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Background To enhance the precision of measuring, analyzing, and forecasting care needs for older adults with physical and/or mental disabilities, we developed the Physical Disability Index (PDI) and Mental Disability Index (MDI). Furthermore, we evaluated the reliability and validity of the PDI and MDI. Additionally, we investigate their associations with falls to further indicate the predictive validity. Methods A total of 11 621 older adults (53.1% women; mean age = 83.2; SD  = 10.8) from 23 provinces in China were investigated in 2017–2018 to assess the reliability and validity of the PDI and MDI among older adults aged 65 to 105. Among which, 6 071 older adults with both baseline (2017–2018) and follow-up (2021) data were included in analyses to evaluate associations between the baseline health status determined by PDI and MDI and the number and severity of falls at baseline and follow-up. Cronbach's alpha was used to determine internal consistency. The convergent and divergent validity, known-group validity and concurrent validity were assessed. Multinomial logistic regression models were utilized to assess associations. Results We found satisfactory internal consistency (Cronbach's alpha ≥ 0.70) of the PDI and MDI in the total sample and sex-specific subgroups. Our results support the convergent and divergent validity, known-group validity, and concurrent validity of the PDI and MDI. We also found baseline physical disability and comorbid physical and mental disability are associated with a higher risk of baseline and follow-up falls. Conclusions The PDI and MDI are reliable and valid instruments to assess physical and mental disability status among older adults, respectively. [ABSTRACT FROM AUTHOR]

Background Chronic pain has been associated with accelerated biological aging, which may be related to epigenetic alterations. We evaluated the association of high-impact pain (ie, pain that limits activities and function) with epigenetic aging, a measure of biological aging, in a nationally representative sample of middle-aged and older adults in the United States. Methods Cross-sectional analysis of adults 50 years of age and older from the 2016 Health and Retirement Study. Epigenetic aging was derived from 13 epigenetic clocks based on DNA methylation patterns that predict aging correlates of morbidity and mortality. Ordinary least squares regressions were performed to test for differences in the epigenetic clocks, adjusting for the complex survey design, as well as biological, social, and behavioral factors. Results The analysis consisted of 3 855 adults with mean age of 68.5 years, including 59.8% with no pain and 25.8% with high-impact pain. Consistent with its operational definition, high-impact pain was associated with greater functional and activity limitations. High-impact pain was associated with accelerated epigenetic aging compared to no pain, as measured via second (Zhang, PhenoAge, GrimAge) and third (DunedinPoAm) generation epigenetic clocks. Additionally, GrimAge was accelerated in high-impact pain as compared to low-impact pain. Conclusions High-impact pain is associated with accelerated epigenetic aging among middle-aged and older adults in the United States. These findings highlight aging-associated epigenetic alterations in high-impact chronic pain and suggest a potential for epigenetic therapeutic approaches for pain management and the preservation of physical function in older adults. [ABSTRACT FROM AUTHOR]

Background Neighborhood walkability may encourage greater out-of-home travel (ie, community mobility) to support independent functioning in later life. We examined associations between a novel walkability audit index and Global Positioning System (GPS)-derived community mobility in community-dwelling older adults. We compared associations with the validated Environmental Protection Agency (EPA) National Walkability Index and further examined moderation by clinical walking speed. Methods Participants were 146 older adults (Mean  = 77.0 ± 6.5 years, 68% women) at baseline of a randomized trial to improve walking speed. A walkability index (range: 0–5; eg, land-use mix, crosswalks, and so on) was created using Google Street View audits within 1/8-mile of the home. Participants carried a GPS device for 5–7 days to derive objective measures of community mobility (eg, time spent out of home, accumulated distance from home). Results Each 1 SD (~1.3-point) greater walkability audit score was associated with a median 2.16% more time spent out of home (95% confidence interval [95% CI]: 0.30–4.03, p  = .023), adjusting for individual demographics/health and neighborhood socioeconomic status. For slower walkers (4-m walking speed <1 m/s), each 1 SD greater audit score was also associated with a median 4.54 km greater accumulated distance from home (95% CI: 0.01–9.07, p (interaction) = .034). No significant associations were found for the EPA walkability index. Conclusions Walkability immediately outside the home was related to greater community mobility, especially for older adults with slower walking speeds. Results emphasize the need to consider the joint influence of local environment and individual functioning when addressing community mobility in older populations. [ABSTRACT FROM AUTHOR]

Background Frailty is associated with urinary and fecal incontinence, which are common geriatric syndromes. This study aims to identify health factors associated with incontinence in prefrail or frail older adults living in the community. Methods This multicenter cross-sectional study included 225 older adults (75.0 ± 6.4 years) with prefrailty or frailty based on the 5-component Fried phenotype. Physical function was assessed using the Short Physical Performance Battery (SPPB). Physical activity, inactivity, and sleep were estimated using a wrist-worn accelerometer. Urinary or fecal incontinence was registered using the Barthel scale (urine and bowel items). Multivariable logistic regression analyses, with age as a covariate, were conducted to identify associations of incontinence. Results In our participants, 27% presented urinary or fecal incontinence with no sex differences (p  = .266). Our results showed that age, daily medication count, and number of falls in the previous year independently predicted incontinence in frail and prefrail older adults (p  < .05). Some Fried's criteria, including self-reported exhaustion, gait speed, and handgrip strength, were associated with the presence of incontinence (p  < .05), but not Fried's classification. The SPPB total score and its isolated variables were significantly associated with the urinary and fecal incontinence (p  < .05). However, none of the accelerometer outcomes showed significant associations with incontinence status. Conclusions According to this study, age, number of medications, and falls (but not sex) are linked to urinary and fecal incontinence in frail or prefrail older adults living in the community, recommending the assessment of physical function using the SPPB rather than estimating daily physical activity, inactivity, or sleep. [ABSTRACT FROM AUTHOR]

Background Gait impairment leads to increased mobility decline and may have neurological contributions. This study explores how neurological biomarkers are related to gait in older adults. Methods We studied participants in the Cardiovascular Health Study, a population-based cohort of older Americans, who underwent a serum biomarker assessment from samples collected in 1996–1997 for neurofilament light chain (NfL), glial fibrillary acidic protein, ubiquitin carboxy-terminal hydrolase L1, and total tau (n  = 1 959, mean age = 78.0 years, 60.8% female). In a subsample (n  = 380), cross-sectional associations with quantitative gait measures were explored. This subsample was assessed on a mat for gait speed, step length, double support time, step time, step length variability, and step time variability. Gait speed was also measured over a 15-ft walkway annually from 1996–1997 to 1998–1999 for longitudinal analyses. Linear regression models assessed cross-sectional associations of biomarkers with gait measures, whereas mixed effects models assessed longitudinal gait speed change from baseline to 1998–1999. Results Neurofilament light chain was significantly associated with annual gait speed decline (standardized β = −0.64 m/s, 95% CI: [−1.23, −0.06]) after adjustment for demographic and health factors. Among gait mat-assessed phenotypes, NfL was also cross-sectionally associated with gait speed (β = 0.001 m/s [0.0003, 0.002]) but not with other gait measures. None of the remaining biomarkers were significantly related to gait in either longitudinal or cross-sectional analyses. Conclusions Higher NfL levels were related to greater annual gait speed decline. Gait speed decline may be related to axonal degeneration. The clinical utility of NfL should be explored. [ABSTRACT FROM AUTHOR]

Background Muscle mass loss may be associated with liver fat accumulation, yet scientific consensus is lacking and evidence in older adults is scant. It is unclear which muscle characteristics might contribute to this association in older adults. Methods We associated comprehensive muscle-related phenotypes including muscle mass normalized to body weight (D3-creatine dilution), muscle fat infiltration (magnetic resonance imaging), carbohydrate-supported muscle mitochondrial maximal oxidative phosphorylation (respirometry), and cardiorespiratory fitness (VO2 peak) with liver fat among older adults. Linear regression models adjusted for age, gender, technician (respirometry only), daily minutes of moderate-to-vigorous physical activity, and prediabetes/diabetes status tested main effects and interactions of each independent variable with waist circumference (high: women—≥88 cm, men—≥102 cm) and gender. Results Among older adults aged 75 (interquartile range: 73, 79 years; 59.8% women), muscle mass and liver fat were not associated overall (N  = 362) but were positively associated among participants with a high waist circumference (β: 25.2; 95% confidence intervals [95% CI]: 11.7, 40.4; p  = .0002; N  = 160). Muscle fat infiltration and liver fat were positively associated (β: 15.2; 95% CI: 6.8, 24.3; p  = .0003; N  = 378). Carbohydrate-supported maximum oxidative phosphorylation (before adjustment) and VO2 peak (after adjustment; β: −12.9; 95% CI: −20.3, −4.8; p  = .003; N  = 361) were inversely associated with liver fat; adjustment attenuated the estimate for maximum oxidative phosphorylation although the point estimate remained negative (β: −4.0; 95% CI: −11.6, 4.2; p  = .32; N  = 321). Conclusions Skeletal muscle-related characteristics are metabolically relevant factors linked to liver fat in older adults. Future research should confirm our results to determine whether trials targeting mechanisms common to liver and muscle fat accumulation are warranted. [ABSTRACT FROM AUTHOR]

