Prevention and early diagnosis of frailty and … and early diagnosis of frailty and functional decline Tomasz Kostka Medical University of Lodz, Poland CONFLICT OF INTEREST DISCLOSURE

Prevention and early diagnosis of frailty and functional decline

Tomasz Kostka Medical University of Lodz, Poland

CONFLICT OF INTEREST DISCLOSURE

I have no potential conflict of interest to report

Tomasz Kostka Medical University of Lodz, Poland

Definitions

Early diagnosis

Prevention

Prof. Tomasz Kostka

EUGMS, Nice, 20-22.09.2017

Definitions

Functional decline

Frailty

Prof. Tomasz Kostka

EUGMS, Nice, 20-22.09.2017

Physical performance (fitness)

1. Cardiorespiratory fitness, cardiorespiratory endurance, aerobic power, aerobic capacity, stamina

2. Muscle strength, power and endurance (muscular fitness)

3. Speed

4. Flexibility, balance…

Body composition (% body fat, BMI, WHR)

Age-related functional decline:

- physiological changes with ageing

- concomitant diseases

Aerobic capacity and age

Booth FW, J Appl Physiol, 1989: 67, 1299-1300

Handgrip and age in 847 men aged 20-100 years.

Kallman et al., J Gerontol MED SCI 1990: 45, M82-M88.

Age (years)

Pm

ax (

W)

200

400

600

800

1000

1200

20 30 40 50 60 70 80 90

r2 = 54.4 p < 0.001

Kostka T., Eur. J. Appl. Physiol.

2005, 95, 140-145

Velocity (rpm)

Pow

er

(W

)

0

200

400

600

800

20 60 100 140 180

young

old

Bonnefoy et al., Eur. J. Appl.

Physiol. 1998, 77, 182-188

Aerobic power

Anaerobic power

Age

Po

we

r (W

)

20 30 40 50 60 70 80 90

0

200

400

600

800

1000

1200

Kostka et al. Int J Sports Med. 2009

Correlations between functional status variables and muscle

strength, power and nopt

baseline

Quantitative

variable Fext·kg−1 Pmax·kg−1 υopt

ADL

(points)

r=0.08 r=0.41* r=0.27

TUG test (s) r=-0.32 r=-0.66*** r=-0.61***

Tinetti test

(points)

r=0.26 r=0.64*** r=0.55**

6-MWT (m) r=0.32 r=0.76*** r=0.59***

after rehabilitation

Quantitative

variable Fext·kg−1 Pmax·kg−1 υopt

ADL (points) r=0.11 r=0.47* r=0.46*

TUG test (s) r=-0.52** r=-0.83*** r=-0.77***

Tinetti test

(points)

r=0.22 r=0.60** r=0.69***

6-MWT (m) r=0.38* r=0.73*** r=0.71***

Kostka J, Czernicki J, Kostka T: Association of muscle strength, power and optimal shortening velocity

with functional abilities of women with chronic osteoarthritis participating in a multi-modal exercise

program. J Aging Phys Act. 2014 Oct;22(4):564-70.

Major age-related diseases leading

to functional decline and disability

Hypertension, CHD, CHF

Stroke

Diabetes

COPD, asthma

Osteoporosis, osteoarthritis

Dementia. AD, PD

Other…

Functional capacity

Age

Functional capacity

Disability threshold

Age

Concepts of frailty

Frailty phenotype Fried et al. J Gerontol Med Sci 2001;56A:M146-56.

Physical frailty, disability as an outcome of frailty Morley et al. JAMDA 2013;14:392-7.

Frailty defined by deficit accumulation, overall state of

health as a measure of frailty, overlaps with disability Rockwood and Mitnitski. Clin Geriatr Med 2011;27:17-26.

Rockwood and Mitnitski. J Frailty Aging 2012;1:8-12.

Sarcopenia as the central biological substrate of physical

frailty

PF & sarcopenia (PF&S) syndrome

Operationalization of the theoretical concept of PF&S

Landi F, Calvani R, Cesari M, et al. Sarcopenia as the biological substrate of physical frailty. Clin

Geriatr Med. 2015;31(3):367–374.

Marzetti E, Calvani R, Cesari M, et al. Operationalization of the physical frailty & sarcopenia

syndrome: rationale and clinical implementation. Translational Medicine @ UniSa. 2015;13:29-32.

Cesari et al. Rationale for a preliminary operational definition of physical frailty and

sarcopenia in the SPRINTT trial. Aging Clin Exp Res. 2017 Feb;29(1):81-88.

