cardiovascular and non-cardiovascular mortality), in both sexes and independently of age and comorbidities (22–25). This relationship is confirmed across different populations and times of follow-up. Rantanen and colleagues studied the relationship between the handgrip strength with incident mobility and functional limitations in a large population (8,006 men from the Honolulu Heart Program and the Honolulu Asia Aging Study) aged at baseline 45-68 years old, with a 25 years follow-up (26). They found a strong association between the muscle strength in midlife and the risk of becoming disabled over the long-term follow-up. The strongest participants (i.e., >42.0 kg) had a significantly better risk profile when compared with those with poorest results at the handgrip, even after adjustment for a number of confounding conditions (Table 1). These results may be explained by greater physiological reserves in these subjects. Dodds and colleagues recently pooled data of grip strength from 8 different studies conducted in Great Britain on the general population. A total of 49,964 persons were considered to produce life-course nomograms of handgrip strength. The generated curves described a three period-evolution, with an increase to peak in early adulthood (i.e., 51 kg between 29-39 years old for men, and 31 kg between 26-42 years old for women), broad maintenance through to midlife, and a declining phase at older age (27). Different cut points were identified in the literature for poor handgrip strength, ranging from 16 to 21 kg for women and 26 to 30 kg for men, defining the risk of adverse events. Values adjusted for BMI or height also exists (23). The EWGSOP proposed values for poor grip strength <27 kg for men and <16 kg for women (7). Data on sensitivity to change in grip strength are still limited and inconsistent, a change of 6 kg was proposed to be significant. Some studies considered also the effect size (difference between the mean/median values of grip strength at baseline and after an intervention, divided by the standard deviation/inter-quartile range of the baseline measurement), and a value of 0.2–0.5 has been considered as indicative of low responsiveness, 0.51–0.8 of moderate responsiveness, and >0.8 of high responsiveness (17).

Table 1
Relationship between the handgrip strength with incident mobility and functional limitations. Adapted from Rantanen
et al. JAMA 1999

Results from multiple logistic regressions testing the predictive capacity of midlife grip strength for functional limitation and disability at advanced age (n=3,218); highest tertile used as reference group. Adjusted for age, weight, height, education, occupation, smoking, physical activity, and chronic conditions (i.e., arthritis, chronic obstructive pulmonary disease, coronary heart disease, stroke, diabetes, and angina).


Gait speed is a strong predictor of negative health outcomes, independently of the presence of common medical conditions and disease risk factors. Many studies demonstrated a strong association with incident disability (intended both as loss of ADL independency and dismobility), cognitive decline and dementia, falls and related fractures, mortality, and healthcare utilization (e.g., hospitalization and institutionalization) (11, 18, 28). Although tested in very different populations (e.g., inpatients and outpatients, independent, frail, and disabled subjects), different walking distances, and studied outcomes, the prognostic value is very consistent (Table 2). Studenski and colleagues studied the relationship between gait speed and mortality in a pooled population of 34,485 community-dwelling older people derived from 9 studies (Cardiovascular Health Study, Health, Established Populations for the Epidemiological Study of the Elderly, Aging and Body Composition study, Hispanic Established Populations for Epidemiological Study of the Elderly, InCHIANTI Study, Osteoporotic Fractures in Men, Third National Health and Nutrition Examination Survey, Predicting Elderly Performance, Study of Osteoporotic Fractures). The Authors found an overall HR for survival per each 0.1 m/s faster gait speed of 0.88 (95% CI, 0.87-0.90; P <0.001) confirmed after further adjustment for sex, BMI, smoking status, systolic blood pressure, diseases, prior hospitalization, and self-reported health (overall HR 0.90; 95% CI, 0.89-0.91; P <0.001). They also estimated the median life expectancy based on sex, age, and gait speed, providing a sort of nomograms (29). The value of 0.8 m/s for a 4-meter distance was found to identify frail patients with a high sensitivity (0.99), moderate specificity (0.64), and a high negative predictive value (0.99), and has been chosen by the EWGSOP2 as cut-off to diagnose severe sarcopenia (7, 30). At the same time, in their systematic review of the literature, Abellan van Kan and colleagues identified multiple cut-points of gait speed related to adverse outcomes, categorizing older people as slow (<0.6 m/s), intermediate (0.6-1.0 m/s), and fast (>1.0 m/s) walkers, demonstrating a continuum gradient of risk ranging from very fit to mobility impaired subjects (11). Furthermore, gait speed at usual pace in a 4-meter walk demonstrated also to be sensible to changes, with 0.05 m/s defining a minimally significant change and 0.1 m/s indicating a substantial change, with a corresponding reduction of 17.7% in absolute risk of death when increases of this value (31).

Table 2
Gait speed and ADL or mobility disability. Adapted from G. Abellan Van Kan et al.
The Journal of Nutrition, Health & Aging, 2009

* These studies analyzed the risk of disability considering gait speed variation rather than a specific cutpoint, as mentioned in the last column of the table; Health ABC study: Health Aging and Body Composition study, CHS: Cardiovascular Health Study, WHAS-I: Women’s Health and Aging Study, Hispanic EPESE: Hispanic Established Population for the Epidemiological Study of the Elderly, RR: relative risk, HR: hazard ratio, OR: odds ratio, ADL: activity of daily living.


The ability to perform the 400-meter walking test in less than 15 minutes defines the presence of mobility disability. This distance, corresponding to the length of about two blocks in the United States, is considered the minimum walking distance needed to have an independent life. The limit of 15 minutes, corresponds to a gait speed of 0.4 m/s, proven to be incompatible with functional autonomy. This instrument has a strong predictive capacity for development of negative health events (disability, mortality). Although this test is mostly used as a dichotomous indicator (presence/absence of mobility disability), its predictive capacity has been established also in relation to some of the parameters characterizing specific aspects of the performance (e.g., mean gait speed, number of stops to rest). Vestergaard and colleagues studied the differences in mortality and functional impairment rates during a 3- and 6-year follow-up period in the InCHIANTI Study population, analyzing the walking time and the variability in lap time. They found these factors to be both a short- and long-term predictors of mortality, and rest stopping mostly a long-term predictor of mortality (Table 3) (32). In a second study, based on the LIFE-P study, they found that the risk of mobility disability at follow-up was higher in those taking longer to complete the baseline 400-MWT and among those who needed to rest during the test (risk adjusted for age, sex, and clinic site: OR 5.4; CI 2.7–10.9) (33).

Table 3
Risk of death according to 400-meter walk test characteristics. Adapted from Vestergaard et al. Rejuvenation research, 2009

The model is adjusted for age, sex, Mini Mental State Examination score, symptoms of depression, education, smoking, body mass index, being sedentary, number of comorbid conditions (max 10, hypertension, coronary heart disease, congestive heart failure, stroke, peripheral artery disease, diabetes, pulmonary disease, hip fracture, cancer, arthritis), and SPPB score; HR: Hazard Ratio, CI: Confidence interval



The protocols presented in this paper are an attempt to standardize the methods of administration of these measures, in order to provide comparable results. Although there is not a unique way to conduct the here described assessments, given the different clinical settings and research protocols in which they can be applied, some steps are recognized as critical and able to affect results.
The absolute values and precision of grip strength measurements can be influenced by aspects of the protocol, such as hand size and dominance, posture (of the whole body and position of joints of the upper limb), provided encouragement, and the use of the maximum or the mean grip strength values (17). The observance of definite instructions in these steps, as already highlighted in the review of Roberts and colleagues, is crucial to ensure homogeneous measures and the training of the examiner assume a special importance to guarantee the reliability of the test (17). Taken with a handheld hydraulic dynamometer, the handgrip strength test demonstrated to have a good test–retest reliability (Intraclass Correlation Coefficient, ICC ≥ 0.85) and an excellent inter-rater reliability (ICC 0.95–0.98) (8, 17). The use of a handheld hydraulic dynamometer (units in Kg) is, therefore, considered the gold standard, but, for patients with upper extremity impairment or musculoskeletal deformations or diseases (as rheumatoid arthritis, osteoarthritis, or carpal tunnel syndrome), may not guarantee an accurate measure of muscle strength and may lead to underestimations, because it can cause stress on weak joints. Other available instruments are pneumatic, which measure grip pressure, mechanical, and strain dynamometer. The dynamometer should be calibrated at least once per year.
Elements of variability in the execution of gait speed test are walk distances (4, 6, or 10 meters, 8 or 15 foots), a static or dynamic start for walking, the usual or maximal gait speed, and the use of walking aids. A distance of 4 meters has been demonstrated to be feasible in different clinical settings, with a better accuracy compared to shorter walks. Moreover, the same distance is one of the components of the SPPB, allowing to deduce comparable measures from the whole battery (11). However, the test is characterized by a ceiling effect in high functioning persons with a high baseline walking speed (8). For these reasons, longer versions of the gait speed test (e.g., using 6- or 10-meter tracks) have been developed and validated in the literature for allowing a better discrimination of results in very fit individuals. Given the growing use of photocell-based systems of measurement, the method here proposed give the chance to have comparable results. Timing can also be measured differently from how we presented in the protocol, as starting and stopping the watch when the foot lands beyond the starting and finish lines. Moreover, some studies report measures of gait speed in full movement, starting the time measurement after the first two meters of walking. However, including the phase of acceleration provides information regarding subject’s abilities of coordination and movement planning, that are influenced by conditions frequently affecting older persons (i.e. Parkinson disease and other movement disorders). In the systematic review of the literature conducted by Peels and colleagues, the use of a moving start showed no significant difference in gait speed compared to a static start. They also found in a single study that subjects using a walking aid (cane) have a slower gait speed compared to those without (34).
To ensure the reproducibility of the 400-meter walking test, the training of the examiner is critical, in order to provide the same instructions and encouragement to participants, and to avoid to affect the results of the test dictating the pace during the walk. To ensure the correct execution the assessment, is also important to respect the provided timing for the stop rest and for the whole test. Moreover, the possibility to use walking aids and to warm up can influence the performance. The 400-meter walking test also demonstrated a high test-retest reliability, but it is mostly applied in research setting, requiring a higher administration time and a bigger space to be performed. On the other hand, being a dichotomous measure able to identify mobility disability, it provides an important and easy-to-understand indication of fitness of the subject, useful to address treatments or other tailored interventions (35).
The hand-grip strength test has been found to correlate with strength of other muscle groups, thus a good indicator of overall strength. The sensitivity to changes of the gait speed, together with an excellent test-retest and inter-rater reliability (ICC, 0.96-0.98) make gait speed a good marker for efficacy of intervention programs and treatments. Test-retest reliability of gait speed has been confirmed across different populations, from healthy older adults, people with comorbidities, to patients affected by stroke, cardiovascular disease, COPD. Compared to other tests (SPPB, chair stand test), gait speed has a stronger or similar predictive capacity for adverse events (ADL and mobility disability, hospitalization, health decline). Composite measures, as the SPPB, may have a better prognostic value, especially for high performance subjects (10, 11). Moreover, a walking speed less than 0.5 m/s is highly predictive of inability to perform the 400-meter walking test. Being very easy to perform, even in restricted places, and with minimal risk, it may be used as an alternative indicator of mobility disability when the performance of the 400-meters walking test is not possible (35).
In conclusion, the strong predictive capacity for adverse outcomes of muscle strength and physical performance measures as well as the reliability and the high feasibility of these tools make them suitable for supporting clinical and research decisions. In particular, the assessment of these measures may support the development of person-tailored interventions aimed at preventing/managing age-related conditions, as frailty and sarcopenia. These measures can both identify subjects at risk (who may benefit from tailored interventions), especially in primary care, but also serve as markers for monitoring the efficacy of the decisions. The dissemination of their use in clinical and research setting with a standard procedure may permit an early application and monitoring of critical aspects of the wellbeing of older persons.


