Associations between physical frailty and dementia incidence: a prospective study from UK Biobank

Background Dementia is associated with a high burden of dependency and disability. Physical frailty (hereafter referred to as frailty) is a multisystem dysregulation that has been identified as a risk factor for dementia. The aim of this study was to examine the association of frailty and its individual components with all-cause dementia incidence in a cohort of UK adults. Methods Participants in UK Biobank with data available for dementia incidence and without any form of dementia at baseline were included in this prospective study. Frailty was defined using a modified version of the frailty phenotype based on five individual components (weight loss, tiredness, physical activity, gait speed, and grip strength), with participants classified as pre-frail if they fulfilled one or two criteria or frail if they fulfilled three or more. Associations between frailty and dementia incidence were investigated using Cox proportional hazard models adjusted for sociodemographic factors, lifestyle factors, and morbidity count. The population attributable fraction was also estimated. Findings Of 502535 participants in UK Biobank, 143 215 met the inclusion criteria and were included in our analyses. 68 500 (47·8%) of the participants were pre-frail and 5565 (3·9%) were frail. During a median follow-up period of 5·4 years, 726 individuals developed dementia. Compared with non-frail individuals, the risk of dementia incidence was increased for individuals with pre-frailty (hazard ratio 1·21 [95% CI 1·04–1·42]) and frailty (1·98 [1·47–2·67]) in the fully adjusted model. Of the five components used to define frailty, weight loss (1·31 [1·09–1·58]), tiredness (1·48 [1·18–1·86]), low grip strength (1·38 [1·17–1·63]), and slow gait speed (1·55 [1·22–1·96]) were independently associated with incident dementia. Based on population attributable fraction analyses, in the study sample, pre-frailty and frailty accounted for 9·9% and 8·6% of dementia cases, respectively. Interpretation Individuals with pre-frailty and frailty were at a higher risk of dementia incidence even after adjusting for a wide range of confounding factors. Early detection and interventions for frailty could translate into prevention or delayed onset of dementia

Understanding the link between physical capability markers, sarcopenia and frailty and adverse health outcomes

