Patients with CKD are characterized by low levels of physical functioning, which, along with low physical activity, predict poor outcomes in those treated with dialysis. The hallmark of clinical care ...in geriatric practice and geriatric research is the orientation to and assessment of physical function and functional limitations. Although there is increasing interest in physical function and physical activity in patients with CKD, the nephrology field has not focused on this aspect of care. This paper provides an in-depth review of the measurement of physical function and physical activity. It focuses on physiologic impairments and physical performance limitations (impaired mobility and functional limitations). The review is based on established frameworks of physical impairment and functional limitations that have guided research in physical function in the aging population. Definitions and measures for physiologic impairments, physical performance limitations, self-reported function, and physical activity are presented. On the basis of the information presented, recommendations for incorporating routine assessment of physical function and encouragement for physical activity in clinical care are provided.
Sedentary behavior is associated with increased mortality in the general population. Whether replacing sedentary behavior with low- or light-intensity activities confers a survival benefit in the ...general or CKD populations is unknown.
This observational analysis of the 2003-2004 National Health and Nutrition Examination Survey examined the associations of low- and light-intensity activities with mortality. On the basis of the number of counts/min recorded by an accelerometer, durations of sedentary (<100/min), low (100-499/min), light (500-2019/min), and moderate/vigorous (≥2020/min) activity were defined and normalized to 60 minutes. The mortality associations of 2 min/hr less sedentary duration in conjunction with 2 min/hr more (tradeoff) spent in one of the low, light, or moderate/vigorous activity durations while controlling for the other two activity durations were examined in multivariable Cox regression models in the entire cohort and in the CKD subgroup.
Of the 3626 participants included, 383 had CKD. The mean sedentary duration was 34.4±7.9 min/hr in the entire cohort and 40.8±6.8 in the CKD subgroup. Tradeoff of sedentary duration with low activity duration was not associated with mortality in the entire cohort or the CKD subgroup. Tradeoff of sedentary duration with light activity duration was associated with a lower hazard of death in the entire cohort (hazard ratio, 0.67; 95% confidence interval, 0.48 to 0.93) and CKD subgroup (hazard ratio, 0.59; 95% confidence interval, 0.35 to 0.98). Tradeoff of sedentary duration with moderate/vigorous activity duration had a nonsignificant lower hazard in the entire cohort and CKD subgroup.
Patients with CKD are sedentary nearly two thirds of the time. Interventions that replace sedentary duration with an increase in light activity duration might confer a survival benefit.
Muscle’s structural composition is an important factor underlying muscle strength and physical function in older adults. There is an increasing amount of research to support the clear disassociation ...between the loss of muscle lean tissue mass and strength with aging. This disassociation implies that factors in addition to lean muscle mass are responsible for the decreases in strength and function seen with aging. Intermuscular adipose tissue (IMAT) is a significant predictor of both muscle function and mobility function in older adults and across a wide variety of comorbid conditions such as stroke, spinal cord injury, diabetes, and COPD. IMAT is also implicated in metabolic dysfunction such as insulin resistance. The purpose of this narrative review is to provide a review of the implications of increased IMAT levels in metabolic, muscle, and mobility function. Potential treatment options to mitigate increasing levels of IMAT will also be discussed.
Considerable evidence now shows that all languages, signed and spoken, exhibit a significant amount of iconicity. We examined how the visual-gestural modality of signed languages facilitates ...iconicity for different kinds of lexical meanings compared to the auditory-vocal modality of spoken languages. We used iconicity ratings of hundreds of signs and words to compare iconicity across the vocabularies of two signed languages - American Sign Language and British Sign Language, and two spoken languages - English and Spanish. We examined (1) the correlation in iconicity ratings between the languages; (2) the relationship between iconicity and an array of semantic variables (ratings of concreteness, sensory experience, imageability, perceptual strength of vision, audition, touch, smell and taste); (3) how iconicity varies between broad lexical classes (nouns, verbs, adjectives, grammatical words and adverbs); and (4) between more specific semantic categories (e.g., manual actions, clothes, colors). The results show several notable patterns that characterize how iconicity is spread across the four vocabularies. There were significant correlations in the iconicity ratings between the four languages, including English with ASL, BSL, and Spanish. The highest correlation was between ASL and BSL, suggesting iconicity may be more transparent in signs than words. In each language, iconicity was distributed according to the semantic variables in ways that reflect the semiotic affordances of the modality (e.g., more concrete meanings more iconic in signs, not words; more auditory meanings more iconic in words, not signs; more tactile meanings more iconic in both signs and words). Analysis of the 220 meanings with ratings in all four languages further showed characteristic patterns of iconicity across broad and specific semantic domains, including those that distinguished between signed and spoken languages (e.g., verbs more iconic in ASL, BSL, and English, but not Spanish; manual actions especially iconic in ASL and BSL; adjectives more iconic in English and Spanish; color words especially low in iconicity in ASL and BSL). These findings provide the first quantitative account of how iconicity is spread across the lexicons of signed languages in comparison to spoken languages.
