CLINICAL NUTRITION HIGHLIGHTS - nestlehealthscience.in · Editorial development by MIMS (Hong Kong) Limited. The opinions expressed in this publication are not necessarily those of

In this issue

Nutrition, frailty and prevention of disabilities with aging

Highlights of the 83rd NNI Workshop on Frailty: Pathophysiology, Phenotype and Patient Care

Science supporting better nutrition2014 • Volume 9, Issue 1

ISSN 1815-7262

CLINICALNUTRITIONHIGHLIGHTS

CLINICAL NUTRITION HIGHLIGHTSScience supporting better nutrition2014 • Volume 9, Issue 1

Feature article 2

Nutrition, frailty and prevention of disabilities with aging Secher M, Guyonnet S, Ghisolfi A, Ritz P, Vellas B

Summary 2 Introduction 2 The frailty syndrome: A common situation in geriatric medical care 3 Observational and interventional studies link nutrition and frailty 3 Results of observational studies 4 Results of interventional studies 6 Incorporating assessment and management of frailty into clinical practice 8 Table 1. Results of observational studies on the relationship between poor

nutrition and frailty risk 10 Table 2. The Mediterranean-style diet 17 Table 3. Randomized controlled trials to evaluate the efficacy of nutrient

supplementation to modify frailty risk 17 Table 4. Randomized controlled trials to evaluate the efficacy of physical

activity to modify frailty risk 18 Table 5. Randomized controlled trials to evaluate the efficacy of multi-domain

Interventions to modify frailty risk 19 Table 6. Characteristics of the first 160 patients evaluated during the first

6 months of operation of the program 22 Table 7. Characteristics of the pre-frail and frail patients evaluated during the

first 6 months of operation of the program 23

Highlights of the 83rd Nestlé Nutrition Institute Workshop 2614−15 March 2014, Barcelona, Spain

Conference calendar 32

Sponsored as a service to the medical profession by the Nestlé Nutrition Institute.

Editorial development by MIMS (Hong Kong) Limited. The opinions expressed in this publication are not necessarily those of the editor, publisher or sponsor. Any liability or obligation for loss or damage howsoever arising is hereby disclaimed. Although great care has been taken in compiling and checking the information herein to ensure that it is accurate, the editor, publisher and sponsor shall not be responsible for the continued currency of the information or for any errors, omissions or inaccuracies in this publication.

© 2014 Société des Produits Nestlé S.A. All rights reserved. No part of this publication may be reproduced by any process in any language without the written permission of the publisher.

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Nutrition, Frailty and Prevention of

Disabilities with AgingSecher M, MD,1 Guyonnet S, PhD,1,2 Ghisolfi A, MD,1 Ritz P, MD PhD,2,3 Vellas B, MD PhD1,2

1. Gérontopôle, CHU Toulouse, France

2. UMR INSERM 1027, University Paul Sabatier, France 3. Pôle cardio-vasculaire et métabolique, CHU Toulouse, France

Address for correspondence: Sophie Guyonnet, Gérontopôle, Centre Hospitalier Universitaire de Toulouse, 170 avenue de Casselardit,

TSA 40039, 31059 Toulouse cedex 9. Email: [email protected]

Summary

Older adults can be categorized into three subgroups to

better develop and implement personalized interventions:

the “disabled’’ if needing assistance in the accomplishment of

basic activities of daily living (ADL), the “frail” if limitations

and impairments are present in the absence of disability, and

“robust” if there is no frailty or disability present. However

despite evidence linking frailty to poor outcomes, frailty is

not a criterion for implementation of clinical interventions in

most countries. Since many elderly are not identified as frail,

they frequently are treated inappropriately in healthcare

settings. Assessment of frailty or pre-frailty in older adults

is recommended to preventively act before the irreversible

cascade of disability commences. Clinical characteristics

of frailty (weakness, low energy, slow walking speed, low

physical activity and weight loss) underline the links between

nutrition and frailty. Physical frailty is also associated with

cognitive frailty. At the Gérontopôle Frailty Clinics, France,

nearly 40% of patients referred by their primary care

physician to evaluate frailty have significant weight loss

(more than 4.5 kg in the past 3 months), 83.9% of patients

present with slow gait speed, 53.8% were sedentary, and

57.7% had poor muscle strength. Moreover, 43% had a

Mini Nutritional Assessment (MNA®) score less than 23.5

and 9% less than 17, reflecting risk for and malnutrition

respectively. Of those with physical frailty, more than 60%

have some cognitive impairment. In this paper we review

clinical evidence on undernutrition and frailty and the

potential for current interventions to help prevent frailty and

disability with aging.

Introduction

Disability that occurs with aging is a clinical issue representing

a priority for public health systems. Indeed, besides posing

a severe burden on the patient’s quality of life, disability is

associated with high healthcare costs.1 Assessment of frailty

and pre-frailty in older adults is recommended to preventively

act before the irreversible cascade of disability commences.2

Over the past two decades, a growing body of literature has

been specifically focused on exploring the “frailty syndrome”.

Frail older adults are at increased risk of negative health-

related events, including hospitalization, institutionalization

and disability. In particular, frailty is usually considered a

pre-disability state which, in contrast to disability, is still

amenable to interventions and, hence, reversible.3 On the basis

of this novel concept, the heterogeneous older population

was subsequently categorized into three subgroups to better

develop and implement personalized interventions. Older

List of abbreviations ADL: Activities of daily livingAFAR: American Federation of Aging Research AMDA: American Medical Directors Association BI: Barthel Index BMI: Body mass indexCGA: Comprehensive Geriatric Assessment CHS-PCF: Cardiovascular Health Study Phenotypic Classification of FrailtyELSA: English Longitudinal Study of Ageing EU: European UnionEUGMS: European Union Geriatric Medicine Society FFC: Fried Frailty CriteriaFFQ: Food Frequency QuestionnairesFI: Frailty Index GEC: Gateway Geriatric Education CenterIADL: Instrumental activities of daily livingIAGG: International Association of Geriatrics and GerontologyIANA: International Academy of Nutrition and Aging InCHIANTI: Invecchiare in ChiantiIOM: Institute of Medicine RCT: Randomized controlled trialSPPB: Short Physical Performance Battery SSCWD: Society on Sarcopenia, Cachexia, and Wasting DisordersWHAS: Women’s Health and Aging Studies

This article was previously published in The Journal of Nutrition Health and Aging

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CLINICAL NUTRITION HIGHLIGHTS • 2014 • Volume 9, Issue 1

persons were considered “disabled” if needing assistance

in the accomplishment of basic ADL; “frail” if presenting

limitations and impairments are present in the absence of

disability; and “robust” if no frailty or disability is present.

Frailty has been conceptualized as a geriatric syndrome

resulting from decreased physiological reserve and resilience,

which may lead to progressive functional decline, vulnerability

to stressors, and an elevated risk of adverse outcomes, including

death. It is a major cause of dependency, yet research suggests

that it may be possible to prevent disability and dependency

by targeting frail and pre-frail older adults with simple

screening tools and effective and sustained interventions.2

Frailty has been recognized as an important condition by

the Institute of Medicine (IOM)3 and the European Union

(EU). While a consensus conference held in 2011 concluded

that frailty has a clear conceptual framework and is useful

to consider in clinical settings, its assessment is not typically

implemented in clinical practice today.4 Another consensus

conference – 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 EU, and the Gateway Geriatric Education Center (GEC)

was convened in October 2012, in Orlando, Florida, USA,

to develop a consensus operational approach (the Orlando

Task Force).5 Nutritional supplementation to address weight

loss and muscle dysfunction, and intervention for conditions

such as sarcopenia, may also represent feasible approaches to

treat the underlying conditions of frailty. Because weight loss

is an important part of the frailty syndrome,6,7 it is obvious

that nutritional assessment and intervention will play a major

role in frailty assessment and treatment. We will review in

this paper the recent data on the links between nutrition and

frailty, and how easily frailty management can be incorporated

into clinical practice.

The frailty syndrome: A common situation in geriatric medical care

Strong evidence supports the definition of frailty as a syndrome

with a distinct etiology that consists of a constellation of

signs and symptoms that increase vulnerability to stressors

and that, taken together, are better at predicting an

adverse outcome than any individual characteristic. Fried

and colleagues proposed that the signs and symptoms of

frailty result from the dysregulation of multiple molecular

and physiological pathways, which lead to sarcopenia,

inflammation, decreased heart rate variability, altered clotting

processes and hormone levels, insulin resistance, anemia and

micronutrient deficiencies.6 These physiological impairments

result in the five clinical characteristics of physical frailty:

weakness, low energy, slow walking speed, low physical

activity and weight loss. These clinical characteristics are

also known as the Fried Frailty Criteria (FFC).6 The presence

of any three of these phenotypes indicates that a person is

“frail”; one or two phenotypes indicate “pre-frail”; while the

absence of any of these characteristics indicates the person is

“robust”.

A systematic review based on 21 cohorts involving

61,500 participants found that, on average, 10.7% of

community-dwelling older persons are frail and another

41.6% are pre-frail.8 Nevertheless, the reported prevalence

differed substantially, ranging from 4.0% to 59.1%. The wide

range in the results was considerably reduced by arranging

the studies according to the frailty definition used. In studies

that used a frailty definition according to purely physical

phenotype, frailty prevalence range from 4.0% to 17.0%.

In studies that used broad definitions (including social and

psychological aspects), prevalence varied from 4.2% to

59.1%.8 While the Fried approach quantifies frailty using

five measures, Rockwood and colleagues have developed

a Frailty Index (FI) based on the Comprehensive Geriatric

Assessment (CGA), which includes up to 70 items. In a study

of community-dwelling older adults in Canada, the FI-CGA

estimated the prevalence of frailty was 22.7%; higher FI-CGA

scores predicted an increased risk of death at 5 years.9 The

mortality risk increased from 22.4% for the one-third of

subjects with FI-CGA values less than 0.15, to 59.9% for the

one-third with FI-CGA values greater than 0.30. At the limit

of the FI-CGA, 5-year mortality was 100%.9

Frailty assessed using the FFC has been linked to

longer hospital stays and increased mortality in hospitalized

patients.10 Moreover, in their study of disability trajectories of

community-dwelling older persons during the last year of life,

Gill and colleagues found that frailty (assessed by the FFC)

was the most common condition leading to death, followed

by organ failure, cancer, other causes, advanced dementia and

sudden death.11 As there is strong evidence linking frailty to

poor outcomes, frailty screening and management should be

implemented in clinical practice in all countries. Since many

people are not identified as frail, they are frequently treated

inappropriately in healthcare settings. Regardless of age, a

frail person may be unable to withstand aggressive medical

treatment that could benefit a non-frail person.

Observational and interventional studies link nutrition and frailty

Frailty can be influenced by a number of factors with poor

nutrition identified as an influencing factor on the development

of frailty. The Orlando Task Force5 considered that evidence

supported three treatments that appeared to be effective in

decreasing the incidence and/or prevalence of frailty:

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- Calorie and protein supplementation

- Vitamin D supplementation

- Exercise (resistance and aerobic)

The aim of this paper is to summarize the recent literature

on the relationship between nutrition and frailty demonstrated

through epidemiological studies, focusing on adiposity measured

by body mass index (BMI); intake of calories, macronutrients

(eg, protein) and micronutrients (particularly vitamin D); and

physical activity. Results from recent meta-analyses, reviews,

longitudinal studies and randomized controlled trials (RCTs)

are included. Because there is no consensus definition of frailty,

the focus is particularly on results of studies that use the clinical

definition of the frailty phenotype developed by Fried. The

results are also presented of some studies that use physical

frailty-related parameters (such as walking speed, handgrip

strength, and disabilities in instrumental activities of daily living

[IADL]). Note that the specific criteria used to define frailty in

each study are described in the accompanying tables. These

tables are included at the end of the article, starting on page 10.

Results of observational studies

Table 1 summarizes observational studies that examine

the relationship between frailty and undernutrition. Note

that these studies were conducted in community-based

populations; hence, the typology of the frail older adults

is probably not of the same severity as those referred to by

primary care physicians as “frail”.

BMI and frailty risk

For the adult population, the BMI cut offs for “underweight”,

“overweight”, and “obesity” are established to be 18.5,

25 to 29.9, and 30 kg/m2, respectively. For older adults,

a BMI of <21 kg/m2 is considered to be “underweight”.

The relationship between BMI and frailty data remains

conflicting.

In the Women’s Health and Aging Studies (WHAS)

(follow-up of 599 women, aged 70−79 years with BMI

greater than 18.5 kg/m²), Blaum and colleagues showed

that being overweight was significantly associated with

pre-frailty, and obesity was associated with pre-frailty and

frailty.12 In multinomial regression models, obesity was

significantly associated with pre-frailty (odds ratio [OR]

2.23; 95% confidence interval [CI] 1.29−3.84) and frailty

(OR 3.52; 95% CI 1.34−9.13), even when controlling for

covariates.

In the WHAS II study (including 250 subjects aged

76−86 years), results showed that there is no statistically

significant difference in BMI between frail, pre-frail and

robust.13

In the English Longitudinal Study of Ageing (ELSA)

that included 3,055 subjects aged 65 years and older,

Hubbard and colleagues showed that the association

between BMI and frailty was U-shaped. The lowest FI

scores (index of accumulated deficits included sensory and

functional impairments, self-reported comorbidities, poor or

fair self-rated health, low mood or depression and a score in

the lowest 10% of a composite measure of global cognitive

function) and lowest prevalence of Fried frailty were in those

with a BMI of 25 to 29.9 kg/m2.14 For each BMI category,

and using either measure of frailty, patients with a high waist

circumference were significantly more frail.

A recent paper that included 4,731 patients aged

60 years or older showed that prevalence of frailty was

highest among people who were obese (20.8%), followed

by overweight (18.4%), normal weight (16.1%) and, lastly,

underweight (13.8%).15 Independent of BMI, daily energy

intake was correlated to frailty risk. Daily energy intake was

lowest in people who were frail (1,587 Kcal), followed by

pre-frail (1,663 Kcal), and highest in people who were not

frail (1,587 Kcal). Energy-adjusted macronutrient intakes

(protein, carbohydrate, fat) were similar in people with

and without frailty. Food insufficiency was self-reported

as “sometimes” or “often” not having enough food to eat.

Frail and pre-frail individuals were more likely to self-report

being food insufficient than robust individuals, and serum

albumin, carotenoids and selenium levels were lower in frail

adults than non-frail adults.15

More recently, Bowen and colleagues used functional

limitations and disabilities in IADL and ADL to define

frailty.16 In 11,491 subjects aged 50 years or older

followed-up for 8 years, it was shown that the highest BMIs

were protective against functional decline. Compared with

the robust, normal weight older adults (BMI 18.6−24.9

kg/m2), pre-frail obese (BMI ≥30 kg/m2) have a 16 %

(p≤0.001) reduction in the expected functional limitations

rate; frail overweight (BMI 25−29 kg/m2) and obese have a

10% (p≤0.01) and 36% (p≤0.001) reduction in the expected

functional limitations rate, respectively.16

Specific nutrients and frailty risk

A recent study has demonstrated the close association

between frailty syndrome and nutritional status in older

persons.17 Moreover, several observational studies have

shown an association between inadequate intake of specific

nutrients and frailty.

