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Abstract Frailty, the state of increased vulnerability to physical stressors as a result of progressive and sustained degeneration in multiple physiological systems, is common in those with chronic kidney disease (CKD). In fact, the prevalence of frailty in the older adult population is reported to be 11%, whereas the prevalence of frailty has been reported to be greater than 60% in dialysis-dependent CKD patients. Frailty is independently linked with adverse clinical outcomes in all stages of CKD and has been repeatedly shown to be associated with an increased risk of mortality and hospitalization. In recent years there have been efforts to create an operationalized definition of frailty to aid its diagnosis and to categorize its severity. Two principal concepts are described, namely the Fried Phenotype Model of Physical Frailty and the Cumulative Deficit Model of Frailty. There is no agreement on which frailty assessment approach is superior, therefore, for the time being, emphasis should be placed on any efforts to identify frailty. Recognizing frailty should prompt a holistic assessment of the patient to address risk factors that may exacerbate its progression and to ensure that the patient has appropriate psychological and social support. Adequate nutritional intake is essential and individualized exercise programmes should be offered. The acknowledgement of frailty should prompt discussions that explore the future care wishes of these vulnerable patients. With further study, nephrologists may be able to use frailty assessments to inform discussions with patients about the initiation of renal replacement therapy.

Danielle Posthuma and colleagues perform a large meta-analysis for intelligence and determine genetic overlap with several neuropsychiatric and metabolic traits. They find 15 new significant loci and implicate 40 new genes, most of which are predominantly expressed in the brain. Intelligence is associated with important economic and health-related life outcomes 1 . Despite intelligence having substantial heritability 2 (0.54) and a confirmed polygenic nature, initial genetic studies were mostly underpowered 3 , 4 , 5 . Here we report a meta-analysis for intelligence of 78,308 individuals. We identify 336 associated SNPs (METAL P < 5 × 10 −8 ) in 18 genomic loci, of which 15 are new. Around half of the SNPs are located inside a gene, implicating 22 genes, of which 11 are new findings. Gene-based analyses identified an additional 30 genes (MAGMA P < 2.73 × 10 −6 ), of which all but one had not been implicated previously. We show that the identified genes are predominantly expressed in brain tissue, and pathway analysis indicates the involvement of genes regulating cell development (MAGMA competitive P = 3.5 × 10 −6 ). Despite the well-known difference in twin-based heritability 2 for intelligence in childhood (0.45) and adulthood (0.80), we show substantial genetic correlation ( r g = 0.89, LD score regression P = 5.4 × 10 −29 ). These findings provide new insight into the genetic architecture of intelligence.

Visual impairment has been associated with lower cognitive ability among older adults, yet little is known about whether improving visual function with cataract surgery would be associated with slower cognitive decline. This study aimed to assess whether trajectories of cognitive decline differed before and after cataract surgery and compare those trajectories between older adults with cataract surgery and without cataract. Data were drawn from the English Longitudinal Study of Ageing (ELSA) Wave 1 (2002/03) until Wave 7 (2014/15). The study population consisted of 2,068 individuals who underwent cataract surgery between Wave 2 and Wave 6 as the treatment group and 3,636 individuals with no cataract as the control group. We included only respondents who took part in a minimum three waves. Propensity score matching method was used to match the individuals in the treatment group with those in the control group. After we put an \"artificial\" intervention point for the individuals in the control group at the point that the matched person has cataract surgery, spline method was used to identify differences in cognitive trajectories pre- and post-cataract surgery. In the treatment group, we found that cataract surgery was positively associated with episodic memory scores after controlling for the potential covariates (β = 4.23, p<0.001). Episodic memory scores declined with older age, but the decline in episodic memory scores was slower after cataract surgery (β = -0.05, p<0.001) than before cataract surgery (β = -0.1, p<0.001). Although the episodic memory among respondents in the control group before intervention (β = -0.08, p<0.001) declined slower than those in the intervention group (β = -0.1, p<0.001), the declines in episodic memory scores were similar in both groups after the intervention (control: β = -0.05, p<0.001; intervention: β = -0.05, p<0.001). Cataract surgery may have a positive impact on trajectories of cognitive decline in later life. Further research is required to identify the mechanism to explain the association between cataract surgery and cognitive ageing, and whether early intervention towards vision correction results in a reduction in dementia risk.