Although chronological age is the main determinant of ageing, physical and social environment factors play a crucial role in healthy ageing, even in earlier stages of life. Physical and biological limitations are not, necessarily, restricted to older ages. Therefore, considering the predicted rapid increase in the number of older people worldwide along with its individual and societal burden, research into healthy ageing – including middle-aged and older individuals – is a priority. Physical capability is the ability to perform the basic and instrumental activities of daily living. As the decline in physical function occurs progressively with age, the study of this process should start earlier in life and not only during older age. Low levels of physical capability markers (such as grip strength, muscle mass and physical performance [gait speed]) are strong predictors of future health, including premature mortality, cardiovascular and neurodegenerative diseases in middle-aged and old-aged populations. With age, the decline in physical function could occur in more than one marker. Consequently, the study of combined physical capability markers and their clinical combinations ‘sarcopenia’ and ‘frailty’ needs to be further explored using prospective data with common and non-common adverse health outcomes. Considering the associations of physical capability, sarcopenia, and frailty with adverse health outcomes are not fully understood (both investigated in isolation and as the combined effect), the main aim of this thesis was to determine the associations between measures of physical capability, sarcopenia, and frailty and a range of health outcomes, including mortality, cardiovascular (CVD) and respiratory diseases. To achieve this general aim, seven papers were completed and included in this thesis. Since the overall prevalence of frailty was already estimated using different classifications, the first paper included in this thesis systematically reports and summarises the overall prevalence of sarcopenia (and severe sarcopenia) using different global classifications. Using 6 main classifications, I estimated that the overall prevalence of sarcopenia ranges from 10% to 27% according to the classification used while the prevalence of severe sarcopenia ranges to 2 to 9%. Then, data from the UK Biobank study was used to investigate the association between the exposures and health outcomes. UK Biobank is a general cohort study that recruited over 500,000 participants between 2006 and 2010. Participants aged 37-73 years attended one of the 22 assessment research centres across Scotland, England and Wales at baseline. Using the UK Biobank data, the other six studies were carried out. Across these manuscripts, the associations between different exposures - combinations of sarcopenia, frailty, and individual physical capabilities – and adverse outcomes were determined in each manuscript included: incident and mortality for CVD, respiratory diseases, osteoporosis, cancer, COVID-19, dementia as well as all-cause mortality. In terms of individuals physical capability markers, the strongest association was identified between slow gait speed and incident COPD and respiratory disease as well as all-cause, respiratory and CVD. For incident osteoporosis instead, low muscle mass, followed by slow gait speed, were associated with a higher risk in both sexes. Regarding combinations of physical capability markers, slow gait speed plus low muscle mass, followed for severe sarcopenia, demonstrated the strongest association with incident respiratory disease and all-cause mortality. In terms of osteoporosis, pre-sarcopenic men and sarcopenic women showed a stronger association with incident osteoporosis. The study of the combination between frailty and sarcopenia categories identified that the highest CVD and respiratory risk was identified among frail and sarcopenic individuals. In addition, individuals with more than one clinical condition (frailty, sarcopenia, cachexia, and malnutrition) had almost five times higher risk of dying than those with none (hazard ratio (HR): 4.96 [95% CI: 2.73 to 9.01]). Finally, when frailty was investigated in isolation, I demonstrated that, independently of the frailty classification used, those with pre-frail or frail had a higher risk of severe covid-19. Moreover, pre-frail and frail individuals had an increased risk of all-cause dementia independently of confounder factors such as morbidity (HR pre-frail: 1.21 [95% CI: 1.04 to 1.42] and HR frail: 1.98 [95% CI: 1.47 to 2.67]). Therefore, this thesis demonstrated that individuals with lower physical capability, sarcopenia and/or frailty had a higher risk of adverse health outcomes, including: incidence and mortality for osteoporosis, CVD, respiratory disease, cancer, COVID-19, dementia, and all-cause mortality. These associations remained even after adjustment for a large range of potential confounders and existed both in middle-aged and older adult sub-groups. Considering that the age-related decline in physical capability markers, and therefore sarcopenia and frailty, could be delay and prevented, health interventions to improve physical capability that may reduce the risk of these outcomes are more urgent than ever

Parental support for physical activity in schoolchildren and its influence on nutritional status and fitness = Apoyo parental para realizar actividad física en escolares de 6 años de edad: influencia sobre el estado nutricional y fitness

Introduction: Parents are key models for transmitting and teaching healthy lifestyle habits to their children. Our objective was to determine the influence of the economic and motivational support, and parental involvement in their children physical activity (PA) and its relationship with nutritio nal status and cardiorespiratory fitness. Subjects and Method: Cross-sectional study which included 70 six-year-old schoolchildren. Parents completed the “The Parental Influence on Physical Activity Scale” questionnaire. Anthropometric variables were measured according to the Chilean Ministerial Technical Standard for the supervision of children from 0 to 9 years old; PA intensity was measured with triaxial accelerometers GT3X and the VO2max estimation was performed using the Navette Course test. Results: The average body mass index was 17.9 ± 2.9 kg/m2, the obesity prevalence and VO2max were 57.1%, and 38.05 ± 16.9 ml/kg/min, respectively. Moderate PA during the physical education (PE) class was significantly higher in boys compared to girls (p < 0.006). The economic and motivational support of the parents did not significantly influence the body weight of the children, BMI, waist circumference, PA intensity, and VO2max. Children supported by their parent showed significant differences with moderate PA performed in PE compared to those who were not suppor ted by parents (p = 0.023). Conclusions: Parental support of their children in performing physical activity influences the levels of moderate PA that they do during PE classes. This type of study should be continued and the PA should be measured daily

Efecto de una consulta nutricional protocolizada sobre el estado nutricional y hábitos alimentarios de adultos con sobrepeso y obesidad = Effect of a structured nutritional consultation on weight loss and eating habits in overweight and obese adults

