SEARCH · PubMed Health

Results for “Frailty”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 775 records · Page 43Linked to original sources

PubMed2000

Discrete duration models combining dynamic and random effects.

Survival data may include two different sources of variation, namely variation over time and variation over units. If both of these variations are present, neglecting one of them can cause serious bias in the estimations. Here we present an approach for discrete duration data that includes both time-varying and unit-specific effects to model these two variations simultaneously. The approach is a combination of a dynamic survival model with dynamic time-varying baseline and covariate effects and a frailty model measuring unobserved heterogeneity with random effects varying independently over units. Estimation is based on posterior modes, i.e., we maximize the joint posterior distribution of the unknown parameters to avoid numerical integration and simulation techniques, that are necessary in a full Bayesian analysis. Estimation of unknown hyperparameters is achieved by an EM-type algorithm. Finally, the proposed method is applied to data of the Veteran's Administration Lung Cancer Trial.

Algorithms↗

PubMed2002

Muscle strength before and mortality after a bone fracture in older people.

We studied whether muscle strength measured before a bone fracture predicts mortality following the fracture. The participants were a sub-cohort of 82 people of a total of 493 Evergreen project participants initially aged 75- and 80 years, who had participated in knee extension strength tests as part of the baseline examinations, and who subsequently suffered at least one bone fracture. Maximal isometric knee extension strength was measured at baseline using an adjustable dynamometer chair. Fracture surveillance was carried out from patient records for 5 years, and mortality surveillance from population register for 10 years after baseline examinations. Average time till a fracture occurred after the baseline was 878 days (SD 576). Subsequent to the fracture, 32 deaths occurred. Using gender-specific cut-offs, three equal distribution-based groups were formed. A gradient risk of mortality was found according to baseline strength. The crude mortality rate per 1000 person-months was 15.2 in the lowest 4.9 in the middle and 1.7 in the highest third of baseline knee extension strength. The adjusted relative risk (RR) of death was 4.40 (95% confidence interval, CI 1.40-13.80) in the lowest and 2.39 (95% CI 0.68-8.4) in the middle tertile vs the highest tertile of muscle strength. Poor muscle strength measured before a fracture occurred was a powerful predictor of increased mortality after the fracture. Poor muscle strength may be a good indicator of overall vulnerability and frailty in old age, and strength testing could be helpful in targeting older people for preventive interventions.

Aged↗

PubMed2003

The MDS-CHESS scale: a new measure to predict mortality in institutionalized older people.

OBJECTIVES: To develop a scale predicting mortality and other adverse outcomes associated with frailty. DESIGN: Observational study based on Minimum Data Set (MDS) 2.0 and mortality data. SETTING: Ontario chronic hospitals. PARTICIPANTS: All chronic hospital patients (N = 28,495) assessed with the MDS 2.0 after mandatory implementation in July 1996 followed until May 1999. MEASUREMENTS: MDS 2.0 assessments done as part of normal practice mainly by registered nurses or multidisciplinary teams in a chronic hospital. Mortality data are available from the accompanying discharge tracking form. RESULTS: The MDS-Changes in Health, End-stage disease and Symptoms and Signs (CHESS) score is a composite measure addressing changes in health, end-stage disease, and symptoms and signs of medical problems. It is a strong predictor of mortality (P <.0001) independent of the effects of age, sex, activities of daily living impairment, cognition, and do-not-resuscitate orders. It is also strongly associated with physician activity, complex medical procedures, and pain (P <.001 for each dependent variable). CONCLUSIONS: The CHESS score provides a useful new MDS-based test to predict mortality and to measure instability in health as a clinical outcome.

Activities of Daily Living↗

PubMed2002

Psychoneuroimmunology: psychological influences on immune function and health.

