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Background Daily physical activity patterns differ by Alzheimer's disease (AD) status and might signal cognitive risk. It is critical to understand whether patterns are disrupted early in the AD pathological process. Yet, whether established AD risk markers (β-amyloid [Aβ] or apolipoprotein E-ε4 [ APOE-ε4 ]) are associated with differences in objectively measured activity patterns among cognitively unimpaired older adults is unclear. Methods Wrist accelerometry, brain Aβ (+/−), and APOE-ε4 genotype were collected in 106 (Aβ) and 472 (APOE-ε4) participants (mean age 76 [standard deviation{ SD }: 8.5) or 75 [ SD : 9.2] years, 60% or 58% women) in the Baltimore Longitudinal Study of Aging. Adjusted linear and function-on-scalar regression models examined whether Aβ or APOE-ε4 status was cross-sectionally associated with activity patterns (amount, variability, or fragmentation) overall and by time of day, respectively. Differences in activity patterns by combinations of Aβ and APOE-ε4 status were descriptively examined (n  = 105). Results There were no differences in any activity pattern by Aβ or APOE-ε4 status overall. Aβ+ was associated with lower total amount and lower within-day variability of physical activity overnight and early evening, and APOE-ε4 carriers had higher total amount of activity in the evening and lower within-day variability of activity in the morning. Diurnal curves of activity were blunted among those with Aβ+ regardless of APOE-ε4 status, but only when including older adults with mild cognitive impairment/dementia. Conclusions Aβ+ in cognitively unimpaired older adults might manifest as lower amount and variability of daily physical activity, particularly during overnight/evening hours. Future research is needed to examine changes in activity patterns in larger samples and by other AD biomarkers. [ABSTRACT FROM AUTHOR]

Background Hearing loss is associated with restricted physical activity (PA) and impaired physical functioning, yet the relationship between severity of hearing impairment (HI) and novel PA measures in older adults with untreated HI is not well understood. Methods Analyses included 845 participants aged ≥70 years (mean = 76.6 years) with a better-hearing ear pure-tone average (PTA) ≥30 and <70 dB in the Aging and Cognitive Health Evaluation in Elders (ACHIEVE) study who wore an ActiGraph accelerometer for 7 days. Physical functioning measures included grip strength and the Short Physical Performance Battery (SPPB). Linear regression models estimated the association by HI level (moderate or greater [PTA ≥ 40 dB] vs mild [PTA < 40 dB]) and continuous hearing with total daily activity counts, active minutes/day, activity fragmentation, grip strength, and gait speed. Logistic regression models estimated odds ratios (ORs) and 95% confidence intervals (CIs) of poor performance on the SPPB (≤6) and its subtests (≤2). Mixed-effects models estimated differences by HI level in activity by time of day. Results Participants with moderate or greater HI had poorer physical functioning, particularly balance (OR = 2.17, 95% CI = 1.29–3.67), versus those with mild impairment. There was no association of HI level with activity quantities or fragmentation. For diurnal patterns of activity, participants with moderate or greater HI had fewer activity counts in the afternoon (12:00 pm –05:59 pm). Conclusions Older adults with worse hearing had shifted diurnal patterns and poorer balance performance. Exercise programs should be tailored to older adults with different levels of HI to maintain PA and physical functioning, particularly balance control. [ABSTRACT FROM AUTHOR]

Background Pain is associated with reports of restricted physical activity (PA), yet the association between musculoskeletal pain characteristics and objectively measured PA quantities and patterns in late life is not well understood. Methods A total of 553 adults (mean age 75.8 ± 8.4 years, 54.4% women) in the Baltimore Longitudinal Study of Aging (BLSA) completed a health interview and subsequent 7-day wrist-worn ActiGraph assessment in the free-living environment between 2015 and 2020. Pain characteristics, including pain presence in 6x sites (ie, shoulders, hands/wrists, low back, hip, knees, and feet), pain laterality in each site, and pain distribution were assessed. PA metrics were summarized into total daily activity counts (TAC), activity fragmentation, active minutes/day, and diurnal patterns of activity. Linear regression models and mixed-effects models examined the association between pain characteristics and PA outcomes, adjusted for demographics and comorbidities. Results Unilateral knee pain was associated with 184 070 fewer TAC (p  = .039) and 36.2 fewer active minutes/day (p  = .032) compared to those without knee pain. Older adults with shoulder pain or hand/wrist pain had more active minutes compared to those without pain (p  < .05 for all). For diurnal patterns of activity, participants with knee pain had fewer activity counts during the afternoon (12:00 pm to 5:59 pm). Analyses stratified by sex showed that these associations were only significant among women. Conclusions Our study highlights the importance of assessing pain laterality in addition to pain presence and suggests that pain interferes with multiple aspects of daily activity. Longitudinal studies are needed to assess the temporality of these findings. [ABSTRACT FROM AUTHOR]