Funding: None.
Conflcit of interest: The authors have no conflicts of interest to disclose.



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18. Cesari M, Kritchevsky SB, Penninx BWHJ, et al. Prognostic value of usual gait speed in well-functioning older people – Results from the health, aging and body composition study. J Am Geriatr Soc. 2005;53(10):1675-1680. doi:10.1111/j.1532-5415.2005.53501.x
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22. Stessman J, Rottenberg Y, Fischer M, Hammerman-rozenberg A, Jacobs JM. Handgrip Strength in Old and Very Old Adults: Mood, Cognition, Function, and Mortality. J Am Geriatr Soc. 2017;(65):526-532. doi:10.1111/jgs.14509
23. Alley DE, Shardell MD, Peters KW, et al. Grip Strength Cutpoints for the Identification of Clinically Relevant Weakness. Journals Gerontol Med Sci. 2014;69(5):559-566. doi:10.1093/gerona/glu011
24. Leong DP, Teo KK, Rangarajan S, et al. Prognostic value of grip strength: Findings from the Prospective Urban Rural Epidemiology (PURE) study. Lancet. 2015;386(9990):266-273. doi:10.1016/S0140-6736(14)62000-6
25. Giampaoli S, Ferrucci L, Cecchi F, et al. Hand-grip strength predicts incident disability in non-disabled older men. Age Ageing. 1999;28(1):283-288.
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35. Rolland YM, Cesari M, Miller ME, Penninx BW, Atkinson HH, Pahor M. Reliability of the 400-M usual-pace walk test as as assessment of mobility limitation in older adults. J Am Geriatr Soc. 2004;52(6):972-976. doi:10.1111/j.1532-5415.2004.52267.x



G. Guaraldi1, S. Marcotullio2, R. Maserati3, M. Gargiulo4, J. Milic1, I. Franconi1,  A. Chirianni4, M. Andreoni5, M. Galli6, A. Lazzarin7, A. D’Arminio Monforte6, G. Di Perri8, C.-F. Perno5, M. Puoti9, S. Vella10, A. Di Biagio11, L. Maia12, C. Mussi13,
M. Cesari14, A. Antinori15


1. Modena HIV Metabolic Clinic, University of Modena and Reggio Emilia, Modena, Italy; 2. Nadir Onlus, Rome, Italy;3. Fondazione IRCCS Policlinico San Matteo, Pavia, Italy;
4. Azienda Ospedaliera D. Cotugno, Napoli, Italy; 5. Università degli Studi di Roma Tor Vergata, Roma, Italy; 6. Università degli Studidi Milano, Milano, Italy; 7. Università Vita-Salute San Raffaele, Milano, Italy; 8. Università degli Studi di Torino, Torino, Italy;9. Azienda Ospedaliera Ospedale Niguarda Ca’ Granda, Milano, Italy; 10. Istituto Superiore di Sanità – Dipartimento del Farmaco, Roma, Italy; 11. Azienda Ospedaliera San Martino, Genova, Italy; 12. Department Infectious Diseases, Centro Hospitalar do Porto, Porto, Portugal; 13. Geriatrics Division, University of Modena and Reggio Emilia, Modena, Italy; 14. Department of Clinical and Community Sciences, Università di Milano, Milan, Italy, Geriatric Unit, Fondazione IRCCS Ca’ Granda – Ospedale Maggiore Policlinico, Milan, Italy; 15. Istituto Nazionale Malattie Infettive L. Spallanzani, Roma, Italy. All members of the Italian HIV Guidelines Working Group are listed in the acknowledgment section.
Corresponding author: Giovanni Guaraldi, Department of Medical and Surgical Sciences for Children & Adults, University of Modena and Reggio Emilia, Via del Pozzo 71, 41124 Modena, Italy. Tel: +39-0594225318; Fax: +39-0594333710; E-mail: giovanni.guaraldi@unimore.it

J Frailty Aging 2018;in press
Published online November 29, 2018, http://dx.doi.org/10.14283/jfa.2018.42



Objective: This article deals with the attempt to join HIV and geriatric care management in the 2017 edition of the Italian guidelines for the use of antiretrovirals and the diagnostic-clinical management of HIV-1 infected persons. Methods: The outlined recommendations are based on evidence from randomized clinical trials and observational studies published in peer-reviewed journals and/or presented at international scientific conferences in recent years. The principles of starting antiretroviral therapy in elderly patients and the viro-immunological goals are the same as in the general HIV population. However, there are some specificities to consider, related to the host as well as the therapy itself. HIV care in elderly patients must shift from a combined AntiRetroviral Therapy specific approach to a more comprehensive management, and from a disease-based model (list of co-morbidities) to a multi-morbidity and frailty standpoint. The implementation of a geriatric approach, based on the Comprehensive Geriatric Assessment, is essential and consists of a broader evaluation of health status. This multidimensional and multidisciplinary evaluation is focused on the development of a tailored intervention plan. Polypharmacy is a frequent condition in the older population and an independent risk factor for negative health-related outcomes. This can be overcome with a multidisciplinary and cooperative approach involving HIV specialists, geriatricians and primary care physicians. Conclusion: The inclusion of geriatric care becomes necessary due to the novel needs of an evolving patient population. It is important to underline that the HIV specialist will continue to lead multidimensional interventions and optimize quality of care for HIV-positive people.

Keywords: Comprehensive geriatric assessment, frailty, HIV, guidelines.



In the context of the global ageing epidemic, HIV infection is not an exception, but rather a paradigm of this relatively new phenomenon. The greying of people living with HIV is – everywhere – part of the HIV landscape (1), arising from two phenomena: the general effectiveness of antiretroviral therapy and the increasing mean age of HIV acquisition (2).
Future projections of the evolving demographics clearly indicate that HIV care will intersect with geriatric medicine (3). This is not merely the result of an age shift. In fact, antiretroviral drugs, patients and, consequently, the disease itself have changed and continue to evolve:
1. Antiretroviral treatment has changed. Drug potency, genetic barriers as well as short- and long-term toxicities have been the determinants of HIV-therapy success/failure during the early Highly Active AntiRetroviral Therapy (HAART) era. Antiretroviral regimens have become more effective and less toxic. Thus, in HIV-negative people aware of their HIV risk, the probability of morbidity and mortality might be lower in the future. This is due to early detection through the efficient continuum of care resting on wise networking strategies.
2. Patients have changed. HIV-infected people have experienced a dramatic improvement in life expectancy during the modern combined antiretroviral therapy (cART) era, particularly those who initiated therapy at earlier stages of the disease (4). Several recent cohort studies have suggested that the life expectancy of HIV-infected individuals may soon approach that of the general population (5). At the same time, an increasing number of people is seroconverting HIV at an older age because of a lower perception of sexual risk in the elderly (6). The net result is that nowadays HIV-people display a heterogeneous clinical presentation with a substantially increased risk for comorbidities in the former group (i.e., ‘HIV-aged people’) compared to the latter (i.e., aged HIV-people) (2).
3. HIV disease itself is changing. A rapid progressive disease is evolving into a chronic condition with a substantial variation in the immunopathological driver of the disease. Immune-deficiency is leaving the room for immune-activation.
Although there is now a broad consensus that immune-activation and inflammation persist in the majority of HIV-infected individuals maintaining long-term ART-mediated viral suppression (even in those that restore normal CD4+ T cell counts) (7), the degree to which inflammation is a direct cause of morbidity and mortality remains controversial.
In this context, in the current edition of the Italian guidelines for the use of antiretroviral agents and the diagnostic-clinical management of HIV-1 infected persons (IHIVGL), the Italian Society of Infectious and Tropical Diseases, in collaboration with the Italian Ministry of Health, have included a chapter entitled: “Management of the ageing, geriatric and frail individuals with HIV”. This could be interpreted as a momentous report, given that specific sections regarding the management of geriatric HIV patients do not exist in other European guidelines.
The objective of the present article is to introduce a first attempt to join HIV and geriatric care management for all the involved healthcare professionals (in particular, geriatricians and HIV-specialists) as well as for people living with HIV and their communities. Such effort reflects the emergence of a novel “Geriatric-HIV” clinical know-how similar to what has previously occurred in other medical specialities like ortho-geriatrics (8), cardio-geriatrics (9), or onco-geriatrics (10).
These guidelines are addressing clinical needs of older adults living with HIV, in the geriatric age definition, over 65 years (according to geriatric age definition) or rather any age but only if they meet frailty criteria.
To conceptualize the age-related increase of vulnerability, the term “frailty” has been commonly used in the medical literature over the past two decades. Frailty is defined as a condition caused by the reduction of homeostatic reserves exposing the individual to higher risk of negative outcomes (11).
Frailty can be considered either as a specific syndrome (12) or as state with degrees of risk for adverse outcomes (13). It might represent much more than a mere condition to be screened for but rather an interval parameter reflecting the “biological age” of the individual. The argument further is that this could replace the obsolete criterion of chronological age in clinical decision algorithms.
In HIV setting, frailty has been operationalized both with a frailty phenotype and frailty index tools. The frailty phenotype (FP) is based on a predefined set of five criteria exploring the presence/absence of signs or symptoms (involuntary weight loss, exhaustion, slow gait speed, poor handgrip strength, and sedentary behavior). The number of criteria (a six-level ordinal variable ranging from 0 to 5) is categorized as a three-level variable depicting robustness (meets none of the criteria), pre- frailty (meets one or two criteria) and frailty (meets three or more criteria) (14).
The only frailty index tool validated in HIV cohorts comprises 37 health variables that are routinely collected at each visit (15). Each variable included in the FI is coded with a value of 1 when a deficit is present, and 0 when it is absent. Missing values are removed from both the numerator and the denominator of the FI (16). FI>0.3 has been used to identify frail individuals.
Frailty as well as falls, urinary incontinence, polypharmacy and delirium describe the so called geriatric syndromes which are multifactorial health conditions that occur when the accumulated effects of impairments in multiple systems render an older person vulnerable to situational challenges (17), posing some special clinical considerations. First, for a given geriatric syndrome, multiple risk factors and multiple organ systems are often involved. Second, diagnostic strategies to identify the underlying causes can sometimes be ineffective, burdensome, dangerous, and costly. Finally, therapeutic management of the clinical manifestations can be helpful even in the absence of a firm diagnosis or clarification of the underlying causes (18).
Geriatric syndromes are more predictive of self-reported health and mortality than diagnoses of chronic diseases or MM alone (19, 20). The majority of existing guidelines, however, remain organ system-based and do not include formal assessment for geriatric conditions (21).



The recommendations issued in IHIVGL are based on evidence from randomized clinical trials and observational studies published in peer-reviewed journals and/or presented at international scientific conferences in recent years. Controlled studies were critically evaluated, in particular by analysing their design, power, sample representativeness, primary and secondary objectives, duration of follow-up, criteria of superiority, non-inferiority and equivalence, methodology, and analytical approach. Information from safety reports drafted by regulatory authorities (FDA – Food and Drug Administration, EMA – European Medicines Agency, AIFA – Italian Medicines Agency) was also considered.
Following governance directions, the IHIVGL expert panel (subdivided into working groups) established a work-plan and drafted a preliminary text after a progressive assessment of electronic contents. Later, in a plenary session, agreements on the contents and degrees of recommendation were reached.
The experts declared their conflicts of interest specifically indicating every potential association (i.e., financial interests, research grants, participation in advisory boards, commissioned lectures at sponsored events) with companies involved in the production of antiretroviral drugs and/or diagnostic materials and/or tools for the monitoring of therapy and disease, over the last five years. LM, CM, JM, IF and MC, co-authors of this paper, are not members of the IHIVGL panel, but helped in the critical revision of the manuscript.
The present text complies with the aims in the methodological introduction to the full text of the Italian Guidelines for the use of antiretroviral drugs and the diagnostic-clinical management of people with HIV-1 infection. The present article should not be considered exhaustive compared to the full text version of the Guidelines (11) available at the website: http://www.salute.gov.it/imgs/C_17_pubblicazioni_2696_allegato.pdf.