Poor intakes of energy, protein, and specific nutrients elevate frailty risk

In the Invecchiare in Chianti (InCHIANTI) study, Bartali

and colleagues found that low daily energy intake

(≤ 21 kcal/kg) was significantly associated with frailty (OR

1.24; 95% CI 1.02−1.5).18 This study also analyzed the

association between frailty and specific nutrients. After

adjusting for energy intake, a low intake of protein, vitamin

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D, vitamin E, vitamin C, and folate, and having a low

intake of more than three nutrients, were significantly and

independently related to frailty.18

Three studies have shown an association between

inadequate protein intake and frailty.19-21 The WHAS study

involved 24,417 subjects aged 65 to 79 years who were

frailty-free at baseline and followed-up for 3 years.19 Among

the 24,417 eligible women, 3,298 (13.5%) developed frailty

over 3 years. After adjustment for confounders, results

showed that a 20% increase in uncalibrated protein intake

(%kcal) was associated with a 12% (95% CI 8−16%) lower

risk of frailty, and that a 20% increase in calibrated protein

intake was associated with a 32% (95% CI 23−50%) lower

risk of frailty. Uncalibrated protein intake values represent

an estimated intake based on food frequency questionnaires

(FFQ). Calibrated protein intake values represent estimates

derived from linear regression equations developed on

the basis of FFQ nutrient measures and participant

characteristics.19 In the second study, protein intake below

0.7 g/kg/day was observed in 10% of the community-dwelling,

frail elderly population, and 35% of institutionalized

elderly.20 Dietary protein intake averaged 1.1 ± 0.3 g/kg/day

in community-dwelling, 1.0 ± 0.3 g/kg/day in frail, and 0.8 ±

0.3 g/kg/day in institutionalized elderly men. The third study

examined the association between protein and amino acid

composition and frailty among elderly Japanese. A total of

2,108 subjects aged 65 years and older participated.21 The

number of subjects with frailty was 481 (23%). Adjusted

ORs for frailty in the first, second, third, fourth and fifth

quintiles of total protein intake were 1.00 (reference), 1.02

(0.72−1.45), 0.64 (0.45−0.93), 0.62 (0.43−0.90) and 0.66

(0.46−0.96), respectively (p for trend=0.0001). Subjects

categorized to the third, fourth, and fifth quintiles of total

protein intake (>69.8 g/day) showed significantly lower

ORs than those to the first quintile (all p<0.03). The intake

of animal and plant protein and all selected amino acids

(leucine, isoleucine, valine, methionine, cysteine, branched-

chain amino acids, sulfur amino acids, essential amino acids)

were also inversely associated with frailty (p for trend <0.04)

with the multivariate adjusted OR in the highest compared

to the lowest quintile of 0.73 for animal protein and 0.66 for

plant protein, and 0.66–0.74 for amino acids.21

In one recent study, conducted in 194 healthy older

persons, amount of protein intake was not associated with

frailty but distribution of protein intake was significantly

different between frail (15.4% of participants), pre-frail

(40.5% of participants) and non-frail participants.22

Finally, two studies showed a preventive association

between a Mediterranean-style diet (based on a Mediterranean

diet score evaluated by an interview-based FFQ) and

frailty.23,24 The Mediterranean-style diet is described in Table

2. In the InCHIANTI study, 690 subjects aged 65 years or

older were followed-up over 6 years.23 Subjects who adhered

to a Mediterranean-style diet had lower risk of becoming frail

than non-adherents, and were less likely be rated as having

“low physical activity” or “slow walking speed”. Parameters

of “feelings of exhaustion” and “poor muscle strength” were

not correlated with the diet.23

Poor intakes of specific micronutrients elevate frailty risk

Poor intakes of specific micronutrients, as indicated by

low serum levels, are associated with elevated frailty risk.

A number of studies have shown that lower serum levels

of 25-hydroxyvitamin D (25[OH]D) are associated with a

higher prevalence of frailty.25-36

In one report from a group of 1,600 men older than

65 years, low serum levels of 25(OH)D (<20.0 ng/mL) were

associated with a higher prevalence of frailty at baseline but

did not predict greater risk for developing frailty during the

follow-up period of 4.6 years.28

In the InCHIANTI cohort, 1,155 subjects aged 65 and

older were followed-up for 6 years. Results showed that pre-frail

individuals with 25(OH)D levels <20 ng/mL were 8.9% (95%

CI 2.5–15.2%) more likely to die, 3.0% (95% CI 5.6–14.6%)

more likely to become frail, and 7.7% (95% CI -3.5–18.7%)

less likely to become robust than pre-frail individuals with

25(OH)D levels of ≥20 ng/mL. Transitions to pre-frailty from

robustness or frailty were not associated with 25(OH)D levels.

The evidence suggested that pre-frailty is an “at-risk” state

from which older adults with high 25(OH)D levels are more

likely to recover than to decline, but high 25(OH)D levels were

not associated with recovery from frailty.32

More recently, Wong and colleagues conducted a

prospective cohort study among 4,203 older men aged

70–88 years.37 At baseline, 676 (16.1%) men were frail, as

defined by having three or more deficits (Frail Scale ≥ 3). In

multivariate cross-sectional analysis, low vitamin D status,

defined by the lowest quartile of 25(OH)D values (<52.9

nmol/L), was associated with increased prevalent frailty in

comparison to the highest quartile of 25(OH)D values (>81.6

nmol/L). After a mean period of 5.3 years, the adjusted OR

of being frail at follow-up for men with low vitamin D and

having zero deficit at baseline (FRAIL scale = 0) was 1.56

(95% CI 1.07–2.27). Low vitamin D also predicted all-cause

mortality over a period of up to 9.2 years, independent of

baseline frailty and other covariates.

Finally, four observational studies have found

an association between frailty and low serum levels of

antioxidants (vitamin E, vitamin C and carotenoids),29,30,38,39

vitamin B6 and folate.29,30 In addition, significant correlations

were found between high Cu/Zn ratios and deficits in femoral

bone mineral density, measures of speed and strength, muscle

mass and hematocrit in 144 frail elderly men suggesting that

serum Cu levels and the Cu/Zn ratio may serve as useful

predictive biomarkers for poor health in the elderly.40

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Physical activity and frailty protection

Numerous studies have shown that physical activity and

exercise are beneficial in older adults along the full spectrum

of health status.41 The demonstrated benefits of exercise

in older adults include increased mobility and strength,

enhanced performance of ADL, improved aerobic capacity,

function (particularly walking), gait and bone mineral

density, decreased falls, and enhanced general well-being.42-44

Decreased muscle strength occurs naturally with aging,

a phenomenon known as “sarcopenia”. Sarcopenia is even

more pronounced in the frail older adult, and more likely to

impact adverse outcomes such as disability.45

Studies suggest that even the most frail and elderly adults

are likely to benefit from physical activity at almost any level

that can be safely tolerated.46 Regular physical activity has

been shown to protect against diverse components of frailty,

such as sarcopenia, functional impairment and depression.47

Results of interventional studies

A critical next step in decreasing adverse health outcomes

of disability is the implementation of feasible interventions

among frail and pre-frail older adults.

Nutrients and frailty protection

Table 3 summarizes the results of interventional studies,

suggesting that supplementation with specific nutrients can

modify frailty risk.

There are few RCTs that evaluate the relationship

between nutrient supplementation and frailty protection as

measured by improvement in physical functionality.

The effect of vitamin D supplementation (a single

dose of calciferol, 300,000 IU) versus placebo on physical

performance was studied in 243 frail adults aged 65 years

and older.48 The results did not show a difference between

treatment groups, even in those who were vitamin D deficient

(< 12 ng/mL) at baseline.

In an RCT on the effect of protein supplementation,

Tieland and colleagues showed an improvement of Short

Physical Performance Battery (SPPB) in frail older adults

randomized to receive 15 g of supplemental protein daily for

24 weeks compared with the placebo group (p=0.02).49

Another RCT on the effect of a daily supplementation

with protein and micronutrients for 12 weeks in 87 frail

older adults (usual gait speed <0.6 m/s; MNA® < 24) has

been published recently.50 Results showed that physical

functioning increased by 5.9% (1 point) in the intervention

group, although no change was observed in the control

group. SPPB remained stable in the intervention group,

although it decreased by 12.5% (1 point) in controls.

While a few RCTs show promising effects of nutritional

supplementation on physical functionality, further long-term

studies are needed, with multi-domain intervention in large

populations of older adults.

Physical activity and frailty protection

Table 4 summarizes the results of interventional studies

suggesting that physical activity can modify frailty risk.51-54

Exercise is believed to be the most effective of all

interventions proposed to improve functionality in older

adults. A systematic review by Theou et al found that

exercise has a positive impact on physical determinants

(cardiorespiratory function, muscle function, flexibility) and

functional ability (including mobility, balance and functional

performance) in frail older adults. Multicomponent training

interventions, of long duration (≥ 5 months), performed three

times per week, for 30–45 minutes per session, generally had

superior outcomes than other exercise programs.55

More recently, another systematic review has been

published on the effect of exercise in frail older adults.56 The

authors concluded that the exercise intervention only slightly

affected physical function, mainly by increasing gait speed

and Berg Balance Scale score and improving performance

in ADL. Nevertheless, they emphasized that participants

included in these trials may not represent the average frail,

elderly population. It is likely that those who would have

benefited from exercise were excluded from the trial due

to age or other comorbidities that prevented them from

exercising. Furthermore, this review does not clarify what type

of exercise is likely to be most beneficial. Similar conclusions

were proposed in the systematic review and meta-analyses

published by Giné-Garriga.57 When compared with control

interventions, exercise was shown to improve normal gait

speed, fast gait speed, and the SPPB. Results are inconclusive

for endurance outcomes, and no consistent effect was observed

on balance and the ADL functional mobility. The evidence

comparing different modalities of exercise remains scarce and

heterogeneous.57

Langlois and colleagues have recently published the

results of an RCT on exercise-training intervention over 12

weeks in 83 frail older adults aged 61–89 years.54 Compared

with the control groups, the intervention group showed

significant improvement in physical capacity (using the

modified Physical Performance Test [PPT] and 6-minute

walk test), cognitive performance and quality of life. Overall

benefits were equivalent between frail and robust individuals.

A study is underway to evaluate the impact of the

Nintendo Wii Active program against standard gym-based

rehabilitation on reducing falls and fear of falling in moderately

frail older adults.58

A recent paper reviewed the literature on the utility of

exercise training as an intervention for frailty.59 While further

long-term RCTs are still needed, the majority of studies

suggest that clinicians should recommend regular physical

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activity or exercise training to frail older adults as a means to

modify frailty risk and its adverse outcomes. Most trials found

benefits associated with resistance exercise training, while an

aerobic activity such as walking offers distinct advantages and

should also be practiced.

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

Multi-domain interventions are currently being tested

in large programs.60 This multi-domain approach will

aim to treat physical and cognitive frailty using nutrition

supplementation in combination with physical and cognitive

exercise.

Table 5 summarizes the results of interventional

studies suggesting that a multi-domain approach can modify

frailty risk.

The combination of exercise and a weight loss diet (a

balanced diet providing an energy deficit of 500–750 kcal/d

from daily energy requirement) as one arm of an RCT for

obese adults aged 65 years or older had greater impact on

measures of frailty (strength, balance, gait, scores on the

PPT, peak oxygen consumption) than either intervention

alone.61 Feasibility and benefits of interventions combining

nutritional supplements and exercise were also previously

demonstrated in very frail elderly nursing home residents.62

Most studies of multi-domain interventions in frail

older adults have evaluated the effect of a combination of

nutritional supplementation and physical activity. In one

study, 96 frail adults older than 75 years were randomized

into one of four groups: physical training program (aerobic,

muscle strength, balance), nutritional intervention program

(individually targeted advice and group sessions), a

combination of these interventions, and a control group.63

Subjects were evaluated at baseline, immediately after the

intervention (which lasted for 12 weeks), and after another 6

months. Significant improvements in lower-extremity muscle

strength were observed in both training groups compared

with the nutrition 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 improvement

in outcomes.63 In addition, both interventions were not

associated with a positive effect on energy intake, resting

metabolic rate or fat-free mass. The participants with a low

energy intake who managed to increase their energy intake

during the study (‘responders’) had a statistically significantly

lower BMI (21 vs 24 kg/m2) and a lower fat percentage (23

vs 30%) at baseline than the ‘non-responders’.64

Similarly, in another randomized clinical trial of

7 weeks’ duration, it was shown that comprehensively

structured, high-intensity regimen comprised of diverse

exercise types (ie, functionally-oriented, progressive

resistance and standard exercises), preferably combined with

nutritional supplementation (200 mL liquid supplying 300

kcal in the form of carbohydrate [49%], lipids [35%] and

protein [16%]), demonstrates clear potential for appreciably

improving overall status in the frail elderly in terms of

individual walking capacity and muscle strength.65

Finally, Tieland and colleagues conducted an RCT

in 62 frail older adults (mean age of 78 years) randomized

into two groups: progressive resistance-type exercise

training program (two sessions per week for 24 weeks) and

supplemented twice a day with either 15 g protein (total

30 g/day) or protein-free placebo.66 Results showed that lean

body mass (measured by DEXA) increased significantly from

baseline (47.2 kg to 48.5 kg) in the protein-supplemented

group but did not change in the placebo group (45.7 kg

to 45.4 kg). Strength and physical performance (SPPB)

improved significantly in both groups (p=0.000) with no

interaction of dietary protein supplementation. Dietary

protein supplementation offered no functional benefit in this

small-scale study that was unlikely powered sufficiently to

detect effects of strength and physical performance.

An RCT testing nutritional and physical activity

interventions in malnourished frail community-dwelling

persons by trained lay buddies is currently in progress. In this

study, malnourished frail persons are visited by buddies at

home twice a week for about 1 hour during an initial period

of 10–12 weeks. Participants allocated to the intervention

group (n=40) receive intervention to improve their fluid

intake, protein and energy intake, perform strength training

and try to increase their baseline activities; the control group

(n=40) receive only home visits without any intervention.67

Since many factors other than exercise influence the

occurrence of frailty, three recent RCTs have explored other

components of this clinical syndrome.68-70

Li and colleagues studied the effect of an intervention

including both CGA and appropriate intervention by

medication adjustment, exercise instruction, nutrition

support, physical rehabilitation, social worker consultation,

and specialty referral versus a control group in 310 frail

older adults (mean age of 79 years) on the FFC and the

Barthel Index (BI) of activities of daily living after 6 months

of follow-up.68 Results showed that compared to the control

group, the FFC and BI of the intervention group were more

likely to improve and less likely to deteriorate but without

a significant difference between the mean values for the two

groups.

More recently, Fairhall and colleagues implemented

a multifactorial, interdisciplinary intervention that targets

defined frailty components (home exercise program targeting

mobility, and coordinated management of psychological

and medical conditions) in 216 frail older adults (mean

age of 83 years). At 12 months, 4 m gait speed in the

intervention group was faster (by 0.05 m/s) than the control

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group (p=0.048).69 In addition, the intervention group had

significantly better performance than the control group, after

controlling for baseline values, in the Physiological Profile

Assessment (PPA) components of quadriceps strength and

body sway. No difference was found in fall rates between

groups.70 Mobility remained stable in the intervention group,

whereas it declined substantially in the control group.71

Finally, in a recent RCT, 117 frail older adults (65–79

years) were randomized into two groups: intervention group

with exercise and nutritional advice (EN) or problem solving

therapy (PST) and a control group (without either EN or

PST).72 EN group subjects received personalized nutrition

advice and a three-times weekly exercise training program,

while PST group subjects received six sessions in 3 months.

The PST is a brief form of evidence-based psychotherapy

that teaches people how to solve the “here-and-now”

problems contributing to their mood-related conditions and

helps increase their self-efficacy. The primary outcome was

improvement of the CHS-PCF (Cardiovascular Health Study

Phenotypic Classification of Frailty) by at least one category,

and the EN group showed a higher improvement rate than

non-EN group subjects (p = 0.008) at 3 months, but not 6 or

12 months.72

Incorporating assessment and management of frailty into clinical practice

Primary care physicians and other healthcare professionals are

essential for assessing frailty risk in older adults incorporating

frailty management in routine patient care. The first step in

the management of frailty is the use of a simple screening test

to identify vulnerable individuals. Several different methods

of screening for frailty have been developed and validated.