Functional capacity


Age

Functional capacity


Age

Functional capacity


Age

Definitions

Early diagnosis

Prevention

Prof. Tomasz Kostka

EUGMS, Nice, 20-22.09.2017

Functional capacity


Age

Early detection/assessment of:

- physical/biological (at the physiological and molecular level)

- psychological

- sociodemographic

- lifestyle

biomarkers/risk factors/subclinical changes/deficits

is a prerequisite to the primary prevention of frailty

Appendicular lean body mass (ALM) cutpoints (ALM

<19.75kg in men and <15.02kg in women) derived from a large,

diverse sample of older adults identified lean mass thresholds

below which older adults had a higher likelihood of weakness

(defined as grip strength <26kg in men and <16kg in women).

Cawthon et al. Cutpoints for low appendicular lean mass that identify older adults with clinically

significant weakness. J Gerontol A Biol Sci Med. Sci 2014;69(5):567-575.

Cut-points for low grip strength (<26kg men and <16kg women),

low grip strength-to-body mass index (BMI) ratio (<1.00 men and

<0.56 women) and low appendicular lean body mass (ALM)-to-

BMI ratio (<0.789 men and <0.512 women) as candidate criteria

for clinically relevant weakness and low lean mass for incident

mobility impairment (gait speed ≤ 0.8 m/s).

McLean et al. Criteria for clinically relevant weakness and low lean mass and their longitudinal

association with incident mobility impairment and mortality: the foundation for the National

Institutes of Health (FNIH) sarcopenia project. J Gerontol A Biol Sci Med Sci 2014;69(5):576-583.

Established Populations for the Epidemiologic Study of the

Elderly (EPESE) performance battery: tests of balance, time

to walk 8 ft, and time to rise from a chair 5 Times

Performance tests of lower extremity function accurately

predict disability

Both the summary score and the gait speed alone allow for

the estimation of risk of disability

Guralnik et al. Lower extremity function and subsequent disability: consistency across studies,

predictive models, and value of gait speed alone compared with the short physical performance

battery. J Gerontol A Biol Sci Med Sci. 2000 Apr;55(4):M221-31.

A gait speed <0.8m/s; a timed-up-and-go test >10s; and a

score of ≥3 on the PRISMA 7 questionnaire can indicate

frailty.

Turner G, Clegg A; British Geriatrics Society; Age UK; Royal College of General Practitioners. Best

practice guidelines for the management of frailty: a British Geriatrics Society, Age UK and Royal

College of General Practitioners report. Age Ageing. 2014 Nov;43(6):744-7.

Clegg A, Rogers L, Young J. Diagnostic test accuracy of simple instruments for identifying frailty in

community-dwelling older people: a systematic review. Age Ageing. 2015 Jan;44(1):148-52.

Highlights

Frailty tool proliferation (identified 67 frailty instruments) is a

challenge for selecting an assessment instrument.

Instruments most used were frailty phenotype, deficit accumulation

index, and VES-13.

Buta et al. Frailty assessment instruments: Systematic characterization of the uses

and contexts of highly-cited instruments, Ageing Research Reviews 2016; 26: 53-61.

Gender

□M

□F

□ Yes

□ Yes

□ Yes

□ Yes

□ Yes

□ Yes

□ Yes

□ Yes

9. Have you had any financial difficulties in

facing dental care and health care costs

during the last year? □ No

6. Have you experienced memory decline

during the last year? □ No

7. Do you feel lonely most of the time? □ No8. In case of need, can you count on

someone close to you? □ No

3. Your physical state made you walking less

during the last year? □ No4. Have you been evaluated by your GP

during the last year? □ No5. Have you fallen 1 or more times during

the last year? □ No

Questions1. Do you regularly take 5 or more

medications per day? □ No

2. Have you recently lost weight such that

your clothing has become looser? □ Yes □ No

BENEFICIARIES

Age

□75-85

Level of education

□ Low (Without studies,

Primary School)

□Medium (Secondary school,

or vocational degree)

□ High (University, Master or

PhD degree)

□65-74

Professional

□ Nurse □ GPs □ Other Professionals

□ Social Worker □ Community Actor □ Caregiver

QUESTIONNAIRE NUMBER ID

Date and place

PROFESSIONALS

Sunfrail Tool

Kroc Ł, Socha K, Sołtysik BK, Cieślak-Skubel A, Piechocka-Wochniak E, Błaszczak R, Kostka T: Validation of the

Vulnerable Elders Survey-13 (VES-13) in hospitalized geriatric patients. Eur Geriatr Med 2016; 7: 449-453.

The quickly and easily administered MNA-SF appears

to be a good tool for predicting both under-nutrition and

frailty in elderly hospitalised people.

Dent et al. Use of the Mini Nutritional Assessment to detect frailty in hospitalised older

people. J Nutr Health Aging. 2012;16(9):764-7.

Risk factors/biomarkers of frailty

Routine blood tests and standard physical measures (blood pressure) Rockwood et al.JAMDA 2015;16:842-7.

Routine blood and urine tests

Ritt et al. Clin Interv Aging 2017;12:1029-40.

Higher TSH in men and lower TSH in women aged≥65 years Veronese et al. Rejuvenation Res 2017;20:3.

