Biological theory for the construct of intrinsic capacity to be used in clinical settings Matteo Cesari, MD, PhD

Biological theory for the construct of intrinsic capacity to be used in clinical settings Matteo Cesari, MD, PhD World Health Organization Geneva (Switzerland) December 1, 2016

World Health Organization. The International Classification of Functioning, Disability and Health. Geneva, Switzerland: World Health Organization; 2001

Disability is an umbrella term for impairments, activity limitations and participation restrictions. It denotes the negative aspects of the interaction between an individual (with a health condition) and that individual s contextual factors (environmental and personal factors). Body functions: The physiological functions of body systems (including psychological functions). Body structures: Anatomical parts of the body such as organs, limbs and their components. Impairments: Problems in body function and structure such as significant deviation or loss. World Health Organization. The International Classification of Functioning, Disability and Health. Geneva, Switzerland: World Health Organization; 2001

World Health Organization. The International Classification of Functioning, Disability and Health. Geneva, Switzerland: World Health Organization; 2001

World Health Organization. The International Classification of Functioning, Disability and Health. Geneva, Switzerland: World Health Organization; 2001

Body functions and structures Mental function FUNCTIONS Sensory functions and pain Voice and speech functions Functions of the cardiovascular, hematological, immunological and respiratory systems Functions of the Digestive, Metabolic, Endocrine Systems Genitourinary and Reproductive Functions Neuro-musculoskeletal and Movement- Related Functions Functions of the Skin and Related Structures STRUCTURES Structure of the nervous system The eye, ear and related structures Structures involved in voice and speech Structure of the cardiovascular, immunological and respiratory systems Structures Related to the Digestive, Metabolic and Endocrine Systems Structure Related to Genitourinary and Reproductive Systems Structure Related to Movement Skin and Related Structures World Health Organization. The International Classification of Functioning, Disability and Health. Geneva, Switzerland: World Health Organization; 2001

Risk factors for functional decline - I Strength of the evidence Domain Specific definition Strength Affect Alcohol Anxiety Depression Heavy alcohol consumption No alcohol consumption Cognition Cognitive impairment +++ Comorbidity Comorbidity +++ Falls Falls ++ Functional limitation Hearing Decline in function (observed and self-reported) Poor observed lower extremity performance Poor observed upper extremity performance Poor self-reported lower extremity function Poor self-reported upper extremity function Decline in hearing function Reduced measured hearing Poor self-reported hearing (+) +++ ++ +++ ++ +++ ++ (+) (+) (+) (+) + Stuck AE et al. Soc Sci Med 1999;48:445-469

Risk factors for functional decline - II Strength of the evidence Domain Specific definition Strength Medication High medication use ++ Nutrition High Body Mass Index Low Body Mass Index Weight loss Physical activity Low physical activity +++ Self-rated health Poor self-rated health +++ Smoking Smoking +++ Social Vision Low level of social activity Low frequency of social activity Low level of social support Decline in visual function Reduced measured visual acuity Poor self-reported vision +++ +++ ++ ++ +++ Not ratable (+) ++ +++ Stuck AE et al. Soc Sci Med 1999;48:445-469

Risk factors for disability in old age Cognitive impairment Depression Disease burden Increased and decreased body mass index Lower extremity functional limitation Low frequency of social contacts Low level of physical activity No alcohol use compared to moderate use Poor self-perceived health Smoking Vision impairment Heikkinen E. What are the main risk factors for disability in old age and how can disability be prevented? Copenhagen, WHO Regional Office for Europe (Health Evidence Network report; http://www.euro.who.int/document/e82970.pdf)

Limitations in activities of daily living in community-dwelling people aged 75 and older Risk factors Age Gender (women) Low education Fractures Heart diseases Number of chronic diseases Low cognitive performance Depressive symptoms Protective factors Physical activity Evidence coming from at least 2 high/3+ low qaulity studies Van der Vorst et al. PLoS ONE 11(10): e0165127