Table 1 Degree of recommendation and level of evidence

Table 1
Degree of recommendation and level of evidence


Ageing, geriatric and frail patients

The principles of starting antiretroviral therapy in elderly patients and the viro-immunological goals are the same as in the general HIV population. However, there are some specificities to consider, related to the host as well as the therapy itself.
In particular, polypharmacy, defined as the concomitant use of five drugs or more, is a very frequent condition in the older population and an independent risk factor of negative health-related outcomes (e.g., hospitalization, institutionalization, functional impairment, malnutrition and adverse drug events) (30, 31). Moreover, age-associated physiological changes altering pharmacokinetics (i.e., decreased GI transit, increased fat-to-lean body ratio, reduced hepatic metabolism and renal elimination) (32) and pharmacodynamics may result in increased sensitivity to medications and a higher risk for adverse side effects.
Consequently, drug-drug interactions in ageing patients with polypharmacy are unavoidable. Nevertheless, they can be curtailed and managed by adopting ad hoc strategies.
In elderly HIV infected patients, a broader evaluation of health status is clearly necessary as part of a multidimensional approach characterizing the Comprehensive Geriatric Assessment (CGA). This methodology is not limited to the evaluation of the individual’s clinical conditions. Rather, it is focused on the development of tailored intervention plans. The geriatric approach is based on a multidimensional and multidisciplinary evaluation of the individual, to which every professional brings his/her own expertise and background in patient management. Consequently, functional capacity, fall risk, neurocognitive disorders and/or dementia, mood, polypharmacy, social support, and economic issues remain of special relevance in optimizing treatment goals according to personal needs (33, 34).

Table 4 reports evidence about specific points to consider in the management of older HIV patients.

Table 2 Specificities of elderly HIV patients

Table 2
Specificities of elderly HIV patients



Table 3 Specificities of the most common clinical conditions in elderly HIV patients

Table 3
Specificities of the most common clinical conditions in elderly HIV patients


Table 4 Evaluation and additional behaviours in the approach to elderly HIV patients

Table 4
Evaluation and additional behaviours in the approach to elderly HIV patients



The debate regarding accentuated or accelerated ageing processes affecting HIV patients is ongoing (41). Several factors have been proposed as detrimental contributors to the ageing process of HIV patients, including chronic inflammation, long-term ART drug toxicity, neurocognitive impairment, and a high prevalence of social and behavioural risk factors. Regardless of the causes, it is evident that HIV-positive persons are characterized by an older biological age compared to the HIV-negative population. Moreover, because elderly HIV patients are generally excluded from clinical trials (42), there is limited information on the efficacy and safety of antiretroviral regimens in this particular population.
As the HIV-positive population grows, the healthcare needs to evolve, especially for the purpose of targeting chronic and disabling conditions more effectively. HIV care must therefore enrich the straightforward ART-specific approach with elements broadening older patients’ assessment to capture their heterogeneity and complexity more accurately. Recommendations are provided to improve the so-called “HIV continuum of care”, which defines the sequential steps that people living with HIV should go through from the initial diagnosis to the achievement of viral suppression. These actions include the optimization of the HIV care environment, an increase in HIV testing and care network, treatment coverage and monitoring of viral suppression (42). It is noteworthy that HIV care is a continuum going beyond the traditional goal of viral un-detectability. So far, no guidelines have included such new paradigms in HIV management.
The new section of the IHIVGL trying to introduce a new cultural paradigm in the management of elderly HIV patients based on the following shifts in clinical perspective:
1. from the assessment of single co-morbidities to the management of multi-morbidity
2. from the assessment of organ impairment to the evaluation of functional capacity
3. from age assessment to frailty evaluation.

Taken together, clinical evaluation is not a list of multiple organ impairments to be considered as a disease status, but rather a wider and more detailed image of health status described in functional capacities.
This change in health perspective is extremely important to adapt care models to the emerging needs of HIV-infected individuals characterized by a complex composition of multi-morbidity, frailty, geriatric syndromes and disability.
The geriatric approach, based on a CGA, establishes a multidimensional and multidisciplinary evaluation of the individual, to which every professional brings his/her own expertise and background in patient management. Therefore, the interdisciplinary team members (including nurses, social workers, pharmacists, psychologists, physical therapists) concur in the evaluation of ageing patients to objectivize their needs and resources to complete a multidimensional evaluation. This work is essential to identify frail patients and to develop tailored intervention plans, indicating priorities and setting goals. The objectives of the evaluation are also changing, shifting from a restricted focus on life expectancy (i.e., the estimated number of years to live) to a broader consideration of quality of life (e.g., expected life free from disability). From this perspective, the active empowerment of patients (through improved information and involvement) becomes crucial to the prevention of negative health-related events.
This multidimensional management can be integrated in “Total Patient Care” (TPC), which results in a more comprehensive patient approach, considering their physical, emotional, social, economic, and spiritual goals (43), as well as personal reactions to illness (including the ability to meet self-care needs). It implies the transition from a model based on a single referral care centre to a coordinated and multidisciplinary network providing primary and specialized support to people living with HIV.
Central to this paradigm shift is the recognition of the need for an active partnership with primary care physicians, who remain in charge of providing proactive, preventive, and chronic care management through all stages of life. Primary care physicians could also be key players in the management of polypharmacy. This condition is common in elderly HIV patients. Consequently, these are at higher risk of drug-drug interactions between antiretroviral drugs and concomitant medications, which may compromise medication effectiveness and can be responsible for serious adverse drug events (including organ system injury, hospitalization, geriatric syndromes, and mortality). Interventions to address polypharmacy in the HIV setting are still missing and primary care physicians can help in this multidimensional approach to elderly patients, because they can share all clinical information across the entire healthcare system, using of registries, information technologies, and health information exchanges.
To conclude, it is also crucial to ensure that patients and their families receive proper education and support to actively participate in the planned care program. Patient risk factors may include social vulnerability, a predictor of mortality and disability in elderly people. In this context, HIV and Ageing stigma plays a crucial role and requires urgent action. HIV stigma is a well-known barrier for HIV testing and treatment in numerous settings, particularly in low-and-medium income countries, contingent on inequalities in social, economic, and political power (44). At the same time, many stereotypes (the so-called “Ageing Stigma”) are typically associated to the older population (e.g., needy, unhappy, senile, inactive, useless to society, not receptive). Apparently, we are indeed in the presence of an augmented risk of stigmatization due to the overlap of two detrimental phenomena, the HIV and Ageing stigmas. This aspect also requires urgent consideration.
Finally, it is important to underline that the HIV specialist will continue to lead multidimensional interventions and optimize quality of care for HIV-positive people. The progress made over the years in the fight against HIV are not underestimated here. HIV care will remain an outstanding example of healthcare management. The inclusion of geriatric care becomes necessary due to the novel needs of an evolving patient population. The collaboration between HIV specialists, geriatricians and general practitioners will follow the already existing (and successful) paradigms developed in other interdisciplinary models of geriatric care, with an utmost respect for each and every stakeholder’s expertise and background.