Routine blood and special blood tests (eg, DNA) Mitnitski et al. BMC Med 2015;13:161.

“Omics”-based laboratory biomarkers Rodrígues-Mañas L. JFA 2015;4:125-8.

673 significant differentially expressed genes

(128 upregulated and 545 downregulated)

in sarcopenia patients of over 60 years of age.

Most of the upregulated genes were involved in metabolic

processes.

Jeong et al. DETERMINATION OF THE MECHANISMS THAT CAUSE SARCOPENIA

THROUGH cDNA MICROARRAY. J Frailty Aging 2017;6(2):97-102.

The pooled OR of frailty for the lowest versus the

highest level of vitamin D was 1.27 (95% CI=1.17-1.38,

I(2)=59%), suggesting that low level of vitamin D was

significantly associated with the risk of frailty.

Zhou et al. Association of vitamin D deficiency and frailty: A systematic review and

meta-analysis. Maturitas. 2016 Dec;94:70-76.

After adjusting for BMI, the relationship of 25(OH)D < 10

ng/mL (vs ≥30 ng/mL) with incident frailty persisted, but

was attenuated after further accounting for

cardiometabolic diseases.

Buta et al. The Association of Vitamin D Deficiency and Incident Frailty in Older

Women: The Role of Cardiometabolic Diseases. J Am Geriatr Soc. 2017

Mar;65(3):619-624.

"inflamm-aging"

High levels of interleukin (IL)-6, IL-1, tumor necrosis

factor-α, and C-reactive protein are associated in the older

subject with increased risk of morbidity and mortality.

The low-grade inflammation characterizing the aging

process notably concurs at the pathophysiological mechanisms

underlying sarcopenia.

Michaud et al. Proinflammatory cytokines, aging, and age-related diseases. J Am Med Dir

Assoc. 2013 Dec;14(12):877-82.

Higher serum levels of anti-inflammatory markers,

and in particular IL-4 and IL-13, may play a protective role

on FFM and performance maintenance in elderly subjects.

Rossi et al. Role of Anti-Inflammatory Cytokines on Muscle Mass and Performance Changes in Elderly

Men and Women. J Frailty Aging. 2017;6(2):65-71.

Frail subjects have lower levels of serum IGF-I and DHEA-S and

higher levels of IL-6 than do non-frail, age-matched individuals.

Leng SX, Cappola AR, Andersen RE, et al. Serum levels of insulin-like growth factor 1 (IGF-1) and

dehydroepiandrosterone sulfate (DHEAS), and their relationships with serum interleukin-6, in the geriatric

syndrome of frailty. Aging Clin Exp Res 2004; 16:153–157.

Higher baseline levels of differential white cell counts (WCC), lower

levels of dehydroepiandosterone sulphate (DHEAS) and higher

cortisol:DHEAS ratio were all significantly associated with increased

odds of frailty at 10-year follow-up.

Baylis et al. Immune-endocrine biomarkers as predictors of frailty and mortality: a 10-year

longitudinal study in community-dwelling older people. Age (Dordr). 2013 Jun;35(3):963-

71.

Residual IGF-I (nmol .l-1)

-20

-10

0

10

20

-1

-0.5

0

0.5

1

-10

-5

0

5

10

-15 -10 -5 0 5 10 15

partial r=0.59 p=0.001



Pm

ax .

kg

-1 (W

. kg

-1)

Pm

ax .

kgQ

uadr

-1 (W

. kgQ

uadr

-1)

Vopt (r

pm

)

Kostka et al. Leg extensor power and

dehydroepiandrosterone sulfate, insulin-

like growth factor-I and testosterone in

healthy active elderly people.

Eur. J. Appl. Physiol. 2000; 82: 83-90.

Partial correlations in older women.

-10

-5

0

5

10

-1.51 -0.58 0 0.58 1.51

-20

-10

0

10

20

-1

-0.5

0

0.5

1

Residual DHEAS ( mol.l-1)




Vop

t (r

pm

)P

max .

kgQ

uad

r-1

(W

. kgQ

uad

r-1

)P

max .

kg

-1 (W

. kg

-1)

Kostka et al. Leg extensor power and

dehydroepiandrosterone sulfate, insulin-

like growth factor-I and testosterone in

healthy active elderly people.

Eur. J. Appl. Physiol. 2000; 82: 83-90.

Partial correlations in older women.

Higher serum IGF-1 was independently associated with

more muscle mass, higher BMD, and better handgrip

performance in both genders.

Chen et al. Association Among Serum Insulin-Like Growth Factor-1, Frailty, Muscle Mass,

Bone Mineral Density, and Physical Performance Among Community-Dwelling Middle-Aged

and Older Adults in Taiwan. Rejuvenation Res. 2017 May 9. doi: 10.1089/rej.2016.1882.

Schwenk et al. Frailty and Technology: A Systematic Review of Gait Analysis in

Those with Frailty. Gerontology 2014;60:79-89.