The FFC was operationalized into a screening algorithm for

use in the Cardiovascular Healthy Study (CHS). Other frailty

measures have also been proposed, including the Study of

Osteoporotic Fractures (SOF) Index.73 All of these measures

count deficits and quantify the degree of frailty and, thus, the

degree of vulnerability to adverse outcomes. Moreover, all

of them reflect an aging-associated failure of physiological

systems.

Another frailty screening tool that relies on the clinical

opinion of the general practitioner was developed in France.

In response to the French government’s policy on preventing

disability in older persons, a day hospital was established in

2011 at the Gérontopôle of Toulouse (ie, the geriatric center

of Toulouse) for the evaluation of frailty and prevention

of disability.74 Geriatric patients are referred to the center

by general practitioners who detect signs and symptoms

of frailty and are screened using a simple, quick frailty

questionnaire, and undergo an assessment of gait speed. The

Frailty Screening Tool asks six questions regarding living

alone, weight loss, fatigue, mobility, memory, and slow gait

speed. If the physician identifies one of these areas as an area

of concern, he/she is asked, “In your own clinical opinion,

do you feel that your patient is frail and at an increased risk

for further disabilities?” It is this last question that is used to

distinguish patients who are frail.

The goal of the Gérontopôle frailty clinics is to

identify frailty in the early stages through a multidisciplinary

evaluation, attempt to identify the cause or causes (ie,

underlying comorbidities or other risk factors), and

implement multidisciplinary interventions adapted to each

patient’s individual needs. These interventions may include

nutrition, physical exercise and/or physical therapy, social

support, and education. Patients are followed-up principally

by their general practitioner, with additional follow-up

through telephone contact and a structured interview

with a nurse from the center to assess the efficacy of the

interventional plan.

We recently published a description of the first 160

patients referred for frailty by general practitioners to the

Gérontopôle Frailty Clinic (Table 6).74 The mean age of this

population is 82.7 years, with the majority aged 75 years and

older. Most patients are women (61.9%). Approximately

two thirds of patients received some kind of regular help at

home. Regarding level of frailty, 65 patients (41.4%) were

pre-frail, and 83 (52.9%) were frail 74.

Nearly 40% had significant weight loss of more than

4.5 kg in the past 3 months. In terms of functional status,

83.9% of patients presented with slow gait speed, 53.8%

were sedentary, and 57.7% had poor muscle strength. Only

27.2% of patients had a SPPB score assessing physical

performance of 10 or higher. Autonomy in ADL was quite

well preserved (mean ADL score 5.6 ± 0.8), as expected.

Collectively, these data suggest that the Frailty Clinic

patients have not yet developed disability and, thus, stand

to benefit from intervention. A marginal loss of autonomy

was observed with a mean score IADL sore of 6.0 ± 2.3.

Numerous patients presented with vision problems. Finally,

it is noteworthy that 9% of the Frailty Clinic population

presented in an objective state of protein-energy malnutrition

(MNA® ≤ 17), and 34% an early alteration of nutritional

status (MNA® 17–23.5); almost all (94.9%) had vitamin D

deficiency as measured by low serum levels.

It is important to underline that in frail older adults

it is easier to successfully intervene on nutrition than in

individuals with an acute or more severe condition who

usually have severe anorexia. We have found that risks for

undernutrition are also present in pre-frail subjects (Table

7). About one third of patients (33.1%) presented with a

Mini Mental State Examination (MMSE) score lower than

25. Dementia (measured by the Clinical Dementia Rating

[CDR] scale) was observed in 11.6% of the Frailty Clinic

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population, whereas 65.8% of subjects had mild cognitive

impairment (CDR equal to 0.5). These data underscore the

link between physical and cognitive frailty. Mild cognitive

impairment is prevalent in frail older adults and is in some

part probably related to poor nutritional status. More data

should be collected in terms of the link between risk of

cognitive frailty and low nutrient levels (eg, folate, vitamin

B12, vitamin D, omega-3 fatty acids) in this population. The

Multidomain Alzheimer’s Preventive Trial (MAPT) study is

currently underway and may provide additional data in the

near future.60

In a study of 754 community-dwelling, non-disabled

older adults, Gill and colleagues showed that frailty is

a dynamic process with frequent transitions. While the

overall trend was towards worsening of frailty status, and

the likelihood of transitioning from being frail to non-frail

was very low, about 10% of pre-frail subjects transitioned

to non-frail during each 18-month follow-up period.75 Early

screening to identify pre-frail and frail older adults and an

early multi-domain intervention is likely to largely increase

this proportion.

Today in most geriatric centers, physicians deal with

patients who already have severe disability that is often

not reversible. Almost 95% of geriatric care providers

are involved in treating already dependent older adults.

Continuing to take care of these individuals with severe

disabilities is essential. Moreover, proactive care of pre-frail

and frail older adults to prevent a rapid rise of disability in

our aging population is also important. Frail older adults

are more likely to become dependent, but today they are not

being readily identified and managed by healthcare systems.

To meet this challenge, collaboration between geriatric care

providers and general practitioners to provide targeted,

strong and sustained intervention is required.

- Targeted intervention (specifically pre-frail and

frail older adults)

Simple screening tools are readily available to be used

by general practitioners and other front-line healthcare

professionals to identify vulnerable individuals. For example,

many studies have found that individuals with an MNA®

score between 17 and 23.5 are more likely to be frail.76,77

In settings where nutritional screening with the MNA® is

routine at admission (eg, acute care, long-term car, and home

care), a poor MNA® score can be considered as an alert to

an individual’s vulnerability, and a prompt for further,

more-comprehensive assessment.

- Strong intervention

To have a real impact, the intervention must be strong

and tailored to the results of a CGA in pre-frail and frail

patients. Specific tools can be used to diagnose potential

age-related disease at the first onset of symptoms, where it is

still possible to cure the patient. The CGA must also include

social, health, economic and psychosocial assessment, as

well as the evaluation of the deficit accumulation.

- Sustained intervention

The growing aging population necessitates having

long-term and sustained intervention. A combination of

physical exercise, cognitive exercise, nutrition intervention,

and social services will be needed for the management

of age-related diseases. The potential to develop more

standardized multi-domain interventions is an important

topic for further research. It is necessary to find a balance

between very strong interventions that will be appropriate

for a select few frail older adults, and interventions that are

too mild to have a real impact on the broad population.

Key points for application to clinical practice• Poor nutrition has been identified as factor influencing the

development of frailty.

• Consideration of BMI alone is not an appropriate nutrition

screening method in older adults

• Poor MNA® score is an alert to an individual’s vulnerability,

and a prompt for further, more-comprehensive assessment

• Frail older adults are a good target for nutritional

assessment and intervention

• Multi-domain intervention (combining physical exercise,

nutrition intervention, cognitive exercice, and social

services) is an important topic for future research on frailty

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

Body mass index

Blaum12 Study: WHASMethod: cross-sectional analysis

Nutritional assessment: BMIFrailty criteria: FFC

Participants: n=599 women, aged 70–79 with BMI ≥ 18.5 kg/m²

- Being overweight was significantly associated with prefrailty, and obesity was associated with prefrailty and frailty- In multinomial regression models, obesity was significantly associated with prefrailty (OR 2.23; 95%CI 1.29–3.84) and frailty (OR 3.52; 95% CI 1.34–9.13), even when controlling for covariates

Hubbard14 Study: English Longitudinal Study of AgeingMethod: cross-sectional analysis

Nutritional assessment: BMIFrailty criteria: Index of accumulated deficits (FI) and FFC. Deficits included sensory and functional impairments, self-reported comorbidities, poor or fair self-rated health, low mood or depression measured by the eight-item Center for Epidemiological Studies-Depression (CES-D8) scale, and a score in the lowest 10% of a composite measure of global cognitive function

Participants: n=3,055, aged ≥ 65 years

- The association between BMI and frailty showed a U-shaped curve. This relationship was consistent across different frailty measures. The lowest FI scores and lowest prevalence of Fried frailty were in those with BMI 25– 29.9 kg/m²- At each BMI category, and using either measure of frailty, those with a high waist circumference were significantly more frail

Frisoli13 Study: WHAS IIMethod: cross-sectional analysis

Nutritional assessment: BMI and body composition (DEXA)Frailty criteria: FFC

Participants: n= 250, aged 76–86 years

- There is no statistically significant difference between frail prefrail and robust in BMI- In an adjusted logistic regression model, severe osteopenia/osteoporosis (OR 2.1; 95% CI 0.68–6.6; p=0.196) and sarcopenia (OR 3.1; 95% CI 0.88–11.1; p=0.077) were individually associated with frailty, though not statistically significant- The likelihood of being frail was substantially higher in the presence of these two syndromes (OR 6.4; 95% CI 1.1–36.8, p=0.037)

Bowen16 Study: Health and Retirement StudyMethod: longitudinal studyFollow-up: 8 years

Nutritional assessment: BMIPhysical function: functional limitations and disabilities in IADL and ADL

Participants: n= 11,491, aged ≥ 50 years

- Compared with the nonfrail normal weight, prefrail obese have a 16% (p≤0.001) reduction in the expected functional limitations rate and frail overweight and obese have a 10% (p≤0.01) and 36% (p≤0.001) reduction in the expected functional limitations rate, respectively- In addition, frail obese have a 27% (p≤0.05) reduction in the expected ADL disability rate

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Smit15 Study: Third National Health and Nutrition Examination Survey

Nutritional assessment: intake assessed by 24 h dietary recall. Food insufficiency was self-reported as ‘sometimes’ or ‘often’ not having enough food to eatFrailty status: meeting ≥ two (frail) or meeting one (pre-frail) of the following four-item criteria: slow walking; muscular weakness; exhaustion; and low physical activity

Participants: 4,731 older adults, aged ≥ 60 years

- Prevalence of frailty was highest among people who were obese (20.8%), followed by overweight (18.4%), normal weight (16.1%) and lowest among people who were underweight (13.8%)- Independent of BMI, daily energy intake was lowest in people who were frail, followed by pre-frail and highest in people who were not frail (1,587 [se 31], 1,663 [se 19] and 1,738 [se 20] kcal, respectively, p<0.01)- Energy-adjusted macronutrient intakes were similar in people with and without frailty. Frail (adjusted OR [AOR] 4.7; 95% CI 1.7–12.7) and pre-frail (AOR 2.1; 95% CI 0.8–5.8) people were more likely to report being food insufficient than non-frail people- Serum albumin, carotenoids and selenium levels were lower in frail adults than nonfrail adults

Macronutrients

Beasley19 Study: WHASMethod: longitudinal studyFollow-up: 3 years

Nutritional assessment: baseline protein intake by FFQ. Calibrated estimates of energy and protein intake were corrected for measurement error using regression calibration equations estimated from objective measures of total energy expenditure (doubly labeled water) and dietary protein (24-hour urinary nitrogen)Frailty status: at least three of the following components: low physical function (measured using the Rand-36 questionnaire); exhaustion; low physical activity; and unintended weight loss

Participants: n=24,417 free of frailty, aged 65–79 years

- 3,298 women (13.5%) developed frailty over 3 years- After adjustment for confounders, a 20% increase in uncalibrated protein intake (%kcal) was associated with a 12% (95% CI 8–16%) lower risk of frailty, and a 20% increase in calibrated protein intake was associated with a 32% (95% CI 23–50%) lower risk of frailty

Bollwein24 Method: cross-sectional study

Nutritional assessment: interview-based FFQ.A MED score (maximum 9 points) was used to evaluate dietary quality.Frailty criteria: FFC

Participants: n=192, aged >75 years

- The risk of being frail was significantly reduced in the highest quartile of the MED score (OR 0.26; 95% CI 0.07–0.98)

Talegawkar23 Study: InCHIANTI Method: longitudinal studyFollow-up: 6 years

Nutritional assessment: interview-based FFQ.A MED score (maximum 9 points) was used to evaluate dietary qualityFrailty status: at least two of the following criteria: poor muscle strength; feeling of exhaustion; low walking speed; and low physical activity

Participants: n=690, aged ≥ 65 years

- Higher adherence (score ≥6) to a MED was associated with lower odds of developing frailty (OR 0.30 [95% CI 0.14–0.66]) compared with those with lower adherence (score ≤3) - A higher adherence to a MED at baseline was also associated with a lower risk of low physical activity (OR 0.62; 95% CI 0.40–0.96) and low walking speed (OR 0.48; 95% CI 0.27–0.86) but not with feelings of exhaustion and poor muscle strength

Tieland20 Method: Secondary analyses were carried out using dietary data collected from several studies

Nutritional assessment: food recordFrailty status: age ≥ 70 years, requiring healthcare, physical inactivity and self-reported BMI of ≤25 kg/m2 or recent involuntary weight loss

Participants: Three groups: Healthy community-dwelling people (n=707), frail independently living elderly people and institutionalized elderly

- Dietary protein intake averaged 1.1 ± 0.3 g/kg/day in community-dwelling, 1.0 ± 0.3 g/kg/day in the frail, and 0.8 ± 0.3 g/kg/day in institutionalized elderly men. Similar protein intakes were found in women - 10% of the community-dwelling and frail elderly and 35% of the institutionalized elderly people showed a protein intake below the estimated average requirement (0.7 g/kg/day)

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Kobayashi21 Method: cross-sectional analyses

Nutritional assessment: intakes of total, animal and plant protein, and eight selected amino acids (leucine, isoleucine, valine, methionine, cysteine, branched chain amino acids, sulfur amino acids, essential amino acids) estimated from a validated brief type self-administered diet history questionnaireFrailty status: presence of three or more of the following four components: slowness and weakness (two points); exhaustion; low physical activity; and unintentional weight loss

Participants: 2,108, aged ≥ 65 years

- The number of subjects with frailty was 481 (23%). - Adjusted ORs for frailty in the first, second, third, fourth and fifth quintiles of total protein intake were 1.00 (reference), 1.02 (0.72–1.45), 0.64 (0.45–0.93), 0.62 (0.43–0.90) and 0.66 (0.46–0.96), respectively (p for trend=0.0001).- Subjects categorized to the third, fourth, and fifth quintiles of total protein intake (>69.8 g/day) showed significantly lower ORs than those to the first quintile (all p<0.03). - The intake of animal and plant protein and all selected amino acids were also inversely associated with frailty (p for trend <0.04) with the multivariate adjusted OR in the highest compared to the lowest quintile of 0.73 for animal protein and 0.66 for plant protein, and 0.66–0.74 for amino acids

Bollwein17 Method: cross-sectional analyses

Nutritional assessment: amount of protein intake and its distribution over the day assessed using FFQ. Unevenness of protein distribution was calculated as coefficient of variation (CV)Frailty status: Fried criteria

Participants: 194 community-dwelling seniors (≥ 75 years)

- 15.4% of the participants were frail, 40.5% pre-frail- Median daily protein intake was 77.5 (38.5–131.5) g, 1.07 (0.58–2.27) g/kg body weight and 15.9 (11.2–21.8) % of energy intake without significant differences between the frailty groups - The risk of frailty did not differ significantly between participants in the higher compared to the lowest quartile of protein intake- Frail participants consumed significantly less protein in the morning (11.9 vs 14.9 vs 17.4%, p=0.007), but more at noon (61.4% vs 60.8% vs 55.3%, p=0.0024) than pre-frail and non-frail- The median (min-max) CV of protein distribution was highest in frail (0.76 (0.18–1.33) compared to pre-frail (0.007–1.29) and non-frail (0.68 (0.15–1.24) subjects (p=0.024)