This review focuses on human psychoneuroimmunology studies published in the past decade. Issues discussed include the routes through which psychological factors influence immune function, how a stressor's duration may influence the changes observed, individual difference variables, the ability of interventions to modulate immune function, and the health consequences of psychosocially mediated immune dysregulation. The importance of negative affect and supportive personal relationships are highlighted. Recent data suggest that immune dysregulation may be one core mechanism for a spectrum of conditions associated with aging, including cardiovascular disease, osteoporosis, arthritis, Type 2 diabetes, certain cancers, and frailty and functional decline; production of proinflammatory cytokines that influence these and other conditions can be stimulated directly by negative emotions and indirectly by prolonged infection.

Health Promotion↗

PubMed1995

Depressive symptoms across older spouses and the moderating effect of marital closeness.

Independent interviews with husbands and wives from 317 community-dwelling older couples showed that depressive symptoms in 1 spouse had a significant impact on depressive symptoms in the other spouse, after controlling for potentially confounding respondent sociodemographic and health status variables. Relationship quality moderated the influence, with spouse depressive symptoms contributing more of the variance to a respondent's symptoms when a couple were close than when they were not and closeness to a spouse buffering the potentially depressive effects of a respondent's own frailty and financial distress. Husband's own variables explained more of the variance in his symptoms when the couple were not close than when they were, and closeness to his wife increased a husband's vulnerability to the impact of the wife's health status.

Aged↗

PubMed1998

The role of gender in very old age: profiles of functioning and everyday life patterns.

Older men and women have different life contexts as a function of differential longevity and socio-structural opportunities over the life course. The question is whether gender-related differences also occur in psychological and everyday functioning in older adults. Examined were 258 men and 258 women between the ages of 70 and 103 years (M = 85 years), participants in the Berlin Aging Study. Significant gender differences were observed in 13 of 28 aspects of personality, social relationships, everyday activity patterns, and reported well-being. Cluster analysis identified 11 subgroups whose profiles of life conditions and health and psychological functioning could be categorized as more or less desirable (functional). The relative risk of a less desirable profile was 1.6 times higher for women than for men. For older adults, gender as a variable carries differences in physical frailty and life conditions that likely have consequences for psychological functioning.

Activities of Daily Living↗

PubMed2004

The impact of childhood intelligence on later life: following up the Scottish mental surveys of 1932 and 1947.

The Scottish Mental Surveys of 1932 and 1947 collected valid IQ-type test scores for almost everyone born in 1921 and 1936 and attending school on June 1, 1932 (N=89,498) and June 4, 1947 (N=70,805). These surveys are described. This research, using the surveys' data, examined (a) the stability of intelligence differences across the life span, (b) the determinants of cognitive change from childhood to old age, and (c) the impact of childhood intelligence on survival and health in old age. Surviving participants of the Scottish Mental Surveys were tested, and the surveys' data were linked with public and health records. Novel findings on the stability of IQ scores from age 11 to age 80; sex differences in cognitive aging; the dedifferentiation hypothesis of cognitive aging; and the effect of childhood IQ on all-cause and specific mortality, morbidity, and frailty in old age are presented.

Adolescent↗

PubMed2004

The effect of social comparison information on the life satisfaction of frail older persons.

In this study, the authors examined the effects of social comparison on the life satisfaction of 455 community-dwelling older persons. These older persons were confronted with a fictitious interview with either an upward or a downward target. After downward comparison, older persons felt more satisfied with their lives than after upward comparison, especially those who had higher levels of frailty. These effects were only found with lower levels of identification. Apparently, downward comparison only serves its self-enhancing function on life satisfaction among frail older persons when they perceive the comparison target as different from themselves.

Aged↗

PubMed2001

Localized Igf-1 transgene expression sustains hypertrophy and regeneration in senescent skeletal muscle.