Greene et al. Frailty status can be accurately assessed using inertial sensors and the

TUG test. Age and Ageing 2014; 43:406–11.

Martinez-Ramirez A, Martinikorena I, Gomez M, Lecumberri P, Millor N,

Rodriguez-Manas L et al (2015) Frailty assessment based on trunk kinematic

parameters during walking. J Neuroeng Rehabil 12:48.

Mohler MJ, Wendel CS, Taylor-Piliae RE, Toosizadeh N, Najafi B (2016) Motor

performance and physical activity as predictors of prospective falls in community-

dwelling older adults by frailty level: application of wearable technology.

Gerontology 2016;62: 654-64.

Dasenbrock et al. Technology-based measurements for screening, monitoring and

preventing frailty. Z Gerontol Geriatr. 2016;49:581-95.

Definitions

Early diagnosis

Prevention

Prof. Tomasz Kostka

EUGMS, Nice, 20-22.09.2017

Lifelong prevention

Midlife prevention

of age-related functional decline

Prof. dr hab. med. Tomasz Kostka

EUGMS, Nice, 20-22.09.2017

Prevention of frailty and functional decline:

1. Physical activity

2. Nutrition

3. Prevention and treatment of concomitant disorders



2. Nutrition


All-cause mortality according to physical activity level in 16 936 absolvents of Harvard

University.

Paffenbarger et al., N Eng J Med 1986: 314, 606-113.

Pahor et al. Effect of structured physical activity on prevention of major mobility disability in older adults: the LIFE Study randomized clinical

trial. JAMA. 2014;311(23):2387-2396.

1. The WHO guidelines for promoting physical

activity among older persons. J. Aging Phys.

Activity 5:1-8, 1997.

2. American College of Sports Medicine position

stand. Exercise and physical activity for older

adults. Med. Sci. Sports Exerc. 30:992-1008, 1998.

3. King, A. C., W. J. Rejeski, and D. M. Buchner.

Physical activity interventions targeting older

adults: a critical review and recommendations. Am.

J. Prev. Med. 15:316-333, 1998.

4. Evans, W. J. Exercise training guidelines for the

elderly. Med. Sci. Sports Exerc. 31:12-17, 1999.

Physical Activity and Public Health in Older Adults

Recommendation From the American College of Sports Medicine and the American Heart Association

Miriam E. Nelson, PhD, FACSM; W. Jack Rejeski, PhD; Steven N. Blair, PED, FACSM, FAHA; Pamela W. Duncan, PhD; James O. Judge, MD; Abby C. King, PhD, FACSM, FAHA; Carol A. Macera, PhD, FACSM; Carmen Castaneda-Sceppa, MD, PhD

Circulation 2007;116;1094-1105; originally published online Aug 1, 2007;

WHO 2010

Recommended levels

of physical activity for health

for 65 years old and above

Chodzko-Zajko WJ, Proctor DN, Fiatarone Singh MA, Minson CT, Nigg CR, Salem GJ, Skinner JS. American College of Sports Medicine position stand. Exercise and physical activity for older adults.Med Sci Sports Exerc. 2009 Jul;41(7):1510-30

Summary of ACSM/AHA physical activity recommendations for older adults.


Endurance exercise for older adults:

Frequency: for moderate-intensity activities, accumulate at least 30 or

up to 60 (for greater benefit) min/day in bouts of at least 10 min each to total 150–300 min/week,

or at least 20–30 min/day or more of vigorous-intensity

activities to total 75–150 min/week, or an equivalent combination of moderate and vigorous

activity.


Frequency: At least 2 days/week Intensity: Between moderate- (5–6) and vigorous- (7–8) intensity on a scale of 0 to 10 Type: Progressive weight training program or weight bearing calisthenics (8–10 exercises involving the major muscle groups of 8–12 repetitions each), stair climbing, and other strengthening activities that use the major muscle groups

Resistance exercise for older adults


Frequency: At least 2 days/week Intensity: Moderate (5–6) intensity on a scale of 0 to 10 Type: Any activities that maintain or increase flexibility using sustained stretches for each major muscle group and static rather than ballistic movements.

Flexibility exercise for older adults:


Activities that include the following:

progressively difficult postures that gradually reduce the base of support (e.g., two-legged stand, semitandem stand, tandem stand, one-legged stand),

dynamic movements that perturb the center of gravity (e.g.,

tandem walk, circle turns),

stressing postural muscle groups (e.g., heel stands, toe stands), or reducing sensory input (e.g., standing with eyes closed).

Balance exercise for frequent fallers or individuals with mobility problems

American College of Sports Medicine position stand. Progression models in resistance training for healthy adults. Med Sci Sports Exerc. 2009 Mar;41(3):687-708.

