Frailty Assessment and Intervention

Ershler, William

Abstract

Older people who develop age-associated involutional changes recognized as frailty are particularly susceptible to negative health outcomes including falls, fractures, dementia, depression, progressive co-morbidities, hospitalization, nursing home placement and shortened survival. Frailty is not a universal phenomenon as it occurs in only a minority of older people, even at advanced ages. The development and validation of an operational definition of frailty based upon a standardized panel of self-report and performance-based measures has greatly facilitated research aimed at understanding the pathophysiology of frailty. Studies to date have indicated that inflammatory processes are involved. It has been our hypothesis that the dysregulation of certain inflammatory pathways occur with advancing age, and to a greater extent in those who are to develop the frail phenotype. In the current research, we intend to identify those individuals over the age of 70 years who meet criteria for 'early frailty' as well as evidence for activated inflammatory pathways (e.g., elevated C Reactive Protein CRP or interleukin-6), and to treat with one of two novel drugs; either lenalidomide or resveratrol. Both of these drugs have been shown to reduce inflammatory mediators. These trials are the first to examine each agent in the context of inflammation and aging. Accordingly, each will have a Phase I/II design and will focus on parameters of safety as well efficacy. For the purpose of these trials, the primary efficacy outcome will be reduced level of inflammatory cytokines. However, we also examine a panel of laboratory and physical performance-based measures. Upon completion of this work, if either or both of the drugs proves well-tolerated and effective at reducing circulating mediators of inflammation, a larger phase II study will be considered.