Aging skeletal muscles suffer a steady decline in mass and functional performance, and compromised muscle integrity as fibrotic invasions replace contractile tissue, accompanied by a characteristic loss in the fastest, most powerful muscle fibers. The same programmed deficits in muscle structure and function are found in numerous neurodegenerative syndromes and disease-related cachexia. We have generated a model of persistent, functional myocyte hypertrophy using a tissue-restricted transgene encoding a locally acting isoform of insulin-like growth factor-1 that is expressed in skeletal muscle (mIgf-1). Transgenic embryos developed normally, and postnatal increases in muscle mass and strength were not accompanied by the additional pathological changes seen in other Igf-1 transgenic models. Expression of GATA-2, a transcription factor normally undetected in skeletal muscle, marked hypertrophic myocytes that escaped age-related muscle atrophy and retained the proliferative response to muscle injury characteristic of younger animals. The preservation of muscle architecture and age-independent regenerative capacity through localized mIgf-1 transgene expression suggests clinical strategies for the treatment of age or disease-related muscle frailty.

Animals↗

PubMed2002

Body mass index and physical function in older women.

OBJECTIVE: We modified existing standardized measurement tools in the Physical Performance Test and tasks from the Frailty and Injuries: Cooperative Studies of Intervention Technique Study to evaluate physical function in older women. Our objectives were (1) to characterize physical function themes based on combinations of tasks (deriving factors or components) and (2) to quantify the correlation between derived factors and body mass index (BMI). RESEARCH METHODS AND PROCEDURES: Nutrition risk screens from enrollees in a Medicare-managed risk program served as the sampling frame. To obtain adequate representation for a range of BMI, a random sample was obtained of 90 women from the following BMI strata: BMI, 22 to <27 kg/m(2); BMI, 27 to <30 kg/m(2); and BMI, > or =30 kg/m(2). Subjects were asked to perform a series of 18 functional tasks during a home visit. RESULTS: The mean age was similar in the three BMI groups with an overall mean age of 71 +/- 4.9 years (SD). Factors characterized by lower-body function, upper-body function, coordination, and strength were responsible for 30%, 11%, 9%, and 9% of the variance in task scores, respectively. BMI, controlling for age, explained 5%, 14%, 3%, and 0% of the variation in these factors, respectively. Higher BMI is associated significantly with poorer upper- and lower-body function but is not associated significantly to strength or coordination. DISCUSSION: Higher BMI seems to differentially impede specific aspects of physical function, especially upper-body function, and to a lesser extent, lower-body function. BMI does not seem to be associated with levels of coordination or strength. Better understanding of how BMI impacts physical function will aid in the design of interventions to promote independent living in elderly, obese women.

Aged↗

PubMed2005

Obesity in older adults: technical review and position statement of the American Society for Nutrition and NAASO, The Obesity Society.

Obesity causes serious medical complications and impairs quality of life. Moreover, in older persons, obesity can exacerbate the age-related decline in physical function and lead to frailty. However, appropriate treatment for obesity in older persons is controversial because of the reduction in relative health risks associated with increasing body mass index and the concern that weight loss could have potential harmful effects in the older population. This joint position statement from the American Society for Nutrition and NAASO, The Obesity Society reviews the clinical issues related to obesity in older persons and provides health professionals with appropriate weight-management guidelines for obese older patients. The current data show that weight-loss therapy improves physical function, quality of life, and the medical complications associated with obesity in older persons. Therefore, weight-loss therapy that minimizes muscle and bone losses is recommended for older persons who are obese and who have functional impairments or medical complications that can benefit from weight loss.

Aged↗

PubMed2026

Inhibiting cyclin D1-CDK6 suppresses senescence-associated inflammatory gene expression and age-related functional decline.

Cellular senescence contributes to aging and age-related diseases by driving chronic inflammation through the senescence-associated secretory phenotype (SASP), including interferon-stimulated genes (ISGs). Here we confirm and extend previous observations that cyclin D1 (CCND1), a key cell cycle regulator, is paradoxically upregulated across models of nonproliferating senescent cells. We show that CCND1 and its kinase partner CDK6 drive SASP and ISG expression in senescent cells by promoting DNA damage accumulation. This leads to the formation of cytoplasmic chromatin fragments that activate pro-inflammatory cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling. In aged mouse livers, senescent hepatocytes show increased Ccnd1 expression. Hepatocyte-specific Ccnd1 knockout or treatment with the clinical grade CDK4/6 inhibitor palbociclib reduces DNA damage and ISGs in aged mouse liver. Further, palbociclib suppresses frailty and improves physical performance of aged mice. These findings demonstrate a role for CCND1/CDK6 in regulating DNA damage and inflammation in senescence and aging, highlighting it as a promising target for therapeutic repurposing.