There is support for the inclusion of power training for the healthy older adult. Muscle atrophy results from fiber denervation with loss of some fibers and atrophy of others, that is, especially fast twitch, with aging and inactivity. Age-related muscle atrophy is associated with reductions in strength and power, and reductions in power exceed decreases in maximal strength. Although most studies in the elderly examined heavy RT programs, power training may optimize functional abilities…

Physical exercise has beneficial effects for frail elderly on gait

speed, physical functioning, mobility, falls, functional abilities,

muscle strength, body composition, and frailty.

Gine-Garriga et al. 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(4):753.e3–769.e3.

de Labra et al. Effects of physical exercise interventions in frail older adults: a systematic

review of randomized controlled trials. BMC Geriatr. 2015;15:154.

The multi-component exercise intervention composed by strength,

endurance and balance training seems to be the best strategy to improve

rate of falls, gait ability, balance, and strength performance in physically

frail older adults.

Cadore et al. Effects of different exercise interventions on risk of falls, gait ability,

and balance in physically frail older adults: a systematic review. Rejuvenation Res.

2013;16:105-14.

Routine multicomponent exercise intervention should be prescribed to

nonagenarians because overall physical outcomes are improved in this

population.

Cadore et al. Multicomponent exercises including muscle power training enhance

muscle mass, power output, and functional outcomes in institutionalized frail

nonagenarians. Age (Dordr). 2014 Apr;36(2):773-85.

Gardening as the dominant leisure time physical activity (LTPA) of older adults from

a post-communist country. The results of the population-based PolSenior Project

from Poland Rafal Rowinski a, Andrzej Dabrowski b, Tomasz Kostka c,

a Faculty of Physical Education, Jozef Pilsudski University of Physical Education in Warsaw, Marymoncka 34, Warsaw, Poland

b Faculty of Physical Education and Sport in Biala Podlaska, Jozef Pilsudski University of Physical Education in Warsaw, Marymoncka 34, Warsaw, Poland

c Department of Geriatrics, Medical University of Lodz, Pl. Hallera 1, Lodz, Poland

Corresponding author at: Department of Geriatrics, Medical University of Lodz, Pl. Hallera 1, Lodz, Poland. Tel.: +48 42 639 3215; fax: +48 42 639 3218. [email protected]

Table 2. Leisure time physical activities of respondents. Have you engaged in the following activities in your free time?

No Yes

Walks farther from home or the place of accommodation 61.0% 39.0% †‡§

Gymnastic exercise, aerobics, etc. 81.8% 18.2% ‡§

Riding a bicycle 62.7% 37.3% *†‡§

Running or jogging 98.4% 1.6% *†

Swimming 93.7% 6.3% *†‡§

Team games (volleyball, basketball, football, etc.) 99.2% 0.8% *§

Tennis 99.6% 0.4% *†‡

Table tennis 99.1% 0.9% *§

Dancing 87.2% 12.8% *†‡§

Gardening 35.4% 64.6% †‡

Results of Chi-square test

* significant for gender (p<0.05) (“no” vs. “yes” answer or distribution of “yes” answers)

† significant for age cohort (p<0.05) (“no” vs. “yes” answer or distribution of “yes” answers)

‡ significant for size of the place of residence (p<0.05) (“no” vs. “yes” answer or distribution of “yes” answers)

§ significant for social class (p<0.05) (“no” vs. “yes” answer or distribution of “yes” answers)

Rafal Rowinski, Andrzej Dabrowski, Tomasz Kostka. Archives of Gerontology and Geriatrics 60 (2015) 486–491



2. Nutrition and pharmacological

interventions


High Prevalence of Physical Frailty Among Community-Dwelling Malnourished Older

Adults–A Systematic Review and Meta-Analysis

Sjors Verlaan, MSc, Gerdien C. Ligthart-Melis, PhD, Sander L.J. Wijers, PhD, Tommy Cederholm, MD, PhD, Andrea B. Maier, MD, PhD,

Marian A.E. de van der Schueren, PhD

Journal of the American Medical Directors Association

Volume 18, Issue 5, Pages 374-382 (May 2017) DOI: 10.1016/j.jamda.2016.12.074

CONCLUSIONS:

The systematic review and meta-analysis revealed that malnutrition and physical frailty

in community-dwelling older adults are related, but not interchangeable geriatric

syndromes. Two out of 3 malnourished older adults were physically frail, whereas

close to 10% of the physically frail older adults was identified as malnourished.

Copyright © 2017 AMDA – The Society for Post-Acute and Long-Term Care Medicine Terms and Conditions

http://www.elsevier.com/termsandconditions

Nutritional supplementation is effective in the treatment of sarcopenia in

old age, and its positive effects increase when associated with physical

exercise.

Malafarina V(1), Uriz-Otano F, Iniesta R, Gil-Guerrero L. Effectiveness of nutritional supplementation on

muscle mass in treatment of sarcopenia in old age: a systematic review. J Am Med Dir Assoc. 2013

Jan;14(1):10-7.

