3-KBR_Frailty phenotypes_final

Frailty Phenotypes
Karen Bandeen-Roche
Johns Hopkins Bloomberg School of Public Health
Johns Hopkins Older Americans Independence Center
Johns Hopkins Alzheimer’s Disease Research Center
NIA Workshop on Synergys between Alzheimer’s Research and Clinical Gerontology and Geriatrics
December 1, 2016
What is frailty?
Classic view
“…the lean and slipper’d pantaloon, with spectacles on nose and
pouch on side, his youthful hose … a world too wide, for his shrunk
shank…”
-- Shakespeare, “As You Like It”
What is frailty?
Classic view
• “reduced physiologic reserve associated with increased susceptibility
to disability” – Buchner & Wagner, in Health Promotion & Disease
Prevention, 1992
• “… loss of physiologic reserves, feebleness, … vulnerability, fragility, or
lack of resilience”– Verbrugge, J Aging Health, 1991
• manifestation of progressive dysregulation in integrated homeostatic
control mechanisms…
Bortz, JAGS, 1993; Lipsitz & Goldberger, JAMA, 1992
What is frailty?
Recent “consensus”
• “medical syndrome with multiple causes and contributors … characterized
by diminished strength, endurance, and reduced physiologic function …
increases an individual's vulnerability for developing increased
dependency and/or death” – Morley et al, JAMDA, 2013
• “a … comprehensive definition … that should include assessment of
physical performance…, nutritional status, mental health, and
cognition…” – Frailty Operative Definition-Consensus Conference Project:
Rodriguez-Manas et al., J Gerontol Med Sci, 2013
• Cognitive frailty: “simultaneous presence of both physical frailty and
cognitive impairment.” IANA/IAGG International Consensus Group:
Kelaiditi et al, J Nutrition Health Aging, 2013
Current state of the art
Review papers!
• De Vries et al, Ageing Res Rev, 2011 – Content, clinimetric properties
(20 instruments)
• Sternberg et al, JAGS, 2011 – Content, quality rating
(22 instruments)
• Bouillon et al, BMC Geriatr, 2013 – Catalog, psychometrics, popularity
(27 instruments)
• Buta et al., Ageing Res Rev, 2016 – Uses and contexts
(67 instruments)
• Panza et al, Rejuv Res, 2015 – Cognitive frailty
Current state of the art
9 “Highly cited” Instruments (~200 or more)
Instrument
Pub. # Cites Brief description
Year 12/13
Physical Frailty Phenotype
2001
1891 5 criteria representing nutrition, muscle, speed, energy
N
Deficit Accumulation
Index
2001
401 Index counting proportion of deficits among “tens” of:
Diseases, disabilities, health attitudes / values,
symptoms / signs, family history, etc.
Y
Gill Frailty Measure
2002
254 Gait speed; chair stand
N
Frailty/Vigor Assessment
1991
246 Age, physical function, physical activity, psychological
function, medications, sensory function
Y
Clinical Frailty Scale
2005
239 Physician rating: activity, functioning, diseases
N
Brief Frailty Instrument
1999
225 Graded incontinence, disability, CIND/dementia
Y
Vulnerable Elders Survey
2001
225 Age, self-rated health, physical function, disability
N
FRAIL Scale
2008
211 Physical function, illnesses, weight loss
N
Winograd Screening
1991
198 15 criteria; similar to DAI
Y
Buta et al., Ageing Res Rev, 2016
Cognition?
Current state of the art
2-3 Predominant Conceptual Frameworks
• Frailty as pre-disability
Vellas et al, J Nutr Health Aging, 2013 (Gérontopôle Frailty Screening Tool (GFST))
Current state of the art
Physiological Frailty – Physical Frailty Phenotype
• Health state – results from a specific, free-standing physiological mechanism
> Disrupts energetics, muscle, nutrition (multiple systems)
> Signifies loss of resilience in homeostatic regulation
> Not only a secondary manifestation of chronic disease(s); also distinct from
chronological age, disability/predisability, cognitive dysfunction
• The free-standing physiological mechanism(s) is intervenable
• Induces vulnerability to experiencing illness, injury, dismobility, disablement,
incident or worsening chronic disease, hospitalization or death subsequent to a
“stressor”; also, diminished resilience
Fried et al., J Gerontol, 2001
Current state of the art
Physiological Frailty – Physical Frailty Phenotype
e1
Inactivity
e2
Weakness
e3
Slowness
e4
Weight loss
e5
Exhaustion
“Frailty”
Syndrome manifestation: Fried et al., J Gerontol, 2001; Bandeen-Roche et al, J Gerontol, 2006
Current state of the art
Attribute of heightened risk– Deficit Accumulation Index
• “A state of increased risk, compared with others of the same age”
• “An attribute of aged people who are at an increased risk of adverse
health outcomes”
> Results from diminished ability to respond to stress; loss of redundancy
> A consequence of the accumulation of multiple deficits
Rockwood & Mitnitski, Clin Geriatr Med 2011,
Mitnitski et al, BMC Med, 2015
Current state of the art
Attribute of heightened risk– Deficit Accumulation Index
Deficit 1
…
(~20-90 deficits)
“Frailty”
Deficit N
Mitnitski et al., Scientific World, 2001
e
Current state of the art
Uses of frailty assessment: Highly-cited instruments
Risk Assessment