Acknowledgments: Institutional referees: Andreoni Massimo, Università degli Studi di Roma Tor Vergata, Roma; Chirianni, Antonio, Azienda Ospedaliera D Cotugno, Napoli. Coordinators: Antinori Andrea, Istituto Nazionale Malattie Infettive L. Spallanzani, Roma; Galli Massimo, Università degli Studi di Milano, Milano; Lazzarin Adriano, Università Vita-Salute San Raffaele, Milano. Executive commitee: d’Arminio Monforte Antonella, Università degli Studi di Milano, Milano; Di Perri Giovanni, Università degli Studi di Torino, Torino; Perno Carlo-Federico, Università degli Studi di Roma Tor Vergata, Roma; Puoti Massimo, Azienda Ospedaliera Ospedale Niguarda Ca’ Granda, Milan; Vella Stefano, Istituto Superiore di Sanità, Roma. Editorial coordinators: Di Biagio Antonio, Azienda Ospedaliera San Martino, Genova; Marcotullio Simone, Nadir Onlus, Roma. Italian HIV Guidelines Working Group: Ammassari Adriana, Istituto Nazionale Malattie Infettive L. Spallanzani, Roma; Angarano Gioacchino, Università degli Studi di Bari, Bari; Antinori Andrea, Istituto Nazionale Malattie Infettive L. Spallanzani, Roma; Armignacco Orlando, Ospedale Belcolle, Viterbo; Babudieri Sergio, Università degli Studi di Sassari, Sassari; Bini Teresa, Azienda Ospedaliera – Polo Universitario San Paolo, Milano; Bonfanti Paolo, Azienda Ospedaliera della Provincia di Lecco, Lecco; Bonora Stefano, Università degli Studi di Torino, Torino; Borderi Marco, Azienda Ospedaliera Sant’Orsola Malpighi, Bologna; Breveglieri Michele, Arcigay, Verona; Bruno Raffaele, Policlinico San Matteo, Pavia; Calza Leonardo, Università di Bologna, Bologna; Capobianchi Maria Rosaria, Istituto Nazionale Malattie Infettive L. Spallanzani, Roma; Cagarelli Roberto, Regione Emilia-Romagna, Prevenzione Collettiva e Sanità Pubblica, Bologna; Calcagno Andrea, Università degli Studi di Torino, Torino; Castagna Antonella, Ospedale San Raffaele, Milano; Castelli Francesco, Università degli Studi di Brescia, Brescia; Cattelan Anna Maria, Azienda Ospedaliera-Universitaria, Padova; Cauda Roberto, Università Cattolica del Sacro Cuore, Roma; Cingolani Antonella, Università Cattolica del Sacro Cuore, Roma; Cinque Paola, Ospedale San Raffaele, Milano; Corbelli Giulio Maria, Plus Onlus, Bologna; d’Arminio Monforte Antonella, Università degli Studi di Milano, Milano; d’Ettorre Gabriella, Università degli Studi di Roma La Sapienza, Roma; De Carli Gabriella, Istituto Nazionale Malattie Infettive L. Spallanzani, Roma; De Luca Andrea, Azienda Ospedaliera Universitaria, Siena; Università Cattolica del Sacro Cuore, Roma; Di Biagio Antonio, Azienda Ospedaliera San Martino, Genova; Di Perri Giovanni, Università degli Studi di Torino, Torino; Di Pietro Massimo, Azienda Sanitaria di Firenze, Firenze; ElHamad Issa, Azienda Ospedaliera Spedali Civili, Brescia; Errico Margherita, NPS Italia Onlus, Napoli; Gaeta Giovanni Battista, II Università di Napoli, Napoli; Galli Massimo, Università degli Studi di Milano, Milano;Gargiulo Miriam, Azienda ospedaliera D. Cotugno, Napoli; Gervasoni Cristina, Azienda Ospedaliera L. Sacco, Milano; Giacomet Vania, Azienda Ospedaliera L. Sacco, Milano; Giannini Adriana, Regione Emilia-Romagna, Prevenzione Collettiva e Sanità Pubblica, Bologna; Gianotti Nicola, Ospedale San Raffaele, Milano; Giaquinto Carlo, Azienda Ospedaliera di Padova, Padova; Girardi Enrico, Istituto Nazionale Malattie Infettive L. Spallanzani, Roma; Gori Andrea, Ospedale San Gerardo, Università di Milano-Bicocca, Monza; Grossi Paolo, Università degli Studi dell’Insubria, Varese; Guaraldi Giovanni, Università degli Studi di Modena e Reggio Emilia, Modena; Lichtner Miriam, Sapienza Università di Roma Polo Pontino, Roma; Liuzzi Giuseppina, Istituto Nazionale Malattie Infettive L. Spallanzani, Roma; Lo Caputo Sergio, Policlinico di Bari, Bari; Maggi Paolo, Policlinico di Bari, Bari; Maggiolo Franco, Ospedali Riuniti di Bergamo, Bergamo; Marchetti Giulia, Università degli studi di Milano, Milano; Marcotullio Simone, Nadir Onlus, Roma; Maserati Renato, Policlinico San Matteo, Pavia; Mastroianni Claudio, Università degli Studi di Roma La Sapienza, Roma; Matteelli Alberto, Università degli Studi di Brescia, Brescia; Mazzotta Francesco, Azienda Sanitaria di Firenze, Firenze; Menichetti Francesco, Azienda Ospedaliero-Universitaria Pisana, Pisa; Mussini Cristina, Università degli Studi di Modena e Reggio Emilia, Modena; Nozza Silvia, Ospedale San Raffaele, Milano; Oldrini Massimo, Lega Italiana per la Lotta contro l’AIDS, Milano; Parruti Giustino, Azienda Sanitaria Locale di Pescara, Pescara; Pascucci Maria Grazia, Regione Emilia-Romagna, Prevenzione Collettiva e Sanità Pubblica, Bologna; Parrella Roberto, Azienda Ospedaliera D. Cotugno, Napoli; Perno Carlo-Federico, Università degli Studi di Roma Tor Vergata, Roma; Prestileo Tullio, Ospedale Civico-Benfratelli, Palermo; Puoti Massimo, Azienda Ospedaliera Ospedale Niguarda Ca’ Granda, Milano; Puro Vincenzo, Istituto Nazionale Malattie Infettive L. Spallanzani, Roma; Rancilio Laura, Caritas Italiana, Milano, Ravizza Marina, Azienda Ospedaliera – Polo Universitario San Paolo, Milano; Rezza Gianni, Istituto Superiore di Sanità – Dipartimento di Malattie Infettive P.I., Roma; Rizzardini Giuliano, Azienda Ospedaliera L. Sacco, Milano; Rusconi Stefano, Università degli Studi di Milano, Milano; Santoro Maria, Università degli Studi di Roma Tor Vergata, Roma; Sighinolfi Laura, Azienda Ospedaliero – Universitaria di Ferrara, Ferrara; Stagnitta Maria, Coordinamento Nazionale delle Comunità di Accoglienza, Firenze; Starnini Giulio, Ospedale Belcolle di Viterbo, Viterbo; Tamburrini Enrica, Università Cattolica del Sacro Cuore, Roma; Tambussi Giuseppe, Ospedale San Raffaele, Milano; Tavio Marcello, Azienda Ospedaliero-Universitaria Ospedali Riuniti di Ancona, Ancona; Torti Carlo, Università Magna Graecia, Catanzaro; Vaccher Emanuela, Centro di Riferimento Oncologico di Aviano, Aviano; Viscoli Claudio, Università di Genova, Genova; Visintini Raffaele, Ospedale San Raffaele, Milano; Vullo Vincenzo, Università degli Studi di Roma La Sapienza, Roma; Zaccarelli Mauro, Istituto Nazionale di Malattie Infettive L. Spallanzani, Roma; Zuccotti Gian Vincenzo, Università degli Studi di Milano, Milano;
Special Acknowledgments: Rastrelli Elena, Ospedale Belcolle di Viterbo, Viterbo; Sticchi Laura, Università degli Studi di Genova, Genova.



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L.-K. CHEN1,2,3, A.-C. HWANG1,2,3, L.-K. LIU1,2, W.-J. LEE1,2,4, L.-N. PENG1,2,3


1. Aging and Health Research Center, National Yang Ming University, Taipei, Taiwan, 2. Institute of Public Health, National Yang Ming University, Taipei, Taiwan; 3. Center for Geriatrics and Gerontology, Taipei Veterans General Hospital, Taipei, Taiwan; 4. Department of Family Medicine, Taipei Veterans General Hospital Yuanshan Branch, Yi-Lan, Taiwan.
Corresponding author: Prof Liang-Kung Chen, Center for Geriatrics and Gerontology, Taipei Veterans General Hospital, No 201, Sec 2, Shih-Pai Road, Taipei, Taiwan,
TEL: +886-2-28757830, FAX: +886-2-28757711, Email: lkchen2@vghtpe.gov.tw


J Frailty Aging 2016;in press
Published online August 10, 2016, http://dx.doi.org/10.14283/jfa.2016.109



Abstract: Objective: To evaluate the prevalence of frailty and the associated multimorbidity and functional impairments among community-dwelling middle-aged and elderly people in Taiwan. Design: a cross-sectional study. Setting: communities in I-Lan County of Taiwan. Participants: 1839 community-dwelling people aged 50 years and older. Intervention: None. Measurements: Frailty defined by Fried’s criteria, Charlson’s comorbidity index (CCI), Functional Autonomy Measurement System (SMAF), Center for Epidemiologic Studies Depression Scale (CES-D), Mini-Nutrition Assessment (MNA), Mini–Mental State Examination (MMSE), and Short Form-12 quality of life questionnaire. Results: Overall, 1839 subjects (mean age: 63.9±9.3 years, 47.5% males) participated in this study and men were more likely to have higher educational level, more smoking and alcohol drinking habit. The prevalence of frailty was 6.8% in this study, while pre-frailty was 40.5% and 53.7% of all participants were robust.  Compared to subjects with different frailty status, age, education year, alcohol drinking, hypertension, diabetes mellitus, hyperlipidemia, CCI, walking speed, handgrip strength, score of SMAF, CES-D, MNA, MMSE, quality of life were significantly different between groups (P all< 0.05). Older age, poorer physical function, poorer cognitive function, poorer nutritional status, more depressive symptoms, higher CCI and poorer quality of life were all independently associated with frailty. Conclusions: Frailty was not simply a geriatric syndrome, but the combination of multiple geriatric syndromes.  Further study is needed to evaluate the clinical benefits of intervention programs for community-dwelling middle-aged and older people to reverse frailty and its associated functional impairments.


Key words: Frailty, geriatric syndrome, comprehensive geriatric assessment.



Frailty, a well-known geriatric syndrome, is featured by the vulnerable state of older people with reduced physiological reserve and increased susceptibility to adverse events health outcomes (1). A number of adverse health outcomes have been reported to be associated with frailty, such as falls, disability, hospitalizations, reduced health-related quality of life, nursing home admissions and mortality (1, 2). The reported prevalence of frailty in Taiwan varied across studies (3, 4) but it was similar to previous studies. Importantly, frailty usually was not present as an independent condition, and it frequently interacted with multimorbidity and disabilities (4). Results from previous studies disclosed that the presence of frailty may complicate the management for individual clinical conditions (5-8). Therefore, managing elderly patients with frailty in clinical settings usually needed a more comprehensive approach. Nevertheless, frailty-related functional impairments of among otherwise healthy people living in the communities were less commonly reported.
I-Lan Longitudinal Aging Study (ILAS) recruited otherwise healthy community-dwelling middle-aged and elderly population for study. ILAS excluded subjects with communication difficulty, dementia, nursing home admissions limited life expectancy, as well as those with significant physical disability (9).  Despite the relatively better health conditions of ILAS participants, results of ILAS have shown associations of frailty with cardiometabolic risk (10), cognitive decline (11), falls, fractures, low bone mineral density, sarcopenia, and hospitalizations (12).  These associations were not different from that of the literature, which confirmed that the frailty defined in ILAS was of similar health characteristics to that in other studies. The main aim of this study was to explore frailty-associated functional impairments among otherwise healthy community-dwelling middle-aged and elderly people to for the further comprehensive intervention programs to promote overall health in the communities.


Materials and methods

Study subjects

The ILAS is a community-based aging cohort study in I-Lan County of Taiwan, which randomly selected community-dwelling people aged 50 years and older to evaluate the complex interrelationship between aging, frailty, sarcopenia and cognitive decline (9). All participants were invited via mail or telephone by the research team, and were enrolled when they signed the consent forms. The inclusion criteria for ILAS were: (1) residents aged 50 years and older, and (2) inhabitants who presently live in Yuanshan Township without a plan to move to other places. Subjects with the following conditions were excluded for study: (1) unable to communicate with the research nurses, (2) unable to complete all evaluation tests, (3) with a limited life expectancy due to major illnesses, (4) unable to complete functional assessments within a reasonable time, and (5) current residents in long-term care facilities. Overall, 1,839 subjects were enrolled in the study. The whole study and the consent procedure had been approved by the Institutional Review Board of Taipei Veterans General Hospital and National Yang Ming University.

Demography, and functional assessments

A questionnaire consisting of demographic information, socioeconomic condition, medical history and quality of life was performed for the subjects by research nurses. The burden of multimorbidity was evaluated by using Charlson’s Comorbidity Index (13).  Tobacco use was categorized as follows: non-smoker, ex-smoker (quit in past 6 months) and current smoker. Alcohol drinking status was categorized as drinkers and non-drinkers. A comprehensive functional assessment was performed for all participants, including the Functional Autonomy Measurement System for physical function test (14), the Center for Epidemiologic Studies Depression Scale (CES-D) for measuring the mood status (15), the Mini-Nutrition Assessment (MNA) for nutritional status measurement (16), and the Mini–Mental State Examination (MMSE) for cognitive function measurement (17).

Quality of life measurement

In this study, quality of life was measured by the Short Form-12 (SF-12) for quality of life, which consisted of physical component summary (PCS) and mental component summary (MCS) (18). Higher score in PCS and MCS was considered having higher quality of life. In this study, subjects with the higher than the mean of total score of PCS and MCS were categorized as having good quality of life.

Muscle strength and physical performance

For all participants, handgrip strength was measured using digital dynamometers (Smedlay’s Dynamo Meter; TTM, Tokyo, Japan), with participants standing in an upright position with both arms down on their sides. The best result for three tests of the dominant hand was used for further analysis (19). Moreover, participants performed a timed 6-meter walk with static start without deceleration for each participant to evaluate their physical performance (20).

Definition of frailty

In this study, frailty was defined by using modified Fried’s criteria, including exhaustion, weakness, slowness, physical inactivity and weight loss (1). Exhaustion was defined using the 2 statements by the CES-D. Weakness was defined by low handgrip strength, and handgrip strength was measured as the maximal strength on the dominant hand by digital dynamometer (Smedlay’s Dynamo Meter; TTM, Tokyo, Japan). Slowness was defined by slow gait speed, measured by timed 6-m walk test.   Physical inactivity was evaluated by using Taiwanese version of International Physical Activity Questionnaire (IPAQ) (21). The cutoff for weakness, slowness and physical inactivity were determined by the gender-specific lowest quintiles of the study subjects. Weight loss was defined as having involuntary weight loss of >5% in the past year or 3kgs within past 3 months. Frailty status (robust, pre-frail and frail) was determined based on the Fried’s criteria.