Macro- and micronutrients

Bartali18 Study: InCHIANTI Nutritional assessment: daily intake of energy and nutrients assessed by the EPIC questionnaire. Low intake was defined using the value corresponding to the lowest sex-specific intake quintile of energy and specific nutrientsFrailty status: having at least two of the following criteria: low muscle strength; feeling of exhaustion; low walking speed; and reduced physical activity


- Daily energy intake ≤ 21 kcal/kg was significantly associated with frailty (OR 1.24; 95% CI 1.02–1.5)- After adjusting for energy intake, a low intake of protein (OR 1.98; 95% CI 1.18–3.31); vitamins D (OR 2.35; 95% CI 1.48–3.73), E (OR 2.06; 95% CI 1.28–3.33), C (OR 2.15; 95% CI 1.34–3.45), and folate (OR 1.84; 95% CI 1.14–2.98); and having a low intake of more than three nutrients (OR 2.12; 95% CI 1.29–3.50) were significantly and independently related to frailty

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Micronutrients

Cesari39 Study: InCHIANTI Method: cross-sectional analyses

Nutritional assessment: plasma vitamin E levelsFrailty status: physical performance tests (knee extension strength; performance of the lower extremities assessed with theuse of 3 tests: walking speed, ability to stand from a chair, and ability to maintain balance)

Participants: n= 827, aged ≥ 65 years

- In adjusted analyses, plasma alpha-tocopherol was significantly correlated with knee extension (beta = 0.566, p=0.003) and the summary physical performance score (beta = 0.044, p=0.008). Plasma gamma-tocopherol was associated only with knee extension strength (beta = 0.327, p=0.04). - Of the daily dietary intake measures, vitamin C and beta-carotene were significantly correlated with knee extension strength, and vitamin C was significantly associated with physical performance (beta = 0.029, p=0.04)

Ble38 Study: InCHIANTI Method: cross-sectional analyses

Nutritional assessment: daily dietary intakes of vitamin C, vitamin E, beta-carotene, and retinol assessed by The EPIC questionnaire; Plasma alpha- and gamma-tocopherol concentrations Physical functions: physical performance tests (knee extension strength; performance of the lower extremities assessed with theuse of thee tests: walking speed, ability to stand from a chair, and ability to maintain balance)


- Age and gender adjusted levels of vitamin E decreased gradually from the nonfrail to the frail group (p for trend=0.015)- In the logistic model adjusted for multiple potential confounders, participants in the highest vitamin E tertile were less likely to be frail than were participants in the lowest vitamin E tertile (OR 0.30; 95% CI 0.10–0.91)

Michelon29 Study: WHASMethod: cross-sectional study

Nutritional assessment: micronutrient serum concentrationsFrailty criteria: FFC

Participants: n=754, aged 70–80 years

- Among nonfrail, prefrail, and frail women, respectively, geometric mean serum concentrations were 1.842, 1.593, and 1.376 µmol/L for total carotenoids (p<0.001); 2.66, 2.51, and 2.43 µmol/L for retinol (p=0.04); 50.9, 47.4, and 43.8 nmol/L for 25(OH)D (p=0.019); 43.0, 35.8, and 30.9 nmol/L for vitamin B6 (p=0.0002); and 10.2, 9.3, and 8.7 ng/mL for folate (p=0.03) - Frail women were more likely to have at least two or more micronutrient deficiencies (p=0.05)- The age-adjusted OR for being frail were significantly higher for those participants whose micronutrient concentrations were in the lowest quartile compared to the top three quartiles for total carotenoids, alpha-tocopherol, 25(OH)D and vitamin B6- The association between nutrients and frailty was strongest for beta-carotene, lutein/zeaxanthin, and total carotenoids (ORs 1.82–2.45, p=0.05), after adjusting for age, sociodemographic status, smoking status, and BMI

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Semba30 Study: WHASMethod: prospective studyFollow-up: 3 years

Nutritional assessment: micronutrient serum concentrationsFrailty assessment: FFC


- Of 463 nonfrail women at baseline who had at least one follow-up visit, 205 (31.9%) became frail, with an overall incidence rate of 19.1 per 100 person-years- Compared with women in the upper three quartiles, women in the lowest quartile of serum carotenoids (hazard ratio [HR] 1.39; 95% CI 1.01–1.92), alpha-tocopherol (HR 1.39; 95% CI 1.02–1.92), and 25(OH)D (HR 1.34; 95% CI 0.94–1.90) had an increased risk of becoming frail- The number of nutritional deficiencies (HR 1.10; 95% CI 1.01–1.20) was associated with an increased risk of becoming frail, after adjusting for age, smoking status, and chronic pulmonary disease- Adjusting for potential confounders, we found that women in the lowest quartile of serum carotenoids had a higher risk of becoming frail (HR 1.54; 95% CI 1.11–2.13)

Boxer25 Study: Cross-sectional study

Nutritional assessment: serum 25(OH)DFrailty assessment: The 6-minute walk distance and FFC

Participants: n=60 patients with a left ventricular ejection fraction of ≤ 40%

- Longer 6-minute walk distance was correlated with higher 25(OH)D level- Higher frailty phenotype score (more frail) was correlated with lower 25(OH)D levels (p<0.05)- Linear regression with the 6-minute walk distance as the dependent variable and independent variables of age, sex, percentage of free testosterone, DHEAS, 25(OH)D, intact PTH, hsCRP, IL6, cortisol/DHEAS ratio, and NTpro-BNP, revealed 25(OH)D to be significant (coefficient of determination=53.5%)- Ordinal logistic regression with the frailty phenotype and hormonal levels revealed that 25(OH)D also predicted frailty status.

Shardell32 Study: InCHIANTI study

Nutritional assessment: serum 25(OH)DFrailty assessment: FFC


- Independent of covariates, men with 25(OH)D <50 nmol/L had greater odds of frailty than those with 25(OH)D ≥50 nmol/L (OR 4.94; 95% CI 1.80–13.61). In women, the adjusted OR for frailty was 1.43 (95% CI 0.58–3.56). The 25(OH)D ORs differed between men and women (p=0.041)

Wilhelm35 Study: NHANES III Nutritional assessment: serum 25(OH)DFrailty assessment: FFC


- 25(OH) D deficiency (defined as a serum concentration <15 ng/mL), was associated with a 3.7-fold increase in the odds of frailty amongst white subjects and a 4-fold increase in the odds of frailty amongst non-white subjects

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Chang26 Study: Observational study

Nutritional assessment: serum 25(OH)DFrailty assessment: FFC and Edmonton Frail Scale

Participants: n=215, aged 65–79 years

- Frail subjects had lower 25(OH)D levels based on the FFI (p<0.009) and the EFS (p<0.004)- The associations between insufficient 25(OH)D status and both frailty scales were significant- After adjustment, the OR of 25(OH)D insufficiency comparing subjects with pre-frailty and frailty to those with robust was 3.14 (95% CI 1.43–6.91) and 10.74 (95% CI 2.60–44.31), respectively, using the FFI

Ensrud28 Method: Cross-sectional and longitudinal analyses of a prospective cohort studyFollow-up: average 4.5 years

Nutritional assessment: serum 25(OH)D Frailty assessment: FFC and Edmonton Frail Scale


- At baseline, there was a U-shaped association between 25(OH)D level and odds of frailty with the lowest risk among women with levels 20.0– 29.9 ng/mL (reference group). Compared with this group, the odds of frailty were higher among those with levels < 15.0 ng/mL (multivariable odds ratio [MOR] 1.47, 95% CI 1.19–1.82), those with levels 15.0–19.9 ng/mL (MOR 1.24, 95% CI 0.99–1.54), and those with levels ≥ 30 ng/mL (MOR 1.32, 95% CI 1.06–1.63)- Among 4,551 nonfrail women at baseline, the odds of frailty (vs robust/intermediate) at follow-up appeared higher among those with levels 15.0–19.9 ng/mL (MOR 1.21, 95% CI 0.99–1.49), but the CI overlapped 1.0

Ensrud29 Method: Prospective cohort studyFollow-up: average 4.6 years

Nutritional assessment: serum 25(OH)D Frailty assessment: FFC


- After adjusting for multiple potential confounders, men with 25(OH)D levels ≤ 20.0 ng/mL had 1.5 times higher odds (MOR1.47; 95% CI 1.07–2.02) of greater frailty status at baseline than men with 25(OH)D levels of 30.0 ng/mL or greater (reference group), whereas frailty status was similar in men with 25(OH)D levels from 20.0 to 29.9 ng/mL and those with levels of 30.0 ng/mL or greater (MOR 1.02; 95% CI 0.78–1.32)- However, in 1,267 men not classified as frail at baseline, there was no association between lower baseline 25(OH)D level and odds of greater frailty status at the 4.6-year follow-up

Shardell33 Study: InCHIANTI Follow-up: 6 years

Nutritional assessment: serum 25(OH)D Frailty assessment: FFC


- The median (interquartile range) 25(OH)D concentration was 16.0 ng/mL (10.4–25.6 ng/mL; multiply by 2.496 to convert to nmol/L)- Prefrail participants with 25(OH)D levels ≤ 20 ng/mL were 3.0% (95% CI -5.6–14.6%) more likely to become frail, and 7.7% (95% CI -3.5–18.7%) less likely to become robust than prefrail participants with 25(OH)D levels of ≥ 20 ng/mL - In prefrail participants, each 5-ng/mL decrement of continuous 25(OH)D was associated with 1.13 higher odds of incident frailty (95% CI 0.90–1.39) than with recovery of robustness- Transitions from robustness or frailty were not associated with 25(OH)D levels

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Smit34 Study: NHANES III Nutritional assessment: serum 25(OH)DFrailty assessment: meeting three or more criteria (frail), or one or two (pre-frail) of the five following criteria: low BMI; slow walking; weakness; exhaustion; and low physical activity


- Serum 25(OH)D concentrations were lowest in participants with frailty, intermediate in participants with pre-frailty and highest in participants without frailty- The odds of frailty in the lowest quartile of serum 25(OH)D was 1.94 times the odds in the highest quartile (95% CI 1.09–3.44)

Tajar35 Study: European Male Ageing Study (EMAS) Method: cross-sectional analysis

Nutritional assessment: serum 25(OH)DFrailty assessment: FFC and FI

Participants: n=1,504, aged 60–79 years

- 5.0% of subjects were classified as frail and 36.6% as prefrail- Lower levels of 25(OH)D were associated with being prefrail (per 1 SD decrease: reporting odds ratio [ROR] 1.45; 95% CI 1.26–1.67) and frail (ROR 1.89; 95% CI 1.30–2.76), after adjusting for age, center and health and lifestyle confounders (robust group = base category)- FI and FFC found similar results

Hirani36 Study: Concord Health and Ageing in Men ProjectMethod: cross-sectional analyses

Nutritional assessment: serum 25(OH)D and 1,25(OH)DFrailty assessment: Cardiovascular Health Study frailty criteria (weight loss; reduced muscular strength/weakness; slow walking speed; exhaustion; and low activity level)

Participants: 1,659 community-dwellers

-Frailty was present in 9.2% of the sample. -Low serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels were independently associated with frailty and with four of the five components of frailty (except weight loss).

Wong37 Method: prospective cohort studyFollow-up: average 9.2 years

Nutritional assessment: 25(OH)DFrailty assessment: the 5-point Frail Scale (fatigue, resistance, ambulation, illness and loss of weight)Mortality: death registry via the Western Australian Data Linkage System

Participants: n=4,203 older men, aged 70–88 years

- At baseline, 676 (16.1%) men were frail, as defined by having ≥3 deficits (FRAIL scale ≥ 3)- In multivariate cross-sectional analysis, low vitamin D status, defined by the lowest quartile of 25(OH)D values (<52.9 nmol/L), was associated with increased prevalent frailty (OR 1.96; 95% CI 1.52–2.52) in comparison to the highest quartile of 25(OH)D values (>81.6 nmol/L) - After a mean period of 5.3 years, the adjusted OR of being frail at follow-up for men with low vitamin D and having zero deficit at baseline (FRAIL scale = 0) was 1.56 (95% CI 1.07–2.27)-Low vitamin D also predicted all-cause mortality over a period of up to 9.2 years (HR 1.20; 95% CI 1.02–1.42), independent of baseline frailty and other covariates

ADL: Activities of Daily Living; BMI: Body mass index; CI: confidence interval; DEXA: Dual-energy X-ray absorptiometry; DHEAS: Dehydroepiandrosterone sulfate; EPIC: European Prospective Investigation into Cancer and Nutrition; FFC: Fried Frailty Criteria; FFQ: Food Frequency Questionnaire; FI: Frailty Index; hsCRP: high-sensitivity C-reactive protein; HR: hazard ratio; IADL: Instrumental Activities of Daily Living; InCHIANTI: Invecchiare in Chianti (aging in the Chianti area); MED: Mediterranean diet; NHANES III: Third National Health and Nutrition Survey; NTproBNP: N-terminal pro b-type natriuretic peptide; 25(OH)D: 25-hydroxyvitamin D; OR: odds ratio; PTH: parathyroid hormone; WHAS: Women’s Health and Aging Studies

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Table 2. The Mediterranean-style diet

Food groups Guidance

Meats and sweets Less often

Poultry, eggs, cheese and yogurt Moderate portions, daily to weekly

Fish and seafood Often, at least twice a week

Fruits, vegetables, grains (mostly whole), olive oil, beans, nuts, legumes, seeds, herbs and spices Base every meal on these foods

Table 3. Randomized controlled trials to evaluate the efficacy of nutrient supplementation to modify frailty risk

Latham48 Outcomes: Physical health according to the short-form health survey assessed at 3 months and falls assessed over 6 months(Assessments took place in the participants’ homes)

Intervention: Single dose of vitamin D (calciferol, 300,000 IU) or placebo tablets and 10 weeks of high-intensity home-based quadriceps resistance exercise or frequency-matched visits6 months

Participants: n=243 frail* older people, aged ≥ 65 years*Frailty criteria: according to simple clinical measures of frailty as described by Winograd et al (participants were screened during their hospitalization in geriatric rehabilitation units)

- There was no effect of either intervention on physical health or falls, but patients in the exercise group were at increased risk of musculoskeletal injury (risk ratio 3.6; 95% CI 1.5–8.0)- Vitamin D supplementation did not improve physical performance, even in those who were vitamin D deficient (<12 ng/mL) at baseline

Tieland49 Outcomes: Skeletal muscle mass (DEXA), muscle fiber size (muscle biopsy), strength (1-RM), and physical performance (SPPB) were assessed at baseline, and at 12 and 24 weeks

Intervention: daily protein supplementation (15 g protein at breakfast and lunch) or placebo24 weeks

Participants: n=65 frail older people

- Skeletal muscle mass did not change in the protein- (from 45.8 ± 1.7 to 45.8 ± 1.7 kg) or placebo-supplemented group (from 46.7 ± 1.7 to 46.6 ± 1.7 kg) following 24 weeks of intervention (p>0 .05)- In accordance, type I and II muscle fiber size did not change over time (p>0.05)- Muscle strength increased significantly in both groups (p<0.01), with leg extension strength tending to increase to a greater extent in the protein (57 ± 5 to 68 ± 5 kg) compared with the placebo group (57 ± 5 to 63 ± 5 kg) (treatment × time interaction effect: p=0 .059)- Physical performance improved significantly from 8.9 ± 0.6 to 10.0 ± 0.6 points in the protein group and did not change in the placebo group (from 7.8 ± 0.6 to 7.9 ± 0.6 points) (treatment × time interaction effect: p=0.02)

Kim50 Primary outcome: Change of the Physical Functioning and SPPB

Intervention: protein-energy supplementation (two 200-mL cans of commercial liquid formula [additional 400 kcal of energy, 25 g of protein, 9.4 g of essential amino acids, 400 mL of water] per day) or placebo 12 weeks