Background The burden of metabolic dysfunction-associated steatotic liver disease (MASLD) is growing rapidly, including among older adults. The number of older adults is also rising with concomitantly increasing rates of age-related physical and cognitive dysfunction. However, data on whether MASLD affects physical and cognitive function in older adults is limited. As such, we aimed to identify whether prevalent MASLD influences the risk of incident physical disability or dementia in initially healthy older adults. Methods A post-hoc analysis of participants from the ASPREE-XT cohort study, which recruited community-dwelling older adults without a history of cardiovascular disease, dementia, or independence-limiting functional impairment. The Fatty Liver Index (to identify MASLD) was calculated in those with complete data. Cox proportional-hazards models were used to investigate the outcomes of dementia and persistent physical disability in participants with MASLD vs those without. Results Of the 9 097 individuals included (mean age 75.1 ± 4.2 years; 45.0% men), 341 (3.7%) developed persistent physical disability and 370 (4.1%) developed dementia over a median follow-up of 6.4 years (IQR 5.3–7.5 years). When adjusting for known contributors including age, gender, education, comorbidity, and functional measures, MASLD was associated with an increased risk of persistent physical disability (HR 1.41 [95% CI: 1.07–1.87]) and reduced risk of incident dementia (HR 0.63 [95% CI: 0.48–0.83]). Conclusions Prevalent MASLD is associated with reduced rates of incident dementia but increased risk of persistent physical disability in initially relatively healthy older adults. Understanding the mechanisms underlying these divergent results to allow appropriate risk stratification and counseling is important. [ABSTRACT FROM AUTHOR]

Background This study examined the relation between declines in physical and cognitive performance in older people. Methods A population-based cohort of 7 483 adults (average age 72 years) were interviewed. Physical performance was assessed with 3 standardized tests and a combination of 4 cognitive tests was used to assess cognitive function. Rate of change in physical and cognitive performance was determined for each interval between interviews. In mixed effects linear regression models adjusted for age, sex, race, and study time, and change in each factor was used to predict change in the other factor. We examined time associations by using changes in the predictor measured at 1, 2, or 3 intervals before the outcome change. Results Decline in cognitive function was most strongly predicted by physical decline in the same 3-year interval. The decline in cognitive function was weaker in the 1-time interval after the decline in physical function and was not significant in later intervals. When a decline in cognitive function was used to predict a decline in physical function, the results were similar. The strongest association occurred in the same time interval so that declines in cognitive and physical performance tend to occur together. Conclusions Decline in cognition and physical function seem to occur together in a short timeframe. It is important to investigate the reasons for these changes that are short-term to guide the development of interventions. [ABSTRACT FROM AUTHOR]

Studies in mice and cross-sectional studies in humans support the premise that cellular senescence is a contributing mechanism to age-associated deficits in physical function. We tested the hypotheses that circulating proteins secreted by senescent cells are (i) associated with the incidence of major mobility disability (MMD), the development of persistent mobility disability (PMMD), and decrements in physical functioning in older adults, and (ii) influenced by physical activity (PA). Using samples and data obtained longitudinally from the Lifestyle Interventions in Elders Study clinical trial, we measured a panel of 27 proteins secreted by senescent cells. Among 1 377 women and men randomized to either a structured PA intervention or a healthy aging (HA) intervention, we observed significant associations between several senescence biomarkers, most distinctly vascular endothelial growth factor A (VEGFA), tumor necrosis factor receptor 1 (TNFR1), and matrix metallopeptidase 7 (MMP7), and the onset of both MMD and PMMD. Moreover, VEGFA, GDF15, osteopontin, and other senescence biomarkers were associated with reductions in short physical performance battery scores. The change in senescence biomarkers did not differ between PA and HA participants. In the whole cohort, higher levels of PA were associated with significantly greater reductions in 10 senescence-related proteins at 12 and/or 24 months. These data reinforce cellular senescence as a contributing mechanism of age-associated functional decline and the potential for PA to attenuate this hallmark of aging. Clinical Trials Registration Number: NCT01072500 [ABSTRACT FROM AUTHOR]

Background Social support predicts functional and cognitive decline in aging. Yet, the associations between social support and gait speed decline—a functional vital sign—are not well understood. This study examined associations between social support and gait speed decline in aging. Methods Social support and gait data from 542 older adults without dementia were examined (mean age 76.1 ± 6.5 years). Baseline emotional support, tangible support, affectionate support, positive social interactions, and overall support from the Medical Outcomes Study Social Support Survey were the predictors of interest. Annual change in simple (normal pace walking) and complex (walking while reciting alternate letters of the alphabet) gait speed (cm/s) were the outcomes of interest. Linear mixed effects models examined associations between social support and gait speed decline, after adjusting for gender, race, depressive symptoms, overall cognition, and comorbidities. Results The mean annual change in gait speed was 1.8 cm/s during simple walking and 1.13 cm/s during complex walking. Tangible support was the only category of social support that predicted decline in simple and complex gait speed over a median follow-up of 3 years. The annual decline in gait speed was 0.51 cm/s (p  = .008, 95% confidence intervals [CI] 0.13, 0.89) and 0.58 cm/s (p  = .007, CI 0.16, 1.0) greater among those with low tangible support than in those with high tangible support during simple and complex walking, respectively. Conclusions Tangible support is a potentially modifiable risk factor for gait speed decline. Further study is needed to examine mechanisms behind the observed associations and the potential for intervention. [ABSTRACT FROM AUTHOR]

Background Poor motor function is associated with brain atrophy and cognitive impairment. Less is known about the relationship between motor domains and brain atrophy and whether associations are affected by cerebrovascular burden and/or physical activity. Methods We analyzed data from 726 Baltimore Longitudinal Study of Aging participants (mean age 70.6 ± 10.1 years, 56% women, 27% Black), 525 of whom had repeat MRI scans over an average of 5.0 ± 2.1 years. Two motor domains, manual dexterity and gross motor, were operationalized as latent variables. Associations between the latent variables and cortical and subcortical brain volumes of interest were examined using latent growth curve modeling, adjusted for demographics, white matter hyperintensities, and physical activity. Results Both higher manual dexterity and gross motor function were cross-sectionally associated with smaller ventricular volume and greater white matter volumes in the frontal, parietal, and temporal lobes (all p  < .05). Manual dexterity was also cross-sectionally associated with parietal gray matter (B  = 0.14; 95% CI: 0.05, 0.23), hippocampus (B  = 0.10; 95% CI: 0.01, 0.20), postcentral gyrus (B  = 0.11; 95% CI: 0.01, 0.20), and occipital white matter (B  = 0.10; 95% CI: 0.01, 0.21) volumes, and gross motor function with temporal gray matter volume (B  = 0.16; 95% CI: 0.05, 0.26). Longitudinally, both higher manual dexterity and gross motor function were associated with less temporal white matter and occipital gray matter atrophy (all p  < .05). Manual dexterity was also associated with a slower rate of ventricular enlargement (B  = −0.17; 95% CI: −0.29, −0.05) and less atrophy of occipital white matter (B  = 0.39; 95% CI: 0.04, 0.71). Conclusions Among cognitively normal middle- and older-aged adults, manual dexterity and gross motor function exhibited shared as well as distinct associations with brain atrophy over time. [ABSTRACT FROM AUTHOR]

Background Frailty can occur in older adults without disability or multimorbidity. Current methods focus on the most frail, but poorly discriminate among those "not frail." Methods The Study of Muscle, Mobility, and Aging (SOMMA) included 879 adults aged 70 years and older without mobility disability. We operationalized frailty domains using: peak oxygen consumption (endurance), digit symbol substitution test (speed), leg power (strength), perceived fatigability, D3 creatine dilution (sarcopenia), and accelerometry (sedentary behavior) to construct a frailty score of 0–12 summing tertiles (0–2) of each component. We used linear or logistic regression with and without adjustment for confounders to examine associations with age, reported, and performance function. Results The SOMMA frailty score distribution was broad and strongly associated with age (r  = 0.33, p  < .0001). Each point was associated with a 30%–50% higher odds of having reported difficulty with activities of daily living or mobility. After grouping the total score (0–3, 4–7, and 8–12) those in the highest group were 9–31 times more likely to have functional limitation, and at least 8 times more likely to have poorer function after full adjustment. Higher scores identified those less likely to report ease of walking or higher physical activity. Peak oxygen consumption, leg power, fatigability, and digit symbol score contributed most to these associations. Conclusions The SOMMA frailty score characterizes frailty as a continuum from frail to vigorous with assessments that are amenable to change. Associations with age and function suggest utility for distinguishing a wide range of vigor and vulnerability in relatively well-functioning older adults. [ABSTRACT FROM AUTHOR]

