Table 4.

Definitions of frailty used in the included studies, measured outcomes and assessment tools

Study	Operational definition of frailty/pre-frailty used by authors of included studies	Measured outcomes*	Tools and time-points assessment
Behm, et al., 201540	Excessive tiredness in daily activities assessed by Mob-T Scale (indicated by affirmation of being too tired to perform the activity) and presence of at least three of eight core frailty indicators: - weakness (< 13 kg for women and < 21 kg for males for the right hand, and < 10 kg for women and < 18 kg for males for the left hand) - fatigue (affirmation of suffering general fatigue over the last 3 months) - weight loss (affirmation of having weight loss over the last 3 months) - low physical activity (1–2 walks/week or less) - poor balance (Berg's balance scale score ≤ 47) - gait speed (walking four meters or less in 6.7 s) - visual impairment (visual acuity < 0.5 in both eyes using the KM chart) - cognition (MMSE score < 25)	FrailtyDeterioration in frailty from baseline based on sum of frailty indicators and tiredness in daily activities	Mob-T ScaleMaximal hand grip strengthGothenburg quality of life instrument (symptom scale)Gothenburg quality of life instrument (symptom scale)Number of walks for weekBerg's balance scaleGait speedKM chartMMSEAssessment at baseline, and one year and two years after intervention
Bonnefoy, et al., 201222	Presence of low gait speed (< 0.8 m/second) and/or poor physical activity (Physical Activity Scale for the Elderly score < 64 for men and < 52 for women)	Physical activityMaximal weekly walking time and distanceFunctional outcomes - walking speed - ADLs - instrumental ADLs - mobilityNutritional outcomesSafety outcomes - injuries during exercise - emergency hospitalization - transfer to long-stay institutions	PASEGait speedTime up-and-go testOne-minute chair-rise countSix-step climb timeFat free Mass and Body Mass indexthe Mini Nutritional AssessmentDietary intakeAssessment at baseline and after four-month study
Cadore et al., 201441	Presence of three or more frailty indicators, as defined by Fried et al. (2001): - weakness - exhaustion - weight loss - low physical activity - slowness	Functional statusDual task performanceIncidence of fallsMaximal isometric and dynamic strengthMuscle powerMuscle cross-sectional areaMuscle tissue attenuation	Time up-and-go testsDual tasksFICSIT-4 tests of static balanceBarthel IndexQuestionnaire of falls incidenceMaximal isometric and dynamic strength and muscle power using 1-repetion maximum testComputer tomography scans using 64-row CT scannerAssessment at baseline and after 12-week intervention
Chan et al., 201242	Frailty indicated by score 3–6 on CCSHA-CFS-TV and then by score ≥ 1 on CHS-PCF. Frailty indicators defined as: - weakness (≤ 29–32 kg for men and ≤ 17–21 kg for women, depending on BMI) - exhaustion (affirmative response for statements “I felt that everything I did was an effort” and “I could not get going” and indication that this situation was present at least occasionally or more frequent) - weight loss (unintentional weigh loss of > 3 kg or > 5% of body weight in the previous year) - low physical activity (weekly energy expenditure for activities ≥ 2 metabolic equivalent tasks of fewer than 383 kcal for men and 270 for women) - gait speed (five-meter walking time ≥ 7 s for men with height ≤ 173 cm or ≥ 6 s for men with height > 173 cm; and walking time ≥ 7 s for women with height ≤ 159 cm or ≥ 6 s for women with height > 159 cm)	Changes in frailtyHealth-related outcomes - cognitive function - mental disorders - ADL - health care re source utilization - health-related quality of lifeComplex body composition and musculoskeletal system domain - body mass index - fat free mass (Inbody 3.0®, as a substitute of lean body mass) - lowest T score from spine and hip bone mineral density - left one-leg-stand time - dominant leg extension powerBlood chemistry - 25(OH) Vitamin D	Maximal hand grip strengthCES-D (two questions)Self-report of weight lossTaiwan International Physical Activity Questionnaire Short FormGait speedMMSEPrimary Care Evaluation of Mental DisordersBarthel IndexHealth care re source utilization questionnaireEQ-5DAssessment at baseline, at the end of intervention (three months after baseline assessments), and six and 12 months after baseline assessmentsFor MMSE, bone mineral density and 25(OH) Vitamin D, data was collected only at baseline and 12 months later.