Statistical analysis

In this study, continuous variables were expressed as the mean ± standard deviation, and the categorical data was expressed by percentages. Comparisons of continuous data were done by Student’s t test and comparisons of categorical data were done by Chi square test when appropriate. Comparisons between groups of different frailty statuses were performed by using one-way ANOVA. To determine the independent associated factors for frailty, logistic regression model was used by inputting variables with P<0.10 in the univariate analysis. Five items of frailty definition were not entered for regression model to avoid over-adjustment. All statistical analysis was performed by the commercial software (SPSS 18.0, SPSS Inc, Chicago, IL, USA). For all tests, the two-tailed P value<0.05 was considered statistical significant.




Overall, 1839 subjects (mean age: 63.9±9.3 years, 47.5% males) participated in this study. Table 1 summarized the demographic characteristics of all study subjects and the comparisons between men and women in this study. In this study, men were older than women (65.1±9.7 vs 62.9±8.7 years, P<0.001) and had higher education (7.1±5.0 vs 5.4±4.8 years, P<0.001). Besides, men were more likely to smoke and to carry current habit of alcohol consumption than women. In the comparisons of multimorbidity, men were similar to women except that women had a higher percentage of hyperlipidemia. Despite men were having faster gait speed (1.6±0.5 vs 1.4±0.4 m/s, P<0.001) and handgrip strength (35.1±8.3 vs 21.8±5.4 kg, P<0.001) than women, the frailty status of men were similar to women. In functional assessment, women were poorer in nutritional status (MNA: 26.9±1.9 vs 27.4±1.7, P<0.001), depressive symptoms (CES-D: 2.8±5.2 vs 2.0±3.7, P<0.001) and cognitive status (25.1±4.4 vs 26.2±3.5, P<0.001) than men. In the comparisons of quality of life, women were poorer in both PCS (49.5±5.7 vs 50.8±5.6, P<0.001) and in MCS (53.6±5.5 vs 54.2±4.4, P<0.001) than men.

Table 1 Baseline demographic characteristics and comparisons between men and women of I-Lan Longitudinal Aging Study

Table 1
Baseline demographic characteristics and comparisons between men and women of I-Lan Longitudinal Aging Study

CCI=Charlson’s comorbidity index; SMAF = the Functional Autonomy Measurement System; CES-D= the Center for Epidemiologic Studies Depression Scale; MMSE = Mini–mental state examination; PCS=physical component summary; MCS=mental component summary

Epidemiology of frailty

In this study, the prevalence of frailty was 6.8%, while pre-frailty was 40.5% and 53.7% of all subjects were robust. The prevalence of frailty status between men and women was similar. Table 2 summarized the comparisons between subjects with different frailty status, which showed that age significantly increased when the subjects became frailer. Similar trends were identified in education year, alcohol drinking habit, hypertension, diabetes mellitus, hyperlipidemia, CCI, walking speed, handgrip strength, score of SMAF, CES-D, MNA, MMSE, PCS and MCS (P all< 0.05).

Table 2 Comparisons of clinical characteristics among subjects with different frailty status

Table 2
Comparisons of clinical characteristics among subjects with different frailty status

CCI=Charlson’s comorbidity index; SMAF = the Functional Autonomy Measurement System; CES-D= the Center for Epidemiologic Studies Depression Scale; MMSE = Mini–mental state examination; PCS=physical component summary; MCS=mental component summary

Associated factors for frailty

Table 3 summarized independent associated factors for frailty in this study. Older age, poorer physical function, poorer cognitive function, poorer nutritional status, more depressive symptoms, higher CCI and poorer quality of life were all independent associative factors for frailty. Education year, alcohol drinking habit and multimorbidity were not statistically significantly associated with frailty in the regression model.

Table 3 Independent associative factors for frailty

Table 3
Independent associative factors for frailty

CCI=Charlson’s comorbidity index; SMAF = the Functional Autonomy Measurement System; CES-D= the Center for Epidemiologic Studies Depression Scale; MMSE = Mini–mental state examination; ** Use robustness as reference group



In this study, the prevalence of frailty was somewhat lower than that in the Cardiovascular Health Study, which may be related to the inclusion and exclusion criteria of ILAS. Independent associated factors of frailty in this study included older age, poorer physical function, poorer cognitive function, poorer nutritional status, more depressive symptoms, more complex multimorbidity, and poorer quality of life.  From results of this study, frailty was not simply a geriatric syndrome, but was the combination of multiple geriatric syndromes. Therefore, frailty may pose a very high risk of health for older people, even among otherwise healthy community-dwelling middle-aged and older people.
A number of frailty intervention programs have been developed, but the effects were inconsistent. The mainstream of frailty intervention programs was exercises and nutrition, either alone or in combinations (22). Different combinations of exercise programs have been reported and the combined aerobic and resistance exercise was considered the most effective approach (23). However, not every intervention program was effective and the newly developed programs were through multifactorial intervention, which was compatible to our study results.  Associations between frailty, depression and cognitive decline have been reported before, but rarely did the frailty intervention programs include these components.  Our previous study in the post-acute settings showed that improvement of physical functional could also improve the depressive symptoms of older people without use of antidepressants (24).
From this study, frailty was not just a geriatric syndrome like others, but a complex geriatric syndrome that was of much greater health risk for older people. The associated conditions of frailty may lessen the benefits of frailty intervention programs if these conditions were not taken as a whole. The principles of comprehensive geriatric assessment (CGA) may play an active role in frailty intervention programs (25). Patients in the post-acute care settings may be the best scenario to demonstrate the benefits because these patients were frail and free from acute illnesses. It has been shown that CGA-based intervention successfully promoted functional recovery for post-acute care patients and the improvements were shown in depressive moods, cognitive function, as well as nutritional status (26). Moreover, these improvements significantly reduced one-year mortality following post-acute care services (27). Although the subjects in the communities were not as frail as patients in the post-acute care settings, they eventually shared similar challenges and deserve a comprehensive approach. A recent study demonstrated the success of an integrated intervention in the reversal of frailty (28).
Despite all the efforts went into this study, there were still some limitations. First, the cross-sectional study design limited the possibilities to explore how frailty interacts with other functional deficits in the long term. However, ILAS was a longitudinal study design, we would be able to evaluate the interaction between frailty and other functional deficits in the future. Second, this is an observational study that limited the possibilities to know how other functional deficits improved along with the improvement of frailty status. Third, results of this study may underestimate the complex care needs for frailty since the study subjects were healthier than the general population. In conclusion, frailty was not simply a geriatric syndrome, but the combination of multiple functional impairments. Early identification of other accompanying functional deficits of frailty was of great importance to design appropriate intervention programs. Further study is needed to evaluate the clinical benefits of integrated health promotion activities in the communities to reverse frailty and associated functional deficits.


Acknowledgement: This study was supported by the Aging and Health Research Center, National Yang-Ming University; Center for Geriatrics and Gerontology, Taipei Veterans General Hospital, as well as the Ministry of Science and Technology of Taiwan (MOST 104-2633-B-400-001; and MOST 105-3011-B-010-001) and Veterans Affair Council of Taiwan.
Conflicts of interest: None



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1. Division of Geriatric Medicine, Geriatric Medicine Research Unit, Dalhousie University, Nova Scotia, Canada; 2. Centre for Research in Geriatric Medicine, School of Medicine, University of Queensland, Brisbane, Australia

Corresponding Author: Judah Goldstein, Dalhousie Division of Geriatric Medicine, Veteran Memorial Building, 1421- 5955 Veterans Memorial Lane, Halifax, Nova Scotia, Canada, B3H 2E1, Tel: 902-473-4994, Fax: 902-473-1050, Email: judah.goldstein@dal.ca

J Frailty Aging 2013;2(1):15-21

Published online February 13 2016, http://dx.doi.org/10.14283/jfa.2013.3


Background: Frailty is a state of increasing vulnerability that places an individual at high risk for adverse health outcomes. The best approach for frailty measurement in clinical practice has not been resolved. Frailty can be measured by deficit accumulation and be derived from a comprehensive geriatric assessment (CGA). In busy clinical practice, it may not be feasible to gather this information entirely from patients, particularly from those with cognitive decline. Objective: We describe the feasibility of a frailty index based upon a care partner derived CGA (CP-CGA). In addition, we sought to establish the acceptability of the questionnaire and explore whether care partners felt that the provided information contribute to patient assessment. Design and Setting: A cross-sectional data analysis of 99 community dwelling older adults attending geriatric ambulatory care clinics at a single tertiary care center. Measurements: Care partners completed the CP-CGA and a Clinical Frailty Scale (CFS; Range 1 -Very fit- to 9 -Terminally ill). We evaluated the time to complete and item completeness. Results: The mean age of patients was 81.3±5.7 years. Most were women (n=54), widowed, lived in their own home, with a median CFS of 5 (Mildly Frail). The care partner respondent was usually an offspring. Item completeness was 95% with a mean time to complete of 15.5±8.6 minutes. Conclusion: The CP-CGA seems feasible for gathering information that would be integral towards determining frailty by deficit accumulation. Future inquiries will evaluate its feasibility in other settings and validity as a form of frailty assessment.

Key words: Frailty, comprehensive geriatric assessment, geriatric care, older persons, deficit accumulation, aging.



Comprehensive geriatric assessment has been essential for understanding frailty and determining how best to provide care in older adults (1). In many fields of medicine, frailty is not fully appreciated as an important determining factor for health outcomes, yet it is one of the most common health problems facing older adults, particularly the oldest old (2). By focusing more attention on frailty, it may be possible to better predict health outcomes that are important to this age group (e.g. institutionalization, functional decline) and improve prognostication and care planning (3). The lack of a widely accepted, feasible frailty assessment is problematic for clinicians. Two approaches have merit: the phenotype of frailty characterized by impairment in at least one of five clinical features (4) and the view of  frailty as the accumulation of health deficits (5). Both have certain drawbacks that impede their widespread use in clinical care. More experimental work is necessary to identify an approach to frailty quantification that is operationally feasible in a variety of settings (6).

The Rockwood-Mitnitski Frailty Index (FI) is appealing in terms of its simplistic approach (count of health problems), reproducible characteristics (e.g. relationship with age, gender, sub-maximal limit) (7), and its amenability for use in a variety of patient populations. It is calculated as the proportion of health deficits (typically 30-40 items – symptoms, diseases, or disabilities) and can be derived from a standard comprehensive geriatric assessment (FI-CGA) (8). In the clinical setting, a strong relationship exists between the frailty index and adverse outcomes (hospitalization, institutionalization and death) (9). One deterrent to its use is that it is thought to be too cumbersome for routine clinical care.

CGA has been used in the geriatric ambulatory care (GAC) setting as a means to manage the care for patients with multiple needs. Collateral information from care partners (typically family) is often essential for determining the health status of the people for whom they care. Much of what needs to be known to feasibly determine frailty status comes from this history. Although CGA is widely used by geriatrics, it is often seen as difficult to implement in other settings (10). Our objective was to determine whether a survey that is based upon CGA could be completed by care partners in GAC clinics so that a frailty index could be calculated based upon the carer’s knowledge of the patient. We were interested to know whether care partners felt they had enough information to complete the questionnaire, whether it was acceptable to them and how they saw such information as contributing to the assessment.


A cross-sectional study was conducted at a single tertiary care center (Capital Health, Halifax, Nova Scotia) between February 2009 and July 2010. A convenience sample of patients aged 70 years and older was enrolled. The survey was presented in English only. Exclusion criteria included age less than 70 years, no care partner available or refusal (either patient or care partner) to participate. We sought to enroll new clinic referrals as these patients have a higher likelihood of a specialist completed CGA. Ultimately, recruitment was at the discretion of clinic staff. The sample size calculation was based on the approach of Kraemer and Thiemann (11) for correlation analysis with the expected correlation of 0.8 (0.2) (geriatrician derived frailty index and care partner derived frailty index). This will be important for future criterion validation.

