Frailty is the result of physical, psychological and social factors that contribute to a decline in the body’s physiological reserve and its reduced ability to maintain homeostasis among life’s stressors (1, 2). While a standardized pragmatic definition of frailty is still debated, Fried’s landmark study operationalized frailty as a phenotype defined by a set of variables: unintentional weight loss of ≥10 lbs, self-reported exhaustion, slow gait speed, low energy expenditure and weak grip strength (frail ≥3, pre-frail 1 or 2, robust =0) (3). Frailty is strongly associated with functional losses, disability, increased healthcare utilization and higher cost of healthcare (1, 4-8).

Weight status is commonly assessed in healthcare settings; however, it may be underutilized as a metric to indicate current and future adverse health outcomes (9, 10). Changes in body composition occur with each decade of life and include a peaking of fat mass in the 7^th decade followed by subsequent decline in both skeletal muscle and fat (11, 12) making the most commonly used metric, body mass index (BMI), a highly insensitive measure of weight status in older adults(13). Some older adults are at risk for what is known as sarcopenic obesity or a disproportionate loss of lean mass to gain of fat mass which is shown to be associated with higher rates of morbidity and mortality outside of both sarcopenia or obesity alone (14, 15). Long-term changes of loss or gain in body weight are associated with the highest mortality rates among persons in the general population while mortality is the lowest among those with modest weight changes(16). Weight cycling, or gaining/losing a similar amount of weight repeatedly, is known to be associated with higher disability and mortality rates(17). This harmful cycle emphasizes the importance of obtaining a weight history in clinical practice as even lower percent changes may be significant in those with frailty (18-22).

Gaining an understanding of longitudinal weight measures over a lifespan could be helpful for predicting future risk of disease and functional status. Such measures are easily captured using most outpatient electronic medical records. As both frailty and obesity are associated with similar adverse outcomes (4-8, 23-25), weight change trajectories may help clinicians assess the risk of development of frailty and other adverse health outcomes in older adulthood. The purpose of this study was to evaluate the relationship between self-reported weight change over a lifespan and frailty in a representative sample of US older adults.

Table 1 presents the baseline characteristics of participants. Of 4,984 participants, 56.5% were female, mean age was 71.1 years and BMI was 28.2 kg/m². Prevalence of pre-frailty and frailty was 40.1% and 9.1%, respectively. Robust participants were more likely to be non-Hispanic white and have a higher education level (p=<0.001). Frail patients were more likely to have comorbidities such as arthritis, diabetes and coronary artery disease (p=<0.001) but not more likely to have cancer (p=0.48). Nearly all frail patients met the criterion of weakness (96.9%) and the most common criterion identified for pre-frailty was slowness of gait (59.1%).

Table 2 outlines participants’ self-reported weights and weight changes over time. Weight increased in all groups over time, with individuals with frailty losing weight, as compared to the pre-frail or robust groups within the past year or 10 years. Weight gain of ≥5% in the past year was associated with higher rates of frailty among those classified in other categories. When comparing each participant’s weight at age 25 years old to his/her current weight, fewer individuals with frailty gained clinically significant weight and most had a greater than 5% weight loss. Changes in weight and rates of combination of frailty, pre-frailty and robust percentages can be found in Supplementary Table 1.

Multivariable logistic regression models evaluating the relationship between weight change during a specific time interval, and risk of frailty or pre-frailty are presented in Table 3. Weight loss of ≥5% was strongly associated with risk of frailty compared to pre-frailty/robust and the relationship strengthens with longer time intervals. A ≥5% weight gain only was associated with frailty if the gain occurred within the last year. Similar associations were seen with pre-frailty when comparing pre-frailty to robust status, albeit weaker than the association seen with frailty.

Figure 1 represents the change in weight as a function of age plotted with a LOESS smoothed line by frailty status. Graphically, a period of increased rate of weight gain is noted prior to a steep decline in weight for individuals who were frail at time of study inclusion; conversely, this was not observed in those with pre-frail or robust status. Additionally, frail individuals had a higher peak weight (87.3 kg), occurring earlier in life (58.4 years), relative to both pre-frail (peak weight 79.9 kg at age 59.9 years) and robust (79.0 kg peak weight at 63.0 years) individuals. This suggests that the earlier one reaches their peak weight in life, the higher risk of incident frailty.

