Ethical questions about biomarkers of ageing the view of geriatrics

Transcription

1 Ethical questions about biomarkers of ageing the view of geriatrics Biomarker of Ageing Halle Manfred Gogol, M.D. Coppenbrügge

2 Definition Biomarker of Ageing (BMA) are agents that allows to describe a disease earlier maybe used to assess a pre- or sub-clinical state maybe for risk estimation for a disease (far in the future) will let us make better diagnosis will let us make better prognosis will let us make better therapeutic approaches will let us better monitor the patient

3 Definition BM are agents that allows to describe a diesase earlier maybe a pre-clinical state maybe for risk estimation for a disease (far in the future) will let us make better diagnosis will let us make better prognosis will let us make better therapeutic approaches will let us better monitor the patient Biomarkers are wonderful

4 Biomarkers are wonderful But most of age-related diseases are not an entity but a syndrome. Furthermore, we have diseases who appear as entity and as syndrome as well.

5 Age-related disease Syndrome Mixed Entity Falls Dementia Malnutrition Sarcopenia Frailty Incontinence Depression Heart failure Delirium Stroke Osteoporosis Osteoarthritis Diabetes COPD Cancer Macula degeneration CHD Parkinson disease

6 Single Disease Multimorbidity Functional health

7 Single Disease co-morbidity Multimorbidity function Functional health

8 Frailty Fried criteria Weight loss > 5 kg / y Exhauston Muscle weakness Slow walking Low physical activity 3 citeria define Frailty 1-2 criteria define Pre-Frailty

9 Frailty Fried criteria Weight loss > 5 kg / y Exhauston Muscle weakness Slow walking Low physical activity II Weight loss / Sarcopenia Activity (but look for other conditions too: depression, dementia, other diseases.

10 Cronic inflammation In basic and clinical research there is a lot of evidence that chronic inflammation play a major (or key) role in cardiovascular disease as in chronic degeneration processes at all

11 Cronic inflammation? Tsimane population in south america (amazonas) CRP Obesity HDL cholestrol Total cholestrol Active lifestyle Lean diet Gurven M et al. PLoS ONE 2009;4(8):e6590

12 Hypertension Besides smoking and hyperlipidemia in mid age the key risk factor The only risk factor, where RCTs have shown a benefit in the elderly 80+ In women [similar in men] 75 % of hypertension are preventable by modifying life style risk factors Forman J JAMA 2009 July 22th

13 Obesity Robert Wood Johnson Foundation 2009

14 Obesity in children, US 2007 Robert Wood Johnson Foundation 2009

15 Obesity Europe - Females

16 Obesity Europe - Male

17 Diabetes

18 Intervention post stroke Ischemic stroke Able to walk at discharge n = 314, mean age 69 y, 55 % male Intervention: n = 157 Intervention: detailed training programme to promote physical activity including 5 follow-up visits over 24 month PASE score 69,1 vs 64,0 (95% CI -5,8 15,9, p = 0,36) No effect on mortality, recurrent stroke, myocardial infarction, falls + fractures Boysen G et al. BMJ 2009;339:b2810

19 Dementia Our possibilities to diagnose Dementia grow by imagine techniques for the brain and also by a various number of biomarkers Our possibilities to predict the conversation from MCI (minimal cognitive impairment) to dementia too

20 But Dementia II Anti-dementia drugs had no or only a modest effect Controlled trials only about 6 month and with multiple bias factors (nutrition, activity, social support, LOCF method) What is the sense for early diagnosis without a specific therapeutic approach besides general recommendations?

21 Why I m pessimistic (about BMA) Our (potential) patients usual do only parts (sometimes more, often less) they are told So BMA have a limited function in special situations, special diseases and often add no or less information for clinical decisions Lots of (risk) factors are easy to assess often by phenotype Man are no yeasts (zebrafish etc) the complexity is not only biological, but also psychological / emotional / spiritual / social / ecological

22 Longevity genes network in yeasts Managbanag JR et al. PLoS ONE 2008;3:e3802

23 Longevity network in yeasts Protein protein interactions Managbanag JR et al. PLoS ONE 2008;3:e3802

24 Why I m pessimistic (about BMA) Man are no yeasts (zebrafish etc) the complexity is not only biological, but also psychological / emotional / spiritual / social / ecological I m doubtful about modelling this (potential) circumstances in the lab Depression leads to stress, but stress in yeast doesn t mean the stress of depression in man (and even not the possibilities of life to change this condition)

25 Health economics (crisis) BMAs for the beginning of the dying process? BMAs for limited life exspectancy?

26 Why I m optimistic (about BMA) Man has the possibilty for plasticity in all compartiments (body, cognition, emotion, spiritual) not only in the brain

27 Life exspectancy US 1997 JAMA 2001; 285:2750-6

28 Effect of training Jerusalem Longitudinal Cohort Study persons, personyears Examination at age 70, 78, 85 y physical active vs. sedentary participants 8-y-Mortality 70 y: 15,2 vs. 27,2 % (p < 0,001) HR 0,61 8-y-Mortality 78 y: 26,1 vs. 40,8 % (p < 0,001) HR 0,69 3-y-Mortality 85 y: 6,8 vs. 24,4 % (p < 0,001) HR 0,42 Initiating PA y: Mortality p = 0,04 Initiating PA a: Mortality p < 0,001 Independent ADL [PA]: OR 1,92 (95%CI 1,11-3,33) Stessmann J et al. Arch Intern Med 2009;169:

29 Why I m optimistic (about BMA) A growing number of aging or elderly people are healthy ager They can have a benefit BMA will help us in future to make decisions about a therapy or another maybe also to negiotate therapy

30 Health recommandations BMAs Lots of questions Some answers More questions More answers 1. Physical activity 2. Cognitive activity 3. Healthy nutrition 4. Social relationships 5. Crisis management 6. CV-risk factors 7. Moderate alcohol 8. Think positive and be happy