Participants: n=87 frail* older people; mean age 78.6 ± 5.7 years*Frailty criteria: usual gait speed < 0.6 m/s and MNA® < 24

- Physical Functioning increased by 5.9% (1 point) in the intervention group, although no change was observed in the control group (p=0.052)- SPPB remained stable in the intervention group, although it decreased by 12.5% (1 point) in controls (p=0.039)

BI: Barthel Index; DEXA: Dual-energy X-ray absorptiometry; FFM: Fat Free Mass; MNA®: Mini Nutritional Assessment; SPPB: Short Physical Performance Battery

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Table 4. Randomized controlled trials to evaluate the efficacy of physical activity to modify frailty risk

Chen51 Outcomes: physical fitness (body composition, cardiovascular-respiratory functions, body flexibility, muscle power and endurance, balance, and agility) assessed at baseline, 12 and 24 weeks

Intervention: Two groups:- senior-tailored silver yoga for transitional frail older group (yoga exercises three times per week, 70 minutes per session) (n=38)- control group (n=31)24 weeks

Participants: n=69 frail elderly living in assisted-care facilities

- 55 participants completed the pretest and post-test study- Physical fitness indicators of participants in the silver yoga group had improved significantly, and they had better physical fitness than participants in the control group (all p values p<0.05)

Hagedorn52 Outcomes: strength, physical endurance, balance and falls efficacy scale scoring assessed at baseline and after end of training

Intervention: Two groups: Both groups received progressive resistance muscle strength training and physical fitness training. Additionally, one group received traditional balance training and the other group received computer feedback balance training. 12 weeks

Participants: n= 27 frail* elderly, mean age 81.3 ± 6.9 years (outpatients referred to a geriatric falls and balance clinic)*Frailty criteria: Dynamic Gait Index Score < 19

- In the combined group, significant mean improvement was observed in knee extension (19%), ankle dorsiflexion (16%), sitting to standing (16%), and in the 6-minute walk test (8%)- In the traditional balance training group, the static balance in the Modified Clinical Test of Sensory Interaction and Balance standing on a foam mat with closed eyes showed a significant increase (80%)- No increase occurred in the computer balance training group. However, the computer feed-back training group showed a marked improvement that was up to 400% in the training specific performance

Giné-Garriga53 Outcomes: measures of physical frailty, function, strength, balance, and gait speed assessed at baseline, 12 and 36 weeks

Intervention: Two groups: - functional circuit-training program (FCT) (n=26)- control group (CG; health education meetings once a week) (n=21)12 weeks

Participants: n=51 frail community-dwelling adults (31 F, 20 M), mean age 84.0 ± 2.9 years

- Physical frailty measures in FCT showed significant (p < 0.05) improvements relative to those in CG (BI at Weeks 0 and 36: 73.4 ± 2.3 and 77.0 ± 2.4; for the FCT and 70. 8 ± 2.5; and 66.7 ± 2.7 for the CG)

Langlois54 Outcomes: physical capacity (modified PPT, grip strength, physical endurance (6-minute walk test), mobility (Timed Up and Go Test) and gait speed; cognitive performance; quality of life assessed at baseline and 12 weeks

Intervention: Two groups: - exercise-training group (3 times a week for 12 weeks)- control group (waiting list)12 weeks

Participants: n=83 frail* elderly, age 61–89 years*Frailty criteria: FFC+ score of ≤28/36 on the modified PPT + geriatrician’s judgment after assessing the 70 possible deficitsof the FI

- Compared with controls, the intervention group showed significant improvement in physical capacity on modified PPT and 6-minute walk test, cognitive performance (executive functions, processing speed, and working memory) and quality of life (global quality of life, leisure activities, physical capacity, social/family relationships, and physical health)- Benefits were overall equivalent between frail and non-frail participants

BI: Barthel Index; FFC: Fried Frailty Criteria; FI: Frailty Index; PPT: Physical Performance Test

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Table 5. Randomized controlled trials to evaluate the efficacy of multi-domain interventions to modify frailty risk

Bonnefoy62 Outcomes: FFM determined by labelled water and muscle power measured by a leg-extensor machine at baseline and at 9 months

Intervention: Progressive exercise program compared with memory training and nutritional supplements compared with placebo9 months

Participants: n= 57 very frail older people living in nursing homes, aged ≥ 72 years*Frailty criteria: not specified

- At 9 months, the compliance was 63% for exercise sessions, and 54% for nutritional supplements- In patients with dietary supplements, muscle power increased by 57% at 3 months (p=0.03), and showed only a tendency at 9 months. Although FFM increased by 2.7% at 9 months, the difference was not significant (p=0.10)- Exercise did not improve muscle power at 9 months, but improved functional tests (five-time-chair rise, p=0.01)

Rydwik63 Outcomes: Physical performance (muscle strength, balance, mobility and ADL) and nutritional aspects (such as energy intake, body weight and FFM) assessed at baseline and, 3 and 9 months after study entry

Intervention: Four groups: -physical training 2 x 45 minutes per week (aerobic, muscle strength, balance) -individual nutritional advice and group sessions on nutrition - combined nutritional and physical intervention- control group12 weeks

Participants: n=96 frail* elderly people; ≥ 75 years (40% men)*Frailty criteria: unintentional weight loss ≥ 5% and/or BMI ≤ 20 kg/m² and low physical activity

- The intention-to-treat analysis indicated significant improvements in lower-extremity muscle strength in both training groups compared with the nutrition 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 did not show any significant results

Lammes64 Outcomes: Energy intake (4-day food diary); RMR (indirect calorimetry) and body composition (anthropometry) performed at baseline, and 3 and 9 months after study entry

Intervention: Four groups: -physical training 2 x 45 minutes per week -individual nutritional advice and group sessions on nutrition - combined nutritional and physical intervention- control group12 weeks

Participants: n= 96 frail* elderly people; ≥ 75 years (40% men)*Frailty criteria : unintentional weight loss ≥ 5% and/or BMI ≤ 20 kg/m² and low physical activity

- The training group showed a significantly increased RMR at 3 months. There were no observed differences within or between the four groups. There was no correlation over time between energy intake, RMR and FFM - The participants with a low energy intake who managed to increase their energy intake during the study (‘responders’) had a statistically lower BMI (21 vs 24 kg/m2) and a lower fat percentage (23 vs 30%) at baseline than the ‘non-responders’

Zak65 Outcomes: Strength with regard to four muscle groups, ie, hip and knee extensors and flexors assessed at 80% (1 RM) weekly, and balance and mobility assessed at baseline and at the end of the study

Intervention: Four groups: -group I: progressive resistance exercises (PRE) + functionally-oriented exercises (FOE) + nutritional supplementation (NS) -group II: PRE + FOE + placebo-group III: standard exercises (SE) + FOE + NS-group IV: SE + FOE + placebo. Each group pursued a 45-minute exercise session five times weekly7 weeks

Participants: n=80 frail* elderly (F 71, M 20), mean age 79 years, community dwellers or nursing home residents*Frailty criteria: Not specified

- Significant differences in muscle strength were noted both in Group I and II (p=0.01; p=0.04; respectively), although this did not translate directly into perceptible improvement in individual mobility- Notable improvements in individual mobility were reported in Group III and IV (p=0.002), although without positive impact on individual muscle strength

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Li68 Outcomes: FFC and BI assessed at baseline and 6 months

Intervention: Two groups:-intervention group by CGA and appropriate intervention by medication adjustment, exercise instruction, nutrition support, physical rehabilitation, social worker consultation, and specialty referral (n=152) - placebo group (n=158)6 months

Participants: n=310 pre-frail or frail* elderly; mean age 78.8 ± 8.4 years*Frailty criteria: FFC

- Compared to the control group, the intervention group tended to have a better outcome, with an OR 1.19 (95% CI 0.48–3.04; p=0.71), and 3.29 (95% CI 0.65–16.64, p=.15) respectively, and were less likely to deteriorate with an OR 0.78 (95% CI 0.34–1.79; p=0.57) and 0.94 (95%CI 0.42–2.12, p=0.88), respectively.- There were no significant differences between the two groups

Fairhall69 Outcomes: Disability in the mobility domain using the International Classification of Functioning, Disability and Health framework; Activity (execution of mobility tasks) using the 4-metre walk and self-report measures; participation (involvement in life situations) using the Life Space Assessment and the Goal Attainment Scale at baseline, and at 3 and 12 months

Intervention: Two groups: -a multi-factorial interdisciplinary treatment program intended to target frailty (home exercise program targeting mobility, and coordinated management of psychological and medical conditions) - a comparison group receiving the usual health care and support services12 months

Participants: n=241 frail* community-dwelling older people, mean age of 83.3 ± 5.9 *Frailty criteria: CHS-PCF

- Study was completed for 216 participants (90%)- At 12 months, the intervention group had significantly better scores than the control group on the Goal Attainment Scale (OR 2.1; 95% CI 1.3–3.3; p=0.004) and Life Space Assessment (4.68 points; 95% CI 1.4–9.9; p=0.005)- There was no difference between groups on the global measure of participation or satisfaction with ability to get out of the house- At the activity level, the intervention group walked 0.05 m/s faster over 4 m (95% CI 0.0004–0.1; p=0.048) than the control group, and scored higher on the Activity Measure for Post Acute Care (p<0.001)

Tieland66 Outcomes: Lean body mass (DEXA), strength (1-RM), and physical performance (SPPB) assessed at baseline, and after 12 and 24 weeks of intervention

Intervention:Two groups: - progressive resistance type exercise training program (two sessions per week for 24 weeks) and supplemented twice daily with either protein (2 * 15 g),- placebo group24 weeks

Participants: n=62 frail elderly subjects, average age 78 ± 1 years

- Lean body mass increased from 47.2 kg (95% CI 43.5–50.9) to 48.5 kg (95% CI 44.8–52.1) in the protein group and did not change in the placebo group (from 45.7 kg [95% CI, 42.1–49.2] to 45.4 kg [95% CI 41.8–48.9]) following the intervention (p value for treatment × time interaction =0.0006)- Strength and physical performance improved significantly in both groups (p = 0.000) with no interaction effect of dietary protein supplementation

Chan72 Primary outcome: Improvement of the CHS-PCF by at least one category from baseline assessment. Subjects were followed-up at 3, 6 and 12 months

Intervention: Two intervention groups: -intervention group with exercise and nutrition (EN*, n = 55) or problem solving therapy (PST, n = 57) - control group (non-EN, n = 62 or non-PST, n = 60). *EN group subjects received nutrition consultation and a thrice-weekly exercise-training program while PST group subjects received six sessions in 3 months.12 months

Participants: n=117 frail* older adults; mean age 71.4 ± 3.7 years (59% females) *Frailty criteria: score of 3–6 on the CCSHA-CFS-TV and score ≥1 on the CHS-PCF

- EN group subjects had a higher improvement rate on the primary outcome than non-EN group subjects (45% vs 27%, adjusted p=0.008) at 3 months, but not 6 or 12 months- They also had greater increase of serum 25(0H) vitamin D level (4.9 ± 7.7 vs 1.2 ± 5.4; p=0.0006) and lower percentage of osteopenia (74% vs 89%; p=0.042) at 12 months- PST group subjects had better improvement (2.7 ± 6.1 vs 0.2 ± 6.7; p=0.0035, 6-month) and less deterioration ( -3.5 ± 9.7 vs -7.1 ± 8.7; p=0.0036, 12-month) of dominant leg-extension power than non-PST subjects

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Cameron73 Primary outcome: Frailty assessed by the Cardiovascular Health Study criteria, and mobility assessed by SPPB at 3 and 12 months after study entry

Intervention: Two groups: -a multi-factorial interdisciplinary treatment program intended to target frailty (home exercise program targeting mobility, and coordinated management of psychological and medical conditions), - a comparison group receiving the usual health care and support services12 months

Participants: n=241 frail* older people, aged ≥ 72 years*Frailty criteria: CHS-PCF

- Study was completed for 216 participants (90%)-In the intention to treat analysis, the between group difference in frailty was 14.7% at 12 months (95% CI 2.4¬27%; p=0.02)The score of the SPPB was stable in the intervention group and had declined in the control group with the mean difference between groups being 1.44 (95% CI 0.80–2.07; p<0.001) at 12 months- There were no major differences between the groups with respect to secondary outcomes including disability, depressive symptoms and health-related quality of life

Fairhall70 Primary outcome: Risk factors for falls measured using the PPA and mobility measures at baseline and 12 months

Intervention: Two groups: -a multi-factorial interdisciplinary treatment program intended to target frailty (home exercise program targeting mobility, and coordinated management of psychological and medical conditions), - a comparison group receiving the usual health care and support services12 months

Participants: n=241 frail* older people, aged ≥ 72 years*Frailty criteria: CHS-PCF

- Study was completed for 216 participants (90%)- After 12 months, the intervention group had significantly better performance than the control group, after controlling for baseline values, in the PPA components of the quadriceps strength (between-group difference 1.84 kg; 95% CI 0.17–3.51; p=0.03) and body sway (-90.63 mm, 95% CI -168.6 – -12.6; p=0.02), SPPB (1.58; 95% CI 1.02–2.14; p<0.001) and 4 m walk (0.06 m/s; 95% CI 0.01–0.10; p=0.02) with a trend toward a better total PPA score (-0.40; 95% CI -0.83 – -0.04; p=0.07) but no difference in fall rates (incidence rate ratio 1.12; 95% CI 0.78–1.63; p=0.53)

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: Compre-hensive Geriatric Assessment; CHS-PCF: Cardiovascular Health Study Phenotypic Classification of Frailty; CI: confidence interval;DEXA: Dual-energy X-ray absorptiometry; FFC: Fried Frailty Criteria; FFM: fat-free mass; OR: odds ratio; PPA: Physical Profile Assessment; PPT: Physical Performance Test; RM: repetition maximum; RMR: resting metabolic rate; SPPB: Short Physical Performance Battery

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Table 6. Characteristics of the first 160 patients evaluated during the first 6 months of operation of the program

Characteristics Mean (SD) or n (%)

GenderFemaleMale

99 (61.9)65 (38.1)

Age (years)<7575–84>85

82.7 ± 6.114 (8.7)92 (57.5)54 (33.7)

Education, n=158Higher educationSenior high schoolJunior high schoolPrimary schoolNo school attendance

44 (27.8)30 (20.9)13 (8.2)64 (40.5)4 (2.5)

Marital statusSingleDivorcedMarriedSeparatedWidowedLiving with partner

15 (9.4)11 (6.9)67 (41.9)2 (1.2)63 (39.4)2 (1.2)

Living environmentAssisted living facilityNursing home for dependent elderlyAt home (communal home)At home (individual home

6 (3.8)5 (3.1)61 (38.1)88 (55.0)

Help at home, n=106Home helpVisiting nursePhysical therapistOld age allowanceOther

55 (51.9)12 (11.3)7 (6.6)15 (14.1)17 (16.0)

Frailty status (FFC), n=158Non-frailPre-frailFrail

9 (5.7)65 (41.4)83 (52.9)

Frailty criteria (FFC)Recent weight loss, n=158Feeling of exhaustion, n=157Decreased muscle strength, n=156Slow gait speed, n=155Sedentary, n=158

52 (32.9)49 (31.2)90 (57.7)130 (83.9)85 (53.8)

MMSE score, n=154<2020–2425–27≥28

25.4 ± 4.2 (range: 12–30)19 (12.3)32 (20.8)41(26.6)62(40.2)

CDR score, n=15500.512

35 (22.6)102 (65.8)14 (9.0)4 (2.6)

MIS score (/8), n=157 6.4 ± 1.9 (0–8)

MIS-D score (/8), n=155 5.5 ± 2.6 (0–8)

AD-8 score (/8), n=157 3.3 ± 2.3 (0–8)

ADL score (/6), n=159 5.6 ± 0.8 (1–6)

IADL score (/8), n=159 6.0 ± 2.3 (0–8)

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Table 7. Characteristics of the pre-frail and frail patients evaluated during the first 6 months of operation of the program

Pre-frail (n=65) Frail (n=85) p

Age (years) 81.4 ± 6.5 84.1 ± 5.5 0.012

Gender (%women) 55.4 68.7 0.097

Gait speed (m/s) 0.8 ± 0.2 0.7 ± 0.2 0.000

Sedentary (%yes) 29.2 77.1 0.000

Decreased muscle strength (% yes) 41.5 74.4 0.000

Feeling of exhaustion (% yes) 3.1 19.5 0.003

Recent weight loss (% yes) 16.9 49.4 0.000

MMSE (/30) 26.7 ± 3.3 24.3 ± 4.4 0.001

CDR score (%)00.512

25.469.84.80.0

16.766.712.83.8

0.103

ADL score (/6) 5.9 ± 0.3 5.5 ± 0.8 0.000

IADL score (/8) 6.8 ± 1.7 5.4 ± 2.5 0.000

SPPB score (/12) 8.6 ± 2.1 6.1 ± 2.3 0.000

ADL: Activities Daily Living, CDR: Clinical Dementia Rating, IADL: Instrumental Activities daily Living, MMSE: Mini Mental State Examination, SPPB: Short Physical Performance Battery.

