https://orcid.org/0000-0001-9244-9267
Evolution of Fatigability Research
Fatigue, a “subjective lack of physical and/or mental energy perceived to interfere with usual or desired activities” (1), is a common symptom among older adults that affects quality of life and foreshadows the onset of frailty, disability, and death. The onset and progression of fatigue with aging remain poorly understood due to its subjective nature and lack of a unified definition as perceptions of fatigue may encompass physical, mental, and emotional components. A central response to fatigue—slowing down and/or reducing activity often in subtle ways—not only accelerates deconditioning and risk of frailty and functional decline, but also complicates recognition of fatigue as persons tend to adjust activity levels to avoid, delay, or diminish sensations of fatigue.
The construct of fatigability has existed for decades in the human physiology literature, applied largely to muscle contractile capacity and exhaustion (2). More recently, fatigability has emerged as a whole-body measure that anchors fatigue in relation to a quantifiable demand task (1,3). To this end, fatigability has become a metric that assesses the degree to which an individual may be limited by perceptions of fatigue. Fatigability can be characterized as a normalized measure of fatigue as it anchors perceptions of exertion or effort to specific type, duration, or intensity of activity. This approach facilitates meaningful comparisons between individuals and in the same individual over time, providing greater capacity to assess the role of fatigue in the disablement pathway. Fatigability can be used as a predictor or early marker or an outcome unto itself and may be more sensitive to intervention, particularly those targeting improved fitness and physical performance.
Over the past decade, several researchers have answered the call to action from the fifth Bedside-to-Bench Research Conference on Idiopathic Fatigue and Aging (1) to develop validated assessment tools to identify and quantify fatigability in older adults and explore predictors, correlates, and consequences of greater fatigability. The report identified 2 dimensions of fatigability: (i) the degree of fatigue experienced in relation to performing a standardized activity and (ii) perceived inability to continue activity at the same intensity with performance deterioration (1). Table 1 summarizes the most commonly used measures, including those featured in this issue.
Frequently Used Physical Fatigability Measures in Studies of Older Adult Populations
| Definition | Assessment Type and Task/Instrument | Scoring/Calculation |
|---|---|---|
| Perceived Fatigability Whole-body measure of an individual’s self-reported feeling of tiredness or exertion as a function of the duration and intensity of a demand task or activity (3) | Self-reported fatigue plus objectively measured demand: | |
| 5-min treadmill walk at 0.67 m/s at 0% grade [RPE fatigability] 6-min walk (self-paced) 10-min walk (self-paced) | Rating of perceived exertion (RPE) using the Borg scale (4–18); higher RPE = greater fatigability; “High” fatigability = RPE ≥10 (19); categorical classification of RPE scores (6–7, 8–9, 10–11, ≥12) (6) Perceived fatigability severity (0–10 scale) or perceived exertion fatigability (0–10 scale): change in fatigue or exertion (post-test – pretest) divided by distance walked, multiplied by 1000 (4) Perceived fatigability severity measured by dividing perceived rating of change in tiredness (1–7 score) by number of meters walked; higher score = greater fatigability (5) | |
| Self-reported fatigue and demand in a single instrument: | ||
| Pittsburgh Fatigability Scale [PFS Fatigability] | PFS physical subscale score (0–50); higher score = greater perceived physical fatigability (8); higher perceived physical fatigability = PFS ≥15 (20); categorical classification of PFS physical scores (0–4, 5–9, 10–14, 15–19, 20–24, and ≥25) (9); imputation algorithm for missing data (21) | |
| Performance Fatigability Decrement in performance during a standardized physical task or activity (3) | 6-min walk (self-paced) 400-m walk (fast-paced) 10-min walk (self-paced) | Mean walking speed more than 6 min, divided by the mean speed in the first 2 min, divided by the total distance walked, multiplied by 1000 (4) Performance deterioration defined as ≥6.5% difference in walking speed (m/s) of lap 9 minus lap 2 (19) Fatigability severity: percentage changes in walk speed over the full time walked divided by speed in first 2.5 min, multiplied by 1000 (5) |
| Definition | Assessment Type and Task/Instrument | Scoring/Calculation |
|---|---|---|
| Perceived Fatigability Whole-body measure of an individual’s self-reported feeling of tiredness or exertion as a function of the duration and intensity of a demand task or activity (3) | Self-reported fatigue plus objectively measured demand: | |