Background Peripheral artery disease (PAD) is associated with lower physical activity but less is known about its association with daily patterns of activity. We examined the cross-sectional association between ankle–brachial index (ABI) and objectively measured patterns of physical activity among Hispanic/Latino adults. Methods We analyzed data from 7 688 participants (aged 45–74 years) in the Hispanic Community Health Study/Study of Latinos. ABI was categorized as low (≤0.90, indicating PAD), borderline low (0.91–0.99), normal (1.00–1.40), and high (>1.40, indicating incompressible ankle arteries). Daily physical activity metrics derived from accelerometer data included: log of total activity counts (LTAC), total log-transformed activity counts (TLAC), and active-to-sedentary transition probability (ASTP). Average differences between ABI categories in physical activity, overall and by 4-hour time-of-day intervals, were assessed using linear regression and mixed-effects models, respectively. Results In Hispanic/Latino adults, 5.3% and 2.6% had low and high ABIs, respectively. After adjustment, having a low compared to a normal ABI was associated with lower volume (LTAC = −0.13, p <.01; TLAC = −74.4, p =.04) and more fragmented physical activity (ASTP = 1.22%, p <.01). Having a low ABI was linked with more fragmented physical activity after 12 pm (p <.01). Having a high ABI was associated with lower volumes of activity (TLAC = −132.0, p =.03). Conclusions Having a low or high ABI is associated with lower and more fragmented physical activity in Hispanic/Latino adults. In adults with low ABI, physical activity is more fragmented in the afternoon to evening. Longitudinal research is warranted to expand these findings to guide targeted interventions for PAD or incompressible ankle arteries. [ABSTRACT FROM AUTHOR]

Background Wearable devices have become widespread in research applications, yet evidence on whether they are superior to structured clinic-based assessments is sparse. In this manuscript, we compare traditional, laboratory-based metrics of mobility with a novel accelerometry-based measure of free-living gait cadence for predicting fall rates. Methods Using negative binomial regression, we compared traditional in-clinic measures of mobility (6-minute gait cadence, speed, and distance, and 4-m gait speed) with free-living gait cadence from wearable accelerometers in predicting fall rates. Accelerometry data were collected with wrist-worn Actigraphs (GT9X) over 7 days in 432 community-dwelling older adults (aged 77.29 ± 5.46 years, 59.1% men, 80.2% White) participating in the Study to Understand Fall Reduction and Vitamin D in You. Falls were ascertained using monthly calendars, quarterly contacts, and ad hoc telephone reports. Accelerometry-based free-living gait cadence was estimated with the Adaptive Empirical Pattern Transformation algorithm. Results Across all participants, free-living cadence was significantly related to fall rates; every 10 steps per minute higher cadence was associated with a 13.2% lower fall rate (p  = .036). Clinic-based measures of mobility were not related to falls (p >.05). Among higher-functioning participants (cadence ≥100 steps/minute), every 10 steps per minute higher free-living cadence was associated with a 27.7% lower fall rate (p  = .01). In participants with slow baseline gait (gait speed <0.8 m/s), all metrics were significantly associated with fall rates. Conclusion Data collected from biosensors in the free-living environment may provide a more sensitive indicator of fall risk than in-clinic tests, especially among higher-functioning older adults who may be more responsive to intervention. Clinical Trial Registration NCT02166333 [ABSTRACT FROM AUTHOR]