SPPB score (/12), n=157Good score (10–12)Medium score (7–9)Poor score(0–6)

7.4 ± 2.9 (0–12)43 (27.2)53 (33.7)61 (38.8)

Gait speed (m/sec), n=155< 0.6O.6–0.790.8–1.0> 1.0

0.8 ± 0.2 (0.2–1.3)38 (24.5)43 (27.7)49 (31.6)25 (16.1)

Abnormal distant vision, n=140 107 (76.4)

Abnormal near vision, n=129 42 (32.5)

Abnormal Amsler grid, n=153 16 (10.4)

HHIES score (/40), n=152No disabilityModerate disabilitySevere disability

7.1 ± 10.4 (0–40)106 (69.3)26 (17.0)21 (13.7)

Raskin score (/12), n=155Signs of depression

7.4 ± 2.9 (0–11)5 (3.2)

Nutritional status (MNA®), n=157Good (MNA® ≥24)Risk of malnutrition (MNA® 17–23.5)Malnourished (MNA® <17)

69 (56.9)54 (34.2)14 (8.9)

Vitamin D status (ng/mL), n=157≤1011–29≥30

14.8 ± 10.1 (4–59)73 (46.5)76 (48.4)8 (5.1)

AD-8: AD8 Dementia Screening Interview; ADL: Activities Daily Living; CDR: Clinical Dementia Rating; FFC: Frailty Fried Criteria; HHIES: Hearing Handicap Inventory for the Elderly - Screening version; IADL: Instrumental Activities Daily Living; MMSE: Mini Mental State Examination; MIS: Memory Impairment Screen; MIS-D: Memory Impairment Screen Differed; MNA®: Mini Nutri-tional Assessment; SPPB: Short Physical Performance Battery

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7. Walston J, Hadley EC, Ferrucci L, et al. Research agenda for frailty in older adults: toward a better understanding of physiology and etiology: summary from the American Geriatrics Society/National Institute on Aging Research Conference on Frailty in Older Adults. J Am Geriatr Soc 2006;54:991–1001.

8. Collard RM, Boter H, Schoevers RA, Oude Voshaar RC. Prevalence of frailty in community-dwelling older persons: a systematic review. J Am Geriatr Soc 2012; 60:1487–1492.

9. Rockwood K, Rockwood MRH, Mitnitski A. Physiological redundancy in older adults in relation to the change with age in the slope of a frailty index. J Am Geriatr Soc 2010;58:318–323.

10. Khandelwal D, Goel A, Kumar U, Gulati V, Narang R, Dey AB. Frailty is associated with longer hospital stay and increased mortality in hospitalized older patients. J Nutr Health Aging 2012;16: 732–735.

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12. Blaum CS, Xue QL, Michelon E, Semba RD, Fried LP. The association between obesity and the frailty syndrome in older women: the Women’s Health and Aging Studies. J Am Geriatr Soc 2005;53:927–934.

13. Frisoli A Jr, Chaves PH, Ingham SJM, Fried LP. Severe osteopenia and osteoporosis, sarcopenia, and frailty status in community-dwelling older women: results from the Women’s Health and Aging Study (WHAS) II. Bone 2011;48:952–957.

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16. Bowen ME. The relationship between body weight, frailty, and the disablement process. J Gerontol B Psychol Sci Soc Sci 2012;67:618–626.

17. Bollwein J, Volkert D, Diekmann R, et al. Nutritional status according the mini nutritional assessment (MNA) and frailty in community dwelling older persons : a close relationship. J Nutr Health Aging 2013;17:351-356.

18. Bartali B, Frongillo EA, Bandinelli S, et al. Low nutrient intake is an essential component of frailty in older persons. J Gerontol A Biol Sci Med Sci 2006;61:589–593.

19. Beasley JM, LaCroix AZ, Neuhouser ML, et al. Protein intake and incident frailty in the Women’s Health Initiative observational study. J Am Geriatr Soc 2010;58:1063–1071.

20. Tieland M, Borgonjen-Van den Berg KJ, Van Loon LJC, De Groot LCPGM. Dietary protein intake in community-dwelling, frail, and institutionalized elderly people: scope for improvement. Eur J Nutr 201 ;51:173–179.

21. Kobayashi S, Asakura K, Suga H, Sasaki S; Three-generation Study of Women on Diets and Health Study Group. High protein intake is associated with low prevalence of frailty among old Japanese women: a multicenter cross-sectional study. Nutr J 2013;12:164.

22. Bollwein J, Diekmann R, Kaiser MJ, et al. Distribution but not amount of protein intake is associated with frailty: a cross-sectional investigation in the region of Nurnberg. Nutr J 2013;12:109.

23. Talegawkar SA, Bandinelli S, Bandeen-Roche K, et al. A higher adherence to a Mediterranean-style diet is inversely associated with the development of frailty in community-dwelling elderly men and women. J Nutr 2012; 142:2161–2166.

24. Bollwein J, Diekmann R, Kaiser MJ, et al. Dietary Quality Is Related to Frailty in Community-Dwelling Older Adults. J Gerontol A Biol Sci Med Sci 2013;68:483-489.

25. Boxer RS, Dauser DA, Walsh SJ, Hager WD, Kenny AM. The association between vitamin D and inflammation with the 6-minute walk and frailty in patients with heart failure. J Am Geriatr Soc 2008;56:454–461.

26. Chang CI, Chan DCD, Kuo KN, Hsiung CA, Chen CY. Vitamin D insufficiency and frailty syndrome in older adults living in a Northern Taiwan community. Arch Gerontol Geriatr 2010; 50(Suppl 1):S17–21.

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28. Ensrud KE, Blackwell TL, Cauley JA, et al. Circulating 25-hydroxyvitamin D levels and frailty in older men: the osteoporotic fractures in men study. J Am Geriatr Soc 2011;59:101–106.

29. Michelon E, Blaum C, Semba RD, Xue QL, Ricks MO, Fried LP. Vitamin and carotenoid status in older women: associations with the frailty syndrome. J Gerontol A Biol Sci Med Sci 2006;61:600–607.

30. Semba RD, Bartali B, Zhou J, Blaum C, Ko CW, Fried LP. Low serum micro-nutrient concentrations predict frailty among older women living in the community. J Gerontol A Biol Sci Med Sci 2006;61:594–599.

31. Shardell M, Hicks GE, Miller RR, et al. Association of low vitamin D levels with the frailty syndrome in men and women. J Gerontol A Biol Sci Med Sci 2009;64:69–75.

32. Shardell M, D’Adamo C, Alley DE, et al. Serum 25-hydroxyvitamin D, transi-tions between frailty states, and mortality in older adults: the Invecchiare in Chianti Study. J Am Geriatr Soc 2012;60:256–264.

33. Smit E, Crespo CJ, Michael Y, et al. The effect of vitamin D and frailty on mortality among non-institutionalized US older adults. Eur J Clin Nutr 2012;66:1024–1028.

34. Tajar A, Lee DM, Pye SR, et al. The association of frailty with serum 25-hydroxyvitamin D and parathyroid hormone levels in older European men. Age Ageing 2013;42:352-359.

35. Wilhelm-Leen ER, Hall YN, Deboer IH, Chertow GM. Vitamin D deficiency and frailty in older Americans. J Intern Med 2010;268:171–180.

36. Hirani V, Naganathan V, Cumming RG, et al. Associations between frailty and serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D concentrations in older Australian men: the Concord Health and Ageing in Men Project. J Gerontol A Biol Sci Med Sci 2013; 68:1112-1121.

37. Wong YY, McCaul KA, Yeap BB, Hankey GJ, Flicker L. Low vitamin D status is an independent predictor of increased frailty and all-cause mortality in older men : the Health in Men Study. J Clin Endocrinol Metab 2013; 98:3821-3828.

38. Ble A, Cherubini A, Volpato S, et al. Lower plasma vitamin E levels are associated with the frailty syndrome: the InCHIANTI study. J Gerontol A Biol Sci Med Sci 2006;61:278-283.

39. Cesari M, Pahor M, Bartali B, et al. Antioxidants and physical performance in elderly persons: the Invecchiare in Chianti (InCHIANTI) study. Am J Clin Nutr 2004;79:289-294.

40. Gaier ED, Kleppinger A, Ralle M, Mains RE, Kenny AM, Eipper BA. High serum Cu and Cu/Zn ratios correlate with impairments in bone density, physical performance and overall health in a population of elderly men with frailty characteristics. Exp Gerontol 2012; 47 :491-496.

41. Taylor D. Physical activity is medicine for older adults. Postgrad Med J 2014;90:26-32.

42. Daley MJ, Spinks WL. Exercise, mobility and aging. Sports Med 2000;29:1-12.43. Keysor JJ. Does late-life physical activity or exercise prevent or minimize

disablement? A critical review of the scientific evidence. Am J Prev Med 2003;25:129-136.

44. Province MA, Hadley EC, Hornbrook MC, et al. The effects of exercise on falls in elderly patients. A preplanned meta-analysis of the FICSIT Trials. Frailty and Injuries: Cooperative Studies of Intervention Techniques. JAMA 1995;273:1341-1347.

45. Roubenoff R. Sarcopenia: a major modifiable cause of frailty in the elderly. J Nutr Health Aging 2000;4:140-142.

46. De Souto Barreto P. What is the role played by physical activity and exercise in the frailty syndrome? Perspectives for future research. Aging Clin Exp Res 2010;22:356-359.

47. Landi F, Abbatecola AM, Provinciali M, et al. Moving against frailty: does physical activity matter? Biogerontology 2010;11:537-545.

48. Latham NK, Anderson CS, Lee A, Bennett DA, Moseley A, Cameron ID. A randomized, controlled trial of quadriceps resistance exercise and vitamin D in frail older people: the Frailty Interventions Trial in Elderly Subjects (FITNESS). J Am Geriatr Soc 2003;51:291-299.

49. Tieland M, Van de Rest O, Dirks ML, et al. Protein supplementation improves physical performance in frail elderly people: a randomized, double-blind, placebo-controlled trial. J Am Med Dir Assoc 2012;13:720-726.

50. Kim CO, Lee KR. Preventive effect of protein-energy supplementation on the functional decline of frail older adults with low socioeconomic status: a community-based randomized controlled study. J Gerontol A Biol Sci Med Sci 2013;68:309-316.

51. Chen KM, Fan JT, Wang HH, Wu SJ, Li CH, Lin HS. Silver Yoga exercices improved physical fitness of transitional frail elders. Nurs Res 2010;59:364-370.

52. Hagedorn DK, Holm E. Effects of traditional training and visual computer feedback training in frail elderly patients. A randomized intervention study. Eur J Phys Rahabil Med 2010;46:159-168.

53. Giné-Garriga M, Guerra M, Pagès E, Manini TM, Jiménez R, Unnithan VB. The effect of functional circuit training on physical frailty in frail older adults: a randomized controlled trial. J Aging Phys Act 2010;18:401-424.

54. Langlois F, Vu TTM, Chassé K, Dupuis G, Kergoat MJ, Bherer L. Benefits

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55. Theou O, Stathokostas L, Roland KP, Jakobi JM, Patterson C, Vandervoort AA, Jones GR. The effectiveness of exercise interventions for the management of frailty: a systematic review. J Aging Res 2011:569194.

56. Chou CH, Hwang CL, Wu YT. Effect of exercise on physical function, daily living activities, and quality of life in the frail older adults: a meta-analysis. Arch Phys Med Rehabil 2012;93:237-244.

57. Giné-Garriga M, Roque-Figuls M, Coll-Planas L, Sitja-Rabert M, Salva A. Physical Exercise Interventions for improving performance-based measures of physical function in community-dwelling, frail older adults: a systematic review and meta-analysis. Arch Phys Med Rehabil 2014;95:753-769.e3.

58. Kwok BC, Mamun K, Chandran M, Wong CH. Evaluation of the Frails’ Fall Efficacy by Comparing Treatments (EFFECT) on reducing fall and fear of fall in moderately frail older adults: study protocol for a randomised control trial. Trials 2011;12:155.

59. Liu CK, Fielding RA. Exercise as an intervention for frailty. Clin Geriatr Med 2011;27:101-110.

60. Carrié I, Van Kan GA, Gillette-Guyonnet S, et al. Recruitment strategies for preventive trials. The MAPT study (MultiDomain Alzheimer Preventive Trial). J Nutr Health Aging 2012;16:355-359.

61. Villareal DT, Chode S, Parimi N, et al. Weight loss, exercise, or both and physical function in obese older adults. N Engl J Med 2011;364:1218-1229.

62. Bonnefoy M, Cornu C, Normand S, et al. The effects of exercice and protein-energy supplements on body composition and muscle function in frail elderly individuals : a long-term controlled randomized study. Br J Nutr 2003;89:731-739.

63. Rydwik E, Lammes E, Frändin K, Akner G. Effects of a physical and nutritional intervention program for frail elderly people over age 75. A randomized controlled pilot treatment trial. Aging Clin Exp Res 2008;20:159-170.

64. Lammes E, Rydwik E, Akner G. Effects of nutritional intervention and physical training on energy intake, resting metabolic rate and body compo-sition in frail elderly. a randomised, controlled pilot study. J Nutr Health Aging 2012;16:162-167.

65. Zak M, Swine C, Grodzicki T. Combined effects of functionally-oriented exercise regimens and nutritional supplementation on both the institution-alised and free-living frail elderly (double-blind, randomised clinical trial). BMC Public Health 2009; 9:39.

66. Tieland M, Dirks ML, Van der Zwaluw N, et al. Protein supplementation increases muscle mass gain during prolonged resistance-type exercise training in frail elderly people: a randomized, double-blind, placebo-controlled trial. J Am Med Dir Assoc 2012;13:713-719.

67. Dorner TE, Lackinger C, Haider S, et al. Nutritional Intervention and physical training in malnourhised frail community-dwelling elderly persons carried out by trained lay “buddies”: study protocol of a randomized controlled trial. BMC Public Health 2013;13:1232.

68. Li CM, Chen CY, Li CY, Wang WD, Wu SC. The effectiveness of a compre-hensive geriatric assessment intervention program for frailty in community-dwelling older people: a randomized, controlled trial. Arch Gerontol Geriatr 2010: 50(Suppl 1):S39–42.

