Association of Total Daily Physical Activity and Fragmented Physical Activity With Mortality in Older Adults

Key Points Question Is the manner in which older adults accumulate physical activity throughout the day, beyond the total amount of physical activity, associated with their mortality risk? Findings In this cohort study of 548 well-functioning adults aged 65 years and older, more fragmentated physical activity, but not total daily activity, was associated with increased mortality risk. Meaning Fragmented physical activity of bouts lasting less than 5 minutes may reveal compensatory changes resulting from impaired physical function and may be associated with increased mortality risk.


Introduction
Physical activity benefits health and quality of life, particularly for adults aged 65 years and older. 1 With aging, functional capability declines, physical activity decreases, 2 and mortality risk increases.
Previous research 3,4 shows that volume and/or intensity measures of physical activity are associated with mortality risk, but technological advances (eg, accelerometers) present the possibility to evaluate and test whether detailed patterns of activity may be more informative to health outcomes than traditional measures of total activity, thus providing an earlier marker of future health and longevity. 5 This is particularly important with regard to older adults, who are one of the most sedentary and rapidly growing segments of the US population. 6 With aging and disease, activity becomes less frequent and shorter in duration, or more fragmented, 7 as physiological capacity declines. Fragmented patterns of activity are associated with poorer physical functioning, 7,8 a precursor of disability and frailty, 9,10 and have been detected in cancer survivors with high fatigability and low endurance performance, 11,12 factors consistent with accelerated aging. Thus, activity fragmentation may be a marker of a compromised physiological state and impending decline in health and functional status, making it a potential early target for intervention.
The primary objective of this study was to evaluate whether total daily physical activity and fragmentation of daily physical activity are associated with mortality among well-functioning older adults. We hypothesized that fragmentation of physical activity is more strongly associated with mortality than total daily activity. The secondary objective was to explore the duration of activity bouts, in association with mortality. We hypothesized that shorter, more fragmented bouts of activity, as opposed to longer bouts, are associated with higher mortality risk.

Study Design and Population
Data are from the Baltimore Longitudinal Study of Aging (BLSA), with mortality data collected between 2007 and 2017. Dates of analysis were November 2016 to June 2019. The BLSA is an ongoing study conducted by the National Institute on Aging Intramural Research Program. The BLSA's enrollment criteria and sample details have been published previously. 13  Only the activity data between 5:00 AM and 10:59 PM (deemed as the waking period) were considered. Three types of summary variables were created in the waking period: total active minutes, an activity fragmentation index, and total minutes spent in each of 3 different activity bout lengths (<5, 5-10, and Ն10 minutes). Total activity minutes were calculated by summing the number of active minutes and calculating the mean across wear days for each participant. Activity fragmentation was defined using the active-to-sedentary transition probability, calculated as the reciprocal of the mean activity bout length for each participant. To gain context of the patterns of bout lengths, active minutes spent in bouts of less than 5, 5 to 10, and 10 or more minutes were calculated. The shorter lengths were chosen on the basis of previous publications to represent short, medium, and long bouts of activity. 16 or renal insufficiency. Responses were summed and categorized into a morbidity index score (0, 1, and Ն2 morbid conditions).

Statistical Analysis
Accelerometer data were collected for 888 BLSA participants between 2007 and 2015. Among them, 849 participants had at least 3 days of valid accelerometer data required for analysis (days with <5% of data missing). 14 Those who were younger than age 65 years (284 participants), missing grip strength data (11 participants), and missing usual gait speed data (6 participants

Results
Of 548 participants in the final analytic sample, the mean (SD) age was 75.8 ( Table 2) but had diurnal patterns of activity similar to those of participants who survived (Figure). However, those similarities largely appeared between participants with low activity fragmentation. Participants with high activity fragmentation exhibited diminished activity throughout the day compared with participants with low activity fragmentation, particularly among participants who died (Figure). [13.7%]) than those who were alive at follow-up (Table 2).
In fully adjusted analyses, activity fragmentation, but not total daily activity, was associated with greater mortality risk (Table 3). Specifically, a greater number of hours spent physically active each day was not associated with lower mortality risk after adjusting for age, sex, race/ethnicity, body mass index, smoking history, employment, self-reported health, grip strength, usual gait speed, When examining time spent in bouts of activity, those who spent more time in shorter rather than longer activity bouts had greater mortality risk (   and time spent in the various bout lengths and mortality remained the same. After excluding individuals who died within 2 years of follow-up (12 deaths), all associations remained nearly identical.

Discussion
In well-functioning older adults, fragmentated daily physical activity is associated with higher mortality risk. Specifically, physical activity fragmented into higher proportions of activity bouts lasting less than 5 minutes appears to be associated with greater mortality risk. These patterns of physical activity appear to be more closely associated with mortality risk than a single measure of total volume of daily activity. Collectively, these results suggest that increasingly fragmented patterns of physical activity may be an early signal of diminished capacity that results in premature mortality.
To this end, capturing fragmentation of physical activity presents a sensitive phenotypic marker of the deterioration of free-living physical activity patterns associated with mortality.
Our study shows that total daily physical activity does not explicitly indicate mortality risk in well-functioning older adults who are free of major disability. This finding appears to be contradictory to published evidence supporting an inverse association between daily physical activity and mortality  Graph depicts activity counts (unitless quantities of movement collected through accelerometers) over time. Participants who remained alive accumulated higher amounts of physical activity compared with participants who died during the course of the study. However, participants with highly fragmented physical activity had compromised diurnal activity patterns, mostly notably seen among the participants who died. Physical activity fragmentation was dichotomized at the sample median of 26%. The mean (SD) fragmentation was 21% (3%) for 255 participants who were alive and had low fragmentation, 32% (4%) for 232 participants who were alive and had high fragmentation, 23% (3%) for 19 participants who were deceased and had low fragmentation, and 35% (7%) for 42 participants who were deceased and had high fragmentation.  in older adult populations. Although many of these studies 18-22 published evidence derived from using self-reported physical activity measures, more recent studies have also detected this association using objective measures of physical activity. Manini and colleagues 23 found that higher levels of free-living energy expenditure assessed with doubly labeled water (reference standard) was associated with a reduction in all-cause mortality in 302 high-functioning adults aged 70 to 82 years.