Background Human motor function is optimised for energetic efficiency, however, age-related neurodegenerative changes affects neuromotor control of walking. Energy utilisation has been associated with motor performance, but its association with cognitive performance is unknown. Methods The study population included 979 Baltimore Longitudinal Study of Aging participants aged |$\ge$| 50 years (52% female, mean age: 70 |$\pm$| 10.2 years) with a median follow-up time of 4.7 years. Energy utilisation for walking was operationalised as a ratio of the energy cost of slow walking to peak walking energy expenditure during standardised tasks ('cost-ratio'). Cognitive functioning was measured using the Trail Making Tests, California Verbal Learning Test, Wechsler Adult Intelligence Scale (WAIS), letter and category fluency and card rotation tests. Linear mixed models adjusted for demographics, education and co-morbidities assessed the association between baseline cost-ratio and cognitive functioning, cross-sectionally and longitudinally. To investigate the relationship among those with less efficient energy utilisation, subgroup analyses were performed. Results In fully adjusted models, a higher cost-ratio was cross-sectionally associated with poorer performance on all cognitive tests except WAIS (P  < 0.05 for all). Among those with compromised energy utilisation, the baseline cost-ratio was also associated with a faster decline in memory (long-delay free recall: β  = −0.4, 95% confidence interval [CI] = [−0.8, −0.02]; immediate word recall: β  = −1.3, 95% CI = [−2.7, 0.1]). Conclusions These findings suggest cross-sectional and longitudinal links between energy utilisation and cognitive performance, highlighting an intriguing link between brain function and the energy needed for ambulation. Future research should examine this association earlier in the life course to gauge the potential for interventive mechanisms. [ABSTRACT FROM AUTHOR]

Background: Higher energetic costs for mobility are associated with declining gait speed, and slow gait is linked to cognitive decline and Alzheimer's disease. However, the physiological underpinnings of gait and brain health have not been well explored. We examined the associations of the energetic cost of walking with brain volume in cognitively unimpaired adults from the Baltimore Longitudinal Study of Aging.Methods: We used brain magnetic resonance imaging (MRI) data from 850 participants (mean baseline age 66.3 ± 14.5 years), of whom 451 had longitudinal MRI data (2.8 ± 1.0 MRI scans over 4.0 ± 2.0 years). The energetic cost of walking was assessed as the average energy expended (V̇O2) during 2.5 minutes of customary-paced overground walking. Multivariable linear mixed-effects models examined the associations between baseline energetic cost of walking and regional brain volumes adjusting for covariates.Results: At baseline, higher energetic cost of walking was cross-sectionally associated with lower gray and white matter volumes within the frontal, parietal, and temporal lobes, as well as hippocampal, total brain, and larger ventricular volumes (all false-discovery rate [FDR] p < .05). A baseline energetic cost of walking × time interaction demonstrated that participants with higher energetic cost of walking had faster annual decline in hippocampal volume (FDR p = .02) and accelerated annual increase in ventricular volumes (FDR p = .02).Conclusions: The energetic cost of walking is associated with gray and white matter volumes and subsequent hippocampal atrophy and ventricular enlargement. Collectively, these data suggest the energetic cost of walking may be an early marker of neurodegeneration that contributes to the gait brain connection. [ABSTRACT FROM AUTHOR]

Background: Self-reported low physical activity is a defining feature of phenotypic frailty but does not adequately capture physical activity performed throughout the day. This study examined associations between accelerometer-derived patterns of routine daily physical activity and frailty.Methods: Wrist accelerometer and frailty data from 638 participants (mean age 77 [SD = 5.5] years; 44% women) were used to derive 5 physical activity metrics: active minutes/day, sedentary minutes/day, total activity counts/day, activity fragmentation (reciprocal of the average active bout length), and sedentary fragmentation (reciprocal of the average sedentary bout length). Robust, prefrail, and frail statuses were identified using the physical frailty phenotype defined as having 0, 1-2, or ≥3 of the following criterion: weight loss, exhaustion, slowness, self-reported low activity, and weakness. Frailty was collapsed into not frail (robust and prefrail) and frail, and each frailty criteria was dichotomized. Multiple logistic regression was used to model each accelerometer metric. Separate frailty criteria and interactions with age and sex were also examined.Results: With higher amounts and intensity of daily activity (more active minutes, fewer sedentary minutes, higher activity counts) and lower activity fragmentation, the odds of frailty were lower compared to robust/prefrail states (p < .02 for all). For interactions, only an age by sedentary fragmentation interaction on the odds of frailty was observed (p = .01). For each separate criteria, accelerometer metrics were associated with odds of slowness, low activity, and weakness.Conclusion: Less favorable patterns of objectively measured daily physical activity are associated with frailty and the components of slowness, low self-reported activity, and weakness. [ABSTRACT FROM AUTHOR]