Chaudhry SI et al. J Am Geriatr Soc 2010;58:1686-92

Geriatric impairments Incident ADL disability Incident mobility disability Muscle strength 1.35 (1.12-1.63) p=0.002 Physical capacity 3.03 (2.56-3.59) p<0.001 Cognition 1.62 (1.30-2.02) p<0.001 Vision 1.52 (1.25-1.85) p<0.001 Hearing 1.15 (0.91-1.45) p=0.24 Depressive symptoms 1.71 (1.46-2.01) p<0.001 1.17 (1.02-1.34) p=0.03 2.24 (1.95-2.57) p<0.001 1.26 (1.06-1.50) p=0.008 1.23 (1.05-1.46) p=0.01 1.26 (1.00-1.58) p=0.04 1.54 (1.36-1.75) p<0.001 Results are expressed as Hazard Ratios (95% confidence interval) Adjusted for age, gender, race, marital status, education, BMI, and chronic diseases Chaudhry SI et al. J Am Geriatr Soc 2010;58:1686-92

Frailty and prediction of dependence in low- and middle-income countries Frailty indicator Mutually adjusted pooled fixed effect size (IRR) for incident dependence Exhaustion 1.03 (0.90-1.17) Weight loss 1.31 (1.06-1.61) Underactivity 1.35 (1.10-1.67) Slow gait speed 1.28 (1.12-1.47) Sensory impairment 1.14 (1.01-1.29) Cognitive impairment 1.53 (1.30-1.79) Undernutrition 1.11 (0.89-1.38) Amuthavalli JT et al. BMC Med 2015;13:138

Cognition and Mental Health Depressive symptoms Sensory Vision, hearing INTRINSIC CAPACITY Mobility Domain and Muscle Strength Nutrition or Metabolic Rate or Energy Utilization

Cognition and Mental Health

Longitudinal cognitive function modifications Wilson RS et al. Arch Neurol 1999;56:1274-9

Cano C et al. J Nutr Health Aging 2012;16:142-147

Atkinson HH et al. J Gerontol A Biol Sci Med Sci 2007;62:844-50

Njegovan V et al. J Gerontol A Biol Sci Med Sci 2001;56:M638-43

Cognitive performance as predictor of functional decline Information processing speed 2.22 (1.26-4.12) Executive function 1.34 (0.82-2.31) Orientation 1.59 (1.13-2.22) Episodic memory 0.99 (0.61-1.54) Decline in BADL (n=313) Higher level of competence (n=272) OR (95%CI) p OR (95%CI) p 0.008 1.45 (1.08-1.96) 0.26 1.38 (1.04-1.83) 0.007 1.22 (0.95-1.58) 0.95 0.93 (0.71-1.21) BADL: Basic Activities of Dailty Living Competence defined according to the Tokyo Metropolitan Instritute of Gerontology Index of Competence Analyses adjusted for age, gender, education, chronic diseases, and depressive status 0.02 0.03 0.12 0.59 Iwasa H et al. Arch Gerontol Geriatr 2008;47:139-49

Cognition and Mental health Depressive symptoms

Robertson DA et al. Ageing Res Rev 2013;12:840-51

A. Depression as a risk factor for disability. B. Mood symptoms as a proxy risk factor for depression s effect on disability. C. Depression and medical illness burden as independent risk factors for disability. D. Cognitive impairment as a mediator of depression s effect on disability. E. Medical illness as a moderator for depression s effect on disability. Schillerstrom JE et al. J Geriatr Psychiatry Neurol 2008;21:183-97

Penninx BW et al. JAMA 1998;279:1720-6

Emotional vitality and depression Penninx BW et al. J Am Geriatr Soc 1998;46:807-15

Self-rated health status and frailty Adjusted* n/n OR 95%CI p Prefrail - Good (ref) - Fair - Poor Frail - Good (ref) - Fair - Poor 213/561 111/319 95/219 7/23 75/561 28/319 34/219 13/23 1 1.27 1.83 1 1.80 8.57-0.83-1.93 0.41-8.22-0.86-3.78 1.73-42.51-0.27 0.43-0.12 0.009 * Adjusted for age, sex, comorbidities, Mini-Mental State Examination, Geriatric Depression Scale, Basic and Instrumental Activities of Daily Living Gonzalez-Pichardo AM et al. J Frailty Aging 2014;3:104-8