Overweight and obesity affect 67% of population in Chile. Different strategies have been developed to reverse and improve this situation, nutritional consultation is one such strategy. However, consultation has not been structured and it is unknown whether this procedure has a positive effect for weight loss. The objective of this study was to assess the effectiveness of a structured nutritional consultation on weight loss and eating habits in overweight and obese adults in a family health center. A pre-post intervention study was performed with 30 participants over 3 months. Anthropometric measures (weight, body mass index (BMI) and waist circumference (WC) and % body fat), dietary intake and eating habits were the main outcomes of the study. A structured nutritional consultation was significantly associated with decreased weight, BMI, WC and % body fat. There were improvements in dietary intake habits. A 92% of the participants incorporated a snack mid-morning and a daily serving of low-fat dairy. Despite benefits observed after a structured nutritional consultation, larger studies with longer duration are warranted

Dietary fat and total energy intake modifies the association of genetic profile risk score on obesity: evidence from 48 170 UK Biobank participants

Background: Obesity is a multifactorial condition influenced by both genetics and lifestyle. The aim of this study was to investigate whether the association between a validated genetic profile risk score for obesity (GPRS-obesity) and body mass index (BMI) or waist circumference (WC) was modified by macronutrient intake in a large general population study. Methods: This study included cross-sectional data from 48 170 white European adults, aged 37–73 years, participating on the UK Biobank. Interactions between GPRS-obesity, and macronutrient intake (including total energy, protein, fat, carbohydrate and dietary fibre intake) and its effects on BMI and WC were investigated. Results: The 93-SNPs genetic profile risk score was associated with a higher BMI (β:0.57 kg.m−2 per standard deviation (s.d.) increase in GPRS, [95%CI:0.53–0.60]; P=1.9 × 10−183) independent of major confounding factors. There was a significant interaction between GPRS and total fat intake (P[interaction]=0.007). Among high fat intake individuals, BMI was higher by 0.60 [0.52, 0.67] kg.m−2 per s.d. increase in GPRS-obesity; the change in BMI with GPRS was lower among low fat intake individuals (β:0.50 [0.44, 0.57] kg.m-2). Significant interactions with similar patterns were observed for saturated fat intake (High β:0.66 [0.59, 0.73] versus Low β:0.49 [0.42, 0.55] kg.m-2, P-interaction=2 × 10-4), and total energy intake (High β:0.58 [0.51, 0.64] versus Low β:0.49 [0.42, 0.56] kg.m−2, P-interaction=0.019), but not for protein intake, carbohydrate intake and fiber intake (P-interaction >0.05). The findings were broadly similar using WC as the outcome. Conclusions: These data suggest that the benefits of reducing the intake of fats and total energy intake, may be more important in individuals with high genetic risk for obesity

Micropollutants removal in tertiary moving bed biofilm reactors (MBBRs): Contribution of the biofilm and suspended biomass

The performance of tertiary moving bed biofilm reactors (MBBRs) was evaluated in terms of micropollutants (MPs) removal from secondary-treated municipal wastewater. After stepwise establishment of a mature biofilm, monitored by scanning electron and confocal microscopies, abiotic and biotic removals of MPs were deeply studied. Since no MPs reduction was observed by the both photodegradation and volatilization, abiotic removal of MPs was ascribed to the sorption onto the biomass. Target MPs i.e. Naproxen, Diclofenac, 17ß-Estradiol and 4n-Nonylphenol, arranged in the ascending order of hydrophobicity, abiotically declined up to 2.8%, 4%, 9.5% and 15%, respectively. MPs sorption onto the suspended biomass was found around two times more than the biofilm, in line with MPs’ higher sorption kinetic constants (ksor) found for the suspended biomass. When comparing abiotic and biotic aspects, we found that biotic removal outperformed its counterpart for all compounds as Diclofenac, Naproxen, 17ß-Estradiol and 4n-Nonylphenol were biodegraded by 72.8, 80.6, 84.7 and 84.4%, respectively. The effect of the changes in organic loading rates (OLRs) was investigated on the pseudo-first order degradation constants (kbiol), revealing the dominant biodegradation mechanism of co-metabolism for the removal of Diclofenac, Naproxen, and 4n-Nonylphenol., while 17ß-Estradiol obeyed the biodegradation mechanism of competitive inhibition. Biotic removals and kbiol values of all MPs were also seen higher in the biofilm as compared to the suspended biomass. To draw a conclusion, a quite high removal of recalcitrant MPs is achievable in tertiary MBBRs, making them a promising technology that supports both pathways of co-metabolism and competitive inhibition, next to the abiotic attenuation of MPs