Physical, nutritional, and cognitive interventional approaches were

effective in reversing frailty among community-living older persons.

Ng et al. Nutritional, Physical, Cognitive, and Combination Interventions and Frailty Reversal Among

Older Adults: A Randomized Controlled Trial. Am J Med. 2015 Nov;128(11):1225-1236.e1.

Multicomponent exercise intervention reverses frailty and improves

cognition, emotional, and social networking in a controlled population of

community-dwelling frail older adults.

Tarazona-Santabalbina et al. A Multicomponent Exercise Intervention that Reverses Frailty and

Improves Cognition, Emotion, and Social Networking in the Community-Dwelling Frail Elderly: A

Randomized Clinical Trial. J Am Med Dir Assoc. 2016 May 1;17(5):426-33.

European Union Geriatric Medicine Society (EUGMS), in cooperation with

other scientific organizations, appointed an international study group to

review dietary protein needs with aging (PROT-AGE Study Group).

To help older people (>65 years) maintain and regain lean body

mass and function, the PROT-AGE study group recommends average

daily intake at least in the range of 1.0 to 1.2 g protein per kilogram of

body weight per day.

Both endurance- and resistance-type exercises are

recommended at individualized levels that are safe and tolerated, and

higher protein intake (ie, ≥ 1.2 g/kg body weight/d) is advised for those

who are exercising and otherwise active.

Most older adults who have acute or chronic diseases need even

more dietary protein (ie, 1.2-1.5 g/kg body weight/d). Older people with

severe kidney disease (ie, estimated GFR <30 mL/min/1.73 m(2)), but who

are not on dialysis, are an exception to this rule; these individuals may

need to limit protein intake.

Bauer et al. Evidence-based recommendations for optimal dietary protein intake in older people: a

position paper from the PROT-AGE Study Group. J Am Med Dir Assoc. 2013 Aug;14(8):542-59.

Deutz et al. Protein intake and exercise for optimal muscle function with aging: Recommendations from the ESPEN Expert Group. Clinical Nutrition 2014;33:929-936

European Society for Clinical Nutrition and Metabolism (ESPEN) recommendations:

(a) for healthy older people, the diet should provide at least 1.0-1.2 g protein/kg body weight/day,

(b) for older people who are malnourished or at risk of malnutrition because they have acute or chronic illness, the diet should provide 1.2-1.5 g protein/kg body weight/day, with even higher intake for individuals with severe illness or injury,

(c) daily physical activity or exercise (resistance training, aerobic exercise) should be undertaken by all older people, for as long as possible.

Muscle protein synthesis enhancement:

Daily protein intake of 1.2-1.5 g/kg (0.4-0.5 g/kg per meal)

Increased proportion of leucine in a given dose of protein

Supplementation with n=3 polyunsaturated fatty acids

Physical activity prior to protein intake Witard et al. Biogerontology 2016;17:529-546.

Supplementation

Vitamin D

BCAA

Leucine

β-hydroxy-β-methylbutyrate (HMB)

Creatine

Summary of the effect of nutrition on sarcopenia in randomised,

controlled studies meeting the inclusion criteria

Refe

rence Popula

tion Num

ber

Age, years,

mean (SD)

[range]

PED

ro

Score

Intervention

(duration) Outcomes

measured Main results

Flakoll et

al. [34]

Communit

y-dwelling

57

(0/57)

76.7

[62–90] 8

ARG + HMB +

LYS; PLA (12

weeks)

MM (BIA), MS

(isometric leg

strength, HS), PP

(get up and go)

MS (P ≤ 0.05) and PP (P = 0.002) significantly improved

with ARG + HMB + LYS versus PLA

ARG + HMB + LYS did not significantly improve MM

versus PLA

Deutz et

al. [32]

Healthy

individual

s on bed

rest

19

(4/15)

PLA: 67.1

(±1.7)

HMB: 67.4

(±1.4)

[60–76]

10

HMB; PLA

Bed rest (10

days) +

rehabilitation (8

weeks)

MM (DEXA), MS

(KE, leg press), PP

(SPPB, get up and

go, 5-item PPB)

Bed rest caused a significant decrease in MM (P = 0.02)

in the PLA group, but MM was preserved in the HMB

group

Changes in MS and PP were not significant for HMB

versus PLA

Stout et

al.[36]

Communit

y-dwelling

98

(49/4

9)

73 (±1 SEM)

[≥65] 9

Phase I: HMB;

PLA (24 weeks)

Phase II: PLA +

RET; HMB +

RET (24 weeks)

MM (DEXA), MS

(isokinetic leg

strength, HS), PP

(get up and go)

HMB alone significantly improved some, but not all

measures of MS versus PLA. No significant changes

were found in MM and PP with HMB versus PLA

Adding HMB to RET did not improve any parameters

over RET alone

Vukovich

et al. [39]

