The first genome-wide association study in the Argentinian and Chilean populations identifies shared genetics with Europeans in Alzheimer's disease.

INTRODUCTION: Genome-wide association studies (GWAS) are fundamental for identifying loci associated with diseases. However, they require replication in other ethnicities. METHODS: We performed GWAS on sporadic Alzheimer's disease (AD) including 539 patients and 854 controls from Argentina and Chile. We combined our results with those from the European Alzheimer and Dementia Biobank (EADB) in a meta-analysis and tested their genetic risk score (GRS) performance in this admixed population. RESULTS: We detected apolipoprotein E ε4 as the single genome-wide significant signal (odds ratio  = 2.93 [2.37-3.63], P = 2.6 × 10-23 ). The meta-analysis with EADB summary statistics revealed four new loci reaching GWAS significance. Functional annotations of these loci implicated endosome/lysosomal function. Finally, the AD-GRS presented a similar performance in these populations, despite the score diminished when the Native American ancestry rose. DISCUSSION: We report the first GWAS on AD in a population from South America. It shows shared genetics modulating AD risk between the European and these admixed populations. HIGHLIGHTS: This is the first genome-wide association study on Alzheimer's disease (AD) in a population sample from Argentina and Chile. Trans-ethnic meta-analysis reveals four new loci involving lysosomal function in AD. This is the first independent replication for TREM2L, IGH-gene-cluster, and ADAM17 loci. A genetic risk score (GRS) developed in Europeans performed well in this population. The higher the Native American ancestry the lower the GRS values.

Grip Strength Trajectories and Cognition in English and Chilean Older Adults: A Cross-Cohort Study.

Growing evidence about the link between cognitive and physical decline suggests the early changes in physical functioning as a potential biomarker for cognitive impairment. Thus, we compared grip-strength trajectories over 12-16 years in three groups classified according to their cognitive status (two stable patterns, normal and impaired cognitive performance, and a declining pattern) in two representative UK and Chilean older adult samples. The samples consisted of 7069 UK (ELSA) and 1363 Chilean participants (ALEXANDROS). Linear Mixed models were performed. Adjustments included socio-demographics and health variables. The Declined and Impaired group had significantly lower grip-strength at baseline when compared to the Non-Impaired. In ELSA, the Declined and Impaired showed a faster decline in their grip strength compared to the Non-Impaired group but differences disappeared in the fully adjusted models. In ALEXANDROS, the differences were only found between the Declined and Non-Impaired and they were partially attenuated by covariates. Our study provides robust evidence of the association between grip strength and cognitive performance and how socio-economic factors might be key to understanding this association and their variability across countries. This has implications for future epidemiological research, as hand-grip strength measurements have the potential to be used as an indicator of cognitive performance.

Exploring the Association between Vitamin D and Changes in Cognitive Function in Chilean Older Adults: Evidence from the ALEXANDROS Cohort Study.

Background: The increasing aging of the population with the consequent increase of age-associated cognitive disorders pose the challenge of controlling its preventable risk factors, among which vitamin D deficit is a putative factor. Thus, our objective is to explore the association between vitamin D and cognitive performance in a cohort study of community-dwelling Chilean older people. Material and Methods: Cohort study of 955 (69.7% female), community-dwelling older Chileans free of cognitive impairment from the Alexandros cohorts, with 25(OH)D measurement at baseline. Cognitive Function was evaluated with the Mini Mental State Examination (MMSE) short-form questionnaire. Plasma levels of 25(OH)D were classified as Normal > 30 ng/mL Insufficiency 20−29 ng/mL, Deficiency 20−12 ng/mL and Severe Deficiency < 12 ng/mL. Penalized regressions models were made to assess associations. Results: Mean age of the sample was 66.6 + 4.5 years, with 8.5 + 4.7 years of education. After a mean follow-up of 9.6 years, 54 new cases of Mild Cognitive Impairment (MCI)were identified (Incidence density rate = 5.9 per 1000 person/years). Mean vitamin D plasma levels were lower in people with MCI than in the normal cognitive ones (23.0 + 12.75 vs. 28.35 + 15.17 ng/mL, p < 0.01). In the fully adjusted model only severe deficiency of vitamin D was associated with MCI (RR = 2.33; 95% CI: (1.03−5.26). Conclusions: In this longitudinal study, our results confirm that low Vitamin D is a risk factor for MCI, and that people with severe deficiency have more than double the risk of MCI people with normal Vitamin D levels. Considering the high frequency of vitamin D deficiency in older people, and its preventability, these results are very valuable for future public health programmes.

