Sign and Symptom Driven Definitions The Syndrome of Frailty

Despite the ongoing debate on the nature of frailty and whether it is an independent clinical entity or syndrome, some investigators have begun to develop syndromic models in order to differentiate frail vs. nonfrail older adults from further study (Walston et al., 2005).

Frailty Older Adults
Figure 57.1 Hypothesized Cycle of Frailty illustrating associated physiologic and functional declines as well as potential entry points into cycle of decline. Adapted from Fried et al. (2003).

These syndromic models have been developed using epidemiologic data on characteristics related to weight loss or muscle weakness based on the conceptualization of frailty as a wasting syndrome. For example, Chin et al. (l999) previously compared three working definitions of frailty, namely, inactivity combined with (l) low energy intake, (2) weight loss, or (3) low body mass index. The combination of inactivity with weight loss was found to be most associated with lower subjective health and performance measures, as well as more disease and disability. In addition, the three-year relative risk for mortality was substantially higher in this group compared to others in the study cohort (odds ratio (OR) 4.l, l.8-9.4) (Chin et al, l999).

Similarly, Fried et al. (200l) utilized a syndromic approach and developed and operationalized a hypothetical frailty phenotype based on common physiologic signs and symptoms described by frail, older adults. This tool consists of five items, including muscle strength (lowest quartile as determined by grip strength dynamometer measurement), weight loss (more than l0 pounds of unintended weight loss in the previous year), walking speed (lowest quartile of timed l5 meter walk), low levels of physical activity as measured by the Minnesota Leisure Time Activities questionnaire, and fatigue (measured by questions from a Depression survey asking about energy level). It was operationalized in the Cardiovascular Health Study (CHS), an epidemiologic study of community-dwelling adults over age 65 followed for nine years in order to better characterize cardiovascular disease and functional decline late in life. If CHS participants met three of five of these criteria, they were deemed frail; if they met one or two of the criteria, they were deemed intermediate; and if they met none of the criteria, they were deemed not frail. Seven percent of CHS participants met the frailty criteria at their baseline exam, and as expected, there was a significant overlap between disability, chronic illness, and frailty (Fried et al., 200l). However, it was also clear that disability and medical illness were not always consistent with frailty, suggesting an etiology independent from disease and disability, and suggesting a separate but perhaps related biology (Fried et al., 200l). Predictive validity analyses were also performed, where the investigators demonstrated that those who were in the frailty category were more likely to fall, enter nursing homes, be hospitalized, and suffer mortality over seven years of follow-up (Fried et al., 200l). These screening criteria were subsequently utilized to identify biologic correlates of frailty as described in more detail later (Walston et al., 2002; Leng et al., 2002; Leng et al., 2004).

The advantage of these models is that the signs and symptoms were chosen because they are consistent with a wasting syndrome, which often appears to have a common biology. A disadvantage may be that by choosing the wasting syndrome signs and symptoms, other important biologic mediators may not be fully explored (Walston et al., 2005).

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