Clegg, et al., 201443	Score > 8 in the Edmonton Frailty Scale that samples 10 domains, including cognitive impairment, functional ability and mobility, measured using the Timed up-and-go test	Basic mobility and functional abilityADLsHealth-related quality of lifeDepression	Edmonton Frailty ScaleTimed up-and-go testEQ-5DGeriatric Depression Scale – Short Form 15Assessment at baseline and at 14 weeks post-randomizationEdmonton Frailty Scale was administrated only at baseline
Cohen, et al., 200244	Presence of at least two of following criteria: - inability to perform one or more basic ADL - a stroke within the previous three months - a history of falls - difficulty walking - malnutrition - dementia - depression - one or more unplanned admissions in the previous three months - prolonged bed rest - incontinence	SurvivalHealth-related quality of life - dimensions of physical functioning, physical limitations, emotional limitations, bodily pain, energy, mental health, social activity, general healthFunctional status - ability to perform basic and instrumental ADLs - physical performance	SF-36Katz Index of ADLFillenbaum brief measure of instrumental ADLsPhysical Performance TestAssessment at baseline, immediately after intervention, and 12 months after randomization:
Eklund, et al., 201329	Presence of more than two frailty indicators: - weakness (<13 kg for women and <21 kg for men for the dominant hand, and < 10 kg for women and <18 kg for men for the non-dominant hand) - fatigue (affirmation of suffering general fatigue or tiredness over the last 3 months) - weight loss (affirmation of having weight loss over the last 3 months) - low physical activity (1–2 walks/week or less) - poor balance (Berg's balance scale score ≤ 47) - gait speed (walking four meters or less in 6.7 s) - visual impairment (visual acuity < 0.5 in both eyes using the KM chart) - cognition (MMSE score < 25)	Changes in levels of frailtyADL	Maximal hand grip strengthGoteborg quality of life instrument (symptom scale)Goteborg quality of life instrument (symptom scale)Number of walks for weekBerg's balance scaleGait speedKM chartMMSEKatz ADL IndexAssessment at baseline, and at three-, six - and 12-month after discharge
Fairhall, et al., 201532	Presence of three or more Fried's frailty criteria: - weakness (grip strength ≤18 kg for women and ≤ 30 kg for men) - fatigue (affirmative response for statements “I felt that everything I did was an effort” and “I could not get going” and indication that this situation was present a moderate amount of time or most of the time) - weight loss/shrinking (self-report of unintentional weight loss ≥ 4.5 kg in previous 12 months or loss of ≥ 5% of weight in prior year by direct measurement of weight) - low physical activity (in the past three months not performing weight-bearing physical activity, spending more than four hours per day sitting or going for a short walk once per month or less) - slowness (≥ 6 seconds to walk four meters, with or without a walking aid)	FrailtyHealth-related Quality of Life	Maximal hand grip strengthCES-D (two questions)Self-report of weight lossPhysical activity questionnaireGait speedEQ-5DAssessment at baseline, at three and 12 months
Favela, et al., 201345	1. Score ≥ 0.14 in Frailty Index integrating 34 variables (Rockwood et al., 2001)2. Presence of three or more Fried's frailty criteria: - weakness (grip strength <17 kg for women and < 30 kg for men) - fatigue (affirmative response for statements “I felt that everything I did was an effort” and “I could not get going” and indication that this situation was present a moderate amount of time or most of the time) - weight loss (unintentional weight loss of 4.5 kg in the prior year or after 9-month of follow-up) - low physical activity (evaluated by International Physical Activity Questionnaire and indicating the following pattern of activity: less than three days of vigorous-intensity activity of at least 20 minutes per day, less than five days of moderate-intensity activity and walking less than 30 minutes per day) - slowness (inability to walk 8 feet or taking more than 7 seconds to walk this distance)	Frailty	Frailty IndexMaximal hand grip strengthCES-D (two questions)Self-report of weight lossInternational Physical Activity QuestionnaireGait speedAssessment at baseline and in the final phase nine months laterFrailty Index was administrated only at baseline
Giné-Garriga, et al., 201046	Presence of:1. poor physical ability - walking along a 3-m course and back at a quick comfortable pace/rapid gait test > 10 seconds - failing to stand up five times from a seated position in a hardback chair with arms folded2. and self-reported exhaustion - affirmative response for statements “I felt that everything I did was an effort” and “I could not get going”, and cumulative score ≥ 2	Physical frailty - ADL - gait speed - balancePhysical performance - balance - speed - strength - mobility	Barthel IndexRapid-gait testStand-up testBalance tests - semitandem - tandem - single legLower Body Strength testModified Timed up-and-go testAssessment at baseline, week 12 and week 36