Dynamic relationships between body fat and circulating adipokine levels from adolescence to young adulthood: The Santiago Longitudinal Study.

BACKGROUND AND AIMS: Adipose tissue secretes adipokines such as adiponectin and leptin, playing important roles in energy metabolism. The longitudinal associations between such adipokines and body fat accumulation have not been established, especially during adolescence and young adulthood and in diverse populations. The study aims to assess the longitudinal association between body fat measured with dual X-ray absorptiometry and plasma adipokines from adolescence to young adulthood. METHODS AND RESULTS: Among Hispanic/Latino participants (N = 537) aged 16.8 (SD: 0.3) years of the Santiago Longitudinal Study, we implemented structural equation modeling to estimate the sex-specific associations between adiposity (body fat percent (BF%) and proportion of trunk fat (PTF)) and adipokines (adiponectin and leptin levels) during adolescence (16 y) and these values after 6 years of follow-up (22 y). In addition, we further investigated whether the associations differed by baseline insulin resistance (IR) status. We found evidence for associations between 16 y BF% and 22 y leptin levels (ß (SE): 0.58 (0.06) for females; 0.53 (0.05) for males), between 16 y PTF and 22 y adiponectin levels (ß (SE): -0.31 (0.06) for females; -0.18 (0.06) for males) and between 16 y adiponectin levels and 22 y BF% (ß (SE): 0.12 (0.04) for both females and males). CONCLUSION: We observed dynamic relationships between adiposity and adipokines levels from late adolescence to young adulthood in a Hispanic/Latino population further demonstrating the importance of this period of the life course in the development of obesity.

Genetic determinants of metabolic biomarkers and their associations with cardiometabolic traits in Hispanic/Latino adolescents.

BACKGROUND: Metabolic regulation plays a significant role in energy homeostasis, and adolescence is a crucial life stage for the development of cardiometabolic disease (CMD). This study aims to investigate the genetic determinants of metabolic biomarkers-adiponectin, leptin, ghrelin, and orexin-and their associations with CMD risk factors. METHODS: We characterized the genetic determinants of the biomarkers among Hispanic/Latino adolescents of the Santiago Longitudinal Study (SLS) and identified the cumulative effects of genetic variants on adiponectin and leptin using biomarker polygenic risk scores (PRS). We further investigated the direct and indirect effect of the biomarker PRS on downstream body fat percent (BF%) and glycemic traits using structural equation modeling. RESULTS: We identified putatively novel genetic variants associated with the metabolic biomarkers. A substantial amount of biomarker variance was explained by SLS-specific PRS, and the prediction was improved by including the putatively novel loci. Fasting blood insulin and insulin resistance were associated with PRS for adiponectin, leptin, and ghrelin, and BF% was associated with PRS for adiponectin and leptin. We found evidence of substantial mediation of these associations by the biomarker levels. CONCLUSIONS: The genetic underpinnings of metabolic biomarkers can affect the early development of CMD, partly mediated by the biomarkers. IMPACT: This study characterized the genetic underpinnings of four metabolic hormones and investigated their potential influence on adiposity and insulin biology among Hispanic/Latino adolescents. Fasting blood insulin and insulin resistance were associated with polygenic risk score (PRS) for adiponectin, leptin, and ghrelin, with evidence of some degree of mediation by the biomarker levels. Body fat percent (BF%) was also associated with PRS for adiponectin and leptin. This provides important insight on biological mechanisms underlying early metabolic dysfunction and reveals candidates for prevention efforts. Our findings also highlight the importance of ancestrally diverse populations to facilitate valid studies of the genetic architecture of metabolic biomarker levels.

Sarcopenic metabolomic profile reflected a sarcopenic phenotype associated with amino acid and essential fatty acid changes.