Key points
Five days of bed rest resulted in a reduction in leg lean mass and strength in older adults.
After bed rest, older (but not younger) adults had reduced amino acid‐induced anabolic ...sensitivity (blunted muscle protein synthesis; MPS) and enhanced markers associated with the ubiquitin proteasome and autophagy–lysosomal systems (increase in molecular markers related to muscle proteolysis).
Younger adults did not lose leg lean mass (via DXA) after 5 days of bed rest despite blunted amino acid‐induced mTORC1 signalling and increased skeletal muscle REDD1, REDD2 and MURF1 mRNA expression.
Exercise rehabilitation restored bed rest‐induced deficits in lean mass, strength, nutrient‐induced protein anabolism (protein synthesis and mTORC1 signalling) and select muscle proteolytic markers in older adults.
Bed rest‐induced muscle loss and impaired muscle recovery may contribute to age‐related sarcopenia. It is unknown if there are age‐related differences in muscle mass and muscle anabolic and catabolic responses to bed rest. A secondary objective was to determine if rehabilitation could reverse bed rest responses. Nine older and fourteen young adults participated in a 5‐day bed rest challenge (BED REST). This was followed by 8 weeks of high intensity resistance exercise (REHAB). Leg lean mass (via dual‐energy X‐ray absorptiometry; DXA) and strength were determined. Muscle biopsies were collected during a constant stable isotope infusion in the postabsorptive state and after essential amino acid (EAA) ingestion on three occasions: before (PRE), after bed rest and after rehabilitation. Samples were assessed for protein synthesis, mTORC1 signalling, REDD1/2 expression and molecular markers related to muscle proteolysis (MURF1, MAFBX, AMPKα, LC3II/I, Beclin1). We found that leg lean mass and strength decreased in older but not younger adults after bedrest (P < 0.05) and was restored after rehabilitation. EAA‐induced mTORC1 signalling and protein synthesis increased before bed rest in both age groups (P < 0.05). Although both groups had blunted mTORC1 signalling, increased REDD2 and MURF1 mRNA after bedrest, only older adults had reduced EAA‐induced protein synthesis rates and increased MAFBX mRNA, p‐AMPKα and the LC3II/I ratio (P < 0.05). We conclude that older adults are more susceptible than young persons to muscle loss after short‐term bed rest. This may be partially explained by a combined suppression of protein synthesis and a marginal increase in proteolytic markers. Finally, rehabilitation restored bed rest‐induced deficits in lean mass and strength in older adults.
To link the Activity Measure for Post-Acute Care (AM-PAC) Applied Cognition to the Patient-Reported Outcomes Measurement Information System (PROMIS) Cognitive Function, allowing for a common metric ...across scales.
Cross-sectional survey study.
Outpatient rehabilitation clinics.
Consecutive sample of 500 participants (N=500) aged ≥18 years presenting for outpatient therapy (physical, occupation, speech).
Not applicable.
AM-PAC Medicare and Generic Cognition short forms and PROMIS Cognitive Function items representing the PROMIS Cognitive Function item bank.
The calibration of 25 AM-PAC cognition items with 11 fixed PROMIS cognitive function item parameters using item-response theory indicated that items were measuring the same underlying construct (cognition). Both scales measured a wide range of functioning. The AM-PAC Generic Cognitive assessment showed more reliability with lower levels of cognition, whereas the PROMIS Cognitive Function full-item bank was more reliable across a larger distribution of scores. Data were appropriate for a fixed-anchor item response theory-based crosswalk and AM-PAC Cognition raw scores were mapped onto the PROMIS metric.
The crosswalk developed in this study allows for converting scores from the AM-PAC Applied Cognition to the PROMIS Cognitive Function scale.
The pro- and anti-inflammatory macrophages are associated with insulin sensitivity and skeletal muscle regeneration. Infiltrating macrophages in skeletal muscle during a period of physical inactivity ...and subsequent reloading/rehabilitation in older adults is unknown, but may provide insight into mechanisms related to the development of metabolic disease and changes in muscle cell size. The purpose of this study was to determine if skeletal muscle macrophage infiltration is modulated differently between young and older adults after bed rest and exercise rehabilitation and if these responses are related to muscle and insulin sensitivity changes. 14 young and 9 older adults underwent 5-days of bed rest followed by 8-weeks of lower limb eccentric exercise rehabilitation (REHAB). Dual-energy X-ray absorptiometry, magnetic resonance imaging and myofiber analysis were used to identify muscle morphology and CLIX-IR and CLIX-β were used to assess insulin sensitivity. Skeletal muscle macrophages, CD68 (pan), CD11b (M1), CD163 (M2), CD206 (M2), were characterized using immunohistochemistry and gene expression. Insulin sensitivity, independent of age, decreased ~38% following bed rest and was restored following REHAB. We found robust age-related differences in muscle atrophy during bed rest, yet older and younger adults equally hypertrophied during REHAB. Interestingly, there were age-related differences in macrophage content (CD68+CD11b+ and CD68+CD11b− cells) but both young and old similarly increased macrophages with REHAB. Satellite cell changes during rehab corresponded to macrophage content changes. Muscle tissue resident macrophages and gene expression, were not associated with changes in insulin sensitivity following bed rest and REHAB. These data suggest that muscle macrophages are modulated as a result of exercise rehabilitation following bed rest and may more associated with muscle regrowth/hypertrophy rather than insulin sensitivity in young or older adults.