Context The Study to Understand Fall Reduction and Vitamin D in You (STURDY), a randomized trial enrolling older adults with low 25-hydroxyvitamin D [25(OH)D], demonstrated vitamin D supplementation ≥ 1000 IU/day did not prevent falls compared with 200 IU/day, with doses ≥ 2000 IU/day potentially showing safety concerns. Objective To examine associations of achieved and change in 25(OH)D concentrations after 3 months of vitamin D supplementation with fall risk. Design Observational analysis of trial data. Setting General community. Participants A total of 637 adults aged ≥ 70 with baseline 25(OH)D concentrations 10 to 29 ng/mL and elevated fall risk. Three-month on-treatment absolute 25(OH)D; absolute and relative changes from baseline. Main Outcome Measures Incident first fall (primary) and first consequential fall (injury or sought medical care) up to 24 months. Cox models were adjusted for sociodemographics, season, Short Physical Performance Battery, and body mass index. Results At baseline, mean (SD) age was 77.1 (5.4) years and 25(OH)D was 22.1 (5.1) ng/mL; 43.0% were women and 21.5% non-White. A total of 395 participants experienced ≥ 1 fall; 294 experienced ≥ 1 consequential fall. There was no association between absolute achieved 25(OH)D and incident first fall (30-39 vs < 30 ng/mL hazard ratio [HR], 0.93; 95% CI, 0.74-1.16; ≥40 vs < 30 ng/mL HR, 1.09; 95% CI, 0.82-1.46; adjusted overall P  = 0.67), nor absolute or relative change in 25(OH)D. For incident consequential first fall, the HR (95% CI) comparing absolute 25(OH)D ≥ 40 vs < 30 ng/mL was 1.38 (0.99-1.90). Conclusion Achieved 25(OH)D concentration after supplementation was not associated with reduction in falls. Risk of consequential falls may be increased with achieved concentrations ≥ 40 ng/mL. Trial Registration ClinicalTrials.gov: NCT02166333 [ABSTRACT FROM AUTHOR]

Background Vitamin D3 supplementation is considered a potential intervention to prevent orthostatic hypotension (OH) based on observational evidence that vitamin D levels are inversely associated with OH. With data from The Study to Understand Fall Reduction and Vitamin D in You (STURDY), a double-blind, randomized, response-adaptive trial, we determined if higher doses of vitamin D3 reduced risk of OH. Methods STURDY tested the effects of higher (1,000+ IU/day, i.e. 1,000, 2,000, and 4,000 IU/day combined) vs. lower-dose vitamin D3 (200 IU/day, comparison) on fall risk in adults ages 70 years and older with low serum 25-hydroxyvitamin D (25(OH)D, 10–29 ng/ml). OH was determined at baseline, 3, 12, and 24 months by taking the difference between seated and standing blood pressure (BP). OH was defined as a drop in systolic or diastolic BP of at least 20 or 10 mm Hg after 1 minute of standing. Participants were also asked about OH symptoms during the assessment and the preceding month. Results Among 688 participants (mean age 77 [SD, 5] years; 44% women; 18% Black), the mean baseline systolic/diastolic BP was 130 (19)/67 (11) mm Hg, serum 25(OH)D was 22.1 (5.1) ng/ml, and 2.8% had OH. There were 2,136 OH assessments over the maximum 2-year follow-up period. Compared with 200 IU/day, 1,000+ IU/day was not associated with seated, standing, or orthostatic BP, and it did not lower risk of OH or orthostatic symptoms. Conclusions These findings do not support use of higher doses of vitamin D3 supplementation as an intervention to prevent OH. Clinical trials registration Trial Number NCT02166333. [ABSTRACT FROM AUTHOR]