| 5-min treadmill walk at 0.67 m/s at 0% grade [RPE fatigability] 6-min walk (self-paced) 10-min walk (self-paced) | Rating of perceived exertion (RPE) using the Borg scale (4–18); higher RPE = greater fatigability; “High” fatigability = RPE ≥10 (19); categorical classification of RPE scores (6–7, 8–9, 10–11, ≥12) (6) Perceived fatigability severity (0–10 scale) or perceived exertion fatigability (0–10 scale): change in fatigue or exertion (post-test – pretest) divided by distance walked, multiplied by 1000 (4) Perceived fatigability severity measured by dividing perceived rating of change in tiredness (1–7 score) by number of meters walked; higher score = greater fatigability (5) | |
| Self-reported fatigue and demand in a single instrument: | ||
| Pittsburgh Fatigability Scale [PFS Fatigability] | PFS physical subscale score (0–50); higher score = greater perceived physical fatigability (8); higher perceived physical fatigability = PFS ≥15 (20); categorical classification of PFS physical scores (0–4, 5–9, 10–14, 15–19, 20–24, and ≥25) (9); imputation algorithm for missing data (21) | |
| Performance Fatigability Decrement in performance during a standardized physical task or activity (3) | 6-min walk (self-paced) 400-m walk (fast-paced) 10-min walk (self-paced) | Mean walking speed more than 6 min, divided by the mean speed in the first 2 min, divided by the total distance walked, multiplied by 1000 (4) Performance deterioration defined as ≥6.5% difference in walking speed (m/s) of lap 9 minus lap 2 (19) Fatigability severity: percentage changes in walk speed over the full time walked divided by speed in first 2.5 min, multiplied by 1000 (5) |
Frequently Used Physical Fatigability Measures in Studies of Older Adult Populations
| Definition | Assessment Type and Task/Instrument | Scoring/Calculation |
|---|---|---|
| Perceived Fatigability Whole-body measure of an individual’s self-reported feeling of tiredness or exertion as a function of the duration and intensity of a demand task or activity (3) | Self-reported fatigue plus objectively measured demand: | |
| 5-min treadmill walk at 0.67 m/s at 0% grade [RPE fatigability] 6-min walk (self-paced) 10-min walk (self-paced) | Rating of perceived exertion (RPE) using the Borg scale (4–18); higher RPE = greater fatigability; “High” fatigability = RPE ≥10 (19); categorical classification of RPE scores (6–7, 8–9, 10–11, ≥12) (6) Perceived fatigability severity (0–10 scale) or perceived exertion fatigability (0–10 scale): change in fatigue or exertion (post-test – pretest) divided by distance walked, multiplied by 1000 (4) Perceived fatigability severity measured by dividing perceived rating of change in tiredness (1–7 score) by number of meters walked; higher score = greater fatigability (5) | |
| Self-reported fatigue and demand in a single instrument: | ||
| Pittsburgh Fatigability Scale [PFS Fatigability] | PFS physical subscale score (0–50); higher score = greater perceived physical fatigability (8); higher perceived physical fatigability = PFS ≥15 (20); categorical classification of PFS physical scores (0–4, 5–9, 10–14, 15–19, 20–24, and ≥25) (9); imputation algorithm for missing data (21) | |
| Performance Fatigability Decrement in performance during a standardized physical task or activity (3) | 6-min walk (self-paced) 400-m walk (fast-paced) 10-min walk (self-paced) | Mean walking speed more than 6 min, divided by the mean speed in the first 2 min, divided by the total distance walked, multiplied by 1000 (4) Performance deterioration defined as ≥6.5% difference in walking speed (m/s) of lap 9 minus lap 2 (19) Fatigability severity: percentage changes in walk speed over the full time walked divided by speed in first 2.5 min, multiplied by 1000 (5) |
| Definition | Assessment Type and Task/Instrument | Scoring/Calculation |
|---|---|---|
| Perceived Fatigability Whole-body measure of an individual’s self-reported feeling of tiredness or exertion as a function of the duration and intensity of a demand task or activity (3) | Self-reported fatigue plus objectively measured demand: | |
| 5-min treadmill walk at 0.67 m/s at 0% grade [RPE fatigability] 6-min walk (self-paced) 10-min walk (self-paced) | Rating of perceived exertion (RPE) using the Borg scale (4–18); higher RPE = greater fatigability; “High” fatigability = RPE ≥10 (19); categorical classification of RPE scores (6–7, 8–9, 10–11, ≥12) (6) Perceived fatigability severity (0–10 scale) or perceived exertion fatigability (0–10 scale): change in fatigue or exertion (post-test – pretest) divided by distance walked, multiplied by 1000 (4) Perceived fatigability severity measured by dividing perceived rating of change in tiredness (1–7 score) by number of meters walked; higher score = greater fatigability (5) | |