Participants came from the Geriatric Ambulatory Care (GAC) clinics including Memory clinics, Geriatric Day Hospital, and the Palliative and Therapeutic Harmonization clinic (PATH) (12). Patients are requested to bring a family member or friend with them to clinic for collateral history regarding cognitive concerns. During the course of a clinic visit, patients undergo a CGA including cognitive testing using validated cognitive scales (Mini-mental Status Exam (13), Frontal Assessment Battery (14), Montreal Cognitive Assessment (15), Brief Cognitive Rating Scale (16) and collateral history from a care partner is used to understand the time course, progression and nature of cognitive deficits. All patients undergo a focused physical examination. Most patients receive a diagnosis (including dementia type and stage where applicable) during their first clinic visit. Patients who attend the GAC clinics follow a bimodal distribution of younger patients (age 50-65), who chiefly have fronto-temporal dementia, early-onset Alzheimer’s disease, or unusual neurodegenerative disorders and older patients (mean age 78 years; 67% women, who mostly have late onset Alzheimer’s disease). Patients attending the PATH clinic have a mean age of 81 years. The Capital Health research ethics committee approved the study (CDHA-RS/2009-138).

Recruitment and Data Collection: The Care Partner – Comprehensive Geriatric Assessment

The care partner – comprehensive geriatric assessment (CP-CGA) was based upon a CGA used by in-hospital staff and  described elsewhere (17, 18). A team comprised of geriatric fellows, geriatricians, graduate students, and other health professionals contributed to the development of the CP-CGA. Members of the interdisciplinary team evaluated the final iteration of the questionnaire for its readability, interpretability and face validity (19). The survey is comprised of 62 questions that address topics such as: the care partner relationship, co-morbidities, history of falls, problems with hearing, memory, sensory function, and functional questions (e.g. toileting, bathing, dressing). The difference between the typical CGA and the CP-CGA is that the latter can be completed by care partners (usually family) and is based upon their opinion rather than formal clinical testing. The CP-CGA contains enough information to construct a frailty index with at least 40 items (Appendix A).

Care partners estimated the subject’s frailty status using the Canadian Study of Health and Aging-Clinical Frailty Scale (CSHA-CFS) (20). The CSHA-CFS was initially developed to stratify patients based upon their relative degree of fitness/frailty (20). The original version included seven clinical descriptors. The revised scale has additional categories for severe frailty (with death expected within six months) and terminal illness that is non-disabling.

Clinic staff screened patients as they registered. The care partner was identified as someone who spent enough time with the patient to be knowledgeable about their health and social circumstances. Both the patient and care partner were asked whether they would be interested in participating in a study that looks at how we gather information from care partners. For those who agreed, the details of the study were explained and a letter inviting the patient and care partner to participate was provided. The care partner completed the CP-CGA while the patient was assessed.

Health care records were reviewed using a structured data collection form for one year outcomes to identify resource use and adverse events including: hospital admission, institutionalization and death. Specialist completed clinic CGAs were obtained if available. The survey included a qualitative component that allows the carer to describe the health status of the patient (in their words) and to express their thoughts about the questionnaire.

Data Analysis

We used descriptive statistics to characterize the sample and attributes of the care partner respondent. Feasibility estimates of time-to-complete and item completeness are presented. Categorical variables were analyzed with the chi square test while continuous variables were compared using the t-test or one way ANOVA as appropriate. The care partner relationship was coded into a dichotomous variable of non-offspring (1) or offspring (2) in order to identify differences in feasibility estimates. Care partner acceptability of the tool was determined using a Likert scale. Free text feedback was assessed by qualitative thematic analysis. Incomplete questionnaires were included in the final data analysis. As this was a feasibility study, our primary outcome was to monitor the completeness of items and time-to-complete. Incomplete forms provided valuable information regarding the acceptability of survey items. Data were analyzed using SPSS version 15.0 (Chicago, IL).


Of 99 participants enrolled, two subjects were withdrawn due to  age being less than 70 years and in one case only the first page (demographic information) was completed, leaving 97 completed CP-CGAs. Refusals were not tracked, however, anecdotally, most people that were asked were willing to complete the survey. Participants were mostly female, older and lived in their own home (Table 1). The median care partner-completed Clinical Frailty Scale rating was category 5 (mildly frail). The survey was typically completed by a relative, usually the spouse or an adult child (Table 2). Many subjects (42%) lived with the respondent and most respondents (73%) indicated they were the primary care provider. The majority of respondents reported a high (16%) or moderate (48%) level of stress with 57% stating that they needed more help with providing care.

Table 1 Baseline characteristics of study population

Table 2 Characteristics of the care partner respondent


The mean time-to-complete was 15.55 ± 8.56 minutes (median – 14 minutes) (Table 3). The completeness of items on the questionnaire was 95.0 ± 8.8 percent. The sample was further explored with respect to the care partner’s relationship with the subject. There were no significant differences in terms of the time-to-complete when analyzed by relationship of respondent; however, there was a trend towards a shorter completion time if the survey was completed by a non-offspring (typically the spouse). Slightly (not statistically significant) higher completion rates for offspring respondents were observed (Table 3). We also evaluated how the care partner’s stress or living arrangement may have impacted the completeness of data. No statistically significant differences were identified. There was a trend towards higher completion rates for those with any level of identifiable stress versus no stress (p>0.05).


Table 3 Feasibility estimates and care partner satisfaction with the survey    

N/A – the satisfaction survey remained anonymous (completed by 72 participants), time to complete was available for 47 subjects. * Median 14 minutes (n=47).

Care Partner Satisfaction

Care partners evaluated the CP-CGA in terms of the clarity of questions, length, and scope. Most care partners strongly agreed (36 %) or agreed (61%) that the questions were clear and easy to understand. They (72%) also felt that the survey was an appropriate length. Some care partners (17%) thought that there were important areas of health not covered (e.g. alcohol consumption, mental health and family health history). Care partners’ comments about the survey can be summarized in four themes: the relationship of the care partner (context), the survey design, health topics not covered, and reasoning for completing the survey (Table 4).


Table 4 Thematic analysis of free text feedback as provided by the care partner

Sixteen care partners provided written feedback with some comments reflected in multiple themes. Care partners were asked if they would like to provide additional comments about the questionnaire.


We aimed to investigate the implementation of a standardized CGA completed by care partners in geriatric ambulatory care. The approach appears feasible, both in terms of the time-to-complete and the completeness of items on the form. In general, care partners felt that the survey was clear, an appropriate length and acceptable in terms of the cross section of questions posed. Most of the care partners commented on the survey design. Of note, care partners thought that a number of the questions required multiple response categories instead of yes or no. It was also mentioned that the time course for change (two weeks) may be too close. The care partners were not informed about the goal of constructing a frailty index and this ultimately led us to pose the questions as we did. In acute care, a two week time period of change (pre-morbid function) is predictive of poor hospital outcomes (21) which may not be the case in ambulatory care. Whether a 14 minute survey in this setting is feasible is debatable. In this study, care partners were approached at a convenient point during the visit. Future work should look at how it could be included as part of the clinical care process (which is the case in the PATH clinic).

Frailty is a term used to describe differences in aging and its associated risks for poor outcomes in people of the same age. The CP-CGA can measure frailty using the CSHA-Clinical Frailty Scale and frailty index. There are sufficient variables to construct a frailty index of over 40 health deficits. Future work will evaluate the validity of measuring frailty based upon the care partner’s responses.

Although percent complete rates were high, one question often missed was the time-to-complete. Only 48% (n=47) of this data was available. This was a convenience sample of patients with enrollment at the discretion of the practitioner potentially limiting the generalizability of the results. Selection bias could be a concern, as refusals to participate were not tracked. The decision to approach a patient was left to the clinic staff. We advised staff to approach care partners that had enough medical and social knowledge of the patient to be able to complete the form. Clinical discretion was necessary to identify care partners that would be able to provide this detailed information. Staff also considered that care partner’s themselves could have cognitive, communication or literacy issues that would prohibit completing the survey. We believe that the CP-CGA may be an adjunct to other methods of frailty assessment especially in high workload areas where this type of assessment is currently not performed. We are currently evaluating this approach in the emergency medical services setting. Participation bias may have existed where those that were too stressed may not have wanted to participate. The majority of respondents (63%) indicated that they experienced moderate to high stress and half required more help in providing care so it appears that this was not the case. Additional qualitative inquiry should explore how care partners and patients view the role of the carer during clinical assessment.

Harnessing care partners’ knowledge and translating it using a standardized tool such as the CP-CGA allows for reproducible measures such as a frailty index to be determined. Such information could provide valuable information in regards to the health status of the patient and in discussions regarding prognosis and care planning. Of interest to our group is how such a form could be used in the acute care setting (emergency department). We believe this survey will be most beneficial in the very frail where communication and cognitive issues are prevalent, provided that there is a suitable care partner available.

Translating the CGA into one that can be completed by care partners (CP-CGA) may be useful for frailty screening, and risk prediction while also acting as a mechanism to facilitate communication between care partners, health care providers and their patients in different out patient settings. The CP-CGA provides information on the patient’s baseline status (e.g. cognition and function) and relative fitness/ frailty before the illness or injury. Research suggests that frail older adults may benefit most from supportive care while the fit older adult from more aggressive “usual” treatment (22). Early evaluation and identification of frailty are important components to providing appropriate care (12, 23-24). Future research will attempt to validate the CP-CGA for frailty quantification. The additional information it provides, with little direct increase in time spent by health providers, may allow it to address the issue of the apparently time-consuming nature of a CGA, which has been seen as an obstacle. This in turn has led to very short screening tools, which may be inadequate to get all the information needed to grade frailty (25).

We have demonstrated that it is feasible to have care partners complete a survey based on the CGA in the outpatient setting. This data can be used to evaluate frailty. The CP-CGA may be beneficial in other medical settings less familiar with geriatric medicine. Future research will evaluate the validity of the CP-CGA in frailty measurement and whether it can be integrated into the care process to aid with decision making.

Acknowledgments: J. Goldstein was supported by a student research award from the Nova Scotia Health Research Foundation and funding from the Atlantic Regional Training Center. This study would not have been possible without the help of the patients, families and clinic staff of the Geriatric Ambulatory Care Clinics at Capital Health, Halifax.  

Conflict of Interest: The authors (JG, MKA, RH, PM) have no financial or other conflicts related to this submission.