Background: Vision loss is associated with increased risk of falls and restricted physical activity, yet the relationship between multiple vision measures and objectively measured physical activity, especially activity patterns, in mid-to-late life is not well understood.Method: This study included 603 participants aged 50 years and older (mean age = 73.5) in the Baltimore Longitudinal Study of Aging who had the following assessments: presenting and best-corrected visual acuity, contrast sensitivity, visual fields, stereo acuity, and free-living physical activity using a wrist-worn ActiGraph accelerometer for 7 days. Linear regression models were used to examine the association between vision measures and daily activity counts, active minutes, and activity fragmentation (defined as an active-to-sedentary transition probability), adjusting for potential confounders. Mixed-effects models estimated differences in activity by time of day comparing those with and without each visual impairment.Results: In the fully adjusted model, worse presenting visual acuity, contrast sensitivity, and visual fields were associated with fewer activity counts, less active time, and more fragmented activity patterns (p < .05 for all). Participants with presenting or best-corrected visual acuity impairment had 19.2 and 29.3 fewer active minutes (p = .05 and p = .03, respectively) per day. Visual field impairment was associated with 268 636 fewer activity counts (p = .02), 46.2 fewer active minutes (p = .02) per day, and 3% greater activity fragmentation (p = .009). Differences in activity levels tended to be greatest from 6 am to 6 pm (p < .05).Conclusions: Older adults with visual impairment have restricted and more fragmented patterns of daily activity. Longitudinal studies to quantify the long-term impacts of visual impairments on activity decline are warranted. [ABSTRACT FROM AUTHOR]

Background: Physical activity becomes increasingly fragmented with age, which may be an early marker of functional decline. Energetic cost of walking and energy capacity are also linked with functional decline, but their associations with activity fragmentation, and the potential modifying roles of total daily physical activity and age, remains unclear.Method: A total of 493 participants (50-93 years) from the Baltimore Longitudinal Study of Aging underwent measures of energetic cost of usual-paced overground walking (mL/kg/m), energy demand during slow walking (mL/kg/min) on a treadmill (0.67 m/s, 0% grade), and average peak walking energy expenditure (mL/kg/min) during a fast-paced 400-m walk. A ratio of slow walking to peak walking energy expenditure ("cost-to-capacity ratio") was calculated. Activity fragmentation was quantified as an active-to-sedentary transition probability (ASTP) using Actiheart accelerometer data. Linear regression models with ASTP as the dependent variable were used to test whether poorer energy cost and capacity were associated with higher ASTP and whether the associations differed by daily physical activity or age.Results: After adjusting for demographics, body composition, comorbidities, and daily physical activity, every 10% higher cost-to-capacity ratio was associated with 0.4% greater ASTP (p = .005). This association was primarily driven by the least active participants (pinteraction = .023). Peak walking energy expenditure was only associated with ASTP among participants aged ≥70 years.Conclusions: Higher cost-to-capacity ratio and lower energy capacity may manifest as more fragmented physical activity, especially among those less active or aged ≥70 years. Future studies should examine whether an increasing cost-to-capacity ratio or declining energy capacity predicts subsequent activity fragmentation. [ABSTRACT FROM AUTHOR]

Background: Larger brain volumes are often associated with more free-living physical activity (PA) in cognitively normal older adults. Yet, whether greater brain volumes are associated with more favorable (less fragmented) PA patterns, and whether this association is stronger than with total PA, remains unknown.Methods: Brain magnetic resonance imaging and wrist-worn accelerometer data were collected in 301 participants (mean age = 77 [SD = 7] years, 59% women) enrolled in the Baltimore Longitudinal Study of Aging. Linear regression models were fit to examine whether brain volumes (cc) were cross-sectionally associated with: (a) total daily PA minutes and (b) activity fragmentation (mean number of PA bouts / total PA minutes × 100). Sensitivity analyses were conducted by adjusting for counterpart PA variables (eg, fragmentation covariate included in the PA minutes model).Results: Greater white matter volumes in the parietal and temporal lobes were associated with higher daily PA minutes (2.6 [SE = 1.0] and 3.8 [0.9] min/day, respectively; p < .009 for both) after adjusting for demographics, behavioral factors, medical conditions, gait speed, apolipoprotein E e4 status, and intracranial volume. Greater temporal white matter volume was associated with lower fragmentation (-0.16% [0.05], p = .003). In sensitivity analyses, observed associations between brain volumes and daily PA minutes remained significant while associations with fragmentation no longer remained significant.Conclusions: Our results suggest white matter brain structure in cognitively normal older adults is associated with the total amount of PA and, to a lesser extent, the PA accumulation patterns. More work is needed to elucidate the longitudinal relationship between brain structure and function and PA patterns with aging. [ABSTRACT FROM AUTHOR]