| Self-reported fatigue and demand in a single instrument: | ||
| Pittsburgh Fatigability Scale [PFS Fatigability] | PFS physical subscale score (0–50); higher score = greater perceived physical fatigability (8); higher perceived physical fatigability = PFS ≥15 (20); categorical classification of PFS physical scores (0–4, 5–9, 10–14, 15–19, 20–24, and ≥25) (9); imputation algorithm for missing data (21) | |
| Performance Fatigability Decrement in performance during a standardized physical task or activity (3) | 6-min walk (self-paced) 400-m walk (fast-paced) 10-min walk (self-paced) | Mean walking speed more than 6 min, divided by the mean speed in the first 2 min, divided by the total distance walked, multiplied by 1000 (4) Performance deterioration defined as ≥6.5% difference in walking speed (m/s) of lap 9 minus lap 2 (19) Fatigability severity: percentage changes in walk speed over the full time walked divided by speed in first 2.5 min, multiplied by 1000 (5) |
Perceived Fatigability
Two primary types of perceived fatigability measures have been developed. One approach assesses perceived effort or level of fatigue following the performance of a standardized task (typically walking-based) that is either self- or machine-paced (4–6,19,22). The other approach queries the expected level of exertion or fatigue associated with a variety of well-characterized activities that range across type, intensity, and duration (7–9).
The instruments using an objective task including (i) a 5-minute slow-paced (0.67 m/s, 0% grade) treadmill test with the Borg rating of perceived exertion (RPE; range 6–20) at the end (“RPE fatigability”) (19) and (ii) self-paced overground walking tests of various durations and distances coupled with a fatigue severity scale (4,5,10) (Table 1). Similar to objective physical performance measures, these approaches provide a direct gauge of fatigability in relation to a commonly performed activity, removing potential error or bias induced by perceptions of “ability” or “difficulty” associated with self-report. Additionally, standardizing the task for speed, distance, or both allows comparison across people of differing ages and abilities.
There is currently a paucity of questionnaire-based instruments to measure perceived physical fatigability which include fatigue and demand together; the Pittsburgh Fatigability Scale (PFS) is the only validated questionnaire-based instrument (8). The PFS, validated against RPE fatigability as well as performance deterioration, asks individuals to “imagine” their fatigue levels across a range of activities commonly performed by older adults (“PFS fatigability”) (8). The PFS was recently validated to also include healthy younger adults, as well as 2 clinical populations (multiple sclerosis and fibromyalgia) (11). The availability of the PFS in 12 languages allows for the global examination of perceived physical fatigability across populations to examine its relation to important health outcomes. Advantages to questionnaire-based tools include (i) low cost, (ii) no special equipment or walking space required, making them practical for research and clinical settings, including remote administration, and (iii) options to self- or interviewer administer among those unable to perform physical testing.
Performance Fatigability
Performance fatigability is assessed as a decrement in a performance task, primarily walking-based (4,5,19,22). Commonly used measures focus on self-paced walking speed during 6- and 10-minute overground walking bouts (4,5) and performance deterioration, defined as either inability to complete or slowing during a fast-paced overground walk (19). There are several limitations in assessing performance fatigability. First, participants must be able to walk a substantial portion, if not all, of the test, limiting its applicability in mobility-limited populations. Second, that there are variations in protocols throughout the literature, with distances ranging from 100 m to 12 minutes, and varying formulas for calculating performance fatigability, making comparisons among cohorts difficult. Third, measures of perceived fatigability typically yield a range of values, whereas performance fatigability tests tend to produce a dichotomous assessment. It is important to note, however, that comparability across measures has not been widely evaluated. The one exception using data from the Baltimore Longitudinal Study of Aging (BLSA) found that perceived RPE fatigability and performance fatigability, defined as an inability to complete or marked slowing during a fast 400 m walk, identified similar proportions meeting high fatigability criteria but little overlap in the actual individuals meeting the respective criteria (19).