This trial was registered at clinicaltrials.gov as NCT01669590.
•Older adults (vs young) experienced atrophy during bed rest, but both groups gained lean mass similarly after rehabilitation.•Insulin sensitivity decreased after bed rest and returned to baseline levels after rehabilitation, independent of age.•There were age-related differences in skeletal muscle macrophages, but both groups increased macrophages after rehabilitation.•Changes in muscle macrophages corresponded to changes in satellite cells, but not insulin sensitivity during rehabilitation.
Introduction: Intramuscular adipose tissue (IMAT) is a potential contributor to declining force production and may be related to impaired central activation; therefore, the purpose of this report is ...to describe IMAT composition and its association with central activation in older adults. The central activation ratio (CAR) of the knee extensors was assessed using a superimposition technique in 15 older adults (29 legs) along with the cross‐sectional area of IMAT and lean tissue. Results: IMAT and CAR are inversely related in older adults (r = −0.51, P = 0.005), and many subjects with high IMAT have deficits in central activation, whereas those with low IMAT have normal central activation. Conclusions: These novel findings may assist in unraveling why muscle force production and lean tissue cross‐sectional area are not strongly linked, as the ability to centrally activate muscle appears to be unrelated to lean muscle area and may be dependent in part on IMAT levels. Muscle Nerve 46:813–816, 2012
Length-dependent neuropathy is the most common and costly complication of diabetes and frequently causes injury primarily to small-diameter cutaneous nociceptive fibers. Not only persistent ...hyperglycemia but also metabolic, endocrine, and inflammatory effects of obesity and dyslipidemia appear to play an important role in the development of diabetic neuropathy. Rational therapies aimed at direct control of glucose or its increased entry into the polyol pathway, oxidative or nitrosative stress, advanced glycation end product formation or signaling, microvascular ischemia, or adipocyte-derived toxicity have each failed in human trials of diabetic neuropathy. Aerobic exercise produces salutary effects in many of these pathogenic pathways simultaneously and, in both animal models and human trials, has been shown to improve symptoms of neuropathy and promote re-growth of cutaneous small-diameter fibers. Behavioral reduction in periods of seated, awake inactivity produces multimodal metabolic benefits similar to exercise, and the two strategies when combined may offer sustained benefit to peripheral nerve function.
Reduced lean mass and physical function is a characteristic of frailty. However, it is currently unknown if proteolysis through the E3 ubiquitin ligases and the autophagic lysosomal pathway is ...dysregulated in inactive frail older women. The purpose of this study was to determine the expression of key markers of ubiquitin-mediated and autophagic lysosomal proteolysis in inactive (N = 7) compared with active (N = 7) older women.
Strength, mobility, leg lean mass, and physical activity assessment were used to characterize activity levels and frailty in older women. Vastus lateralis biopsies were collected after an overnight fast and were assessed for gene and protein targets related to E3 ubiquitin ligases and the autophagic lysosomal system.
We found that AMP-activated protein kinase alpha (Thr172) was increased (p = .045), and forkhead box O3A (FOXO3A) gene expression (p = .047) was lower in inactive frail older women. Foxo3a (Ser253), Beclin1 (Ser93/96), and class III phosphatidylinositol-3-kinase (VPS34) protein expression were not different between the groups (p > .05). Neural precursor cell-expressed developmentally downregulated protein 4, muscle ring finger 1, muscle atrophy F-box, and the autophagy/mitophagy gene expression markers, Beclin1, autophagy-related-7, BCL2/adenovirus E1B 19 kDa interacting protein 3 (BNIP3), dynamin-related protein 1, and Parkinson protein 2 (PARKIN) were lower in inactive frail older women (p < .05). Autophagy/mitophagy markers were positively correlated with the 6-minute walk and leg lean mass (p < .05).
We conclude that physical inactivity in frail older women is associated with a downregulation of ubiquitin-mediated and autophagic lysosomal skeletal muscle gene expression, perhaps related to low muscle mass and poor physical function.
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