Predictive ability of both the healthy aging index and the frailty index for all-cause mortality

Aim: We aimed to develop and assess a modified healthy aging index (HAI) among Chileans aged 60 years and older and compare its predictive ability for all-cause mortality risk with the frailty index (FI). Methods: This prospective study analyzed data from the Chilean National Health Survey (CNHS) conducted in 2009–2010. We included 847 adults with complete data to construct the HAI and FI. The HAI comprised five indicators (lung function, systolic blood pressure, fasting glucose, cognitive status, and glomerular filtration rate), while the FI assessed frailty using a 36-item scale. HAI scores were calculated by summing the indicator scores, ranging from 0 to 10, with higher scores indicating poorer health. Receiver operating curves (ROC) and area under the curve (AUC) were used to assess predictive validity. Associations with all-cause mortality were assessed using Cox proportional hazard models adjusted by confounders. Results: The mean HAI score was 4.06, while the FI score was 0.24. The AUC for mortality was higher for the HAI than the FI (0.640, 95% confidence interval (CI) 0.601 to 0.679 vs. 0.586, 95% CI 0.545 to 0.627). After adjusting for confounders, the FI showed a higher mortality risk compared to the HAI (2.63, 95% CI 1.76 to 3.51 vs. 1.16, 95% CI 1.08 to 1.26). Conclusion: The FI and HAI were valid predictors for all-cause mortality in the Chilean population. Integrating these indices into research and clinical practice can significantly enhance our capacity to identify at-risk individuals

Associations between diabetes and both cardiovascular disease and all-cause mortality are modified by grip strength: evidence from UK Biobank, a prospective population-based cohort study

OBJECTIVE Grip strength and diabetes are predictors of mortality and cardiovascular disease (CVD), but whether these risk factors interact to predispose to adverse health outcomes is unknown. This study determined the interactions between diabetes and grip strength and their association with health outcomes. RESEARCH DESIGN AND METHODS We undertook a prospective, general population cohort study by using UK Biobank. Cox proportional hazards models were used to explore the associations between both grip strength and diabetes and the outcomes of all-cause mortality and CVD incidence/mortality as well as to test for interactions between diabetes and grip strength. RESULTS 347,130 UK Biobank participants with full data available (mean age 55.9 years, BMI 27.2 kg/m2, 54.2% women) were included in the analysis, of which 13,373 (4.0%) had diabetes. Over a median follow-up of 4.9 years (range 3.3–7.8 years), 6,209 died (594 as a result of CVD), and 4,301 developed CVD. Participants with diabetes were at higher risk of all-cause and CVD mortality and CVD incidence. Significant interactions (P < 0.05) existed whereby the risk of CVD mortality was higher in participants with diabetes with low (hazard ratio [HR] 4.05 [95% CI 2.72, 5.80]) versus high (HR 1.46 [0.87, 2.46]) grip strength. Similar results were observed for all-cause mortality and CVD incidence. CONCLUSIONS Risk of adverse health outcomes among people with diabetes is lower in those with high grip strength. Low grip strength may be useful to identify a higher-risk subgroup of patients with diabetes. Intervention studies are required to determine whether resistance exercise can reduce risk