69. Fairhall N, Sherrington C, Kurrle SE, Lord SR, Lockwood K, Cameron ID. Effect of a multifactorial interdisciplinary intervention on mobility-related disability in frail older people: randomised controlled trial. BMC Med 2012;10:120.

70. Fairhall N, Sherrington C, Lord SR, et al. Effect of a multifactorial, interdisci-plinary intervention on risk factors for falls and fall rate in frail older people: a randomized controlled trial. Age Ageing 2013;Dec 30.

71. Cameron ID, Fairhall N, Langron C,et al. A multifactorial interdisciplinary intervention reduces frailty in older people : randomized trial. BMC Medicine 2013;11:65.

72. Chan DCD, Tsou HH, Yang RS, et al. A pilot randomized controlled trial to improve geriatric frailty. BMC Geriatr 2012;12:58.

73. Ensrud KE, Ewing SK, Taylor BC, et al. Comparison of 2 frailty indexes for prediction of falls, disability, fractures, and death in older women. Arch Intern Med 2008; 168:382-389.

74. Subra J, Gillette-Guyonnet S, Cesari M, Oustric S, Vellas B. The integration of frailty into clinical practice: preliminary results from the Gérontopôle. J Nutr Health Aging 2012;16:714-720.

75. Gill TM, Gahbauer EA, Allore HG, Han L. Transitions between frailty states among community-living older persons. Arch Intern Med 2006;166:418-423.

76. Abellan Van Kan G, Vellas B. Is the Mini Nutritional Assessment an appropriate tool to assess frailty in older adults? J Nutr Health Aging 2011;15:159-161.

77. Dent E, Visvanathan R, Piantadosi C, Chapman I. Use of the mini nutritional assessment to detect frailty in hospitalised older people. J Nutr Health Aging 2012;16:764-767.

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“Important breakthroughs have been made in discovering

the biological basis of frailty, and from these discoveries

new future treatments can be developed”, said meeting

Co-Chairman, Professor Roger A. Fielding, Director of The

Nutrition, Exercise Physiology and Sarcopenia Laboratory

at Tufts University, USA. Inflammation, oxidative stress,

mitochondrial dysfunction and cell senescence lie at the core

of dysregulation in frailty. It is these areas that present great

potential for innovations to support the current multi-modal

interventions for frailty of nutrition, exercise and pharmaco-

therapy. Several lines of evidence have shown that there is a

distinct phenotype for frailty. In addition, there are cognitive

aspects which have similar biological origins to physical

frailty and these can co-exist in some patients. In the future,

international teams of researchers will collaborate on topics

for investigation, with the aim of further improving patient

outcomes while remaining cost-effective.

European initiatives underway to address the problem of frailty An estimated 17.5% of the EU population (over 500

million in 27 countries), are older than 65 years of age and

Professor Bruno Vellas

Professor Cornel Sieber

Professor Roger A. Fielding

this percentage will increase over the coming years as the

population ages.

Professor Jean-Pierre Michel, Geneva Medical School,

Switzerland, and Chairman of the European Union Geriatric

Medicine Society (EUGMS) Board, described evidence collected

in the population screened by general practitioners and referred

for care in the Toulouse Gerontopôle Frailty Clinic.

Around 40% of 1,108 community-dwelling adults were

found to be pre-frail and 55% frail. These results were based

on frailty evaluation using a screening questionnaire: the

Gerontopôle Frailty Screening Scale. Observations revealed

that 62% of patients were recommended a nutritional

intervention and over 55% were recommended a physical

intervention.

Professor Michel explained the far-reaching effects of

these results: “This model prompted several organizations

in France to act on frailty; for example, the French

National Health Authority, the French National Society

of Geriatrics and the French Academy of Medicine, all

of which are now involved in frailty education and offer

advice on its management”. EUGMS initiatives include

several activities relating to sarcopenia as well as to frailty,

including the recently published PROT-AGE evidence-based

recommendations for optimal dietary protein intake in

older people. Other expert consensus papers are due to be

published this year, including the importance of nutrition,

such as protein-enriched diets, on these conditions and a

working group to validate the Gerontopôle questionnaire

Report from the 83rd Nestlé Nutrition Institute workshop on: ‘Frailty: Pathophysiology, Phenotype and Patient Care’

The quest to better understand frailty: Improved treatments and prevention are on the horizon

Frailty in the elderly population is a growing problem globally

and the quest for a better understanding of this condition was

the topic of a landmark meeting in Barcelona, Spain, which took

place on 14–15 March 2014, and was chaired by Professors

Roger A. Fielding, Cornel Sieber and Bruno Vellas. At this

event, experts from around the world met to share their cutting

edge research on the central aspects of frailty pathophysiology,

phenotype and patient care, and to define the way forward.

“A Europe-wide longitudinal study has

shown that frailty can be reversed.

This was one of the key findings of the

Survey of Health, Ageing and Retirement

in Europe (SHARE), which included over

85,000 individuals"

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across Europe. Finally, the European Union has several

research initiatives. The European Innovation Partnerships

(EIPs), a new approach to EU research and innovation, and

the MID-FRAIL study are examples. The MID-FRAIL study

is a Phase IIb open, randomized, clinical trial to evaluate

the effectiveness of a multi-modal intervention (optimizing

medical management, resistance-based exercise program

and educational/nutritional intervention) in 1,704 frail or

pre-frail subjects (aged >70 years) with type 2 diabetes to

prevent functional decline and maintain or improve quality

of life and its associated costs.

Frailty is a syndrome with several underlying mechanisms Age-related biological decline is connected to frailty. However,

not all elderly people are frail. Ultimately, it is hoped that a

better understanding of the internal physiologic and molecular

changes will lead to identification of a biomarker to the frailty

phenotype, in order to facilitate early detection and track

progression of the condition. Professor Jeremy Walston from

Johns Hopkins University, USA, identified several possible

physiologic and molecular mechanisms by which frailty may

be induced, such as inflammation and insulin resistance.

Recently, important progress has been made in understanding

the relationship of the dysregulated stress response systems in

relation to frailty, with chronic activation of stress hormones

such as cortisol driving further changes.

Recent research focused on aging at the cellular level has

identified approaches that can prevent or markedly delay frailty

as well as well as other conditions such as Alzheimer’s disease,

diabetes and cancer. Cellular senescence has been found to be

one possible pathway to frailty development, as this appears

to be a driver of aging and age-related conditions. Professor

Nathan K. LeBrasseur from the Robert and Arlene Kogod

Center on Aging at the Mayo Clinic, USA, showed in a mouse

model of accelerated aging that preventing or delaying frailty

can be achieved by removing senescent cells – or inhibiting the

senescence-associated secretory phenotype (SASP).

In addition, animal data from the Mayo Clinic show that

chronic consumption of a fast food diet significantly increases

both the abundance of senescent cells in middle-aged mice and

the expression of SASP components in fat tissue. However,

physical activity dramatically prevented the effects of fast food

on senescence and the SASP. Many questions remain, and

research into various aspects of senescence is ongoing.

As well as inflammation and senescence, there is also the

autophagy theory of aging related to aberrant mitochondrial

fission and fusion. According to Professor Christiaan

Leeuwenburgh from the Institute on Aging at the University

of Florida, USA, aging cells have a reduced turnover of

cellular components (ie, reduced ‘garbage disposal’) with

intracellular accumulation of altered macromolecules and

organelles (ie, accumulation of ‘garbage’). This highlights the

importance of changes at a cellular level in the development

of frailty. Other factors include telomere changes, as well

as mitochondrial DNA instability, mutations and deletions,

such as in sirtuin-3 (SIRT3) which normally scavenges

reactive oxygen species and can lead to elevated oxidative

stress and a variety of adverse outcomes on the aging process.

Physical frailty is linked to psychological and cognitive frailty Professor L. Jaime Fitten of the Department of Psychiatry

and Biobehavioral Sciences at UCLA, USA, described what

is commonly observed in clinical practice: an association

between psychological frailty (PsyF) and physical frailty.

Patients with both types have a poorer prognosis. PsyF is

part of the clinical frailty syndrome that considers cognition,

mood and motivation, but very little about it is currently

described. PsyF represents one of several possible aging

trajectories, and may be worsened by chronic brain disease;

however, disease and normal aging do not damage the same

networks or to the same degree. More research in this area is

needed to answer the outstanding questions regarding PsyF.

Physical performance indicated by gait measures is

a strong independent predictor of future cognitive decline

and dementia risk. Furthermore, multiple lifestyle factors

(such as insufficient nutrient intake, low levels of physical

activity) and biological mechanisms (such as inflammation

and impaired insulin sensitivity) are closely involved in the

development of frailty, therefore offering numerous targets

for intervention by healthcare professionals. Longitudinal

studies suggest a link between physical and cognitive frailty.

As such, individuals with physical frailty may also have

deficits in executive function – termed ’cognitive frailty’. This

term has recently been defined by an international consensus

group (from the International Academy on Nutrition

and Aging [IANA] and the International Association of

Gerontology and Geriatrics [IAGG]) as ‘a heterogeneous

clinical manifestation characterized by the simultaneous

“In the future we need to be able

to identify and target ‘vulnerability’

pathways to try and slow functional

impairment – a decline that appears to

be linked to chronic disease states and

adverse health outcomes in older adults"

“In order to slow the aging process,

lifestyle factors such as diet and exercise

can be important”

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presence of physical frailty and cognitive impairment, in the

absence of Alzheimer’s Disease or other dementia’. Research

by Professor Marco Pahor and his team from the University

of Florida Institute on Aging has shown that diet alone was

able to significantly reduce interleukin-6 (IL-6), a marker of

age-related chronic low-grade systemic inflammation.

Large, long-term, randomized controlled trials

are needed to test the efficacy of combined behavioral,

nutritional, physical, and pharmacological interventions on

frailty, cognitive impairment and health outcomes.

Screening for malnutrition is important for frailty prevention A multi-national research initiative identified that malnu-

trition, and the risk of malnutrition, are present in over

two-thirds of older people in various formal care settings

(ie, hospitals, nursing homes, and rehabilitation centers).

Professor Cornel Sieber, Chair of Internal Medicine-

Geriatrics, Friedrich-Alexander-Universität Erlangen-

Nürnberg, Germany, suggested that the weight loss cut-off

to indicate a nutrition issue in the Fried frailty criteria may

underestimate the problem of malnutrition in older adults.

The Mini Nutritional Assessment (MNA®) may

be a more sensitive screening method, as it is the only

malnutrition screening/assessment tool specifically developed

for older people. Data show that use of the MNA® is more

closely indicative of survival risk than the use of the Fried

criteria, since the MNA® also takes into account depression,

dementia, motivation, fatigue and mobility. “Malnutrition

measured by the MNA® is closely linked to reduced

strength, functionality and mobility, and therefore to frailty

risk,” said Prof Sieber, “so it is important to routinely screen

for malnutrition in older patients”.

Nutrition and exercise have demonstrated benefits for the frail Over the last few years evidence has been mounting to

support a significant role for vitamin D in the treatment

of frailty, partly at least because of its signaling effect on

muscle explained Professor Heike A. Bischoff-Ferrari, Chair

of the Department of Geriatrics and Ageing Research at the

University of Zurich, Switzerland.

Numerous meta-analyses show the positive impact of

supplemental vitamin D on fall prevention (reduced by up to

34%), a fact recognized in guidelines and recommendations

from several national and international societies. Vitamin

D status also has other positive benefits on mobility and

physical performance measures, and in chronic conditions

such as cardiovascular disease. The largest ongoing longevity

trial funded by the European Commission Framework 7, a

public-private partnership with numerous sponsors including

Nestlé Health Science, is testing the clinical and economic

impact of three broadly applicable interventions: vitamin D,

omega-3 fatty acids and exercise on five primary endpoints

(fractures, functional decline, blood pressure, cognitive

decline, and infections) in 2,152 people aged 70 years and

older. The results will be published in due course.

The benefits of remaining active, although intuitive,

have now been demonstrated in frail people. Dr Dennis T.

Villareal of the University of New Mexico, USA, described

several studies in which exercise in older adults led to

improvements in physical performance.

An association between obesity and the frailty

syndrome has also been noted, with obese elderly people

having poor muscle quality. Since obesity is an increasing

problem, healthcare professionals should be aware of how

to manage it in the context of frailty. Evidence shows that

“The study demonstrated how a

behavioral program designed to change

eating habits and lower weight by 5%

in obese older adults can significantly

improve mediators of frailty risk”

“As the presence of unintentional weight

loss (>10 pounds [4.5 kg] in 1 year) is

one of the five criteria evaluated for an

individual to be considered frail, adequate

nutrition is very important for healthy and

active aging”

“Notably, 90% of the at-risk/

malnourished population detected by

the MNA® are also pre-frail/frail. Thus,

among those who screen positive for

malnutrition/risk, it is important to

proactively evaluate for and manage

frailty issues”

“Standard supplementation of vitamin D

may be a good strategy due to the high

frequency of deficiency in seniors (50%)

and frail elderly (80%)”

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exercise programs, along with dietary interventions, are

successful in reducing aspects of frailty, including in obese

older patients, as well as improving quality of life. However,

Dr Villareal recommended that interventions should be

personally tailored.

Further information on the exact type, duration,

frequency, setting and intensity of exercise training is still

required.

Hip fracture is a common problem in the frail, requiring multi-component intervention Older people and particularly the frail are at risk of hip

fracture if they suffer a fall. There is an ever-increasing

personal, social and economic burden associated with hip

fractures. A drastic change in lean body mass occurs during

the first 60 days after hip fracture. In comparison, fat mass

is relatively stable during that period. The prevalence rate

of sarcopenia increases 1.5 fold between pre-fracture to 60

days post-fracture. Among individuals with no previous

impairment, 90% are unable to climb five stairs unassisted

at 12 months post-fracture. Professor Jay Magaziner from

the Department of Epidemiology and Public Health at the

University of Maryland, Baltimore, USA, explained that hip

fracture is a multi-faceted problem which requires multi-

component, multi-disciplinary treatments and intervention

programs to improve short-and long-term outcomes.

Over the past 25 years the Baltimore Hip Studies

have aimed to identify gaps, develop evidence and evaluate

strategies to optimize recovery from hip fracture. These

studies have recorded numerous functional and quality of

life deficits following hip fracture, and identified an orderly

sequence of functional recovery which seems to parallel

the process by which function is lost. Research is ongoing

into multidisciplinary/ multi-component interventions that

have the greatest impact at specific times post-fracture.

Professor Magaziner gave his thoughts on the direction of

future investigations: “As systems of care delivery change

to improve outcomes and reduce costs, we need to evaluate

the cost-effectiveness of patient-focused/need-based

interventions”.

Improving quality of life and maintaining independence for frail people Professor Leocadio Rodríguez Mañas, Head of the

Department of Geriatrics at Hospital Universitario de Getafe,

Madrid, Spain, asked: “There is a complex relationship

between longevity and frailty, but do they share the same

determinants?” Some cellular and chemical mechanisms

operate mainly on longevity, while others operate on frailty.

Although some mechanisms may be shared, longevity and

frailty cannot work on exactly the same pathway, otherwise

all elderly would be frail, which is not the case. Evidence

suggests that physical inactivity, inflammation and sex

hormones play important roles in both reducing longevity

and promoting frailty.

What is becoming clear is that overlaps exist between

definitions of frailty and sarcopenia. Sarcopenia is also

emerging as a major threat to quality of life in our aging society.

Initiating early strategies to maintain independence and avoid

disability must be key goals for patients with these conditions.