Communit

y-dwelling

31

(15/1

6)

70 (±1) 10

HMB + RET;

PLA + RET (8

weeks)

MM (DEXA, CT

scan), MS (misc.

upper and lower

body strength press,

flexion and extension

measurements)

MM improved with HMB + RET versus PLA + RET, but

not significantly (P = 0.08)

MS did not improve with HMB + RET versus PLA +

RET

Prevalence of and interventions for sarcopenia in ageing adults: a systematic review. Report of the International Sarcopenia Initiative (EWGSOP and IWGS), 2014

Summary of studies involving creatine supplementation in

older adults (Candow, 2011)

Study Population Dosage Findings

Bermon et al.1998 Male/female (70 years)

CR: 16; PL: 16

CR: 20 g for 5 days

Maintenance: 3 g for 47 days ↔ lower-limb muscle volume

Brose et al. 2003 Male/female (68 years)

CR: 14; PL: 14 CR: 5 g, 98 days ↑ fat-free mass

Candow et al.2008 Male (66 years)

CR: 23; PL: 12 CR: 0.1 g kg−1, 30 days ↑ muscle hypertrophy

Chrusch et al.2001 Male (71 years)

CR: 16; PL: 14

CR loading: 0.3 g kg−1 for 5 days

Maintenance: 0.07 g kg−1 79 days ↑ fat-free mass, strength

Eijnde et al.2003 Male (64 years)

CR: 23; PL: 23 CR: 5 g for 1 year ↔ fat-free mass

Gotshalk et al.2008 Female (63 years)

CR: 15; PL: 12 CR: 0.3 g kg−1 for 7 days ↑ fat-free mass, strength

Gotshalk et al. 2001 Male (65 years)

CR: 10; PL: 8 CR: 0.3 g kg−1 for 7 days ↑ fat-free mass

Jakobi et al.2001 Male (72 years)

CR: 7; PL: 5 CR : 20 g for 5 days ↔ force production

Rawson et al.1999 Male (74 years)

CR: 10; PL: 10

CR: 20 g for 10 days

Maintenance: 4 g for 20 days ↔ fat-free mass

Tarnopolsky et al.

2007

Male/female (70 years)

CR: 21, PL: 18 CR: 5 g/days for 6 months ↑ fat-free mass, strength

CR creatine,

PL placebo

Creatine vs. chest press strength

Candow, 2014

Creatine and carbohydrates

Carbohydrate coingestion is important to

optimize creatine effects on body composition,

strength, and functional performance in older

adults

Creatine should be coingested with a carbohydrate

drink (for example with juice)

Devries MC, Phillips SM. Creatine supplementation during resistance training in older adults-a meta-analysis.

Med Sci Sports Exerc. 2014 Jun;46(6):1194-203.

Pharmacological interventions targeting the underlying biology of

sarcopenia

GH/IGF-1

DHEAS

Testosterone/androgens

Selective Androgen Receptor Modulators (SARMs)

TGFβ family members: myostatin, follistatin and GDF11

Myostatin antagonists

Becker et al. reported the improvement of power-demanding

performance measures (stair climbing, five-chair rise, fast gait speed)

in the older individuals after the treatment with the humanized

monoclonal antibody LY2495655.

For less power-intensive performance-based measures (6-min

walking distance, usual gait speed) and muscle strength no important

treatment effects were observed.

Becker et al. Myostatin antibody (LY2495655) in older weak fallers: a proof-of-concept,

randomised, phase 2 trial. Lancet Diabetes Endocrinol, 2015;3: 948-57.

Spearman correlation coefficients for women (n=56).

Myostatin

(ng/ml)

Follistatin

(pg/ml)

GDF11

(pg/ml)

Body mass (kg) 0.002 -0.070 -0.301*

Body Mass Index (kg/m²) 0.022 -0.013 -0.354**

Waist circumference (cm) -0.043 0.083 -0.372**

Body fat % -0,084 0,035 -0,458***

Fat free mass (%) (n=52) 0,073 -0,083 0,359**

Fat mass (kg) (n=52) -0.071 0.006 -0.331**

Timed Up&Go test (s) -0.071 0.366** -0.163

Handgrip strength L (kG) -0.296* -0.063 -0.080

P70% LP (kG) -0.117 -0.279* -0.250

Pmax (W) -0.141 -0.387** -0.186

Pmax·kg-1 (W·kg-1) -0.156 -0.405** -0.049

νopt (rpm) -0.329* -0.183 -0.220

*p<0.05, **p<0.01, ***p<0.001

Fife et a. Submitted



2. Nutrition

3. Prevention and treatment

of concomitant disorders

Frail and pre-frail older people corresponded to a substantial proportion of those

with more CVD risk factors, especially diabetes mellitus, highlighting the need

for preventive strategies in order to avoid the co-occurrence of CVD and frailty.

Ricci NA et al.: Frailty and cardiovascular risk in community-dwelling elderly: a population-based study.