Background Older adults reporting higher energy levels have better physical function. It is not known if these associations persist among older adults reporting fatigue or if higher energy is associated with cognitive function. We examined longitudinal associations between self-reported energy, gait speed, and cognition, stratified by fatigue, in 2 613 participants (aged 74.6 ± 2.87 years) in the Health, Aging and Body Composition Study. Methods Self-reported energy (0–10, dichotomized at median) and fatigue (present/absent) were measured at baseline. Usual and rapid-paced gait speed (m/s), modified Mini-Mental State Examination (3MS), and Digit Symbol Substitution Test (DSST) were measured at baseline and annually over 8 years. Linear mixed effect models compared changes in gait speed, 3MS, and DSST between higher and lower energy groups within fatigue strata. Results At baseline, 724 participants (27%) were fatigued; 240 (33%) coreported higher energy (9% of total). The remaining 1 889 participants were fatigue-free (73%); 1 221 (65%) coreported higher energy (47% of total). Those with fatigue and higher energy had average rapid gait declines of 0.007 m/s per year (p  = .04) after adjustment for demographics, comorbidities, depressive symptoms, and exercise. DSST declines were found among only fatigue-free participants (β = 0.17, p  = .01). No statistically significant associations with energy were found for fatigue-free participants, or for usual gait or 3MS. Conclusions Asking about older adults' energy levels as well as fatigue may identify a subgroup of older adults protected against physical and cognitive decline, even among those with fatigue. [ABSTRACT FROM AUTHOR]

Background Older adults with discordant biological and chronological ages (BA and CA) may vary in cognitive and physical function from those with concordant BA and CA. Methods To make our approach clinically accessible, we created easy-to-interpret participant groups in the Health, Aging, and Body Composition Study (N  = 2 458, 52% female participants, 65% White participants, age: 73.5 ± 2.8) based on medians of CA, and a previously validated BA index comprised of readily available clinical tests. Joint models estimated associations of BA–CA group with cognition (Modified Mini-Mental State Examination [3MS] and Digit Symbol Substitution Test [DSST]) and frailty over 10 years. Results The sample included the following: 32%, Young group (BA and CA < median); 21%, Prematurely Aging group (BA ≥ median, CA < median), 27%, Old group (BA and CA ≥ median), and 20%, Resilient group (BA < median, CA ≥ median). In education-adjusted models of cognition, among those with CA < median, the Prematurely Aging group performed worse than the Young at baseline (3MS and DSST p  < .0001), but among those with CA ≥ median, the Resilient group did not outperform the Old group (3MS p  = .31; DSST p  = .25). For frailty, the Prematurely Aging group performed worse than the Young group at baseline (p  = .0001), and the Resilient group outperformed the Old group (p  = .003). For all outcomes, groups did not differ on change over time based on the same pairwise comparisons (p  ≥ .40). Conclusions Discordant BA and CA identify groups who have greater cognitive and physical functional decline or are more protected than their CA would suggest. This information can be used for risk stratification. [ABSTRACT FROM AUTHOR]

Background Based on studies from animal models, growth differentiation factor-11 (GDF-11) may have rejuvenating effects in humans. GDF-11 has high sequence homology with GDF-8 (also known as myostatin); follistatin and follistatin-like protein-3 (FSTL-3) are inhibitory proteins of both GDF-8 and GDF-11. Methods Using highly specific liquid chromatography with tandem mass spectrometry assays for GDF-11 and GDF-8 and immunoassays for follistatin and FSTL-3, we quantified the association of these factors with muscle size, strength, and physical performance in 2 prospective cohort studies of community-dwelling older adults (Health, Aging, and Body Composition study [Health ABC] and Cardiovascular Health Study [CHS]). Results GDF-8 levels were positively associated with thigh muscle cross-sectional area and density in Health ABC (data not available in CHS). GDF-8 levels were positively associated with lean mass (a surrogate of muscle mass) in Health ABC but not CHS, and grip strength in CHS but not Health ABC. FSTL-3 (and perhaps follistatin) was negatively associated with lean mass and had variable associations with other variables. In contrast, GDF-11 was not significantly associated with strength or performance. Conclusions GDF-8 and its binding proteins, follistatin and FSTL-3, may constitute a counterregulatory system (chalones) to restrain age-related loss of muscle mass and strength. [ABSTRACT FROM AUTHOR]

Background: Multisystem dysregulation (Dm) shows promise as a metric of aging and predicts mortality. However, Dm needs to be studied with less severe endpoints indicating modifiable aging stages. Physical function, reflecting healthy longevity rather than just longevity, is more relevant to the goals of geroscience but has not been well investigated.Methods: We tested the association of midlife Dm and its change over ~20 years with physical function in later life in 5,583 ARIC cohort participants (baseline mean age 54.7). Dm quantifies the multivariate statistical deviation of 17 physiologically motivated biomarkers relative to their distribution in a young healthy sample at baseline. Physical function was assessed from grip strength and the Short Physical Performance Battery (SPPB). Associations were quantified using linear regression and ordinal logistic regression adjusting for age, sex, race, and education.Results: Each unit increment in midlife Dm was associated with 1.71 times the odds of having a lower SPPB score. Compared to the 1 st quartile of midlife Dm, the odds ratios of having a lower SPPB score were 1.25, 1.56, and 2.45, respectively, for the 2 nd-4 th quartiles. Similar graded association patterns were observed for each SPPB component test and grip strength. An inverse monotonic relationship also was observed between annual growth rate of Dm and physical function.Conclusions: Greater multisystem dysregulation and progression in midlife were associated with lower physical function in later life. Future studies on the factors that lead to progression of multisystem dysregulation may highlight opportunities to preserve physical function. [ABSTRACT FROM AUTHOR]

Background To evaluate whether contrast sensitivity is associated with lower extremity physical function in cognitively intact older adults. Methods Cross-sectional analysis of the relationship of binocular and worse eye log contrast sensitivity (LCS) to expanded Short Physical Performance Battery (eSPPB) and its components (gait speed, narrow walking speed, chair stand pace, and balance) in 192 cognitively healthy older adults. The association of LCS with postural sway and gait was also tested with tasks that further challenged functional reserve. Results Mean age was 76.4 years with 56% identifying as female and over 98.5% having good corrected visual acuity. Lower LCS was significantly associated with worse performance on the eSPPB, 4-M gait speed, narrow walking speed, and balance time in unadjusted and adjusted models. The relationship between worse eye LCS and larger postural sway was 3 times greater on a foam surface (beta 1.07, 95% CI [0.35, 1.80]) than a firm surface (beta 0.35, 95% CI [0.05, 0.65]), and both were robust to adjustment for confounders; similar findings were observed with binocular LCS. Lower binocular LCS had a greater decremental effect on gait velocity during the fast pace (beta −0.58, 95% CI [−0.90, −0.27]) than the usual pace (Beta −0.39 [−0.63, −0.15]) gait task. Conclusions These findings suggest that cognitively unimpaired older adults without significant visual acuity impairment can have subtle preclinical deficits in contrast sensitivity and physical function that could place them at risk of mobility and balance issues. Future studies should determine whether this subset of older adults may benefit from targeted intervention to prevent disability. [ABSTRACT FROM AUTHOR]

Background Cardiorespiratory fitness and perceived fatigability are interrelated components of physical capacity that may jointly influence movement within one's living environment (life-space mobility). We examined whether fitness and fatigability were associated with life-space mobility in community-dwelling older adults, and whether the association of fitness with life-space varied by the level of perceived fatigability. Methods Participants were from the Study of Muscle, Mobility and Aging (SOMMA) baseline cohort (N = 775, mean age 76.1 years). Life Space Assessment scores incorporated level, frequency, and assistance used (personal, devices) for life-space mobility. Fitness was measured as VO2peak from symptom-limited treadmill testing. Fatigability cut-points included: (i) Borg Rating of Perceived Exertion (RPE) ≥ 10 after a fixed-speed (1.5 mph) treadmill test, (ii) the Pittsburgh Fatigability Scale (PFS) Physical ≥ 15, and (iii) PFS Mental ≥ 13. The total count of cut-points was used as a composite fatigability measure (range: 0–3). Linear regressions were adjusted for demographic, lifestyle, and health confounders. Results Better fitness was associated with greater life-space, but the association plateaued at higher fitness levels (VO2peak > 18). Life-space was significantly lower for individuals meeting ≥2 fatigability criteria (vs none), attributable mainly to more severe physical, but not mental, fatigability. In moderation analyses, the fitness–life-space association was significant only for those with RPE ≥ 10 but did not differ by PFS. Conclusion Fitness below a critically low threshold was associated with limited life-space mobility, suggesting that certain older individuals may need to operate close to their maximum aerobic capacity to traverse daily environments; these associations were driven by those with more severe physical fatigability. [ABSTRACT FROM AUTHOR]

Background: A systematic review and network meta-analysis was undertaken to examine the effectiveness of different modes of resistance exercise velocity in fast walking speed, timed-up and go, five-times sit-to-stand, 30-sec sit-to-stand and 6-min walking tests in older adults.Methods: CINAHL, Embase, LILACS, PubMed, Scielo, SPORTDiscus and Web of Science databases were searched up to February 2022. Eligible randomised trials examined the effects of supervised high-velocity or traditional resistance exercise in older adults (i.e., ≥ 60 years). The primary outcome for this review was physical function measured by fast walking speed, timed up and go, five times sit-to-stand, 30-sec sit-to-stand and 6-minute walking tests, while maximal muscle power and muscle strength were secondary. A random-effects network meta-analysis was undertaken to examine the effects of different resistance exercise interventions.Results: Eighty articles describing 79 trials (n= 3,575) were included. High-velocity resistance exercise was the most effective for improving fast walking speed [standardised mean difference (SMD) -0.44, 95% CI: 0.00 to 0.87], timed-up and go (SMD -0.76, 95% CI: -1.05 to -0.47) and five times sit-to-stand (SMD -0.74, 95% CI: -1.20 to -0.27), while traditional resistance exercise was the most effective for 30-sec sit-to-stand (SMD 1.01, 95% CI: 0.68 to 1.34) and 6-min walking (SMD 0.68, 95% CI: 0.34 to 1.03).Conclusion: Our study provides evidence that resistance exercise velocity effects are specific in older adults as evidenced by physical function test dependence. We suggest that prescription based on the velocity of contraction should be individualised to address specific functional needs of participants. [ABSTRACT FROM AUTHOR]