Care partner comprehensive geriatric assessment (CP-CGA). Copyright of the Dalhousie Geriatric Medicine Research Unit, copy but do not change (Version 2, Oct 17, 2008)


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1. Gérontopôle, CHU Toulouse, Toulouse, France; 2. UMR INSERM 1027, Université de Toulouse III Paul Sabatier, Toulouse, France; 3. Pôle cardio-vasculaire et métabolique, CHU Toulouse, Toulouse, France;

Corresponding author: Sophie Guyonnet, PhD. Gérontopôle, Centre Hospitalier Universitaire de Toulouse, 170 avenue de Casselardit, TSA 40039, 31059 Toulouse cedex 9, France. Phone: +33 (0)5 61776405; email: guyonnet.s@chu-toulouse.fr 

J Frailty Aging 2015;4(1):13-25
Published online February 2, 2015, http://dx.doi.org/10.14283/jfa.2015.36


The heterogeneous group of older adults may be differentiated into three subgroups in order to facilitate the development and implementation of personalized healthcare interventions: 1) “disabled individuals” (i.e., those needing assistance in the accomplishment of basic activities of daily living), 2) “frail individuals” (i.e., those presenting some limitations and impairments in the absence of functional disability), and 3) the “robust individuals” (i.e., those who are neither frail or disabled). Despite the growing evidence linking frailty to poor outcomes, this syndrome is yet adequately considered in the clinical practice. There is indeed a lack of recognition of frail individuals, frequently leading to inadequate or inappropriate offer of healthcare services. The assessment of frailty in older adults is recommended to preventively act before the activation of the irreversible cascade of disability. Characteristic features of frailty (e.g., weakness, low energy, slow walking speed, low physical activity, and weight loss) clearly suggest the existence of a close link between nutrition and the status of extreme vulnerability (to intend both from a physical and cognitive viewpoint). Interestingly, recent clinical experiences in the field of frailty and nutrition have demonstrated that this syndrome is often related to relevant prevalence of malnutrition and risk of becoming malnourished. In the present article, it is proposed a review of existing evidence in the field of nutrition and frailty. Potential nutritional interventions for preventing frailty and age-related disabling conditions are also discussed.


Key words: Nutrition, physical activity, multidomain intervention, frailty, nutrition, comprehensive geriatric assessment.



Age-related disabling conditions represent a relevant clinical issue to prioritize public health interventions. In fact, besides of posing a severe burden to the elder’s quality of life, disabilities are responsible for significant augmentations of healthcare expenditures (1). The assessment of frailty in older adults has been recommended as a mean for preventively acting before the irreversible vicious cycle of disability takes place (2). 

Over the past two decades, a growing body of literature has been devoted to the exploration of the “frailty syndrome”. Frail older adults are individuals exposed to an increased risk of negative health-related events, including hospitalization, institutionalization, disability, and mortality. Frequently, frailty has been considered as a pre-disability, reversible status. Differently from disability, it may be still amenable of preventive interventions aimed at restoring the individual’s robustness (3). Consistently, the heterogeneous older population has started being subdivided into three practical subgroups in order to facilitate the development and implementation of more targeted and personalized interventions: 1) “disabled individuals”(i.e., those requiring assistance in the accomplishment of basic Activities of Daily Living [ADL]), 2) “frail individuals” (i.e., those presenting limitations and impairments, but still presenting independent living and functional autonomy), and 3) “robust individuals” (i.e., those characterized by a clinical phenotype of successful or normal aging).

Frailty has been defined as a geriatric syndrome resulting from decreased physiological reserves and resilience. Such increased vulnerability to stressors may cause progressive functional decline and increase the risk for adverse outcomes. Frailty may be indicated as a major cause of disability. Thus, it has been proposed that the prevention of disability may pass through the proper detection and targeting of frailty. For doing this, adequate screening strategies and effective interventions are needed (2).

Several attempts have been done in these last years for improve awareness about frailty and facilitate its introduction in the daily clinical practice. Namely, a first document originated through a Delphi methodology aimed at posing the basis for a shared definition of frailty (4). Subsequently, an international group of experts (including delegates from the International Association of Geriatrics and Gerontology [IAGG], the American Medical Directors Association [AMDA], the American Federation of Aging Research [AFAR], European Union Geriatric Medicine Society [EUGMS], International Academy of Nutrition and Aging [IANA], Society on Sarcopenia, Cachexia, and Wasting Disorders [SSCWD], the European Commission, and the Gateway Geriatric Education Center [GEC]) proposed more practical insights about the implementation of this condition in the geriatric medicine practice (5).

It is now well established that frailty is a condition closely linked to malnutrition. Weight loss is a cardinal sign of the frail person (6-7), indicating as particularly relevant the nutritional assessment of the older person when approaching to frailty. Malnutrition is indeed a risk condition significantly affecting the health status of the individual (making him/her more vulnerable to stressors), and generating functional impairment and specific features of frailty (e.g., sarcopenia). It is also noteworthy that several factors may induce and sustain frailty. Malnutrition is thought to play a major role in this context. In this domain, the above-mentioned international task force (5) recently identified three interventions against frailty as the most promising to consider:

– Energy and protein supplementation

– Vitamin D supplementation

– Physical exercise

In the present review article, available evidence linking nutrition to frailty is presented. Possible clinical interventions in this field are also discussed. Since no definitive consensus exists around the operational definition of the frailty syndrome, the article will specially focus on the frailty phenotype proposed by Fried and colleagues since this seems to be the most commonly used.

The frailty syndrome:  A common condition in geriatric medical care 

As mentioned, frailty is a syndrome characterized by constellation of signs and symptoms responsible for increasing the organism’s vulnerability to stressors and exposing it to adverse outcomes. Fried and colleagues graphically depicted frailty as a vicious cycle including multiple signs and symptoms finally resulting in the deregulation of multiple molecular and physiological pathways, and leading to typical geriatric conditions (e.g., sarcopenia, chronic inflammatory status, decreased heart rate variability, altered clotting processes, insulin resistance…) (6). Such pathophysiological modifications were clinically operationalized by the same Authors into five criteria defining physical frailty: weakness, exhaustion, slow gait speed, sedentary behavior, and involuntary weight loss. These criteria are commonly referred as the “frailty phenotype” (6). The presence of three or more of these criteria indicates the clinical presence of “frailty”; the presence of one or two criteria has been indicated as a transition status of “pre-frailty”; the absence of criteria confers the status of “robustness”.

A recent systematic review based on 21 cohorts including 61,500 participants reported 10.7% and 41.6% of frailty and pre-frailty in community-dwelling older persons, respectively (8). Nevertheless, the included studies were characterized by quite heterogeneous prevalence, ranging from 4.0% to 59.1%, given the differences in the adopted operational definitions of frailty. Studies using the frailty phenotype to measure the individual’s vulnerability, the prevalence ranged from 4.0 to 17.0%.

A study conducted in community-dwelling older adults in Canada, the prevalence of frailty measured using the Frailty Index was 22.7% (9). Differently from the frailty phenotype, Rockwood and colleagues proposed the Frailty Index to measure the age-related accumulation of deficits basing their parameter on the results of the Comprehensive Geriatric Assessment (CGA).

Frailty has also been associated with risk of longer hospital stays and increased mortality in hospitalized patients (10). Gill and colleagues have reported that frailty represents the most common cause of death in elders (11). Given the relatively high prevalence in community-dwelling individuals and its strong predictive value for poor outcomes, the screening and assessment of frailty has been repeatedly proposed to be included in the standard geriatric clinical practice. There is indeed a lack of recognition of frail individuals, frequently leading to inadequate or inappropriate offer of healthcare services. The assessment of frailty in older adults is recommended to preventively act before the activation of the irreversible cascade of disability.

Results of observational studies

Table 1 summarizes observational studies looking at the relationship between frailty and malnutrition in community-dwelling older persons.

Table 1 Results of observational studies on the relation between poor nutrition and frailty risk

25(OH)D: 25-hydroxyvitamin D; ADL: Activities of Daily Living; BMI: Body Mass Index; DXA: Dual-energy X-ray absorptiometry; EPIC: European Prospective Investigation into Cancer and Nutrition; FP: Frailty Phenotype (according to Fried and colleagues); FFQ: Food Frequency Questionnaire; FI: Frailty Index (according to Rockwood and colleagues); IADL: Instrumental Activities of Daily Living; InCHIANTI: Invecchiare in Chianti; MED: Mediterranean diet; NHANES III: Third National Health and Nutrition Survey; SPPB: Short Physical Performance Battery; WHAS: Women’s Health and Aging Studies

Body mass index (BMI) and risk of frailty 

In the Women’s Health and Aging Studies (WHAS) (n=599 women, aged 70 to 79 years), Blaum and colleagues showed that being overweight was significantly associated with pre-frailty, and obesity was associated with both pre-frailty and frailty, independently of potential confounders (12). Differently, no statistically significant relationship between BMI and frailty status was reported in the WHAS II study (including 250 subjects aged 76 to 86 years) (13).

In the English Longitudinal Study of Ageing (n=3,055 older persons), Hubbard and colleagues showed a U-shaped relationship between BMI and frailty. Participants with BMI between 25 and 29.9 kg/m2 tended to present both low scores at the Frailty Index and low prevalence of physical frailty (according to the frailty phenotype). High waist circumference was always associated with a frailer health status (14).

A recent paper that included 4,731 patients aged 60 years and older showed a direct association between BMI and frailty. The study also reported that the daily energy intake was correlated to frailty, independently of BMI. Energy-adjusted macronutrient intakes (protein, carbohydrate, fat) were similar in people with and without frailty. Frail and pre-frail individuals were more likely to self-report having insufficient food availability (15).

Bowen and colleagues used functional limitations and disabilities in ADL and Instrumental ADL (IADL) to measure the participants’ vulnerability to stressors (16). In 11,491 subjects aged 50 years and older (follow-up 8 years), higher BMI was protective for functional decline. Compared with the robust normal weight older adults, pre-frail obese ones, frail overweight ones, and frail obese ones had a 16%, 10%, and 36% reduction of the expected functional limitations rate, respectively.

Specific nutrients and frailty risk 

Frailty syndrome and nutritional status are closely related in older persons (17). Several observational studies have demonstrated a close relationship between this syndrome and specific deficits of nutrients.

In the Invecchiare in Chianti (InCHIANTI) study, Bartali and colleagues (18) found that low daily energy intake was significantly associated with frailty. After adjusting for energy intake, low intakes of protein, vitamin D, vitamin E, vitamin C, and folates seemed particularly linked to the frailty phenotype.

Three studies have shown an association between inadequate protein intake and frailty. In the WHAS study, 3,298 (13.5%) of the 24,417 participants developed frailty over the three years of follow-up. After adjustment for potential confounders, it was shown that an inverse relationship between protein intake and incident frailty (19). A second study estimated the mean protein intake according to the setting (20). Community-dwelling elders, frail participants, and institutionalized individuals presented 1.1 (standard deviation [SD] 0.3) g/kg/day, 1.0 (SD 0.3) g/kg/day, and 0.8 (SD 0.3) g/kg/day, respectively. Finally, a third article has examined the association of protein and amino acid composition intakes with frailty in Japanese older persons (21). Among the 2,108 subjects aged 65 years and older 481 (23%) were frail. Higher intake of proteins were associated with a lower risk of being frail. The intakes of animal and plant proteins as well as all the selected amino acids (leucine, isoleucine, valine, methionine, cysteine, branched chain amino acids, sulfur amino acids, essential amino acids) were inversely associated with frailty.

In a recent study conducted in 194 healthy older persons, the amount of protein intake was not found to be statistically associated with frailty, although poor protein intake differed according to frailty status (22). Finally, two studies showed a preventive association between a Mediterranean diet and frailty (23, 24). In the InCHIANTI study, 690 older adhering to Mediterranean diet were more physically active, had higher gait speed, and presented a reduced risk of becoming frail compared to non-adherents (23).

Poor intakes of specific micronutrients elevate frailty risk 

Several studies have shown that low serum concentrations of 25-hydroxy-vitamin D (25(OH)D) are associated with a higher prevalence of frailty (25, 36). In one report, serum concentrations of 25(OH)D below 20.0 ng/mL were cross-sectionally, but not longitudinally associated with frailty in a sample of 1,600 older men (28). In the InCHIANTI cohort, it was demonstrated that pre-frail individuals with low 25(OH)D concentrations were more likely to die, to become frail. Moreover, Authors showed that the pre-frail participants with low vitamin D concentrations were more unlikely to reverse their frailty status compared to those in the normal range (32).