Global ageing poses a substantial economic burden on health and social care costs. Enabling a greater proportion of older people to stay healthy for longer is key to the future sustainability of health, social and economic policy. Frailty and associated decrease in resilience plays a central role in poor health in later life. In this study, we present a population level assessment of the metabolic phenotype associated with frailty. Analysis of serum from 1191 older individuals (aged between 56 and 84 years old) and subsequent longitudinal validation (on 786 subjects) was carried out using liquid and gas chromatography-mass spectrometry metabolomics and stratified across a frailty index designed to quantitatively summarize vulnerability. Through multivariate regression and network modelling and mROC modeling we identified 12 significant metabolites (including three tocotrienols and six carnitines) that differentiate frail and non-frail phenotypes. Our study provides evidence that the dysregulation of carnitine shuttle and vitamin E pathways play a role in the risk of frailty. Risk of age-related chronic disorders and decrease in resilience is associated with ageing. Here the authors analyse the human blood metabolome and identify metabolites associated with frailty.

The investigators sought evidence-based criteria for identifying late-onset hypogonadism in men between the ages of 40 and 79 years on the basis of the association between symptoms and a low testosterone level. The data suggest that late-onset hypogonadism can be defined by the presence of at least three sexual symptoms with a total testosterone level of less than 11 nmol per liter and a free testosterone level of less than 220 pmol per liter. The data suggest that late-onset hypogonadism can be defined by the presence of at least three sexual symptoms with a total testosterone level of less than 11 nmol per liter and a free testosterone level of less than 220 pmol per liter. The clinical importance of an age-related reduction in the testosterone level 1 – 3 remains controversial. 4 , 5 Because of the uncertainty regarding the nature of testosterone deficiency in aging men, 6 – 9 recent guidelines have suggested that so-called late-onset hypogonadism be regarded as a clinical and biochemical state with advancing age, characterized by particular symptoms and a low level of serum testosterone. 10 , 11 However, few data on hypogonadism in aging men are available 4 , 8 , 12 because of the lack of evidence regarding the exact criteria for identifying testosterone deficiency in older men who do not have pathological hypogonadism. 6 , 13 Although a familiar array . . .

Frailty is associated with adverse health outcomes in people with chronic kidney disease (CKD). Evidence supporting targeted interventions is needed. This pilot randomised controlled trial (RCT) aimed to inform the design of a definitive RCT evaluating the effectiveness of a home-based exercise intervention for pre-frail and frail older adults with CKD. Six hundred and sixty-five patients had an eligibility assessment with 217 (33%; 95% CI 29, 36) eligible. Thirty-five (16%; 95% CI 12, 22) participants were recruited. Six were categorised as robust and withdrawn prior to randomisation. Fifteen participants were randomised to exercise and 14 to usual care. Eleven (73%; 95% CI 45, 91) participants completed [greater than or equal to]2 exercise sessions/week. Retained participants completed all outcome measures (n = 21; 100%; 95% CI 81, 100). Eight (28%; 95% CI 13, 47) participants were withdrawn. Fifteen participated in interviews. Decision to participate/withdraw was influenced by perceived risk of exercise worsening symptoms. Participant perceived benefits included improved fitness, balance, strength, well-being, energy levels and confidence. This pilot RCT demonstrates that progression to definitive RCT is possible provided recruitment and retention challenges are addressed. It has also provided preliminary evidence that home-based exercise may be beneficial for people living with frailty and CKD.

ObjectivesExposures in utero and during infancy may impact the development of diseases later in life. They may be linked with development of frailty, although the mechanism is unclear. This study aims to determine the associations between early life risk factors and development of frailty among middle-aged and older adults as well as potential pathways via education, for any observed association.DesignA cross-sectional study.SettingsThis study used data from UK Biobank, a large population-based cohort.Participants502 489 individuals aged 37–73 years were included in the analysis.Primary and secondary outcome measuresEarly life factors in this study included being breast fed as a baby, maternal smoking, birth weight, the presence of perinatal diseases, birth month and birth place (in or outside the UK). We developed a frailty index comprising 49 deficits. We used generalised structural equation modelling to examine the associations between early life factors and development of frailty and whether any observed association was mediated via educational attainment.ResultsA history of breast feeding and normal birth weight were associated with a lower frailty index while maternal smoking, the occurrence of perinatal diseases and birth month with a longer day length were associated with a higher frailty index. Educational level mediated the relationship between these early life factors and frailty index.ConclusionsThis study highlights that biological and social risk occurring at different stages of life are related to the variations in frailty index in later life and suggests opportunities for prevention across the life course.