Background This study develops a new concept, dual functionality, that integrates physical and cognitive function. We use the concept to define a measure of dual-function life expectancy (2FLE) and assess racial–ethnic inequalities in aging. Methods Drawing on data from the National Health Interview Survey Linked Mortality Files and the Health and Retirement Study, we define dual functionality as having no limitations in activities of daily living and being free of dementia. We use this measure and Sullivan life tables to estimate age-50 total life expectancy and age-50 2FLE for women and men across 4 racial–ethnic and nativity groups. Results At ages 50–54, between 79.0% (95% CI: 73.5, 84.5) and 87.6% (95% CI: 84.0, 91.2) of (non-Hispanic) Black, foreign-born Hispanic, and U.S.-born Hispanic women and men remain dual functional as compared with 90.4% (95% CI: 89.3, 91.4) and 91.4% (95% CI: 90.2, 92.5) of (non-Hispanic) White women and men, respectively. These and corresponding racial–ethnic disparities in dual functionality through ages 85 and older translate into substantial inequalities in 2FLE. For instance, the Black–White gap in age-50 2FLE is 6.9 years (95% CI: −7.5, −6.4) for women and 6.0 years (95% CI: −6.6, −5.4) for men. Conclusions Black, foreign-born Hispanic, and U.S.-born Hispanic older adults are estimated to live a smaller percentage of their remaining years with dual functionality than White older adults. These results reveal stark racial–ethnic inequalities in aging that have significant implications for quality of life, caregiving, and health needs. [ABSTRACT FROM AUTHOR]

In recent years, several new classes of therapies have been investigated with their potential for restoring or improving physical functioning in older adults. These have included Mas receptor agonists, regulators of mitophagy, skeletal muscle troponin activators, anti-inflammatory compounds, and targets of orphan nuclear receptors. The present article summarizes recent developments of the function-promoting effects of these exciting new compounds and shares relevant preclinical and clinical data related to their safety and efficacy. The development of novel compounds in this area is expanding and likely will need the advent of a new treatment paradigm for age-associated mobility loss and disability. [ABSTRACT FROM AUTHOR]

Physical activity and exercise training exert multiple and varied beneficial effects on a wide array of human tissues, making them therapeutic modalities that can prevent and treat age-related decline in physical function. The Molecular Transducers of Physical Activity Consortium is currently working to elucidate the molecular mechanisms underlying how physical activity improves and preserves health. Exercise training, especially when task specific, is an effective intervention for improving skeletal muscle performance and physical function in everyday activities. As seen elsewhere in this supplement, its adjunctive use with pro-myogenic pharmaceuticals may prove to be synergistic in effect. Behavioral strategies aiming to promote exercise participation and sustain adherence are being considered as additional adjuncts to further improve physical function in comprehensive, multicomponent interventions. One application of this combined strategy may be to target multimodal pro-myogenic therapies in prehabilitation to optimize physical preoperative health to enhance functional recovery postsurgery. We summarize here recent progress on biological mechanisms of exercise training, behavioral approaches to exercise participation, and the role task-specific exercise plays in synergy with pharmacologic therapies with a particular focus on older adults. Physical activity and exercise training in multiple settings should serve as the baseline standard of care around which other therapeutic interventions should be considered when the goal is restoring or increasing physical function. [ABSTRACT FROM AUTHOR]

Background This narrative review describes foundational and emerging evidence of how dietary protein intakes may influence muscle-related attributes of older adults. Methods PubMed was used to identify pertinent research. Results Among medically stable older adults, protein intakes below the recommended dietary allowance (RDA) (0.8 g/kg body weight [BW]/d) exacerbate age-related reductions in muscle size, quality, and function. Dietary patterns with total protein intakes at or moderately above the RDA, including one or preferably more meals containing sufficient dietary protein to maximize protein anabolism, promote muscle size and function. Some observational studies suggest protein intakes from 1.0 to 1.6 g/kg BW/d may promote greater muscle strength and function more so than muscle size. Experimental findings from randomized controlled feeding trials indicate protein intakes greater than the RDA (averaging ~1.3 g/kg BW/d) do not influence indices of lean body mass or muscle and physical functions with non-stressed conditions, but positively influence changes in lean body mass with purposeful catabolic (energy restriction) or anabolic (resistance exercise training) stressors. Among older adults with diagnosed medical conditions or acute illness, specialized protein or amino acid supplements that stimulate muscle protein synthesis and improve protein nutritional status may attenuate the loss of muscle mass and function and improve survival of malnourished patients. Observational studies favor animal versus plant protein sources for sarcopenia-related parameters. Conclusions Quantity, quality, and patterning of dietary protein consumed by older adults with varied metabolic states, and hormonal and health status influence the nutritional needs and therapeutic use of protein to support muscle size and function. [ABSTRACT FROM AUTHOR]

We generated a genetically heterogenous rat model by a 4-way cross strategy using 4 inbred strains (Brown Norway [BN], Fischer 344 [F344], Lewis [LEW], and Wistar Kyoto [KY]) to provide investigators with a highly genetically diverse rat model from commercially available inbred rats. We made reciprocal crosses between males and females from the 2 F1 hybrids to generate genetically heterogeneous rats with mitochondrial genomes from either the BN (OKC-HETB, a.k.a "B" genotype) or WKY (OKC-HETW a.k.a "W" genotype) parental strains. These two mitochondrial genomes differ at 94 nucleotides, more akin to human mitochondrial genome diversity than that available in classical laboratory mouse strains. Body weights of the B and W genotypes were similar. However, mitochondrial genotype antagonistically affected grip strength and treadmill endurance in females only. In addition, mitochondrial genotype significantly affected multiple responses to a high-fat diet (HFD) and treatment with 17α-estradiol. Contrary to findings in mice in which males only are affected by 17α-estradiol supplementation, female rats fed a HFD beneficially responded to 17α-estradiol treatment as evidenced by declines in body mass, adiposity, and liver mass. Male rats, by contrast, differed in a mitochondrial genotype-specific manner, with only B males responding to 17α-estradiol treatment. Mitochondrial genotype and sex differences were also observed in features of brain-specific antioxidant response to a HFD and 17α-estradiol as shown by hippocampal levels of Sod2 acetylation, JNK, and FoxO3a. These results emphasize the importance of mitochondrial genotype in assessing responses to putative interventions in aging processes. [ABSTRACT FROM AUTHOR]

Background: Knee osteoarthritis(KOA) is the most prevalent type of OA and a leading cause of disability in the United States. Falls are a major public health concern in older adults. Our aim was to examine how the severity of radiographic KOA impacts recurrent falls in a cohort of middle and older aged individuals enrolled in the Osteoarthritis Initiative (OAI).Methods: 3,972 participants, mean age of 63 years, 58% female were included. Participants were divided into 5 mutually exclusive groups based on their worst Kellgren-Lawrence grade of radiographic KOA from annual x-rays from baseline to 36-months. Generalized estimating equations for repeated logistic regression were used to model the association between KOA severity and the likelihood of recurrent falls (≥ 2 falls/year) over 5 years follow-up (>36-96 months).Results: Older adults (≥age 65) with KOA were at higher odds of recurrent falls in comparison to individuals without KOA in multivariate models (possible OA OR= 2.22, 95% CI= 1.09-4.52; mild OA OR=2.48, 95% CI= 1.34-4.62; unilateral moderate-severe OA OR= 2.84, 95% CI= 1.47- 5.50; bilateral moderate-severe OA OR= 2.52, 95% CI= 1.13-5.62). Middle aged adults(age 45-64) with KOA did not have increased odds of recurrent falls in comparison to those without KOA except for possible KOA (OR= 1.86, 95% CI=1.01-2.78) (KOA severity*age interaction = 0.025).Conclusions: Older adults with radiographic evidence of KOA have an increased likelihood of experiencing recurrent falls in comparison to those without KOA independent of established risk factors. Our results suggest fall prevention efforts should include older adults with all stages of KOA. [ABSTRACT FROM AUTHOR]

Background Computed tomography (CT)-scan measures of muscle composition may be associated with recovery post hip fracture. Methods In an ancillary study to Baltimore Hip Studies Seventh cohort, older adults were evaluated at 2 and 6 months post hip fracture. CT-scan measures of muscle were acquired at 2 months. Short Physical Performance Battery (SPPB) was measured at 2 and 6 months. Generalized estimating equations were used to model the association of muscle measures and physical function, adjusting for age, sex, body mass index, and time postfracture. Results Seventy-one older adults (52% males, age 79.6 ± 7.3 years) were included. At 2-months, males had greater thigh cross-sectional area (CSA, p <.0001) and less low-density muscle (p =.047), and intermuscular adipose tissue (p =.007) than females on the side of the fracture, while females performed better on the SPPB (p =.05). Muscle measures on the fractured side were associated with function at 2 months in both sexes. Participants with the lowest tertile of muscle CSA difference at 2-months, indicating greater symmetry in CSA between limbs, performed better than the other 2 tertiles at 6-months. Males performed worse in functional measures at baseline and did not recover as well as females (p =.02). Conclusion CT-scan measures of muscle CSA and fatty infiltration were associated with function at 2-months post hip fracture and with improvement in function by 6 months. Observed sex differences in these associations suggest that rehabilitation strategies may need to be adapted by sex after hip fracture. [ABSTRACT FROM AUTHOR]