Previous work has shown that poorer mitochondrial function is associated with age-related perceived fatigability. However, whether glucose oxidation and anaerobic metabolism are intermediate factors underlying this association remains unclear. We examined the total cross-sectional association between mitochondrial function and perceived fatigability in 554 adults aged 22-99 years. Mitochondrial function was assessed by skeletal muscle oxidative capacity (kPCr) using 31P magnetic resonance spectroscopy. Perceived fatigability was measured by rating of perceived exertion after a 5-minute (0.67 m/s) treadmill walk. The intermediate role of glucose oxidation (measured by the rate of change of respiratory exchange ratio [RER change rate] during the 5-minute treadmill walk) and anaerobic metabolism (measured by ventilatory threshold [VeT] during a maximal treadmill test) was evaluated by examining their cross-sectional associations with kPCr and perceived exertion. For each 0.01/s lower kPCr, perceived fatigability was 0.47 points higher (p = .002). A 0.01/s lower kPCr was also associated with 8.3 L/min lower VeT (p < .001). Lower VeT was associated with higher fatigability at lower levels of kPCr but not at higher kPCr levels (β for interaction = 0.017, p = .002). kPCr and RER change rate were not significantly associated (p = .341), but a 0.01/min higher RER change rate was associated with 0.12-point higher fatigability (p = .001). Poorer mitochondrial function potentially contributes to higher perceived fatigability through higher glucose oxidation and higher anaerobic metabolism. Future studies to further explore the longitudinal mechanisms between these metabolic changes and fatigability are warranted. [ABSTRACT FROM AUTHOR]

The health benefits of physical activity (PA) have been widely recognized, yet traditional measures of PA, including questionnaires and category-based assessments of volume and intensity, provide only broad estimates of daily activities. Accelerometers have advanced epidemiologic research on PA by providing objective and continuous measurement of PA in free-living conditions. Wrist-worn accelerometers have become especially popular because of low participant burden. However, the validity and reliability of wrist-worn devices for adults have yet to be summarized. Moreover, accelerometer data provide rich information on how PA is accumulated throughout the day, but only a small portion of these rich data have been used by researchers. Last, new methodological developments are emerging that aim to overcome some of the limitations of accelerometers. In this review, we provide an overview of accelerometry research, with a special focus on wrist-worn accelerometers. We describe briefly how accelerometers work; summarize the validity and reliability of wrist-worn accelerometers; discuss the benefits of accelerometers, including measuring light-intensity PA; and discuss pattern metrics of daily PA recently introduced in the literature. A summary of large-scale cohort studies and randomized trials that implemented wrist-worn accelerometry is provided. We conclude the review by discussing new developments and directions of research using accelerometers, with a focus on wrist-worn accelerometers. [ABSTRACT FROM AUTHOR]

Background: Cognitive decline is consistently associated with diminished life satisfaction and inability to live independently. Identifying early, novel markers of cognitive decline is imperative for improving clinical detection and promoting long-term quality of life. Fatigability, one's perceived exertion after a standardized walking task, has been associated with declines in physical function; however, it remains unclear as to whether these effects may also extend to cognitive function.Methods: We examined whether perceived fatigability, assessed as the rating of perceived exertion (RPE) after a 5 min slow-paced treadmill walk (0.67 m/s, 0% grade), is longitudinally associated with cognitive performance in the domains of memory, executive functions, language, and attention among 934 cognitively intact individuals aged at least 50 years participating in the Baltimore Longitudinal Study of Aging (BLSA); Mage = 69.6 ± 10.1, 51.9% female participants. Continuous associations between RPE and each domain (individual test and composite scores) were assessed using linear mixed-effect models adjusted for demographics and comorbid conditions.Results: In fully adjusted models, higher fatigability at baseline was associated with declines in all cognitive domains over an average 2.2 years of follow-up (p < .04 for all). Longitudinally, increased fatigability over time was associated with worsened executive functions (β= -0.01, p = .002).Conclusions: These findings suggest that perceived fatigability after a standardized walking task may aid in identification of individuals at a higher risk of future cognitive decline. Future research should examine underlying biological mechanisms contributing to this relationship as well as whether future interventions may target fatigability in midlife to attenuate age-related cognitive decline. [ABSTRACT FROM AUTHOR]