INTRODUCTION: Although sarcopenia greatly affects health and quality of life in older people, its pathophysiological causes are not fully elucidated. To face this challenge, omics technologies can be used. The metabolome gives a vision of the interaction between the genome and the environment through metabolic networks, thus contributing in clarifying the pathophysiology of the sarcopenic phenotype. OBJECTIVES: The main goal of this study was to compare the plasma metabolome of sarcopenic and non-sarcopenic older people. METHODS: Cross-sectional study of 20 sarcopenic and 21 non-sarcopenic older subjects with available frozen plasma samples. Non-targeted metabolomic study by ultra-high-performance liquid chromatography-electrospray ionization tandem mass spectrometry (UHPLC-ESI-MS/MS) analysis with later bioinformatics data analysis. Once the significantly different metabolites were identified, the KEGG database was used on them to establish which were the metabolic pathways mainly involved. RESULTS: From 657 features identified, 210 showed significant differences between the study groups, and 30 had a FoldChangeLog2 > 2. The most interesting metabolic pathways found with the KEGG database were the biosynthesis of amino acids, arginine and proline metabolism, the biosynthesis of alkaloids derived from ornithine, linoleic acid metabolism, and the biosynthesis of unsaturated fatty acids. CONCLUSIONS: The study results allowed us to confirm that the concept of "sarcopenic phenotype" is also witnessed at the plasma metabolite levels. The non-targeted metabolomics study can open a wide view of the sarcopenic features changes at the plasma level, which would be linked to the sarcopenic physiopathological alterations.

Calidad de vida en personas mayores con depresión y dependencia funcional: validez del cuestionario SF-12 / Quality of life of older people with depression and dependence: validity of the SF-12 (short form health survey) questionnaire

Background: Depression and dependence have a great impact on the quality of life of older people. Aim: To validate the SF-12 (short-form) health related quality of care questionnaire (HRQOL) as an alternative of the SF-36 to estimate health-related quality of life (HRQoL) and its association with depression and dependence in Chilean older people living in the community. Material and Methods: The questionnaire was answered by 4,124 Chilean older people (61% women). HRQoL was evaluated with the SF-36 questionnaire. The SF-12 questionnaire includes 12 items from the SF-36. Results: The internal consistency of the SF-12 questionnaire was high (0.88). The effect size of the differences in the averages of the SF-12 and SF-36 scales was small (0.06-0.41). Good agreement was found between the physical and mental components of the SF-12 and SF-36 (0.94 and 0.89). Logistic regressions determined that people with dependence and depression have a higher risk of poor HRQoL. The figures for the physical component were, mild depression: odds ratio (OR) (95% confidence intervals (CI) = 3.28 (2.74-3.93), severe depression: OR (IC95%CI) = 4.66 (3.55-6.11), mild to moderate dependence: OR (95CI%) = 3.67 (2.97-4.54), severe dependence: OR (95%CI) = 13.06 (7.23-23.61). For the mental component, the figures were: mild depression: OR (95CI%) = 6.11(5.05-7.38), severe depression: OR (95CI%) = 22.01(14.47-33.49), mild to moderate dependence: OR (95CI%) = 1.59 (1.28-1.97), severe dependence: OR (95CI%) = 1.60 (1.04-2.47), adjusting for sociodemographic and health-related variables. Conclusions: The validity of the SF-12 for measuring HRQoL was demonstrated. People with depression and dependence have a worse physical and mental quality of life.

Besides Sarcopenia, Pre-Sarcopenia Also Predicts All-Cause Mortality in Older Chileans.

PURPOSE: Many studies have demonstrated that Sarcopenia causes a serious impact on health, including death in older adults. The objective of this study was to determine the association of sarcopenia and pre-sarcopenia with all-cause mortality in older Chileans. SUBJECTS AND METHODS: Follow-up of 2311 community-dwelling people ≥ 60y from the Alexandros cohort. Anthropometric measurements, handgrip strength, mobility, and physical performance tests were performed. Sarcopenia, pre-sarcopenia, and severe sarcopenia were defined using the 2010 European Working Group on Sarcopenia in Older People (EWGSOP1) algorithm. Muscle mass was estimated using a prediction model with cut-off points validated for the Chilean population. Physical performance was determined by 3 m walking speed or five chair-stands or time up go test (TUG). Mortality data were obtained from death certificates of the National Civil Registry. Life tables for survival data, Kaplan Meier estimations, and Cox regression were calculated. RESULTS: The prevalence of sarcopenia was 20.2% (95% CI:18.6% to 21.9%) and similar in both sexes; pre-sarcopenia was identified in 20.4% (95% CI:18.8% to 22.1%) of the sample. Kaplan Meier survival estimates demonstrated lower survival rates for the people with sarcopenia and pre-sarcopenia (Log rank test for equality of survivor functions: p<0.0001). A dose-response was observed in the survival rates according to the stages of sarcopenia, showing the lowest survival rates for the people with severe sarcopenia, followed by older adults with sarcopenia, pre-sarcopenia, and without sarcopenia (Log rank test for equality of survivor functions: p<0.0001). After adjusting for age, sex, nutritional status, and number of chronic diseases, hazard ratios for death showed higher risk for subjects with sarcopenia (HR=1.47, 95% CI:1.17-1.83) and pre-sarcopenia (HR=1.35, 95% CI:1.03-1.78) in comparison with people without sarcopenia. CONCLUSION: The results confirm a dose-response increase in the risk of all-cause death in older adults with sarcopenia and pre-sarcopenia compared to non-sarcopenic individuals.