Gustafsson, et al., 201247	Sum of six core frailty indicators: - weakness (grip strength < 13 kg for women and < 21 kg for males for the right hand, and < 10 kg for women and < 18 kg for males for the left hand) - fatigue (affirmation of suffering general fatigue over the last 3 months) - weight loss (affirmation of having weight loss over the last 3 months) - low physical activity (1–2 walks/week or less) - poor balance (Berg's balance scale score ≤ 47) - slow gait speed (walking four meters or less in 6.7 s)	FrailtySelf-rated healthADL	Maximal hand grip strengthGothenburg quality of life instrument (symptom scale)Gothenburg quality of life instrument (symptom scale)Number of walks for weekBerg's balance scaleGait speedSelf-Related Health QuestionnaireADL cumulative scale focusing on nine personal and instrumental activitiesAssessment at baseline and at 3-month follow-up
Hars et al., 201448	Presence of at least one of Fried's frailty criteria: - low grip strength - exhaustion - unintentional weight loss - low physical activity - slow walking speed	FrailtyPhysical activity level - Gait - Balance - StrengthFunctional performanceFall historyNutritional StatusQuality of lifeAnxietyDepressionCognitive functionSelf-rated health statusMedications	Stride length variabilityUsual gait speedOne-legged stanceTimed up-and-go testFive-Times-Sit-to-Stand-TestStructured face-to-face interviewsMini-Nutritional Assessment Short Form12-Item Short Form Health SurveyHospital Anxiety and Depression ScaleMMSEClock-drawing testSelf-rated healthOriginal assessment at baseline and after one year of interventionExtension study assessment: four years after original trial enrolment
Kim, et al., 201549	Presence of three or more Fried's frailty criteria: - weakness (grip strength <19 kg) - fatigue (affirmative response for statements “I felt that everything I did was an effort” and “I could not get going”) - weight loss (unintentional weight loss > 2–3 kg in the last 6 months, or > 1–1.5 kg post-intervention, or > 1.3–2 kg at follow up) - low physical activity (affirmative response to at least 3 of the following 4 statements: “I regularly takes walks less than once a week”, “I do not exercise regularly”, “I do not actively participate in hobbies or lessons of any sort”, “I do not participate in any social groups for elderly people or volunteering”) - slowness (usual walking speed < 1.0 m/s)	Frailty statusBody composition (muscle mass, bone mineral density, body fat)Functional FitnessHematological Parameters (BDNF, IGF-I, IGFBP-3, serum myostatin)	Maximal hand grip strengthCES-D (two questions)Self-report of weight lossPhysical activity questionnaireGait speedInterview SurveyDual-energy X-ray absorptiometryKnee extension strengthWalking speedTimed up-and-go testHuman BDNF, IGF-I and IGFBP-3 Quantikine ELISA kitsHuman Myostatin ELISA kitAssessment at baseline, after three-month intervention and at four-month follow-up after intervention
Kim & Lee, 201323	Presence of low mobility (usual gate speed < 0.6 m/second) and poor nutrition (Mini Nutritional Assessment score < 24)	Functional statusFunctional performancePhysical performanceWeakness (grip strength)Nutritional statusMobilityAdverse effects	Physical Functioning testsShort Physical Performance Battery testsTimed up-and-go test and one-legged stanceMaximal hand grip strengthDietary intake assessed by three non-consecutive 24-hour recallsGait speedSign or symptom that the participant complained about after initiation of nutritional supplementAssessment at baseline and after 12-week intervention
Li, et al., 201050	Sum of five frailty indicators as defined by Fried (2001): - unintentional weigh loss of at least 4.5 kg in the previous year - self-reported exhaustion - weaknesses (grip strength) - slow walking speed - low physical activity	FrailtyFunctional Status including ADL	Frailty assessment as defined by Fried (2001) – without detailed descriptionBarthel IndexAssessment at baseline and six months later
Monteserin et al., 201051	Presence of at least two of the following conditions: - age of 85 years or more - Gijón Social Scale score ≥ 9 - Pfeiffer Scale score ≥ 2 - Yesavage Depression Scale score ≥ 1 - Charlson Comorbidity Index score ≥ 2 - Barthel Index score ≥ 91 - Mininutritional Assessment Short Form score ≥ 12 - polimedication (higher than the mean number of drugs taken by the study population) - having fall history in the last six months (> one fall in the last six months) - having daily urinary incontinence in the last six months	Functional statusInstrumental ADLsCognitive statusDepressionNutritional statusSocial support evaluationComorbidityComposite outcome of all causes of death, admissions to nursing home facilities and admissions to a home care progra	Scale of GijónPfeiffer ScaleYesavage Depression scaleCharlson Comorbidity IndexBarthel IndexLawton IndexMininutritional Assessment Short FormFalls registerAssessment at baseline and at the end of the study (after 18-month intervention)
Muller et al., 200652	Physical frailty measured by means of specific test battery, including isometric grip strength, leg extensor power and physical performance	FrailtyADLCognitive functionBone mineral densityBody compositionAtherosclerosisBlood pressureHormone levels	Grip strengthLeg extensor powerPhysical performance - standing balance - walking speed - chair riseModified Stanford Health Assessment QuestionnaireMMSE7.5-MHz linear array transducerx-ray absorptiometryBlood samples analyzed by RIA using commercial kitsAssessment at baseline and on the end point one to four times in 36 week.