Background: Deficits in energy production and utilization have been linked to higher fatigue and functional decline with aging. Lesser known is whether individuals with a combination of low peak energy capacity and high energy costs for mobility (eg, impaired energy regulation) are more likely to experience the onset and progression of high fatigability with aging.Methods: Participants in the Baltimore Longitudinal Study of Aging (n = 651, 49.0% male, mean age 71.9, range 50-94) with ≥2 visits who completed fatigability (Borg rating of perceived exertion [RPE] after a 5-minute 1.5 mph treadmill walk), slow walking energy expenditure (VO2 mL/kg/min), and peak walking energy expenditure (VO2 mL/kg/min), testing between 2007 and 2018. The longitudinal association between each measure of energy expenditure, a ratio of energy cost-to-capacity, and perceived fatigability was modeled using mixed effects models adjusted for age, body composition, and comorbidities. Time to higher perceived fatigability (RPE ≥ 10) was modeled using Cox proportional hazards models.Results: In continuous analyses, higher slow walking energy expenditure (p < .05) and a higher cost ratio (p ≤ .001) were associated with greater perceived fatigability over time. Cox proportional hazards models using tertiles of the cost ratio suggest that, compared to those in the lowest tertile, those in the middle and highest tertiles had 1.89 (95% confidence interval [CI]: 1.57-5.16) and 2.85 (95% CI: 1.05-3.40) times greater risk of developing higher fatigability, respectively.Conclusion: Findings suggest that strategies to prevent fatigability should consider methods to improve energy regulation by targeting both the independent and combined effects of declining peak capacity and rising energy costs for mobility with aging. [ABSTRACT FROM AUTHOR]

Background: Poor sleep may increase the likelihood of fatigue, and both are common in later life. However, prior studies of the sleep-fatigue relationship used subjective measures or were conducted in clinical populations; thus, the nature of this association in healthier community-dwelling older adults remains unclear. We studied the association of actigraphic sleep parameters with perceived fatigability-fatigue in response to a standardized task-and with conventional fatigue symptoms of low energy or tiredness.Methods: We studied 382 cognitively normal participants in the Baltimore Longitudinal Study of Aging (aged 73.1 ± 10.3 years, 53.1% women) who completed 6.7 ± 0.9 days of wrist actigraphy and a perceived fatigability assessment, including rating of perceived exertion (RPE) after a 5-minute treadmill walk or the Pittsburgh Fatigability Scale (PFS). Participants also reported non-standardized symptoms of fatigue.Results: After adjustment for age, sex, race, height, weight, comorbidity index, and depressive symptoms, shorter total sleep time (TST; <6.3 hours vs intermediate TST ≥6.3 to 7.2 hours) was associated with high RPE fatigability (odds ratio [OR] = 2.56, 95% confidence interval [CI] = 1.29, 5.06, p = .007), high PFS physical (OR = 1.88, 95% CI = 1.04, 3.38, p = .035), and high mental fatigability (OR = 2.15, 95% CI = 1.02, 4.50, p = .044), whereas longer TST was also associated with high mental fatigability (OR = 2.19, 95% CI = 1.02, 4.71, p = .043). Additionally, longer wake bout length was associated with high RPE fatigability (OR = 1.53, 95% CI = 1.14, 2.07, p = .005), and greater wake after sleep onset was associated with high mental fatigability (OR = 1.14, 95% CI = 1.01, 1.28, p = .036).Conclusion: Among well-functioning older adults, abnormal sleep duration and sleep fragmentation are associated with greater perceived fatigability. [ABSTRACT FROM AUTHOR]