More recently, Wong and colleagues (37) conducted a prospective cohort study among 4,203 older men (age 70–88 years). At baseline, 676 (16.1%) participants were defined as frail. In multivariate cross-sectional analysis, low vitamin D status was confirmed to be associated with increased prevalence of frailty independently of potential confounders. Vitamin D status was also shown to be longitudinally predictive of incident frailty. Moreover, participants with low vitamin D concentrations at the baseline were more likely to die during the 9.2 years of follow-up, independent of baseline frailty and other covariates.

Finally, four observational studies have demonstrated the association of frailty with low concentrations of antioxidants (i.e., vitamin E, vitamin C and carotenoids) (29, 30, 38, 39), vitamin B6, and folic acid (29, 30). In addition, significant inverse correlations have been reported between the ratio copper/zinc and bone mineral density, gait speed, muscle strength, lean mass, and hematocrit in 144 frail older man. These findings suggest that serum copper and their ratio with zinc may serve as predictive biomarkers for poor health in the elderly (40).

Results of Interventional Studies 

Nutrients and protection from frailty

Results of the main interventional studies suggesting that supplementation of specific nutrients may modify the frailty profile are presented in Table 2. Latham and colleagues studied the effects of vitamin D supplementation (versus placebo) on physical performance in 243 frail elders (41). Results did not show a significant difference between treatment groups, even among participants with vitamin D deficiency at the baseline.

Table 2 RCTs exploring the efficacy of nutrient supplementations with the objective of modifying the frailty profile

DXA: Dual-energy X-ray absorptiometry; FFM: Fat Free Mass; MNA: Mini Nutritional Assessment; SD: standard deviation; SPPB: Short Physical Performance Battery

In a randomized controlled trial (RCT) testing the effect of protein supplementation, Tieland and colleagues showed a significant improvement of the Short Physical Performance Battery score in frail older adults from a 24-week supplementation of proteins (42). Another recent RCT explored the effect of daily supplementation with protein and several micronutrients for 12 weeks in 87 frail older adults (i.e., subjects with usual gait speed <0.6 m/s and Mini Nutritional Assessment <24) (43). Overall, results tended to demonstrate improvements of physical performance in the intervention group.

Although some RCTs show promising effects of nutritional supplementation on physical function, further long-term studies are needed. In particular, nutrition should be considered as key component of multidomain interventions targeting age-related conditions.

Efficacy of a multi-domain approach in the management of frailty

An increasing number of multidomain interventions is currently tested in large research programs (44).

Table 3 summarizes the results of several intervention studies suggesting that a multidomain approach may improve the frailty profile of older persons. The feasibility and benefits of combined interventions (for example, combining nutritional supplements and physical exercise) have been well demonstrated, even in very frail subjects living in nursing homes (45).

Villareal and colleagues (46) tested the combination of physical exercise and balanced diet (providing an energy deficit of 500–750 kcal/day in obese older persons. Results showed that the combination of the interventions had the greatest (positive) impact on measures of frailty (i.e., muscle strength, balance, gait, peak oxygen consumption).

In one study, 96 frail elders were randomized into 4 groups: physical training program (i.e., aerobic, muscle strength, balance), nutritional intervention program (i.e., individually targeted advice and group sessions), a combination of these interventions, and control group. Subjects were evaluated at baseline, at the end of the 12-week intervention, and after 6 additional months. Significant improvements in lower extremity muscle strength were observed in both training groups compared with the nutrition alone group at 12 weeks. There were small significant changes for some of the balance measurements in the training group without nutrition treatment. The nutrition intervention alone did not show any significant result (47, 48).

In another 7-week RCT, a comprehensively structured, high-intensity physical exercise program demonstrated a clear potential for improving walking capacity and muscle strength, especially when combined with nutritional supplementation (i.e., 200 ml of liquid supplying 300 kcal in the form of carbohydrate [49%], lipids [35%] and protein [16%] mixture) (49).

Tieland and colleagues (50) compared the results of a progressive resistance exercise program (two sessions per week for 24 weeks) plus protein supplementation (total 30 g/day) versus a protein-free placebo in 62 frail older adults (mean age 78 years). Significant results were reported for the increase of lean body mass (measured by DXA) in the protein-supplemented group. Strength and physical performance significantly improved in both groups.

A RCT testing nutritional and physical activity interventions in malnourished frail community-dwelling persons by trained lay buddies is currently ongoing (51). In this study, malnourished frail persons are followed at home for 10–12 weeks. Participants allocated to the intervention group (n=40) receive intervention to improve their fluid, protein and energy intake, and increase their physical performance and muscle strength training. The control group (n=40) only receives home visits without any further intervention.

Since many factors other than nutrition and exercise may potentially influence the onset/development of frailty, three recent RCTs have explored additional possible contributors of this clinical syndrome.

Li and colleagues (52) studied the effect of an intervention based on the comprehensive geriatric assessment in 310 frail older adults (mean age 79 years) on physical function over a 6 months follow-up. Results showed that compared to the control group, physical function in the intervention group was more likely to improve and less likely to deteriorate, although without reaching statistical significances between the two groups.

More recently, Fairhall and colleagues (53) implemented a multidomain, multidisciplinary intervention targeting frailty by implementing specific protocols of home physical exercise, psychological counseling, and management of medical conditions) in 216 frail older adults (mean age 83 years). After 12 months, participants in the intervention group presented faster gait speed (about 0.05 m/s), better physical performance, and improved balance. No difference was found in fall rates between the two groups. Mobility remained stable in the intervention group, whereas it declined substantially in the control group (54). 

Finally, in a recent RCT, 117 frail older adults were randomized into three groups: an intervention group receiving physical exercise and nutritional advice, another receiving physical exercise and problem solving therapy (a brief form of evidence-based psychotherapy), and a control group. Participants in the physical exercise plus nutritional advice group showed higher improvements at the frailty phenotype compared to the other groups, especially over the short-term (55).

Table 3 RCTs to evaluate the efficacy of multi-domain intervention to modify frailty risk

ADL : Activities of Daily Living ;  BI : Barthel Index ;  BMI : Body Mass Index ;  CCSHA-CFS-TV : Chinese Canadian Study of Health and Aging Clinical Frailty Scale Telephone Version; CGA : Comprehensive Geriatric Assessment ; CHS-PCF : Cardiovascular Health Study Phenotypic Classification of Frailty ;  DEXA : Dual-energy X-ray absorptiometry; FFC: Fried Frailty Criteria ; FFM: Fat Free Mass; PPA: Physical Profile Assessment; PPT : Physical Performance Test; RM : Repetition Maximum ; RMR : Resting Metabolic Rate; SPPB : Short Physical Performance Battery.   

Incorporating assessment and management of frailty into clinical practice

The first step in the management of frailty is the use of a simple screening test to identify vulnerable individuals. Several different screening tools of frailty have been developed and validated over the years. The frailty phenotype is probably the best known; it was operationalized and validated in the Cardiovascular Healthy Study. Subsequently, other frailty measures have been proposed, such as the index developed in the Study of Osteoporotic Fractures (56). All of these measures count deficits, quantify the degree of frailty, providing an estimate of the degree of vulnerability for adverse outcomes.

We also recently developed a new frailty screening tool largely relying on the clinical opinion of the general practitioner (57). In 2011, a novel day hospital was established at the Gérontopôle of the Centre Hospitalier Universitaire de Toulouse (Toulouse, France) for the evaluation of frailty and prevention of disability (58). Geriatric patients are here referred by their general practitioners who have been trained at detecting signs and symptoms of frailty. The instrument we provided them is a simple and easy-to-complete questionnaire (i.e., the so-called Gérontopôle Frailty Screening Tool, GFST). The instrument is characterized by being largely based on the subjective perception of the general practitioner about the frailty status of his/her patient. Obviously, nutrition is represented in the instrument by a specific question about “involuntary weight loss”.

The goal of the Gérontopôle frailty clinic is to identify frailty at its earliest stages through a comprehensive geriatric evaluation, attempt to identify its determinant(s), and implement multidomain interventions tailored to the older person’s needs and resources. The interventions may include nutritional recommendations, physical exercise protocols, referral to social care, and/or simply raising awareness about risky conditions. It is important to note that the general practitioners will still remain the primary referents and responsible for the health of their patients. They will simply be supported in their clinical activities by a multidisciplinary team in the early detection and treatment of frailty.

Preliminary data from the first 160 patients assessed in this service (58) have shown that the mean age of this population is 82.7 years, with a large majority aged 75 years and older. Most patients are women (61.9%), and approximately two thirds of the patients already receive some type of social/care support. According to the frailty phenotype, 65 patients (41.4%) were pre-frail, and 83 (52.9%) frail.

Nearly 40% of the subjects experiences an involuntary weight loss of >4.5 kg during the past 3 months. For concerns their functional status, 83.9% of the sample presented slow gait speed, 53.8% had sedentary behavior, and 57.7% had muscle weakness. Autonomy in ADL was quite well preserved (mean ADL score 5.6, SD 0.8) as expected. Differently, IADL showed an initial loss of independence reporting a mean score of 6.0 (SD 2.3). Overall, these data support the idea that patients referring to this frailty clinic have not yet developed disability, but are at increased risk of falling in the disabling cascade; thus, they might represent an ideal target for preventive interventions. It is noteworthy that 9% of the assessed population presented an objective state of protein-energy malnutrition (MNA <17), and more than 30% an early alteration of nutritional status (MNA 17-23.5). Almost every patient (94.9%) had vitamin D deficiency.

About one third of the patients (33.1%) presented abnormal results at the Mini Mental State Examination (MMSE) score. Dementia (measured by the Clinical Dementia Rating [CDR] scale) was observed in 11.6% of the Frailty Clinic population, whereas 65.8% of subjects had mild cognitive impairment (CDR equal to 0.5). These data may suggest a link between the physical and cognitive domains in the frailty syndrome. It cannot be excluded that (at least part of) the cognitive impairment of this frail population might be due to poor nutrition. More data are needed in this field, and intervention trials (such as the Multidomain Alzheimer’s Preventive Trial (44)) may provide useful insights in the field.

To better appreciate the importance of acting in prevention in the domain of disability, it is worth to mention the recent work by Gill and colleagues (59). In their study of 754 community-dwelling, non-disabled older adults, Authors showed that frailty is a dynamic process with frequent transitions across stages of severity. Nevertheless, the overall trend was described as tending towards the worsening of frailty status with a very low likelihood of restoring robustness when frail or disability are present. However, it was reported that about 10% of prefrail subjects were still able to come back to the robust condition during the 18-month follow-up. This may imply that an early screening of (pre-)frailty in older adults followed by specific multidomain interventions may be of benefit and potentially of interest for a larger proportion of individuals.

Today, geriatric medicine is largely devoted at assessing and treating elders who already present severe disabilities, often at irreversible stages. Of course, such task cannot be abandoned and geriatricians should continue taking care of disabled individuals. However, at the same time, proactive care of pre-frail and frail older adults to prevent a worrying increase of disability prevalence in our aging population is also important. Frail older adults are a subpopulation of elders who are particularly exposed to the risk of becoming disabled, but their clinical needs remains still too often unmet by healthcare systems. To counteract the disabling cascade, a close collaboration between geriatricians, general practitioners, and healthcare professionals (more in general) is necessary. Such unity of intent should lead to the development of preventive and therapeutic interventions characterized by being specifically targeted, sufficiently strong, and adequately sustained over time.

Conflicts of interest: None declared by the Authors.


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