Background: It is important to understand the factors associated with life-space mobility so that mobility disability can be prevented/treated. The purpose of this study was to identify the association between mobility determinants and life space among older adults.Methods: This study was a cross-sectional analysis of 249 community-dwelling older adults (mean age = 77.4 years, 65.5% female, 88% White), who were recruited for a randomized, controlled, clinical intervention trial. Associations between cognitive, physical, psychosocial, financial, and environmental mobility determinants and the life-space assessment (LSA) at baseline were determined using Spearman's correlation coefficients and one-way analysis of variance. Multivariate analysis was performed using multivariable linear regression models.Results: The mean LSA score for the sample was 75.3 (SD = 17.8). Personal factors (age, gender, education, comorbidities), cognitive (Trail Making Test A and B), physical (gait speed, lower extremity power, 6-Minute Walk Test, Figure of 8 Walk Test, tandem stance, energy cost of walking, and Late-Life Function and Disability Function Scale), psychosocial (Modified Gait Efficacy Scale), and financial (neighborhood socioeconomic status) domains of mobility were significantly associated with LSA score. In the final regression model, age (β = -0.43), lower extremity power (β = 0.03), gait efficacy (β = 0.19), and energy cost of walking (β = -57.41) were associated with life space (R2 = 0.238).Conclusions: Younger age, greater lower extremity power, more confidence in walking, and lower energy cost of walking were associated with greater life space. Clinicians treating individuals with mobility disability should consider personal, physical, and psychosocial factors when assessing barriers to life-space mobility. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to examine whether select baseline characteristics influenced the likelihood of an overweight/obese, older adult experiencing a clinically meaningful gait speed response (±0.05 m/s) to caloric restriction (CR).Methods: Individual level data from 1 188 older adults participating in 8, 5/6-month, weight loss interventions were pooled, with treatment arms collapsed into CR (n = 667) or no CR (NoCR; n = 521) categories. Exercise assignment was equally distributed across groups (CR: 65.3% vs NoCR: 65.4%) and did not interact with CR (p = .88). Poisson risk ratios (95% confidence interval [CI]) were used to examine whether CR assignment interacted with select baseline characteristic subgroups: age (≥65 years), sex (female/male), race (Black/White), body mass index (BMI; ≥35 kg/m2), comorbidity (diabetes, hypertension, cardiovascular disease) status (yes/no), gait speed (<1.0 m/s), or inflammatory burden (C-reactive protein ≥3 mg/L, interleukin-6 ≥2.5 pg/mL) to influence achievement of ±0.05 m/s fast-paced gait speed change. Main effects were also examined.Results: The study sample (69.5% female, 80.1% White) was 67.6 ± 5.3 years old with a BMI of 33.8 ± 4.4 kg/m2. Average weight loss achieved in the CR versus NoCR group was -8.3 ± 5.9% versus -1.1 ± 3.8%; p < .01. No main effect of CR was observed on the likelihood of achieving a clinically meaningful gait speed improvement (risk ratio [RR]: 1.09 [95% CI: 0.93, 1.27]) or gait speed decrement (RR: 0.77 [95% CI: 0.57, 1.04]). Interaction effects were nonsignificant across all subgroups.Conclusion: The proportion of individuals experiencing a clinically meaningful gait speed change was similar for CR and NoCR conditions. This finding is consistent across several baseline subgroupings. [ABSTRACT FROM AUTHOR]

Background: Good sit-to-stand (STS) performance is an important factor in maintaining functional independence. This study investigated whether free-living STS transition volume and intensity, assessed by a thigh-worn accelerometer, is associated with characteristics related to functional independence.Methods: Free-living thigh-worn accelerometry was recorded continuously for 3-7 days in a population-based sample of 75-, 80-, and 85-year-old community-dwelling people (479 participants; women n = 287, men n = 192). The records were used to evaluate the number and intensity (angular velocity of the STS phase) of STS transitions. Associations with short physical performance battery (SPPB), 5-times-sit-to-stand test (5×STS), isometric knee extension force, self-reported fear of falls, and self-reported difficulty in negotiating stairs were also assessed.Results: The number of STS transitions, mean and maximal angular velocity were lower in older age groups (p < .05). All variables were higher in men than in women (p < .001) and were positively associated with SPPB total points, knee extension force (r ranged from 0.18 to 0.39, all p < .001) and negatively associated with 5×STS (r = -0.13 - -0.24, all p < .05), lower extremity functional limitations (p < .01), fear of falls (p < .01), and stair negotiation difficulties (p < .01).Conclusions: Free-living STS characteristics were related to lower-extremity performance, lower extremity functional limitations, self-reported fear of falls, and stair negotiation difficulties, which can be a sensitive indicator of impending functional decline. Moreover, STS transitions may provide an indicator of adequacy of lower-limb muscle strength among older individuals. [ABSTRACT FROM AUTHOR]

Background: Motor function affects ability to perform daily activities and maintain independence. Yet, the interrelatedness of upper and lower extremity motor impairments and the magnitude of their contribution to slow gait and mobility difficulty are not well investigated.Methods: Participants in the Baltimore Longitudinal Study of Aging (N = 728, aged 50-99) completed motor and physical function tests including grip and knee extension strength, pegboard, finger tapping, standing balance, chair stands, fast-paced 400-m walk, and usual gait speed. Slow gait was defined as usual gait speed <1.0 m/s. Mobility difficulty was defined as self-reported difficulty walking ¼ mile or climbing stairs. Structural equation modeling examined the interrelationships of motor measures and their contributions to slow gait and mobility difficulty, adjusting for demographics and comorbidities.Results: Poorer manual dexterity (-0.571 standard deviation [SD] units, p < .001) and lower muscle strength (upper and lower extremity; -0.447 SD units, p = .014) were most strongly associated with slow gait speed, followed by slower chair stand pace (-0.195 SD units, p = .002) and greater lap time variation (0.102 SD units, p = .028). Lower muscle strength (-0.582 SD units, p = .001) was most strongly associated with mobility difficulty, followed by slower chair stand pace (-0.322 SD units, p < .001), slower gait speed (-0.247 SD units, p < .001), and poorer standing balance (-0.190 SD units, p = .043).Conclusions: Components of manual dexterity and strength were the strongest correlates of slow gait and mobility difficulty in mid-to-late life. Longitudinal studies examining relationships between changes in these motor parameters and mobility are needed to elucidate possible causal effects. [ABSTRACT FROM AUTHOR]

Background: Although both the patterns and accumulation of multimorbidity are important for predicting physical function, studies have not simultaneously examined their impact on functional decline. This study aimed to associate multimorbidity patterns and subsequently developed conditions with longitudinal trajectories of functional decline, and it tested whether the effects of newly developed conditions on functional decline varied across distinct multimorbidity patterns.Methods: We included 6 634 participants aged at least 60 years from the China Health and Retirement Longitudinal Survey. Latent class analysis identified multimorbidity patterns from 14 chronic conditions. Mixed negative binomial models estimated the changes in physical function measured across 4 waves as a function of multimorbidity patterns, subsequently developed conditions, and their interactions.Results: Five distinct patterns were identified 3 years before Wave 1: stomach/arthritis (15.7%), cardiometabolic (6.7%), arthritis/hypertension (47.9%), hepatorenal/multisystem (18.3%), and lung/asthma (11.4%). The hepatorenal/multisystem and the lung/asthma pattern were associated with worse baseline physical function, and the hypertension/arthritis pattern was associated with greater decline of physical function. The effect of developing new conditions on decline of physical function over time was most evident for individuals from the cardiometabolic pattern.Conclusions: Considering both the combinations and progressive nature of multimorbidity is important for identifying individuals at greater risk of disability. Future studies are warranted to differentiate the factors responsible for the progression of chronic conditions in distinct multimorbidity patterns and investigate the potential implications for improved prediction of functional decline. [ABSTRACT FROM AUTHOR]

Background: Although a few studies reported an association between varicose veins and physical function, this potentially bidirectional association has not been systematically evaluated in the general population.Method: In 5 580 participants (aged 71-90 years) from the Atherosclerosis Risk in Communities study, varicose veins were identified in outpatient and inpatient administrative data prior to (prevalent cases) and after (incident cases) visit 5 (2011-2013). Physical function was evaluated by the Short Physical Performance Battery (SPPB, score ranging from 0 to 12). We evaluated (i) cross-sectional association between prevalent varicose veins and physical function, (ii) association of prevalent varicose veins with subsequent changes in physical function from visit 5 to visits 6 (2016-2017) and 7 (2018-2019), and (iii) association of physical function at visit 5 with incident varicose veins during a median follow-up of 3.6 years (105 incident varicose veins among 5 350 participants without prevalent cases at baseline).Results: At baseline, varicose veins were recognized in 230 (4.1%) participants and cross-sectionally associated with reduced physical function. Longitudinally, prevalent varicose veins were not significantly associated with a decline in SPPB over time. In contrast, a low SPPB ≤6 was associated with a greater incidence of varicose veins compared to SPPB ≥10 (adjusted hazard ratio 2.13 [95% confidence interval = 1.19, 3.81]).Conclusion: In community-dwelling older adults, varicose veins and low physical function were associated cross-sectionally. Longitudinally, low physical function was a risk factor for incident varicose veins, but not vice versa. Our findings suggest an etiological contribution of low physical function to incident varicose veins. [ABSTRACT FROM AUTHOR]