Physical Frailty Phenotype (132 uses)
Deficit Accumulation Index (37 uses)
Gill Frailty Measure (12 uses)
Clinical Frailty Scale & Vulnerable Elders Survey
(11 uses each)
 Winograd Screening Instrument (10 uses)
 Brief Frailty Instrument (6 uses)
Methodology
 Physical Frailty Phenotype (33 uses)
 Deficit Accumulation Index (32 uses)
 Brief Frailty Instrument & Vulnerable Elders
Survey (11 uses each)
 FRAIL Scale (10 uses)
Etiology of Frailty
 Physical Frailty Phenotype (121 uses)
 Deficit Accumulation Index (37 uses)
Biological Mechanisms
 Physical Frailty Phenotype (77 uses)
 Deficit Accumulation Index & FRAIL Scale (5
uses each)
Buta et al., Ageing Res Rev, 2016
Current state of the art
Uses of frailty assessment: Highly-cited instruments
Inclusion / Exclusion Criteria
 Physical Frailty Phenotype (22 uses)
 Vulnerable Elders Survey & Brief Frailty
Instrument (11 uses each)
 Winograd Screening Instrument (10 uses)
 Deficit Accumulation Index, Frailty / Vigor
Assessment, & Clinical Frailty Scale (5 each)
Guide for clinical decision-making
 Physical Frailty Phenotype (11 uses)
 Vulnerable Elders Survey (5 uses)
Estimating prevalence as primary goal
 Physical Frailty Phenotype (33 uses)
 Vulnerable Elders Survey (5 uses)
Frailty as a target for intervention
 Physical Frailty Phenotype (11 uses)
 Clinical Frailty Scale (5 uses)
Buta et al., Ageing Res Rev, 2016
Current state of the art
Cognitive frailty
• Considerable work demonstrating relationship between frailty and cognitive
decline
Recent review: Gross et al, J Gerontol Med Sci, 2016
• Simple PubMed Search on “Cognitive Frailty”: 43 articles
• Woods, Cohen, Pahor, J Nutr Aging, 2013: 199 articles (title or keyword)
In the vast majority of these…, frailty was examined as a manifestation of cognitive
dysfunction. Only recently has cognitive frailty itself become the focus of inquiry.
Current state of the art
Cognitive frailty – PubMed Search (n=41 obtainable)
• IANA/IAGG definition – 16 articles
• Measurement of cognitive frailty per se – much less than for physical frailty:
• Clock drawing as a “marker” – 1 article plus 1 through review paper
• Cognitive complaints + slow gait – 4 articles
• Predementia – 6 articles
• Biomarkers – 2 articles
• Undefined or not fully defined – 12 articles
What next?
• Studies of frailty usefulness in clinical practice
• Does it identify at-risk persons more effectively than “standard” measures?
• If so, and it is applied in practice, are patient outcomes improved?
• Geriatrics and subspecialties
• Intervention studies
• Prehabilitation
• Alternative treatment modes for frail persons
• Direct intervention
What next?
• Direct intervention studies
• Improved ascertainment
• Improved reliability and validity
• More comprehensive – but then, unidimensional or multidimensional?
• A consensus??
• Etiology (e.g. cellular determinants; the multisystem dysregulation hypothesis)
• Practical consideration: General versus specific contexts?
What next?
• Cognitive frailty: Still early! Still needed:
• How to operationalize its definition
• The supporting epidemiological data
• The underlying clinical and biological characteristics
Canevelli, M. & Cesari, M. J Nutr Health Aging (2015) 19: 273.
• Further conceptualization per se?
Thank you
EXTRA SLIDES
What is frailty?
Classic view
• “reduced physiologic reserve associated with increased susceptibility to
disability” – Buchner & Wagner, in Health Promotion & Disease Prevention,
1992
• “… loss of physiologic reserves, feebleness, … vulnerability, fragility, or lack
of resilience”– Verbrugge, J Aging Health, 1991
• manifestation of progressive dysregulation in integrated homeostatic
control mechanisms…
• results in part from disengagement from beneficial stressors in one’s environment …
• confers a loss of robustness in the functioning of the whole physiological system
Bortz, JAGS, 1993; Lipsitz & Goldberger, JAMA, 1992
Current state of the art
Cognitive frailty – Pubmed Search
• IANA/IAGG definition – 16 articles
• Measurement of cognitive frailty per se – much less than for physical frailty:
• Clock drawing as a “marker” – 1 article plus 1 through review paper
Ferrucci et al., JAGS, 1996; Paganini-Hill et al., JAGS, 2001
• Motoric cognitive risk syndrome – Cognitive complaints + slow gait – 4 articles
Verghese et al., J Gerontol Med Sci, 2012
• Predementia – 6 articles
Panza et al., Neurobiol Aging, 2006
• Biomarkers – 2 articles
• Undefined or not fully defined – 12 articles

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