JAMA Network Open | Geriatrics
Using an activity monitor, Ensrud and colleagues 24 observed that less time spent in light-and moderate-intensity activities was associated with higher mortality risk in 2918 men aged 71 years and older. LaMonte and colleagues 25 found that daily accelerometer-measured physical activity at either light or moderate-to-vigorous intensity levels was associated with lower mortality in 6382 women aged 63 to 99 years. In 3029 men and women aged 50 to 79 years old, Fishman and colleagues 3 observed that higher volumes of total physical activity were associated with lower mortality, particularly explained by more time spent in both light and moderate-to-vigorous intensity physical activity. Although the results of our study support the magnitude and directionality of an inverse association between the amount of time spent in an active state and mortality, our findings did not achieve statistical significance. This is likely because BLSA participants were healthier and higher functioning than the general population of older adults. Together, our findings suggest that lower total physical activity among higher functioning older adults may not adequately represent increased risk of mortality.
In contrast, more fragmented daily activity appears to act as a more sensitive marker of mortality risk in healthier older adults. These results complement recent findings showing that physical activity is negatively associated with mortality, whereas sedentary time is positively associated with mortality risk. 21,26 The concept of activity fragmentation goes beyond traditional measures of active and sedentary time by using minute-by-minute data to capture the probability of transitioning from an active to a sedentary state in free-living settings. 7,8,11 Yet, the issue of whether deliberative or compensatory alterations in physical activity are associated with functional decline and accelerated mortality risk remains complex. Although current clinical-based functional assessments measure functional limitations, 9,27 ceiling effects limit their ability to assess higherorder physical functioning, such as endurance capacity, fatigability, or walking efficiency. [28][29][30][31] It is plausible that higher degrees of activity fragmentation may reflect important declines in functional capacity that limit individuals to shorter bout lengths of activity that current measurement tools cannot capture. Furthermore, activity fragmentation may capture diminished stamina, or the need to  rest once active that often accompanies declining functional status, 31 indicative of impending mortality. 27 Additionally, previous work by our group 32 observed that higher levels of fatigability are associated with diminished and delayed diurnal patterns of activity throughout the day and may partly explain trajectories toward premature mortality. Although these changes are largely attributable to physiological changes contributing to declines in physical function, psychological (eg, perception of the inability to climb stairs) and ecological (eg, use of elevator instead of stairs) factors contributing to activity fragmentation are possible. The current results suggest that activity fragmentation may reflect early and clinically meaningful declines in total physical activity and argue for further explorations of the underlying biological and physiological mechanisms of aging, including mitochondrial dysfunction, 33 cellular senescence, 34 and metabolic dysregulation. 35 Detecting activity fragmentation may serve as an important step toward prescribing and monitoring physical activity clinically. Bayán-Bravo and colleagues 36 showed that sedentary patterns predict greater mortality risk, whereas active patterns predict mortality risk reduction in 2851 adults aged 60 years and older. Also, Schmid and colleagues 4 showed that a combination of high sedentary time and low physical activity was associated with short-term mortality risk in 1677 adults aged 50 years and older. Furthermore, published evidence 2,16,37,38 shows that physical activity is typically performed in shorter rather than longer bouts of continuous activity in older adults. Our findings extend this work by providing activity fragmentation cut points that offer promising clinical utility, because fragmentation of activity into a higher number of bouts lasting less than 5 minutes, or a greater than 30% probability of transitioning into a sedentary state, may be a signal of declining functional status and impending mortality. Collectively, these results suggest that objective measures of activity fragmentation present a unique method of evaluating patterns of physical activity indicative of future health and mortality. In addition, current physical activity interventions for older adults largely focus on increasing structured physical activity at moderate or higher intensities but do little to prolong light-intensity activity engagement, particularly to reduce sedentary behavior. 17,39,40 Reducing fragmented patterns of physical activity fits well within the World Health

JAMA Network Open | Geriatrics
Organization's 2017 Integrated Care for Older People 41 guidelines as a novel opportunity to curb sedentary behaviors, complementary to-or possibly before-initiation of structured physical activity for the maintenance of health, intrinsic capacity, and well-being in older adults.

Limitations
Limitations of this study include the analytic sample being largely non-Hispanic white (72%), physical activity profiles measured at 1 time point, a sample of older adults who tend to be higher functioning than the general older adult population, and low numbers of mortality events. Strengths of the study include objectively measured physical activity patterns, reduced potential residual confounding of the association between physical activity and mortality associated with recruitment of a large sample of older adults without functional decline and major disease, and the adjustment of a wide range of covariates in the analyses.

Conclusions
In this cohort study of well-functioning adults aged 65 years and older, fragmented daily physical activity, particularly activity bouts lasting less than 5 minutes, was associated with greater mortality risk. Measures of activity fragmentation illuminate patterns of daily activity deterioration that occur with aging and disease, which potentially serve as early and sensitive markers of premature mortality.
Future research is needed to assess how longitudinal changes in activity fragmentation may estimate risk of morbidity and mortality.