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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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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
Participants: n=802, aged ≥ 65 years
- 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)
Participants: n=986, aged ≥ 65 years
- 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
Participants: n=766, aged ≥ 65 years
- 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
Participants: n=1,005, aged ≥ 65 years
- 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
Participants: n=5,048, aged ≥ 60 years
- 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
Participants: n=6,307, aged ≥ 69 years
- 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
Participants: n=1,600, aged ≥ 65 years
- 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
Participants: n=1,155, aged ≥ 65 years
- 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
Participants: n=4,731, aged ≥ 60 years
- 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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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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of Physical Exercise Training on Cognition and Quality of Life in Frail Older Adults. J Gerontol B Psychol Sci Soc Sci 2013;68:400-404.
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