Our findings demonstrate the importance of dynamic weight changes over a lifetime in the future development of frailty. While frailty is classically defined by weight loss (3), here we show that significant changes in weight gain or loss over a lifetime were associated with frailty progression making this a more complicated relationship than was previously thought. We created two separate analyses looking at frailty versus pre-frail and robust participants and pre-frail vs robust participants alone. Pre-frailty has individually been associated with an increase in overall mortality and cardiovascular mortality (26). Here we demonstrate that significant weight loss or weight gain is strongly associated with frailty and has a weaker, but statistically significant, association with pre-frailty supporting the significance of each step along the frailty spectrum.

While weight loss’ association with frailty is well accepted, the relationship of weight gain with frailty is less understood. A 22 year follow-up study demonstrated obesity was associated with higher rates of pre-frailty and frailty compared to robust individuals, suggesting obesity could be a contributing factor to progression along the frailty spectrum (32, 33). Unsurprisingly, we showed that older adults with a ≥5% weight loss compared to 1 year ago, 10 years ago, and age 25 have significantly increased odds of developing frailty suggesting that weight loss is a strong indicator of potential frailty development. Yet, a ≥5% weight gain only increased odds of frailty when this occurred within the last year, but not compared to 10 years ago or age 25. This seems to suggest that a sudden increase in weight may not be marker of health, but a weight trajectory trending more toward the concept of sarcopenic obesity (34).

Prior work has shown that when evaluating weight gain and loss, more lean mass is lost than is gained over repeated fluctuations suggesting weight cycling could accelerate sarcopenia in older adults and contribute to saecopenic obesity (35). Weight cycling leads to greater central body fat and increased mortality (22). Some theorize that the trajectory of pathological aging is to move from robust status to sarcopenic obesity to frailty then to disability and mortality (36). Our previous data suggest that late adulthood weight changes over a 10 year period are predictive of sarcopenia development and that there is a healthy, natural propensity to gain weight over a life course (37). Our current findings demonstrate a similar trend as robust participants were more likely than those pre-frail or frail to have gained ≥5% weight over the course of the prior 10 years.

A natural, healthy trend toward weight gain could explain why the classification of overweight status in older adults, in part, has been noted as somewhat “protective” (38). Overweight status could be beneficial for reducing disability and functional loss with reduced osteoporosis and injuries from falls (39). An ability to gain or maintain weight demonstrates a reduced vulnerability to stressors from comorbid health conditions (40).

This study is not without limitations. First, the analysis relied on self-reported weights which may be impacted by recall bias. In clinical practice, weight 10 years prior and at age 25 would most likely be ascertained by recall, and therefore, use of self-report is ecologically valid. Second, the sample was comprised of community dwelling adults. Individuals living in facilities were not included, which limits the ability to generalize these findings to the older adult population as a whole. To operationalize Fried’s frailty criteria in NHANES, it was necessary to modify some of the original definitions such as endurance. The prevalence of each component, however, is comparable to those observed in other studies (3, 41, 42). As walking speed was missing for 3,645 patients, multiple imputations needed to be performed to maximize the number of participants with appropriate data. Multivariate imputation by chained equations, a robust method that generates multiple predictions for each missing value, taking the uncertainty of the imputations into account and yielding accurate standard errors (43), was used to handle missing data. As with all cross-sectional studies, we are not able to make causal inferences. Lastly, the true relationship between weight change and incident to frailty may not necessarily be linear.

The results demonstrate an association between frailty and weight change over time. Weight loss over a lifespan is strongly associated with frailty while weight gain in the last year also is association with higher rates of frailty and can therefore be a marker of declining health. A natural trend toward weight gain and overweight status in a lifetime could actually be a sign of metabolic health and longevity. These findings demonstrate the clinical value in weight trends obtained at most clinical visits and highlight potential trends that may warrant closer evaluation for syndromes like frailty that require additional intervention to help curb poorer health outcomes.