Biomarkers of Frailty: Explorative research with a multi-domain approach

Abstract

Frailty is an age-associated syndrome and can be described as a state of increased vulnerability to adverse health outcomes when exposed to stressors (e.g. an infection), caused by the cumulative decline in one or more domains of functioning. To prevent frailty, we need to better understand the underlying mechanisms and identify at an early stage people at risk of becoming frail. The aim of this thesis is therefore to identify (bio)markers (based on questionnaire data, anthropometric measurements, biochemical markers, and genetic data) of frailty, which could be indicative of the underlying processes that cause frailty and/or could help to detect people at risk. In this thesis, frailty is defined using a multi-domain approach based on the Tilburg Frailty Indicator (TFI) which allowed us to study (bio)markers for the physical, cognitive, psychological, and social frailty domains. For this research, data of two cohort studies was used, the Doetinchem Cohort Study (DCS) and the European study to establish biomarkers of human Ageing (MARK-AGE). In addition, multiple research designs and various analysis techniques were used. The research shows that physical and cognitive frailty is more common in older age, while psychological frailty is equally common at all ages. Further, the four frailty domains consist of different groups of frail people with similar characteristics. Therefore, prevention strategies should target multiple frailty domains (e.g. physical, cognitive, psychological, and social frailty) rather than one domain only. Biomarkers for early detection of frailty and that can be used to better target preventive measures have not been found. With the development of new assays and laboratory techniques in the field of omics (metabolomics, transcriptomics and proteomics) one might be able to identify frail groups at an early stage and gain more insight in the near future in the underlying processes that cause frailty. The biomarker results in this thesis do suggest that inflammation and the possible involvement of the immune system may play a role in the development of physical and cognitive frailty. Finally, people who are physically active have a lower risk of being frail. The findings of this thesis underline the importance of a healthy lifestyle for healthy ageing.