Sarcopenia is a syndrome characterized by progressive

loss of muscle mass and strength with a risk of adverse

outcomes, whereas frailty is a syndrome with multiple causes,

characterised by diminished strength and endurance that

increases vulnerability for dependency and death. Although

there are differences in these conditions, clear overlaps are

“Studies suggest that exercise should be an

integral part of the strategy to reduce frailty”

“It is necessary to individualize

exercise programs according to the

older individual’s health condition and

ability, and to start slow and go slow

to promote adherence and minimize

musculoskeletal injuries”

“Possible components of treatment for

hip fracture recovery include surgical

repair; nutritional supplementation

(ie, vitamin D, calcium and protein);

psychological, physical, and occupational

therapy; and pharmacological (ie, bone

strengthening) agents”

“Today, the focus of healthcare should

be on improving quality of life rather

than increasing longevity. By addressing

issues early and improving nutritional

status, we can impact an improvement in

functional status”

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apparent. Both sarcopenia and frailty are catabolic conditions

with negative effects on function and outcomes in older and

ill adults, and these conditions are associated with a rise in

age-related inflammation and its associated reactions in the

body – which has been termed ‘inflammaging’. Professor

Tommy Cederholm, Head of Department for Clinical Nutrition

and Metabolism at Uppsala University in Sweden, said the

management of frailty and sarcopenia is currently similar in

terms of screening, assessment, treatment and monitoring, but

as more becomes known, differences might be revealed.

Future pharmacological therapies for frailty in the pipeline What can be done in the future to address the pharmaco-

therapy of frailty? Professor Shalender Bhasin, Director of

the Research Program in Men’s Health: Ageing and Metab-

olism at Harvard Medical School, USA, presented ongoing

research on pharmaceutical agents currently in development

for frailty, such as promyogenic agents (eg, testosterone and

selective androgen receptor modulators [SARMs]), orexi-

genic agents and fast troponin activators. These agents are

designed to address the balance between the regulation of

atrophy and the regulation of growth, and to target four

interconnected signaling pathways that are considered to be

major regulators of skeletal muscle mass.

A call to action for healthcare professionals to address frailty in clinical practice The care of older people should be improved, and strategies

should be initiated before individuals become disabled and

institutionalized, a prophylactic approach that has already

been successfully implemented in other conditions such as

cancer and cardiovascular disease.

Professor Bruno Vellas of the Department of Internal

Medicine and Geriatrics at the Université de Toulouse,

France, summed up the large-scale changes that need to

occur: In order to support this shift of focus we need to build

the infrastructure to care for older patients before frailty

develops.

International interest and urgency in addressing frailty

is increasing. Data show that interventions in older patients,

such as comprehensive geriatric assessment in hospital and

preventive home visitation programs, do produce benefits

such as decreasing physical and functional decline, decreasing

mortality, decreasing nursing home use and increasing the

possibility of remaining at home. The Gerontopôle example

of implementing frailty into clinical practice incorporates

a screening tool for frailty (that factors-in the opinion of

the GP), a multidisciplinary team approach across France,

health promotion efforts for older people in the community,

and targeted interventions with structured follow-up and

re-evaluation for identified people at risk. There is also a

considerable body of ongoing research into areas such as

sarcopenia and nutritional aspects of frailty.

The quest to better understand and increase awareness

of the expanding geriatric syndrome of frailty is underway.

There are many facets to the condition, so there are many

challenges ahead. With international expertise focused on

the epidemiology and pathophysiology of frailty, and the

exploration of new treatments, improved outcomes for frail

older adults are on the horizon.

“Sarcopenia and frailty are ‘the new

giants of geriatric syndromes’, and

awareness of both conditions needs

to be increased across all healthcare

organizations, particularly in primary

care, so that diagnosis and treatment are

routinely co-ordinated"

“The considerable number of products in

research and development for age-related

functional limitations emphasizes the

importance being placed on this area of

medicine”

“Overall, frailty needs to be moved up the

healthcare agenda globally in order to

reduce the burden of frailty on healthcare

resources and society in general”

“Today, treatments clearly exist and frailty can be reversed.

Management starts with simple screening tests. A consensus

paper from six medical societies recommends…

All persons older than 70 years and all individuals with significant weight loss (>5%) due to chronic disease, should

be screened for frailty”

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Ongoing research into exercise, nutrition and

pharmacological interventions is creating the potential for

future multi-modal solutions, not just to the physical and

cognitive aspects of frailty but also to the social and economic

challenges associated with this condition.

Key references 1. American Geriatric Society/British Geriatric Society Clinical Practice Guideline, 2010. Available at:

http://www.americangeriatrics.org/health_care_professionals/clinical_practice/clinical_guide-lines_recommendations/2010/

2. Barja G, Herrero A. Oxidative damage to mitochondrial DNA is inversely related to maximum life span in the heart and brain of mammals. FASEB J 2000;14:312-318.

3. Barzilay JI, Blaum C, Moore T, et al. Insulin resistance and inflammation as precursors of frailty: the Cardiovascular Health Study. Arch Intern Med 2007;167:635-641.

4. Beswick AD, Rees K, Dieppe P, et al. Complex interventions to improve physical function and maintain independent living in elderly people: a systematic review and meta-analysis. Lancet 2008;371:725-735.

5. Bischoff-Ferrari HA, Dawson-Hughes B, Staehelin HB, et al. Fall prevention with supplemental and active forms of vitamin D: a meta-analysis of randomised controlled trials.Br Med J 2009;339:b3692.

6. Bollwein J, Volkert D, Diekmann R, et al. Nutritional status according to the mini nutritional assessment (MNA®) and frailty in community dwelling older persons: a close relationship. J Nutr Health Aging 2013;17:351-356.

7. Bonnefoy M, Cornu C, Normand S, et al. The effects of exercise and protein-energy supplements on body composition and muscle function in frail elderly individuals: a long-term controlled randomised study. Br J Nutr 2003;89:731-739.

8. Börsch-Supan A, Brandt M, Hunkler C, et al. Data Resource Profile: the Survey of Health, Ageing and Retirement in Europe (SHARE). International J Epidemiol 2013;42:992-1001.

9. Cameron ID, Gillespie LD, Robertson MC, et al. Interventions for preventing falls in older people in care facilities and hospitals. Cochrane Database Syst Rev 2012;12:CD005465.

10. Cruz-Jentoft AJ, Baeyens JP, Bauer JM, et al. Sarcopenia: European consensus on definition and diagnosis: Report of the European Working Group on Sarcopenia in Older People. Age Ageing 2010;39:412-423.

11. Dent E, Visvanathan R, Piantadosi C, Chapman I. Use of the Mini Nutritional Assessment to detect frailty in hospitalised older people. J Nutr Health Aging 2012;16:764-767.

12. Ellis G, Whitehead MA, Robinson D, O’Neill D, Langhorne P. Comprehensive geriatric assessment for older adults admitted to hospital: meta-analysis of randomised controlled trials. BMJ 2011;343:6553.

13. Ferrucci L, Corsi A, Lauretani F, et al. The origins of age-related proinflammatory state. Blood 2005;105:2294-2299.

14. Fried LP, Xue QL, Cappola AR, Ferrucci L, et al. Nonlinear multisystem physiological dysregulation associated with frailty in older women: implications for etiology and treatment. J Gerontol A Biol Sci Med Sci 2009;64:1049-1057.

15. Fried LP, Tangen CM, Walston J, J et al. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci 2001;56:M146-M156.

16. Gullberg B, Johnell O, Kanis JA. World-wide projections for hip fracture. Osteoporos Int 1997;7:407-413.

17. Kiesswetter E, Pohlhausen S, Uhlig K, et al. Malnutrition is related to functional impairment in older adults receiving home care. J Nutr Health Aging 2013;17:345-350.

18. Kujoth GC, Hiona A, Pugh TD, So et al. Mitochondrial DNA mutations, oxidative stress, and apoptosis in mammalian aging. Science 2005;309:481-484.

19. Macklai NS, Spagnoli J, Junod J, Santos-Eggimann B. Prospective association of the SHARE-operationalized frailty phenotype with adverse health outcomes: evidence from 60+ community-dwelling Europeans living in 11 countries. BMC Geriatr 2013;13:3.

20. Magaziner J, Hawkes W, Hebel JR, et al. Recovery from hip fracture in eight areas of function. J Gerontol A Biol Sci Med Sci 2000;55:M498-M507.

21. Morley JE, Vellas B, van Kan GA, et al. Frailty consensus: a call to action. J Am Med Dir Assoc 2013;14:392-397.

22. Nicklas BJ, Ambrosius W, Messier SP, et al. Diet-induced weight loss, exercise, and chronic inflam-mation in older, obese adults: a randomized controlled clinical trial. Am J Clin Nutr 2004;79:544-551.

23. Sahin E, Colla S, Liesa M, et al. Telomere dysfunction induces metabolic and mitochondrial compromise. Nature 2011;470:359-365.

24. Saletti A, Johansson L, Yifter-Lindgren E, Wissing U, Osterberg K, Cederholm T. Nutritional status and a 3-year follow-up in elderly receiving support at home. Gerontology 2005;51:192-198.

25. Santos-Eggimann B, Cuénoud P, Spagnoli J, Junod J. Prevalence of frailty in middle-aged and older community-dwelling Europeans living in 10 countries. J Gerontol A Biol Sci Med Sci 2009;64:675-681.

26. Someya S, Yu W, Hallows WC, et al. Sirt3 mediates reduction of oxidative damage and prevention of age-related hearing loss under caloric restriction. Cell 2010;143:802-812.

27. Stuck AE, Egger M, Hammer A, Minder CE, Beck JC. Home visits to prevent nursing home admission and functional decline in elderly people: systematic review and meta-regression analysis. JAMA 2002;287:1022-1028.

28. Tieland M, van de Rest O, Dirks ML, et al. Protein supplementation improves physical performance in frail elderly people: a randomized, double-blind, placebo-controlled trial. J Am Med Dir Assoc 2012;13:720-726.

29. Villareal DT, Banks M, Siener C, Sinacore DR, Klein S. Physical frailty and body composition in obese elderly men and women. Obes Res 2004;12:913-920.

30. Wahrendorf M, Reinhardt JD, Siegrist J. Relationships of disability with age among adults aged 50 to 85: evidence from the United States, England and continental Europe. PLoS One 2013;8:e71893.

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September 2014

36th ESPEN Congress 6–9 September 2014 Geneva, SwitzerlandOrganizer:The European Society for Clinical Nutrition and Metabolism

Web site: http://www.espen.org/geneva-2014

10th International Congress of the EUGMS17–19 September 2014 Rotterdam, The NetherlandsOrganizer:European Union Geriatric Medicine Society (EUGMS)

Web site: http://www.eugms2014.org/en/Home_10_6_12.html

ESICM LIVES 2014 Annual Congress 27 September – 1 October 2014 Barcelona, Spain Organizer:The European Society of Intensive Care Medicine (ESICM)

Web site: http://www.esicm.org/events/annual-congress

Food and Nutrition Conference and Expo 2014 (FNCE 2014)18–21 October 2014Atlanta, Georgia, USAOrganizer:Academy of Nutrition and Dietetics

Web site: http://www.eatright.org/FNCE/

NASPGHAN Annual Meeting and Postgraduate Course23–26 October 2014Atlanta, Georgia, USAOrganizer:North American Society for Pediatric Gastroenter-ology, Hepatology and Nutrition (NASPGHAN)

Web site: http://www.naspghan.org

American College of Surgeons (ACS) Annual Clinical Congress26–30 October 2014San Francisco, California, USA

Organizer:American College of Surgeons (ACS)

Web site: http://www.facs.org/clincon2014/

2014 AAP National Conference and Exhibition11–14 October 2014San Diego, California, USA Organizer:American Academy of Pediatrics (AAP)

Web site: www.aapexperience.org

4th ESSD Congress 23–25 October 2014 Brussels, Belgium Organizer:The European Society for Swallowing Disorders (ESSD)

Web site: http://www.essd2014.org/

November 2014

The 2014 Annual Meeting of the American College of Allergy, Asthma & Immunology 6–10 November 2014 Atlanta, Georgia, USA Organizer:American College of Allergy, Asthma & Immunology (ACAAI)

Web site: www.acaai.org/annual_meeting/Pages/default.aspx

December 2014

2014 Advances in Inflammatory Bowel Diseases4–6 December 2014 Orlando, Florida, USA Organizer:Crohn’s & Colitis Foundation of America (CCFA)

Web site: http://www.advancesinibd.com/

Calendar 2014Conference

Nutrition Screening®

As as

Malnutrition is associated with a 3 times higher infection rate and higher mortality rate1,2

• Most validated tool for the elderly

• Quick, convenient and easy to use

• Identifies patients who need nutrition intervention

• Most commonly used nutrition screening tool by geriatricians3

• The new Self-MNA® is valid for use by older adults4

MNA®: The GOLD standard in nutrition screening for the older adult

1. Sorensen J et al. Clin Nutr 2008; 27(3):340-349. 2. Schneider SM et al. Br J Nutr 2004; 92(1):105-111. 3. Vandewoude M et al. European Geriatric Medicine 2011; vol 2, issue 2:67-70.4. Huhmann et al. J Nutr Health Aging 2013; 17(4):339-344.

Screen and intervene. Nutrition can make a difference.

Visit:

www.mna-elderly.com

Print CMYK | Blue = C 100% / M 72% / B 18% | Green = C 80% / Y 90%

Screening

F2 Calf circumference (CC) in cm 0 = CC less than 31 3 = CC 31 or greater

Last name: First name:

Sex: Age: Weight, kg: Height, cm: Date:

A Has food intake declined over the past 3 months due to loss of appetite, digestive problems, chewing or swallowing difficulties?

0 = severe decrease in food intake 1 = moderate decrease in food intake 2 = no decrease in food intake

B Weight loss during the last 3 months 0 = weight loss greater than 3 kg (6.6 lbs) 1 = does not know 2 = weight loss between 1 and 3 kg (2.2 and 6.6 lbs) 3 = no weight loss

C Mobility 0 = bed or chair bound 1 = able to get out of bed / chair but does not go out 2 = goes out D Has suffered psychological stress or acute disease in the past 3 months? 0 = yes 2 = no

E Neuropsychological problems 0 = severe dementia or depression 1 = mild dementia 2 = no psychological problems

F1 Body Mass Index (BMI) (weight in kg) / (height in m2) 0 = BMI less than 19 1 = BMI 19 to less than 21 2 = BMI 21 to less than 23 3 = BMI 23 or greater

Complete the screen by filling in the boxes with the appropriate numbers. Total the numbers for the final screening score.

12-14 points: Normal nutritional status8-11 points: At risk of malnutrition0-7 points: Malnourished

References1.Vellas B, Villars H, Abellan G, et al. Overview of the MNA® - Its History and Challenges. J Nutr Health Aging. 2006;10:456-465. 2.Rubenstein LZ, Harker JO, Salva A, Guigoz Y, Vellas B. Screening for Undernutrition in Geriatric Practice: Developing the Short-Form Mini Nutritional Assessment (MNA-SF). J. Geront. 2001;56A: M366-377. 3.Guigoz Y. The Mini-Nutritional Assessment (MNA®) Review of the Literature - What does it tell us? J Nutr Health Aging. 2006; 10:466-487.4.Kaiser MJ, Bauer JM, Ramsch C, et al. Validation of the Mini Nutritional Assessment Short-Form (MNA®-SF): A practical tool for identification of nutritional status. J Nutr Health Aging. 2009; 13:782-788. ® Société des Produits Nestlé, S.A., Vevey, Switzerland, Trademark Owners © Nestlé, 1994, Revision 2009. N67200 12/99 10M For more information: www.mna-elderly.com

IF BMI IS NOT AVAILABLE, REPLACE QUESTION F1 WITH QUESTION F2.DO NOT ANSWER QUESTION F2 IF QUESTION F1 IS ALREADY COMPLETED.

Mini Nutritional Assessment MNA®

Screening score (max. 14 points)

69715_MNA_Screening_A4-2.indd 1 23/08/2013 15:35

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