Published Findings to Date
Fatigability studies have become increasingly popular in recent years. A PubMed search for studies using fatigability shows a rapid increase during the last 15 years, with an average of about 60 articles per year in 2005 and 161 articles in 2019 (Figure 1). Higher RPE fatigability has been shown to predict meaningful declines in physical functioning (6) and persistent suboptimal or worsening hemoglobin levels (12). Also, in this issue, Salerno et al. (13) link higher RPE fatigability with cognitive decline, providing an intriguing brain/body link between perception of physical effort and cognitive performance. Cross-sectionally higher RPE fatigability has been associated with lower and more fragmented physical activity (14,15), higher chronic inflammation (16), suboptimal thyroid hormone level (17), elevated core body temperature (18), excess adiposity (23), subclinical peripheral artery disease (24), and greater cardiovascular burden (25). RPE fatigability has also emerged as a tool to potentially discriminate between healthy and accelerated aging; older cancer survivors participating in the BLSA showed greater fatigability during follow-up compared to their healthy counterparts (26). Importantly, RPE fatigability has consistently outperformed traditional measures of “tiredness” and “low energy,” and in this issue, it has been linked to longitudinal changes in energy utilization and efficiency (27).
A search of PubMed for keyword “fatigability” by year.
Similarly, higher PFS fatigability also predicts meaningful functional decline in older adults (9). In cross-sectional analyses, greater body mass index, lower skeletal muscle mass (28), lower physical activity levels (29), chronic low-grade inflammation (21), and lower brain volumes of the thalamus, hippocampus, and putamen, as well as structural connectomes (20,30) were all associated with greater PFS fatigability. The articles in this collection extend previous work with the PFS, with the work of LaSorda et al. (31), showing that PFS fatigability was highly prevalent across older adulthood, more so for women than men, with higher PFS fatigability ranging from 24.6% (60- to 69-year-old men) to 94.3% (older than 90 years women). Replication of the above analysis using a traditional single-item fatigue measure revealed prevalence rates about one-third lower, and no sex differences, underscoring the merits of assessing an individual’s fatigability. This article is also the first to show that perceived physical fatigability has some genetic basis (heritability estimate h2 = 0.263). Additionally, in this issue, Stuber et al. (32) published the first drug intervention trial to explore change in PFS fatigability among older adults with mild subclinical hypothyroidism. The lack of a significant decline in PFS fatigability after 1 year of levothyroxine treatment may be due to dosage and relatively low baseline levels of perceived physical fatigability.
Notably, in this issue, Alfini et al. (33) assessed the association between actigraphic sleep parameters and both RPE and PFS fatigability. Shorter- and longer total sleep time, longer wake bout length, and greater wake after sleep onset were associated with higher fatigability (33). However, the results were not uniform across the RPE and PFS methods. More studies are needed to understand the difference in measurement properties of the RPE and PFS methods, as well as the underlying mechanisms fueling the onset and meaningful change in each.
Lastly, Palmberg et al. (34) strengthened prior work and demonstrated consistency across fatigability measures by showing accelerometry-derived activity fragmentation is associated with several measures of perceived and performance fatigability, namely, perceived exertion fatigability (RPE at the end of a 6-minute walk), self-report physical fatigability (using the Situational Fatigue Scale), and modified performance fatigue severity.
Future Directions
Fatigability joins a long line of reliable, validated well-documented “red flags” or early markers of something amiss in the lives of older adults including the Short Physical Performance Battery (35), usual gait speed (36), grip strength (37), the 6-minute (38) and long-distance corridor walks (39), and the frailty phenotype (40). Importantly, fatigability has been shown to precede the onset/progression of deficits in many of these other functional tools (6,9,26). This is not meant to discount the importance of these established tools, but to leverage the complementary potential of using multiple assessment methods to understand the underlying relationship between fatigability and healthy aging. To this end, fatigability may act as an early prognostic indicator that captures impending declines in physical and cognitive functioning and the onset of subclinical disease burden, signaling a need for further health and functional screening. Yet at this time, fatigability has little to no clinical presence. The scientific evidence published over the past decade, augmented by the new publications in this issue, warrants the expansion of perceived or performance fatigability assessments into clinical trials and practice. The time has never been better.