Dysphagia has been estimated to affect around 8–16 % of healthy elderly individuals living in the community. The present study investigated the stability of perceived dysphagia symptoms over a 3-year period and whether such symptoms predicted death outcomes. A population of 800 and 550 elderly community-dwelling individuals were sent the Sydney Swallow Questionnaire (SSQ) in 2009 and 2012, respectively, where an arbitrary score of 180 or more was chosen to indicate symptomatic dysphagia. The telephone interview cognitive screen measured cognitive performance and the Geriatric Depression Scale measured depression. Regression models were used to investigate associations with dysphagia symptom scores, cognition, depression, age, gender and a history of stroke; a paired t test was used to examine if individual mean scores had changed. A total of 528 participants were included in the analysis. In 2009, dysphagia was associated with age ( P  = 0.028, OR 1.07, CI 1.01, 1.13) and stroke ( P  = 0.046, OR 2.04, CI 1.01, 4.11) but these associations were no longer present in 2012. Those who had symptomatic dysphagia in 2009 ( n  = 75) showed a shift towards improvement in swallowing ( P  < 0.001, mean = −174.4, CI −243.6, −105.3), and for those who died from pneumonia, there was no association between the SSQ derived swallowing score and death ( P  = 0.509, OR 0.10, CI −0.41, −0.20). We conclude that swallowing symptoms are a temporally dynamic process, which increases our knowledge on swallowing in the elderly.

Verbal memory is typically studied using immediate recall (IR) and delayed recall (DR) scores, although DR is dependent on IR capability. Separating these components may be useful for deciphering the genetic variation in age-related memory abilities. This study was conducted to (a) construct individual trajectories in IR and independent aspects of delayed recall, or residualized-DR (rDR), across older adulthood; and (b) identify genetic markers that contribute to four estimated phenotypes: IR and rDR levels and changes after age 60. A cognitively intact sample (N = 20,650 with 125,164 observations) was drawn from the U.S. Health and Retirement Study, a nationally representative study of adults aged 50 and older. Mixed effects regression models were constructed using repeated measures from data collected every two years (1996-2012) to estimate level at age 60 and change in memory post-60 in IR and rDR. Genome-wide association scans (GWAS) were conducted in the genotypic subsample (N = 7,486) using ~1.2 million single nucleotide polymorphisms (SNPs). One SNP (rs2075650) in TOMM40 associated with rDR level at the genome-wide level (p = 5.0x10-08), an effect that replicated in an independent sample from the English Longitudinal Study on Ageing (N = 6,898 with 41,328 observations). Meta-analysis of rDR level confirmed the association (p = 5.0x10-11) and identified two others in TOMM40 (rs71352238 p = 1.0x10-10; rs157582 p = 7.0x10-09), and one in APOE (rs769449 p = 3.1 x10-12). Meta-analysis of IR change identified associations with three of the same SNPs in TOMM40 (rs157582 p = 8.3x10-10; rs71352238 p = 1.9x10-09) and APOE (rs769449 p = 2.2x10-08). Conditional analyses indicate GWAS signals on rDR level were driven by APOE, whereas signals on IR change were driven by TOMM40. Additionally, we found that TOMM40 had effects independent of APOE e4 on both phenotypes. Findings from this first U.S. population-based GWAS study conducted on both age-related immediate and delayed verbal memory merit continued examination in other samples and additional measures of verbal memory.

Accumulating evidence points to a relationship between hearing function and cognitive ability in later life. However, the exact mechanisms of this relationship are still unclear. This study aimed to characterise latent cognitive trajectories in recall memory and identify their association with subsequent risk of hearing impairment. We analysed data from the English Longitudinal Study of Ageing Wave 1 (2002/03) until Wave 7 (2014/15). The study population consisted of 3,615 adults aged 50+ who participated in the first wave of the English Longitudinal Study of Ageing, who had no self-reported hearing impairment in Wave 1, and who underwent a hearing test in Wave 7. Respondents were classified as having hearing impairment if they failed to hear tones quieter than 35 dB HL in the better ear. The trajectories of recall memory scores were grouped using latent class growth mixture modelling and were related to the presence of hearing impairment in Wave 7. Models estimating 1-class through 5-class recall memory trajectories were compared and the best-fitting models were 4-class trajectories. The different recall memory trajectories represent different starting points and mean of the memory scores. Compared to respondents with the highest recall memory trajectory, other trajectories were increasingly likely to develop later hearing impairment. Long-term changes in cognitive ability predict hearing impairment. Further research is required to identify the mechanisms explaining the association between cognitive trajectories and hearing impairment, as well as to determine whether intervention for maintenance of cognitive function also give benefit on hearing function among older adults.