Background: The ratio of creatinine to cystatin C (Cr:Cyc) has been proposed as a biomarker of sarcopenia, as greater Cr:Cyc is typically associated with greater muscle mass. We examined the relationship between Cr:Cyc with individual sarcopenia measures, 5-year self-reported falls, and 12-year fall-related hospitalizations in a prospective cohort study of 1 118 community-dwelling older women (mean age 75.2 ± 2.7 years).Methods: Serum Cr:Cyc, hand grip strength, and timed-up-and-go performance were assessed at baseline (1998), while dual-energy x-ray absorptiometry-derived appendicular lean mass (ALM)/height2 (m) was obtained in a subset of women at baseline and 1 year (n = 334). Incident 5-year self-reported falls and 12-year falls-related hospitalizations were considered.Results: In a multivariable-adjusted model, women with the lowest Cr:Cyc (Quartile [Q] 1) had 5% (1.0 kg) weaker grip strength, as well as 3.7% (0.22 kg/m2) and 5.5% (0.031) lower ALM adjusted for height2 or body mass index, respectively, compared to women in Q4 (all p < .05). 329 women reported an incident fall over 5 years, and 326 fall-related hospitalizations were recorded over 12 years. Women in Q1 of Cr:Cyc had a greater relative hazard for a fall over 5 years (hazard ratio [HR] 1.50; 95% confidence interval [CI] 1.11-2.01) and fall-related hospitalization over 12 years (HR 1.53; 95% CI 1.13-2.07) compared to Q4 in the multivariable-adjusted model.Conclusion: These findings support further investigation into the use of Cr:Cyc as a muscle biomarker to help clinicians identify individuals at risk of falls for early inclusion into evidence-based primary prevention programs targeting improvements to diet and exercise. [ABSTRACT FROM AUTHOR]

Background: We examined the relationship of midlife cardiovascular health (CVH) with late-life robustness among men and women and the impact of survivorship bias on sex differences in robustness.Methods: Prospective analysis of 15 744 participants aged 45-64 (visit 1 median age: 54 years, 55% female, 27% Black) in 1987-1989 from the population-based Atherosclerosis Risk in Communities Study. CVH was operationalized according to the Life's Simple 7 (LS7) metric of health behaviors (smoking, weight, physical activity, diet, cholesterol, blood pressure, and glucose); each behavior was scored as ideal (2 points), intermediate (1 point), or poor (0 points) and summed. Late-life robust/prefrail/frailty was defined at visit 5 (2011-2013). Multinomial regression estimated relative prevalence ratios (RPRs) of late-life robustness/prefrailty/frailty/death across overall midlife LS7 score and components, for the full visit 1 sample. Separate analyses considered visit 5 survivors-only.Results: For each 1-unit greater midlife LS7 score, participants had a 37% higher relative prevalence of being robust versus frail (overall RPR = 1.37 [95% confidence interval {CI}: 1.30-1.44]; women = 1.45 [1.36-1.54]; men = 1.24 [1.13-1.36]). Among the full visit 1 sample, women had a similar 1-level higher robustness category prevalence (RPR = 1.35 [95% CI: 1.32-1.39]) than men (RPR = 1.31 [95% CI: 1.27-1.35]) for every 1-unit higher midlife LS7 score. Among survivors, men were more likely to be robust than women at lower LS7 levels; differences were attenuated and not statistically different at higher midlife LS7 levels.Conclusions: Midlife CVH is positively associated with robustness in late life among men and women. Accounting for mortality in part explains documented sex differences in robustness across all levels of LS7. [ABSTRACT FROM AUTHOR]

Background: A systematic review and meta-analysis was performed to evaluate the short- and long-term effects of exercise therapy on physical function, independence, and well-being in older patients following hip fracture and, secondly, whether the effect was modified by trial-level characteristics such as intervention modality, duration, and initiation timepoint.Method: Medline, CENTRAL, Embase, CINAHL, and PEDro were searched up to November 2020. Eligibility criteria were randomized controlled trials investigating the effect of exercise therapy on physical function, independence, and well-being in older patients following hip fracture, initiated from time of surgery up to 1 year.Results: Forty-nine studies involving 3 905 participants showed a small-to-moderate effect of exercise therapy at short term (end of intervention) on mobility (standardized mean difference [SMD] 0.49, 95% confidence interval [CI]: 0.22-0.76); activities of daily living (ADL) (SMD 0.31, 95% CI: 0.16-0.46); lower limb muscle strength (SMD 0.36, 95% CI: 0.13-0.60); and balance (SMD 0.34, 95% CI: 0.14-0.54). At long term (closest to 1 year), small-to-moderate effects were found for mobility (SMD 0.74, 95% CI: 0.15-1.34), ADL (SMD 0.42, 95% CI: 0.23-0.61), balance (SMD 0.50, 95% CI: 0.07-0.94), and health-related quality of life (SMD 0.31, 95% CI: 0.03-0.59). Certainty of evidence was evaluated using Grading of Recommendations Assessment, Development and Evaluation ranging from moderate to very low, due to study limitation and inconsistency.Conclusion: We found low certainty of evidence for a moderate effect of exercise therapy on mobility in older patients following hip fracture at end of treatment and follow-up. Further, low evidence was found for small-to-moderate short-term effect on ADL, lower limb muscle strength and balance.Clinical Trials Registration Number: CRD42020161131. [ABSTRACT FROM AUTHOR]

Background: Delirium is common, distressing, and associated with poor outcomes. Despite this, delirium remains poorly recognized, resulting in worse outcomes. There is an urgent need for methods to objectively assess for delirium. Physical function has been proposed as a potential surrogate marker, but few studies have monitored physical function in the context of delirium. We examined if trajectories of physical function are affected by the presence and severity of delirium in a representative sample of hospitalized participants older than 65 years.Method: During hospital admissions in 2016, we assessed participants from the Delirium and Cognitive Impact in Dementia study daily for delirium and physical function, using the Hierarchical Assessment of Balance and Mobility (HABAM). We used linear mixed models to assess the effect of delirium and delirium severity during admission on HABAM trajectory.Results: Of 178 participants, 58 experienced delirium during admission. Median HABAM scores in those with delirium were significantly higher (indicating worse mobility) than those without delirium. Modeling HABAM trajectories, HABAM scores at first assessment were worse in those with delirium than those without, by 0.76 (95% CI: 0.49-1.04) points. Participants with severe delirium experienced a much greater perturbance in their physical function, with an even lower value at first assessment and slower subsequent improvement.Conclusions: Physical function was worse in those with delirium compared to without. This supports the assertion that motor disturbances are a core feature of delirium and monitoring physical function, using a tool such as the HABAM, may have clinical utility as a surrogate marker for delirium and its resolution. [ABSTRACT FROM AUTHOR]

Frailty is a state of heightened vulnerability and susceptibility to physiologic stressors that increases with age. It has shown increasing utility in predicting a range of adverse health outcomes. Here, we characterize a 67-item deficit-accumulation frailty index (FI) in 19 110 community-dwelling individuals in the ASPirin in Reducing Events in the Elderly clinical trial. Participants aged 65-98 years were recruited from the United States and Australia and were without diagnosed dementia and cardiovascular disease, and major physical disability. The median FI score was .10 (interquartile range: .07-.14) at baseline, and the prevalence of frailty (FI > .21) increased from 8.1% to 17.4% after 6 years. FI was positively associated with age, and women had significantly higher scores than men at all ages. The FI was negatively correlated with gait speed (r = -.31) and grip strength (r = -.46), and strongly associated with a modified Fried's frailty phenotype (p < .0001, for all comparisons). Frailty was associated with the primary composite outcome capturing independent life lived free of major disability and dementia, and increased the rate of persistent physical disability (hazard ratio: 21.3, 95% confidence interval: 15.6-28.9). It added significantly to the predictive capacity of these outcomes above age, sex, and ethnicity alone. The FI is thus a useful biomarker of aging even among relatively healthy older individuals and provides important information about an individual's vulnerability to and risk of disease. [ABSTRACT FROM AUTHOR]