Sensory domain Vision, hearing

Stevens GA et al. Ophtalmology 2013;120:2377-84

Stevens GA et al. Ophtalmology 2013;120:2377-84

Vision impairment, hearing impairment, and ADL disability The Health and Retirement Study Vision impairment Hearing impairment Prevalence RR (95%CI) Prevalence RR (95%CI) 1 ADL disability 31.8 1.7 (1.6-1.9) 14.5 1.0 (1.0-1.1) Bathing 24.1 1.7 (1.5-1.9) 10.4 1.0 (0.9-1.1) Dressing 20.1 1.6 (1.5-1.8) 9.4 1.0 (0.9-1.1) Eating 13.7 2.2 (1.9-2.5) 4.8 0.9 (0.8-1.0) Transferring 12.5 1.9 (1.6-2.2) 4.6 0.9 (0.8-1.0) Toileting 10.2 1.7 (1.3-2.0) 4.1 0.9 (0.8-1.0) N=11,093 adults age 65 years and older (representing 34.5 million older Americans) Adjusted for sociodemographics, clinical chronic conditions, and geriatric syndromes Cigolle CT et al. Ann Intern Med Sci 2007;147:156-64

Chen DS et al. J Gerontol A Biol Sci Med Sci 2016 ahead of print

Hearing impariment, incident disability and institutionalization The Health ABC study Total (n=2,190) Men (n=1,048) Women (n=1,142) Normal Ref. Ref. Ref. Incident disability MHI 1.11 (0.99-1.24) 1.15 (0.96-1.37) 1.11 (0.96-1.28) SHI 1.25 (1.09-1.43) 1.21 (0.99-1.46) 1.31 (1.08-1.60) Normal Ref. Ref. Ref. Institutionalization MHI 1.12 (0.99-1.27) 1.13 (0.93-1.38) 1.09 (0.93-1.29) SHI 1.18 (1.01-1.37) 1.09 (0.88-1.35) 1.31 (1.05-1.62) MHI: Mild hearing impairment; SHI: Severe hearing impairment Results are expressed as HR (95%CI) Incident disability: any incident self-reported severe difficulty to walk 1/4 mile and/or climb 10 steps, needing equipment to ambulate, or having any difficulty performing ADL Chen DS et al. J Gerontol A Biol Sci Med Sci 2016 ahead of print

Nutrition

Biolo G et al. Clin Nutr. 2014;33:737-48

Prevalence of malnutrition (MNA) 70% Well nourished At risk Malnourished 60% 50% 40% 30% 20% 10% 0% Community (n=964) Nursing home (n=1,586) Hospital (n=1,384) Rehabilitation (n=345) Combined (n=4,507) Kaiser MJ et al. J Am Geriatr Soc 2010;58:1734-8

Social changes - Isolation - Poverty - Reliance on others Physiological changes - Functional disability - Oronasal conditions - GI conditions - Satiety Psychological changes - Depression - Foods are less liked - Less motivation to eat Eating process - Slower eating - Less snacking - Less dietary variety Decreased food intake - Calories - Nutrients - Food and drinks MALNUTRITION Nieuwenhuizen WF et al. Clin Nutr 2010;29:160-9

Thomas DR et al. J Gerontol A Biol Sci Med Sci 2000;55A:M725-34

As with other aspects of geriatric care, the management of malnutrition in older age needs to be multidimensional Various types of interventions are effective in reversing these patterns of malnutrition, and have been shown to delay care dependency, improve intrinsic capacity and revert frail states The nutrient density of food should be improved, particularly that of vitamins and minerals, but energy and protein intake are important targets Individualized nutritional counseling has been shown to improve the nutritional status of older people within 12 weeks

Mobility and muscle strength

Dickinson MH et al. Science 2000;288:100-6

Justice J et al. J Gerontol A Biol Sci Med Sci 2016;71:1243-53

Abellan van Kan G et al. J Nutr Health Aging 2009;13:881-9

Studenski S et al. JAMA 2011;305:50-8

Studenski S et al. JAMA 2011;305:50-8

Dodds RM et al. Age Ageing 2016 [ahead of print]

Cognition and Mental Health Depressive symptoms Sensory Vision, hearing INTRINSIC CAPACITY Mobility Domain and Muscle Strength Nutrition or Metabolic Rate or Energy Utilization

Points to discuss In a two-step model (screening/monitoring and assessment), which is the position of the different domains? Nutrition Is this indeed part of the intrinsic capacity or feeding it? Metabolism? Body composition? Energy production? Other domains to consider E.g., Anxiety? Pain? Fatigue? Specific biomarkers? Should cognition be separeted from or combined to mental health (depressive symptoms)? Place of syndromic and/or geriatric conditions E.g., COPD, urinary incontinence