Animals↗

PubMed2000

Interventions aimed at dietary and lifestyle changes to promote healthy aging.

Desirable dietary habits and other lifestyle practices reduce premature mortality and compress the period of morbidity experienced towards the end of life. Aging adults are at risk of nutritionally inadequate diets especially in relation to protein, vitamins D, B1, B6, B12, fluid and other food components. Interventions aimed at ensuring dietary adequacy also need to consider the social and cultural aspects of eating as food is fundamental to a person's well-being and quality of life. The nutrition-related health problems associated with aging such as frailty, depression, incontinence and chronic non-communicable diseases should be identified in both the individual and in the community before dietary and other health interventions are implemented. In older adults, these dietary and health promoting interventions should then focus on maximizing function and quality of life, be acceptable and finally, measurable in terms of effectiveness.

Aged↗

PubMed2003

Impaired cognitive function and mental performance in mild dehydration.

Dehydration is a reliable predictor of impaired cognitive status. Objective data, using tests of cortical function, support the deterioration of mental performance in mildly dehydrated younger adults. Dehydration frequently results in delirium as a manifestation of cognitive dysfunction. Although, the occurrence of delirium suggests transient acute global cerebral dysfunction, cognitive impairment may not be completely reversible. Animal studies have identified neuronal mitochondrial damage and glutamate hypertransmission in dehydrated rats. Additional studies have identified an increase in cerebral nicotinamide adenine dinucleotide phosphate-diaphorase activity (nitric oxide synthase, NOS) with dehydration. Available evidence also implicates NOS as a neurotransmitter in long-term potentiation, rendering this a critical enzyme in facilitating learning and memory. With ageing, a reduction of NOS activity has been identified in the cortex and striatum of rats. The reduction of NOs synthase activity that occurs with ageing may blunt the rise that occurs with dehydration, and possibly interfere with memory processing and cognitive function. Dehydration has been shown to be a reliable predictor of increasing frailty, deteriorating mental performance and poor quality of life. Intervention models directed toward improving outcomes in dehydration must incorporate strategies to enhance prompt recognition of cognitive dysfunction.

Aging↗

PubMed2003

Emerging relationships of inflammation, cardiovascular disease and chronic diseases of aging.

The last 10 y have seen an enormous surge in research focused on inflammation and atherosclerotic heart disease. In parallel, inflammation (used as a term to represent a broad array of response systems) has become a topic of interest in a number of different areas of chronic disease including type II diabetes, cognitive decline and frailty, among others. These discoveries are opening up many new opportunities for risk assessment. For example, markers of inflammation such as C-reactive protein are becoming established as important additions in helping to define those at the greatest risk of progressive vascular disease. These discoveries are also important in the area of risk management. Older medications now in wide use are being found to have previously unknown anti-inflammatory effects (eg, statins); these effects are now viewed as being important to the overall effectiveness of these compounds. In addition, the many different aspects of inflammation provide a wealth of targets for new therapeutics, which will be increasingly important as the population continues to age. Although daunting in complexity, studies on the relation of inflammation to disease have already proven useful, and hold promise for providing fundamental advances in both basic biology and clinical medicine.

Aged↗

PubMed2003

Osteoporosis: pathogenesis and clinical intervention.

Osteoporosis is a very common disorder and much has been learnt in recent years about the many pathogenic processes that contribute to bone loss and fragility. Drug treatments are now available to prevent bone loss and reduce fracture, and there are prospects for modifying some of the pathogenic processes themselves. In common with other structures, the tissues of the musculoskeletal system undergo many changes with aging, and some of the commonest skeletal disorders are seen in the elderly. The changes in bone lead to osteoporosis and fractures, whereas muscle changes (sarcopenia) contribute to frailty, and changes in cartilage lead to osteoarthritis.