Clinical Interventions in Aging 2014:9 1677–1685

Abdominal obesity, insulin resistance, and inflammation were significantly associated

with frailty, and the effect was independent of functional measurement and decline of

skeletal muscle mass.

Hwang et al. Association of Frailty and Cardiometabolic Risk Among Community-Dwelling Middle-Aged

and Older People: Results from the I-Lan Longitudinal Aging Study. Rejuvenation Res. 2015

Dec;18(6):564-72.

Cardiometabolic risk assessment:

- diet, smoking status, family history,

- fasting lipids (TC, triglycerides, HDL cholesterol, LDL Cholesterol,

TC/HDL ratio)

- glucose

- blood pressure

- weight, height, waist and hip circumference (BMI, WHR)

- blood count, electrolytes, creatinine, eGFR, microalbuminuria

ACE inhibitor treatment may halt or slow decline in muscle

strength in elderly women with hypertension and without

CHF.

Onder G, et al. Relation between use of angiotensin-converting enzyme inhibitors and muscle

strength and physical function in older women: an observational study. Lancet.

2002;359(9310):926-30.

The I/I ACE genotype is associated with a lower risk of frailty

and a lower frailty level relative to the D-carrying genotypes

among older Han people.

Chen et al. Association between Angiotensin-converting enzyme insertion/deletion polymorphisms and

frailty among chinese older people. J Am Med Dir Assoc. 2015 May 1;16(5):438.e1-6.

J Kostka, J Sikora, T Kostka: Relationship of quadriceps muscle power and optimal shortening velocity with angiotensin converting enzyme activity in older women. Clinical Interventions in Aging– in press.

Women taking

ACEI

N=22

Women taking

ARBs or ARBs

+ACEI

N=12

Women taking

MCRA or

MCRA+ACEI or

MCRA +ARB

N=10

Women taking no

ASBMs

N=51

mean±SD

mean±SD mean±SD mean±SD

Age 73.6±4.7 70.8±4.4 73.1±3.9 71.5±4.4

Hand grip strength – left (kgf) 24.2±9.8 23.3±7.8 18.1±5.3 23.5±7.8

Hand grip strength – right (kgf) 25.6±9.1 24.4±7.0 22.7±6.5 25.5±7.9

Pmax (W) 217±88 221±52 233±44 230±65

Pmax (W·kg-1) 3.11±1.20 3.25±0.88 3.38±0.95 3.49±1.05

Ʋopt (rep/min) 65.2±11.7 69.6±8.4 67.0±13.3 69.2±9.1

ACE (U/L) 27.4±13.4 38.9±12.9 37.1±12.3 46.2±17.5*

The influence of Angiotensin System Blocking Medications (ASBMs) blockers on muscle function and Angiotensin Converting Enzyme (ACE) activity

J Kostka, J Sikora, T Kostka: Relationship of quadriceps muscle power and optimal shortening velocity with angiotensin converting enzyme activity in older women. Clinical Interventions in Aging– in press.

The relationship between optimal shortening velocity (Ʋopt) and angiotensin converting enzyme activity in women not taking any ASBMs

rho = - 0.37 p=0.01

ACE activity (U/L)

Vo

pt

(re

p/m

in)

0 20 40 60 80 100 120

47

57

67

77

87

97

Other diseases, e.g.:

Michel JP et al. Advocating vaccination of adults aged 60 years and

older in Western Europe:statement by the Joint Vaccine Working

Group of the European Union Geriatric Medicine Society and the

International Association of Gerontology and Geriatrics-European

Region. Rejuvenation Res. 2009 Apr;12(2):127-35.

Liljas AEM et al. Self-Reported Hearing Impairment and Incident

Frailty in English Community-Dwelling Older Adults: A 4-Year

Follow-Up Study. J Am Geriatr Soc. 2017 May;65(5):958-965.

COPD, dementia, depression…

Acute care of frail elderly patients in a CGA unit was

independently associated with lesser loss of functional

ability and lesser increase in frailty after 3 months. Ekerstad et al. Clin Interv Aging 2017;12:1239-49.

Prevention of hospital-associated functional decline:

appropriate nutrition, early mobilisation, care of

comorbidities (incontinence, decubitus) Zisberg et al. JAGS 2015;63:55-62.

Benefits of early rehabilitation in hospitalised older subjects Kosse et al. BMC Geriatr 2013;13:107.

Summary

Early diagnosis and prevention of frailty

and functional decline:

1. Building-up physiological potential throughout

the lifetime

2. Identification of people at risk.

3. Identification and combatting of risk factors

4. Prevention and treatment of concomitant

disorders

Thank you for your attention

Documents

Prevention and early diagnosis of frailty and … and early diagnosis of frailty and functional decline Tomasz Kostka Medical University of Lodz, Poland CONFLICT OF INTEREST DISCLOSURE