Bruno Vellas M.D, Ph. D

Gérontopôle / UMR 1027 - Inserm Université de Toulouse

Implementing Frailty into Clinical Practice

Life Expectancy Without Disabilities

• Many scientific publications on Frailty and on the impact of interventions on the prevention of further disabilities, in major journals

• But not yet in usual clinical practice, why ?

• Geriatric medicine was born 40 years ago, because many older adults with severe disabilities and dementia came to hospital emergency room

• Geriatric medicine was a new field

• The governments have not anticipated aging

• Not a simple drug, like statins…

• We cannot wait to implement Frailty into clinical practice

(Nutr Health Aging 2013, J Frailty Aging 2013, JAMDA 2013)

Older Adults: 3 categories

Robust or Healthy Aging

• 60%

Frail and Pre Frail • 30%, Reversibility • fatigue, slow gait speed, weigth loss,

sédentarity, muscle weakness

Dependent • 10% • Basic ADL

Active Aging

Frail

Dependent for basic ADL

Lancet, March 2013

Frailty Consensus: A Call to Action Morley J.E et al., JAMDA, 2013

Letter of Mission Ministry of Health

« Implementing Frailty into Clinical Practice»

1. How to screen frail older adults in clinical practice

2. How to assess frail older adults, look out after the causes of frailty and propose strong and long term usefull interventions

3. Develop translational, clinical, interventional and cost effective research on Frailty

Recommandations HAS

Implementing Frailty into Clinical Practice

Frailty Screening

Older patients 65 yrs +, not dependent (ADL >= 5 /6)

YES NO UNKNOWN

Is your patient living alone ?

Unvoluntary weight loss in the past 3 months ?

Fatigability during the last 3 months ?

Mobility difficulties for the last 3 months ?

Memory complaints ?

Slow gait speed (+ 4s for 4 meters ? )

If yes to at least one of these questions:

In your own clinical opinion, do you feel that your patient is frail and at an increased risk for further disabities ? YES NO

If yes , kindly propose to the patient an assessment of the causes of frailty and prevention of disabilities in a day hospital.

Gerontopole Frailty Screening Tool

Target

Sustained

Strong

Implementing Frailty into Clinical Practice:

TARGETED, STRONG, SUSTAINED INTERVENTION

Assess the degree of frailty and the causes of frailty,

Objectives: • Assess the degree of frailty: fried Criteria

• Explore the causes of frailty: vision, hearing, mobility, cognitive, nutrition, sarcopenia…

• Elaborate a personalized Intervention plan

• Access to innovation and clinical research

Excellence of care, clinical and research

Strong Evaluation and Intervention:

in Hospital Outpatient Clinic

Gerontopole Frailty Clinic: Targeted, Strong and Sustained Intervention

2011 : Hôpital Garonne

2013: Hôpital La Grave City center, close to the Gerontopole Clinical Research Center

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5/6/2013: + 828

Gerontopole Frailty Assessment Clinic

• I - ANAMNESE

• II - CLINICAL EXAMINATION

Clinical examination

• III - TESTS

Cognitive: MMSE, CDR, F.C.S.R.T.

Functional & physical: IADL, SPPB, Fried

Visual functions: Monoyer Parinaud, Amsler Scale

Audition: HHIES

Depression & anxiety: GDS, Raskin, Covi, NPI

Nutrition (MNA), oral status

Falls

Social

• IV - OTHER INVESTIGATIONS

Biology

Vit D

ECG

I Dexa, Body composition

Retinography

Amyloïd TEP, MRI if needed

• V - SYNTHESIS

Preventive Personalized Plan

Description of the population (n=160)

• Age: 82,7 6,1 yrs

• 62 % women

• 66 % receive some assistance at home

– 50 % «aide ménagère» (helper)

– 14 % APA

• 41% pre-frail; 53% frail, total: (94%)

• 84% slow gait speed < 1 m/s

• 54% high sedentarity

• 58% decrease of muscular strength

Subra, JNHA, 2012

• 11,6% mild dementia

• 66 % CDR 0.5

• Basic Activity Daily Living maintained: ADL (/6) = 5.6 0.8)

• IADL 6.0 2.3 / 8

• 76% vision problems, 10 % Amsler (DMLA) abnormal

• 31 % hearing impairment

• 9 % protein caloric undernutrition, 34 % at risk for malnutrition ; 95 % vitamin D deficiency

Description of the population (n=160)

Subra, JNHA, 2012

• Age: 82. 9 6 years • 62,5 % women • 42% alone at home, 59.3% high sedantarity • 31.1% pre-frail; 64.1% frail (95.2%) (Fried) • 58.5% SPPB <10/12)) • ADL (/6) = 5.6 0.8 (N=360) • IADL (/8)= 5.7 2.4 (N= 360) • 83.1% vision problem 17.6% Amsler • 7.8% undernutrition 36.8% at risk , weigth loss 37.9% • Gait speed 0.8 0.3 m/s • CDR 0.5: 53.4%, CDR 1: 12.7% • Vit D: 29.2% < 10 ng/l, 34% 10 -20 ng/l • Earing problem 41%

Description of the population (n=466)

Gerontopole Frailty Clinic Associated Morbidity (n=481)

Comorbidity N %

No 16 3.44

Cardio vascular 364 78.28

MI 49 10.54

Cardiac Failure 55 11.83

Vascular 78 16.77

Others 321 69.03

Cancers 104 22.37

Cancer without metastasis 81 17.42

Cancers with metastasis 10 2.15

Myeloma 18 3.87

Lymphome 5 1.08

Psychiatric Diseases 74 15.91

Diabetes 64 13.76

Surgery 61 13.12

BPCO 59 12.69

Gastro-duodenale ulcer 56 12.04

Stroke 56 12.04

Fractures 41 8.82

Renal failure 28 6.02

Connectivite 24 5.16

Dementia 16 3.44

Liver failure 2 0.43

Others 308 66.24

Gerontopole Frailty Clinic Associated Morbidity (n=481)

