PMC

Schematic conceptual representation of clinical conditions defined by the terms “disease”, “syndrome” and “geriatric syndrome”, illustrating differences in numbers and complexity of relevant factors, including etiological risk factors, pathophysiologic mechanisms and presenting symptoms. Adapted with permission from Olde Rikkert et al. ().

A unifying conceptual model demonstrates that shared risk factors may lead to geriatric syndromes, which may in turn lead to frailty, with feedback mechanisms enhancing the presence of shared risk factors and geriatric syndromes. Such self-sustaining pathways may result in poor outcomes involving disability-dependence, nursing home placement, and ultimately death, thus holding important implications for elucidating pathophysiologic mechanisms and designing effective intervention strategies.

Mechanistic research addressing the pathophysiology of complex multifactorial geriatric syndromes will require the development of new conceptual models. The traditional linear model (A) has proven highly effective for the discovery of pathophysiologically relevant mechanisms in conditions such as inborn errors of metabolism, yet it does not adequately capture the multifactorial nature of geriatric syndromes. The concentric model (B) was developed by cancer researchers as a means of designing more effective cancer treatments by targeting multiple distinct oncogenic pathways(). This approach may also not be suitable for geriatric syndromes since interventions targeting only one risk factor would address only a small portion of the overall risk for such conditions, while multi-component pharmaceutical interventions risk being unfocussed and could lead to adverse effects typically associated with geriatric polypharmacy. We propose an interactive concentric model (C) as a means of reconciling the need for mechanistic research with the conditions’multifactorial complexity, by focusing on pathways associated with risk factor synergisms, thus offering a locus for the design of targeted interventions. Modified from Decker and Sausville()