Aging↗

PubMed2005

Myostatin: a modulator of skeletal-muscle stem cells.

Myostatin, or GDF-8 (growth and differentiation factor-8), was first identified through sequence identity with members of the BMP (bone morphogenetic protein)/TGF-beta (transforming growth factor-beta) superfamily. The skeletal-muscle-specific expression pattern of myostatin suggested a role in muscle development. Mice with a targeted deletion of the myostatin gene exhibit a hypermuscular phenotype. In addition, inactivating mutations in the myostatin gene have been identified in 'double muscled' cattle breeds, such as the Belgian Blue and Piedmontese, as well as in a hypermuscular child. These findings define myostatin as a negative regulator of skeletal-muscle development. Myostatin binds with high affinity to the receptor serine threonine kinase ActRIIB (activin type IIB receptor), which initiates signalling through a smad2/3-dependent pathway. In an effort to validate myostatin as a therapeutic target in a post-embryonic setting, a neutralizing antibody was developed by screening for inhibition of myostatin binding to ActRIIB. Administration of this antimyostatin antibody to adult mice resulted in a significant increase in both muscle mass and functional strength. Importantly, similar results were obtained in a murine model of muscular dystrophy, the mdx mouse. Unlike the myostatin-deficient animals, which exhibit both muscle hypertrophy and hyperplasia, the antibody-treated mice demonstrate increased musculature through a hypertrophic mechanism. These results validate myostatin inhibition as a therapeutic approach to muscle wasting diseases such as muscular dystrophy, sarcopenic frailty of the elderly and amylotrophic lateral sclerosis.

Animals↗

PubMed2000

Age-related changes of serum sex hormones, insulin-like growth factor-1 and sex-hormone binding globulin levels in men: cross-sectional data from a healthy male cohort.

The age-dependent decline of the gonadal and somatotopic axis has been causally linked to frailty in the elderly by their effects on muscle mass and bone mineral density. However, for healthy men data on serum oestrogens and androgens, as well as IGF-1, as a common outcome measure covering the whole adult age range are scarce. We therefore studied healthy, nonobese male subjects between 20 and 80 years of age to asses their morning concentrations of total (T), free (FT), bioavailable testosterone (bT), oestradiol (E2), bioavailable oestradiol (bE2), oestrone (E1), sex-hormone binding globulin (SHBG), and insulin-like growth factor 1 (IGF-1). Five hundred and seventy-two male healthy volunteers with a BMI < 30 kg/m2 recruited from regular blood donors and senior sports clubs participated in the study. Serum samples were obtained during morning hours and T, FT, E2, E1, SHBG, albumin and IGF-1 were measured by radio-immunoassay systems. In addition, bT and bE2 were calculated. A potential relationship between sex hormones and IGF-1 was tested by multiple regression analysis including age and BMI. Ageing was negatively related to serum levels of sex steroids and IGF-1 (both P < 0.0001) with a mean decrease (youngest vs. oldest) of 51% for T, 64% for FT, 78% for bT, 32% for E2, 62% for bE2, 29% for E1 and 51% for IGF-1 starting in early adulthood whereas SHBG increased after the 5th decade of life (ANOVA P < 0.001). The decline of sex hormones and IGF-1 remained relatively unchanged after adjustment for BMI. Multiple regression analysis revealed an age-and BMI- independent association between oestradiol and IGF-1. In contrast to the female situation sex hormones in healthy, nonobese men decline continuously with age. This process has already started in the third decade, and is paralleled by a decline of IGF-1 serum levels leading to a substantial proportion of elderly men with markedly lowered serum levels of bioavailable sex hormones and IGF-1 compared to the young adult male range. With the recent demonstration of beneficial effects of androgen replacement therapy in healthy males on general well being, muscle mass and bone mineral density the present data may underline the importance of more detailed studies on the biological significance of hormonal changes in men with age.

Adult↗