Patients without cancer

n= 392 (84.1%)

Patients with cancer

n= 74 (15.9%) P

Associated

Pathologies 4.2 (+/- 2.4) 5.2 (+/- 2.7) < 0.001

Charlson Score 1.4 (+/- 1.5) 3.9 (+/- 2.7) < 0.001

New medical problem

189 (48,2 %)

43 (58,1 %)

NS

Vision, earing deficit 330 (84%) 67 (90%) NS

Pre-Frail (n=65) Frail (n=85) P

Age (yrs) 81,44 6,46 84,12 5,52 P=0.0125

Sex (% women) 55,38 68,67 P=0.097

Gait speed (m/s) 0,85 0,16 0,66 0,22 P=0.000

Sedentarity (% yes) 29,23 77,11 P=0.000

Poor muscular strength (% yes) 41,54 74,39 P=0.000

Exhausting (% yes) 3,08 19,51 P=0.003

Recent weight Loss (% yes) 16,92 49,40 P=0.000

Which Target: Frail vs Pre-Frail (n=160)

Pre-Frail (n=65)

Frail (n=85)

P

MMSE (/30) 26,70 3,34 24,35 4,43 P=0.0006

Score CDR (%) 0 0.5 1 2

25,40 69,84 4,76 0,00

16,67 66,67 12,82 3,85

P=0.103

Score ADL(/6) 5,87 0,26 5,47 0,83 P=0.0002

Score IADL(/8) 6,78 1,71 5,38 2,48 P=0.0002

Score SPPB (/12) 8,58 2,10 6,06 2,78 P=0.0000

Which Target: Frail vs Pre-Frail (n=160)

Fried criteria CDR 0.5

Cognitive Frailty

0 28.5 %

1 36.6 %

2 43.7 %

3 56.2 %

4 58.3 %

MAPT: Frailty status and CDR (n=1680)

Cognitive Frailty: IANA/IAGG Consensus paper: J Nutr Health Aging 2013

• “Cognitive Frailty” as an heterogeneous clinical manifestation characterized by: –Presence of physical frailty and cognitive

impairment (CDR=0.5); with –Exclusion of concurrent AD dementia or

other dementias. - Cognitive frailty may represent a precursor of neurodegenerative processes. - A potential for reversibility may also characterize this entity. A psychological component of the condition must be taken into consideration.

Cognitive Frailty: IANA IAGG J Nutr Health Aging 2013

Institut of Aging Sciences / Gérontopole

8

• Randomised, placebo control study • 1680 subjects; 70 yrs and older, living in the community • Inclusion criteria: Pre-frail subjects

– Slow walking speed (4 meters test) – Subjective memory complaint expressed to P.C.P – A limitation in one instrumental activity of daily living

(IADL) • Exclusion criteria: dementia, dependency for basic ADL • Randomisation in 4 groups (N=420 each), 3 years of

follow-up: Omega 3 alone, Placebo, Omega 3 + Multidomain, Placebo + Multidomain

• End Point: Cognitive decline FCRST, MRI (500), Florbetapir PET (250)

M.A.P.T: Multidomain Alzheimer Preventive Trial

SUVr 50-60 min

SUVr 50-60 min

Amyloid Image Florbetapir F 18

Cognitively Healthy Control

Aβ+ AD patient

Aβ+ MCI Aβ- MCI

SUVr 1.03, VR 0 SUVr 1.61, VR 4

SUVr 1.68, VR 3 SUVr 0.98, VR 0

Amyloid negatif Amyloid positif

Variable N Moyenne N Moyenne p

Age, (sd) 126 75.6 (4.2) 72 76.63 (4.5) 0.1163

TEP Amyloid , Florbetapir

36,4 % des sujets de MAPT sont amyloide positif

Future Preventive Trials

• DO-Health: Vit D 3:2000 UI, Omega 3, Multi-domain, European Commission

• HATICE : Multidomain Prevention Trials, new Technologies , e-Health, for monitoring, European Commission

• New technology

HATICE: European Dementia Prevention Initiative

Age-associated loss of skeletal muscle mass Rosenberg, Summary Comments

Am J Clin Nutr 1989;50:1231-3

Sarcopenia Clinical Research and Practice : Drug Discovery

Functional Decline

Biomarkers: FRAILOMIC

Cohortes prospectives avec suivi ≥ 3 ans

+ Biobanques

BioMarqueurs (BM) Génomiques Protéomiques Métabolomiques Classiques

BM potentiels - Facteurs de risque - Diagnostic - Facteurs pronostic

PHASE 1 PHASE 2

Suivi durant 2.5 ans + prélèvements

BioMarqueurs (BM) Génomiques Protéomiques Métabolomiques Classiques

Validation - Facteurs de risque - Diagnostic - Facteurs pronostic

Sous études dans des populations et conditions spécifiques : diabète, pathologies cardiovasculaires, facteurs de risque vasculaire, nutrition, activité physique

Modèles les plus pertinents en terme de prédiction, diagnostic et pronostic

PHASE 3

PHASE 4

Outils Dissemination Exploitation

Futur of Geriatric Medicine

• Target the Frail, strong evaluation, sustained intervention

• Propose Multi-Domain Intervention

– Physical Exercise Program

– Nutrition Intervention

• New Drug Discovery

– For Prodromal Alzheimer; eg: anti-amyloid drugs

– For Cognitive Frailty, nutritional products

– For Sarcopenia: eg anti-myostatin