Background: Chronically elevated interleukin-6 (IL-6) levels contribute to fatigue and functional decline via multiple pathways that often lead to frailty. Lesser known is the contribution of IL-6 to fatigue in relation to a standardized workload (fatigability), a precursor to functional decline. Therefore, the purpose of this study was to examine the longitudinal relationship between IL-6 and fatigability.Methods: About 985 participants from the Baltimore Longitudinal Study of Aging (mean age: 70 ± 10 years) were evaluated every 1-4 years. IL-6 was measured in fasting serum samples at each visit and log-transformed for analyses. Perceived fatigability (PF) was defined as self-reported exertion (rate of perceived exertion; RPE) after a 5-min, 0.67 m/s, 0% grade treadmill walk. Continuous and categorical associations between IL-6 (baseline and repeated measures) and PF were assessed using generalized estimating equations, adjusting for demographics, behavioral factors, and comorbid conditions.Results: In fully adjusted continuous models, twofold higher baseline IL-6 was associated with a 0.28 higher RPE (p = .03). This relationship tended to remain constant annually (baseline log IL-6 by time interaction p = .29). To provide clinical relevance, the sample median (3.7 pg/mL) was used to examine high versus low IL-6 levels. Over time, the high group reported an average 0.25 higher RPE (p = .03) than the low group. Annual change in logged IL-6 was not associated with annual change in PF (p = .48).Conclusion: Findings suggest that elevated IL-6 is a biomarker of physiological dysregulation associated with greater fatigability, but there is no longitudinal association between IL-6 and fatigability. Future studies should evaluate whether interventions that aim to reduce inflammation also attenuate fatigability. [ABSTRACT FROM AUTHOR]

Background: With aging, daily physical activity (PA) becomes less frequent and more fragmented. Accumulation patterns of daily PA-including transitions from active-to-sedentary behaviors-may provide important insights into functional status in older, less active populations.Methods: Participants of the Baltimore Longitudinal Study of Aging (n = 680, 50% male, aged 27-94 years) completed a clinical assessment and wore an Actiheart accelerometer. Transitions between active and sedentary states were modeled as a probability (Active-to-Sedentary Transition Probability [ASTP]) defined as the reciprocal of the average PA bout duration. Cross-sectional associations between ASTP and gait speed (m/s), fatigability (rating-of-perceived-exertion [RPE]), 400 m time (seconds), and expanded short physical performance battery score were modeled using linear and logistic regression, adjusted for chronic conditions. Further analyses explored the utility of ASTP over-and-above total daily PA.Results: In continuous models, each 0.10-unit higher ASTP was associated slower gait (β = -0.06 m/s, SE = 0.01), higher fatigability (β = 0.60 RPE, SE = 0.12), slower 400 m time (β = 16.31 s, SE = 2.70), and lower functioning (β = -0.13 expanded short physical performance battery score, SE = 0.03; p < .001). In categorical analyses, those in the highest tertile of ASTP were >2 times more likely to have high fatigability (rating of perceived exertion ≥10), slow 400 m time (>300 seconds) and reduced functional performance (expanded short physical performance battery score < 3.07) than those in the lowest tertile (p < .01). Further analyses demonstrated ASTP provided additional insight into functional outcomes beyond total daily PA.Conclusion: Fragmented daily PA-as measured by ASTP-is strongly linked with measures of health and functional status and may identify those at risk of high fatigability and reduced functional performance over and above traditional PA metrics. [ABSTRACT FROM AUTHOR]

Background: Fatigability, defined as fatigue in relation to a standardized task, predicts functional decline in older adults independent of reported tiredness or energy level. Although the sensation of fatigue, tiredness, and energy level adversely affect physical activity (PA), the association between fatigability and objectively measured PA is unknown.Methods: Participants in the Baltimore Longitudinal Study of Aging (n = 557, 50% women, aged 50-97 years) were instructed to wear an Actiheart accelerometer for 7 consecutive days in the free-living environment. Perceived fatigability was assessed using the Borg rating of perceived exertion (RPE) after 5 minutes of treadmill walking at 1.5 mph (0.67 m/s) and categorized as low (6-7 RPE), intermediate (8-9 RPE), and high (10+ RPE) fatigability. Time-of-day PA differences between fatigability groups were assessed using mixed-effects modeling.Results: Total daily PA was 1.3% lower for every unit increment in perceived fatigability after adjusting for demographic, behavioral, and medical factors (p = .01). In time-of-day analyses, the high fatigability group was less active compared to the low fatigability group throughout the day (8:00 am to 8:00 pm) and the intermediate fatigability group in the morning (8:00 am to 12:00 pm). Patterns of PA within the high fatigability group differed from both the intermediate and low groups in the morning but mirrored the intermediate group in the afternoon and evening.Discussion: These results suggest that RPE is a bio-marker of fatigability associated with progressively lower PA with aging. Whether the effects of fatigability occurring at the end of the day reflect waning energy levels or a voluntary choice that could be modified remains to be evaluated. [ABSTRACT FROM AUTHOR]