Background: Cerebrovascular events, dementia, and cancer can contribute to physical disability with activities of daily living (ADL). It is unclear whether low-dose aspirin reduces this burden in aging populations. In a secondary analysis, we now examine aspirin's effects on incident and persistent ADL disability within a primary prevention aspirin trial in community-dwelling older adults.Methods: The ASPREE (ASPirin in Reducing Events in the Elderly) trial of daily 100 mg aspirin versus placebo recruited 19 114 healthy adults aged 70+ years (65+ years if U.S. minority) in Australia and the United States. Six basic ADLs were assessed every 6 months. Incident ADL disability was defined as inability or severe difficulty with ≥1 ADL; persistence was confirmed if the same ADL disability remained after 6 months. Proportional hazards modeling compared time to incident or persistent ADL disability for aspirin versus placebo; death without prior disability was a competing risk.Results: Over a median of 4.7 years, incident ADL disability was similar in those receiving aspirin (776/9525) and placebo (787/9589) with walking, bathing, dressing, and transferring the most commonly reported. Only 24% of incident ADL disability progressed to persistent. Persistent ADL disability was lower in the aspirin group (4.3 vs 5.3 events/1000 py; hazard ratio [HR] = 0.81, 95% confidence interval [CI]: 0.66-1.00), with bathing and dressing the most common ADL disabilities in both groups. Following persistent ADL disability, there were more deaths in the aspirin group (24 vs 12).Discussion: Low-dose aspirin in initially healthy older people did not reduce the risk of incident ADL disability, although there was evidence of reduced persistent ADL disability. [ABSTRACT FROM AUTHOR]

Background: Gait speed is a powerful indicator of health with aging. Potential genetic contributions to gait speed and its decline with aging are not well defined. We determined the heritability of and potential genetic regions underlying change in gait speed using longitudinal data from 2379 individuals belonging to 509 families in the Long Life Family Study (mean age 64 ± 12, range 30-110 years; 45% men).Methods: Gait speed was measured over 4 m at baseline and follow-up (7 ± 1 years). Quantitative trait linkage analyses were completed using pedigree-based maximum likelihood methods with logarithm of the odds (LOD) scores greater than 3.0, indicating genome-wide significance. We also performed linkage analysis in the top 10% of families contributing to LOD scores to allow for heterogeneity among families (HLOD). Data were adjusted for age, sex, height, and field center.Results: At baseline, 26.9% of individuals had "slow" gait speed less than 1.0 m/s (mean: 1.1 ± 0.2 m/s) and gait speed declined at a rate of -0.02 ± 0.03 m/s per year (p < .0001). Baseline and change in gait speed were significantly heritable (h2 = 0.24-0.32, p < .05). We did not find significant evidence for linkage for baseline gait speed; however, we identified a significant locus for change in gait speed on chromosome 16p (LOD = 4.2). A subset of 21 families contributed to this linkage peak (HLOD = 6.83). Association analyses on chromosome 16 showed that the strongest variant resides within the ADCY9 gene.Conclusion: Further analysis of the chromosome 16 region, and ADCY9 gene, may yield new insight on the biology of mobility decline with aging. [ABSTRACT FROM AUTHOR]

Background: Among older adults, walking performance is a reliable indicator of adverse health outcomes including incident mobility impairment. Whereas, attention and executive functions have been implicated in cognitive control of locomotion, much less is known about the role of cognitive reserve (CR) in predicting mobility impairments among older adults. Specifically, whether CR moderates the relationship between gait performance and incident mobility impairment has not been reported. To address this gap in the literature, we examined whether gait performance under single-task walk (STW) and dual-task walk (DTW) conditions predicted incident mobility impairment and whether CR moderated this relationship.Method: Participants were 176 (mean age = 75.57; % female = 53) older adults with baseline Short Physical Performance Battery (SPPB) scores of 10-12. Participants completed neuropsychological testing, the SPPB, and a DTW protocol. CR was evaluated using the Wide Range Achievement Test, third edition. Participants were followed for 3 years; individuals whose SPPB scores declined below 10 were defined as incident cases of mobility impairment (n = 42).Results: Moderation analyses revealed significant interaction effects of CR with walking velocity under STW (b = 0.09, 95% CI [0.01, 0.17], z = 2.30, p = .02) and DTW (b = 0.10, 95% CI [0.02, 0.17], z = 2.55, p = .01) conditions, wherein slower gait predicted increased risk of incident mobility impairment among individuals with lower CR.Conclusion: These findings extend knowledge about the interrelation of cognitive and mobility functions, revealing the critical role of CR in identifying older adults at risk of developing incident mobility impairment. [ABSTRACT FROM AUTHOR]

Background: Although hearing impairment (HI) is linked to poorer physical functioning, the longitudinal associations between HI and higher-level functional measures are unclear.Method: Data are from the Baltimore Longitudinal Study of Aging (2012-2019). Using pure-tone audiometry, we categorized hearing into normal, mild, and moderate or greater HI. Physical function was assessed with the expanded Short Physical Performance Battery (eSPPB) and walking endurance with time to walk 400 m. Multivariable and mixed-effects linear models tested the hypotheses that participants with HI, at baseline, have poorer physical performance and walking endurance, and faster decline over time (up to 6 measurements). In a subset (n = 526), we further adjusted for vestibular function. Among participants with HI, we evaluated the differences in eSPPB scores and walking endurance between hearing aid users and nonusers.Results: Of 831 participants, 26% had mild, and 17% moderate or greater HI. After adjustment for demographics and medical history, moderate or greater impairment versus normal hearing was associated with poorer function (0.17 [95% CI: 0.09, 0.26] lower eSPPB score, and 13.3 [95% CI: 3.31, 23.4] seconds slower 400-m walk time) and faster decline in these parameters over 6 years. Adjustment for vestibular function did not attenuate these associations. Hearing aid users walked 400 m 24 seconds faster than nonusers (p = .001).Conclusion: Moderate or greater HI is associated with poorer initial and greater decline in higher-level physical performance. The observation that hearing aid users had better walking endurance suggests that screening for and treatment of HI may delay or slow progression of hearing-related functional decline. [ABSTRACT FROM AUTHOR]

In the 1990s and early 2000s, the common definition for sarcopenia was age-related loss of skeletal muscle, and low levels of muscle mass were central to sarcopenia diagnosis. In more recent consensus definitions, however, low muscle strength displaces low muscle mass as a defining feature of sarcopenia. The change stems from growing evidence that muscle weakness is a better predictor of adverse health outcomes (eg, mobility limitations) than muscle mass. This evidence accompanies an emerging recognition that central neural mechanisms are critical determinants of age-related changes in strength and mobility that can occur independently of variations in muscle mass. However, strikingly little practical attention is typically given to the potential role of the central nervous system in the etiology or remediation of sarcopenia (ie, low muscle function). In this article, we provide an overview of some mechanisms that mediate neural regulation of muscle contraction and control, and highlight the specific contributions of neural hypoexcitability, dopaminergic dysfunction, and degradation of functional and structural brain connectivity in relation to sarcopenia. We aim to enhance the lines of communication between the domains of sarcopenia and neuroscience. We believe that appreciation of the neural regulation of muscle contraction and control is fundamental to understanding sarcopenia and to developing targeted therapeutic strategies for its treatment. [ABSTRACT FROM AUTHOR]

Background: Lower physical activity levels and greater fatigability contribute independently to slower gait speed in older adults. To fully understand the bidirectional relations between physical activity and fatigability, and to inform potential intervention strategies, we examined whether physical activity or fatigability explains more of the other factor's association on slower gait speed.Methods: Two generations (probands and offspring) of older adults (N = 2079, mean age 73.0 ± 10.0 years, 54.2% women, 99.7% White) enrolled in the Long Life Family Study were assessed at Visit 2 (2014-2017). Self-reported physical activity was measured with the Framingham Physical Activity Index and perceived physical fatigability using the Pittsburgh Fatigability Scale. Statistical mediation analyses were conducted separately by generation with linear mixed-effect models accounting for family relatedness and adjusted for demographics, health conditions, and field center.Results: Greater perceived physical fatigability explained the association of lower physical activity on slower gait speed via a 22.5% attenuation of the direct association (95% confidence interval [CI]: 15.0%-35.2%) for the probands and 39.5% (95% CI: 22.8%-62.6%) for the offspring. Whereas lower physical activity explained the association of greater perceived fatigability on slower gait speed via a 22.5% attenuation of the direct association (95% CI: 13.4%-32.8%) for the probands and 6.7% (95% CI: 3.8%-15.4%) for the offspring.Conclusions: Our findings suggest that the impact of greater perceived physical fatigability on the association between lower physical activity and slower gait speed differs between younger-old and middle-to-oldest-old adults, indicating perceived physical fatigability as a potential mediator in the disablement pathway. [ABSTRACT FROM AUTHOR]

Background: There is a need to know the relationship between function and hospitalization risk in older adults. We aimed at investigating whether the Functional Continuum Scale (FCS), based on basic (BADL) and instrumental (IADL) activities of daily living and frailty, is associated with hospitalization density in older adults across 12 years of follow-up.Methods: Cohort study, with a follow-up of 12 years. A total of 915 participants aged 70 years and older from the Frailty and Dependence in Albacete (FRADEA) study, a population-based study in Spain, were included. At baseline, the FCS, sociodemographic characteristics, comorbidity, number of medications, and place of residence were assessed. Associations with first hospitalization, number of hospitalizations, and 12-year density of hospitalizations were assessed using Kaplan-Meier curves, Poisson regression analyses, and density models.Results: The median time until the first hospitalization was shorter toward the less functionally independent end of the FCS, from 3917 days (95% confidence interval [CI] 3701-3995) to 1056 days (95% CI 785-1645) (p < .001). The incidence rate ratio (IRR) for all hospitalizations increased from the robust category until the frail one (IRR 1.89), and thereafter it decreased until the worse functional category. Those who were BADL dependent presented an increased hospitalization density in the first 4 follow-up years (58%), those who were frail in the third-to-sixth follow-up years (55%), while in those prefrail or robust the hospitalization density was homogeneous during the complete follow-up.Conclusions: The FCS is useful for stratifying the risk of hospitalization and for predicting the density of hospitalizations in older adults. [ABSTRACT FROM AUTHOR]