Ng, et al., 201553	Sum of five frailty indicators as defined by Fried (2001): - unintentional weigh loss (BMI: weight/height2 <18.5 kg/m2 or self-reported unintentional weight loss ≥ 10 pounds (4.5 kg) in the last 6 months) - self-reported exhaustion (composite score < 10 on 3 questions: “Did you feel worn out?,” “Did you feel tired?,” “Did you have a lot of energy?,” with appropriate reversed scorings). - weaknesses (muscle strength assessed by knee extension in the dominant leg; lowest quartile of values stratified for BMI and sex was used to denote weaknesses) - slowness (6-meter fast gait speed test; the lowest quintile of values stratified for height and age was used to denote slowness) - low activity (frequency and duration of six different activities in the past two weeks; the lowest quintile was used to classify participants with low activity)Presence of one or two symptoms indicates pre-frailty, presence of three symptoms or more indicates frailty	Changes in frailty statusChanges in frailty componentsChanges in frequency of hospitalizationsChanges in frequency of fallsDependency in instrumental ADLs	Self-reported weight loss or BMIGait speedPhysiological Profile Assessment (weakness component)Medical Outcomes Study SF-12 scale (vitality domain)Longitudinal Ageing Physical Activity QuestionnaireSelf-report of falls and hospitalizationsIndex of instrumental ADLsAssessment at baseline and at three-, six - and twelve months
Van Hout et al., 201054	Frailty defined by self-reported score in the worst quartile of at least two of six COOP-WONCA charts: - overall health (score ≥ 4) - physical fitness (score ≥ 5) - changes in health (score ≥ 4) - daily activities (score ≥ 4) - mental health (score ≥ 3) - social activities (score ≥ 3)Scoring range varied from 1(excellent) to 5 (very bad).	Functional statusDisability in ADL and instrumental ADLHospital admittanceTime until placement in nursing homes or homes for disabled older personsTime until death	COOP-WONCA charts measuring functional healthSF-36Groningen Activity Restriction ScaleLocal hospital registry, supplemented with self-report dataPrimary care physicians medical records, hospital database and nursing homes registriesAssessment at baseline and at six and 18 monthsGroningen Activity Restriction Scale was administrated only at baseline and at 18 months
Vriendt, et al., 201621	Impairment in the basic ADL functioning	Basic ADLsHealth-related Quality of Life - dimensions of physical functioning, physical role functioning, bodily pain, mental health, vitality	BEL-profile Scale/WHO – questionnaireSF-36Assessment at baseline and at the end point of the program (between 8 and 10 weeks after randomization)
Wolf et al., 200355	Frailty identified by the presence of biomedical, functional and psychosocial indicators	Biomedical outcomes - strength - flexibility - cardiovascular endurance - body compositionFunctional outcomes - instrumental ADLPsychosocial well-being outcomes - depression - fear of falling - self-perception of present and future health - quality of sleep and intrusivenessFalls and injurious falls incidence	Functional performance testsHeart rate and blood pressure records after 12-minute walkSkinfold measuresLawton and Brody IADL scaleCES-DFear of falling questionnaireQuestionnaire related to psychosocial outcomesNicholas MMT 0116 muscle tester (Lafayette Instruments)The average force developed from three contractions using the Jamar Smedley-type hand dynamometer (Therapeutic Equipment Corporation)Assessment at baseline, after 15-week intervention, and at four-month follow upAssessment of heart rate, blood pressure and skinfold thickness only before and after intervention

^*The outcomes measured only at baseline were not included.

ADL, Activities of daily living; BDNF, Brain-derived neurotrophic factor; IGF-I, Insulin-like growth factor 1; IGFBP-3, insulin-like growth factor-binding protein 3; CCSHA-CFS-TV, Chinese Canadian Study of Health and Ageing – Clinical Frailty Scale (telephone version); CES-D, Center for Epidemiological Studies - Depression Scale; CHS-PCF, Cardiovascular Health Study Phenotypic Classification of Frailty; EQ-5D, EuroQol Group 5-Dimension Self-Report Questionnaire; IADL, Instrumental activities of daily living; KM chart, visual acuity chart; MMSE, Mini-Mental State Examination; PASE, Physical Activity Scale for the Elderly; SF-36, Medical Outcomes Study 36-Item Short-Form General Health Survey.