Mouse models are often used to validate novel interventions prior to human testing, although biological differences between mice and humans limit the translatability of outcomes. A common assumption in animal research is that maximal physical performance will be present at a young age, and that differences in task performance between young and old can be attributed to the aging process. However, this may not be true for all physical function tasks, and leaving out intermediate time points could drastically alter data interpretation. Here, we document age-related changes in forelimb and hindlimb grip strength, balance and coordination, and body composition in mice (n = 43) collected at multiple time points between 4 and 24 months of age. Maximal forelimb grip strength was recorded at 4 months of age, but maximal hindlimb grip strength was recorded at 15 months of age. Balance performance was stable from 4 to 15 months of age, declining significantly at 18 months. Both lean and fat mass peaked at 18 months before declining steadily. We conclude that the inclusion of intermediate time points is essential for the accurate evaluation of physical function status in mice, particularly in the context of translating intervention outcomes into strategies to be tested in humans. [ABSTRACT FROM AUTHOR]

Background: Higher levels of ceramides have been linked to several chronic diseases; also there is emerging cross-sectional evidence that ceramides are associated with lower physical functioning. This research assessed for the first time the prospective relationship between ceramide species and impaired lower-extremity function (ILEF) in older adults.Methods: Case-control study with 43 cases of ILEF and 86 age- and sex-matched controls, which was nested in the Seniors-ENRICA cohort of community-dwelling older adults. Incident ILEF from 2015 to 2017 was ascertained with the Short Physical Performance Battery. In 2015, 27 ceramide species were measured in plasma by liquid chromatography-tandem mass spectrometry. Conditional logistic regression models were used to assess the longitudinal relationship between ceramides concentration and incidence of ILEF.Results: After adjusting for education level, body mass index, alcohol and total energy intake, physical activity, and presence of chronic conditions, some ceramide species were related to 2-year incidence of ILEF. Specifically, the odds ratios of ILEF per 1-SD increase in ceramide concentration were: 1.66 [95% CI = (1.03, 2.68)] for ceramide C14:0, 1.61 (1.00, 2.59) for ceramide C16:0, and 1.64 (1.03, 2.60) for ceramide C16:1 (n-7). In the case of ceramides C16:0 and C16:1 (n-7), a stronger relationship was found in those with a higher body mass index; systolic blood pressure could also mediate the relationship between ceramide C16:1 (n-7) and ILEF (p for interaction = .03).Conclusions: Higher plasma levels of ceramides C14:0, C16:0, and C16:1 (n-7) are associated with higher risk of ILEF, and might serve as risk markers for functional decline in older adults. [ABSTRACT FROM AUTHOR]

Background: This study examined educational differences in decline in maximum gait speed over an 11-year follow-up in the general Finnish population aged 55 years and older and assessed the contribution of lifestyle factors, body mass index, physical workload, and chronic conditions on the association.Method: Data from the nationally representative Health 2000 Survey and its 11-year follow-up were used. Participants aged 55 years and older with maximum gait speed measured at both time points were included (n = 1128). Information on education, age, sex, lifestyle factors, body mass index, physical workload, and chronic conditions was collected at baseline. General linear model was used to examine differences in decline in maximum gait speed between education groups. Mediation analyses using the product method was conducted to partition the total effect of education on decline in maximum gait speed into direct effect and indirect effect acting through mediators.Results: Decline in maximum gait speed was greater in low and intermediate education groups in comparison to the high education group (0.24 m/s [95% confidence interval 0.21-0.26], 0.24 m/s [0.21-0.28], 0.10 m/s [0.07-0.14], respectively]. The most important mediators were higher body mass index and lifetime exposure to physical workload among the less educated, accounting for 10% and 11% of the total effect, respectively.Conclusions: Education-based disparities in objectively measured mobility increase with age as lower education is associated with greater decline in gait speed. Higher body mass index and physical workload among less educated contributed most to the educational disparities in age-related decline in maximum gait speed. [ABSTRACT FROM AUTHOR]

Background: National guidelines promote physical activity to prevent cardiovascular disease (CVD), yet no randomized controlled trial has tested whether physical activity reduces CVD.Methods: The Women's Health Initiative (WHI) Strong and Healthy (WHISH) pragmatic trial used a randomized consent design to assign women for whom cardiovascular outcomes were available through WHI data collection (N = 18 985) or linkage to the Centers for Medicare and Medicaid Services (N30 346), to a physical activity intervention or "usual activity" comparison, stratified by ages 68-99 years (in tertiles), U.S. geographic region, and outcomes data source. Women assigned to the intervention could "opt out" after receiving initial physical activity materials. Intervention materials applied evidence-based behavioral science principles to promote current national recommendations for older Americans. The intervention was adapted to participant input regarding preferences, resources, barriers, and motivational drivers and was targeted for 3 categories of women at lower, middle, or higher levels of self-reported physical functioning and physical activity. Physical activity was assessed in both arms through annual questionnaires. The primary outcome is major cardiovascular events, specifically myocardial infarction, stroke, or CVD death; primary safety outcomes are hip fracture and non-CVD death. The trial is monitored annually by an independent Data Safety and Monitoring Board. Final analyses will be based on intention to treat in all randomized participants, regardless of intervention engagement.Results: The 49 331 randomized participants had a mean baseline age of 79.7 years; 84.3% were White, 9.2% Black, 3.3% Hispanic, 1.9% Asian/Pacific Islander, 0.3% Native American, and 1% were of unknown race/ethnicity. The mean baseline RAND-36 physical function score was 71.6 (± 25.2 SD). There were no differences between Intervention (N = 24 657) and Control (N = 24 674) at baseline for age, race/ethnicity, current smoking (2.5%), use of blood pressure or lipid-lowering medications, body mass index, physical function, physical activity, or prior CVD (10.1%).Conclusion: The WHISH trial is rigorously testing whether a physical activity intervention reduces major CV events in a large, diverse cohort of older women. Clinical Trials Registration Number: NCT02425345. [ABSTRACT FROM AUTHOR]

Background: Herpes zoster may significantly impact quality of life (QoL) in older adults. The recombinant zoster vaccine (RZV) is efficacious in adults aged ≥50 and older and is associated with increased reactogenicity compared to placebo. We report here on the impact of reactogenicity of the second RZV dose on the QoL and physical functioning (PF) of vaccine recipients, and summarize findings following both doses.Method: In this single-arm study, 401 adults aged ≥50 and older were enrolled to receive two RZV doses 2 months apart. Change in mean Short Form Survey-36 (SF-36) PF and EuroQol-5 Dimension (EQ-5D) scores, reactogenicity, safety, productivity loss, and healthcare resource utilization were evaluated.Results: In total, 391 (97.5%) participants received dose 2. Post-dose 2, the most common solicited local symptoms were injection site pain (75.1%), erythema (22.4%), and swelling (13.9%), and the most common systemic symptoms were fatigue (46.3%), headache (37.5%), and myalgia (32.9%). Grade 3 solicited (local and systemic) adverse events were reported by 61 (15.6%) participants and were associated with a transient clinically significant decrease in SF-36 PF score on Days 1-2 post-dose 2 that recovered by Day 3. Overall, no clinically important reduction in mean SF-36 PF scores was observed from baseline to post-dose 2 (mean change -0.4), and no quality-adjusted-life-year loss was recorded.Conclusions: Overall, QoL and PF of RZV vaccinees were not affected by vaccine-related reactogenicity. A transient reduction was observed in the first 2 days after RZV vaccination in individuals with Grade 3 adverse events. No safety concerns were identified. [ABSTRACT FROM AUTHOR]

Background: The Lifestyle Interventions and Independence for Elders (LIFE) Study physical activity (PA) intervention was found to be cost-effective compared to health education (HE). However, long-term effects postintervention are unknown.Method: This was a secondary analysis of LIFE Study data linked to Medicare claims data (2014-2016). Participants were linked via Social Security Numbers to Medicare claims data. Utilization and cost variables were analyzed using generalized linear models with negative binomial and Tweedie distributions. Unadjusted means and 95% confidence intervals were compared by year and overall stratified. Each model compared PA versus HE and adjusted for other baseline characteristics and stratified by study site. Additional models were stratified by baseline physical functioning assessment scores.Results: Of the 1,635 LIFE Study participants, 804 (53.5%) were linked to Medicare claims with an average of 33 months of follow-up time during the 3-year data linkage period. Mean outpatient (6.6 vs 6.8), inpatient (0.40 vs 0.40), and other utilization metrics were similar between PA and HE groups. Costs were also similar for each group and each type of service, for example, outpatient: $2,070 versus $2,093 and inpatient: $4,704 versus $4,792. Regression results indicated no statistically significant differences between PA and HE groups.Conclusions: While the LIFE Study demonstrated that PA reduced mobility disability in older adults and was cost-effective, it did not appear to affect long-term health care utilization costs posttrial. These findings suggest that it remains challenging to affect long-term health care costs using PA interventions effects. [ABSTRACT FROM AUTHOR]