[Quality of life of older people with depression and dependence: validity of the SF-12 (short form health survey) questionnaire]. / Calidad de vida en personas mayores con depresión y dependencia funcional: Validez del cuestionario SF-12.

BACKGROUND: Depression and dependence have a great impact on the quality of life of older people. AIM: To validate the SF-12 (short-form) health related quality of care questionnaire (HRQOL) as an alternative of the SF-36 to estimate health-related quality of life (HRQoL) and its association with depression and dependence in Chilean older people living in the community. MATERIAL AND METHODS: The questionnaire was answered by 4,124 Chilean older people (61% women). HRQoL was evaluated with the SF-36 questionnaire. The SF-12 questionnaire includes 12 items from the SF-36. RESULTS: The internal consistency of the SF-12 questionnaire was high (0.88). The effect size of the differences in the averages of the SF-12 and SF-36 scales was small (0.06-0.41). Good agreement was found between the physical and mental components of the SF-12 and SF-36 (0.94 and 0.89). Logistic regressions determined that people with dependence and depression have a higher risk of poor HRQoL. The figures for the physical component were, mild depression: odds ratio (OR) (95% confidence intervals (CI) = 3.28 (2.74-3.93), severe depression: OR (IC95%CI) = 4.66 (3.55-6.11), mild to moderate dependence: OR (95CI%) = 3.67 (2.97-4.54), severe dependence: OR (95%CI) = 13.06 (7.23-23.61). For the mental component, the figures were: mild depression: OR (95CI%) = 6.11(5.05-7.38), severe depression: OR (95CI%) = 22.01(14.47-33.49), mild to moderate dependence: OR (95CI%) = 1.59 (1.28-1.97), severe dependence: OR (95CI%) = 1.60 (1.04-2.47), adjusting for sociodemographic and health-related variables. CONCLUSIONS: The validity of the SF-12 for measuring HRQoL was demonstrated. People with depression and dependence have a worse physical and mental quality of life.

Osteosarcopenia Predicts Falls, Fractures, and Mortality in Chilean Community-Dwelling Older Adults.

OBJECTIVES: The objective of this study was to describe the prevalence of osteosarcopenia and its association with falls, fractures, and mortality in community-dwelling older adults. DESIGN: Follow-up of ALEXANDROS cohorts designed to study disability associated with obesity in older adults. SETTING AND PARTICIPANTS: Community-dwelling people aged 60 years and older living in Chile. MEASURES: At baseline, 1119 of 2372 participants had a dual-energy X-ray absorptiometry scan and the measurements for the diagnosis of sarcopenia. World Health Organization standards for bone mineral density were used to classify them as normal, osteopenia, and osteoporosis. Sarcopenia was identified using the algorithm from the European Working Group on Sarcopenia in Older People 1, validated for the Chilean population. Osteosarcopenia was defined as having sarcopenia plus osteoporosis or osteopenia. RESULTS: The sample of 1119 participants (68.5% female) had a mean age of 72 years. At baseline, osteoporosis was identified in 23.2%, osteopenia in 49.8%, sarcopenia in 19.5%, and osteosarcopenia in 16.4% of the sample. The prevalence of osteosarcopenia increases with age, reaching 33.7% for those older than 80 years. Sarcopenia was found in 34.4% of osteoporotic people and osteoporosis in 40.8% of those with sarcopenia. After 5640 person-years of follow-up, 86 people died. The mortality was significantly higher for the group with osteosarcopenia (15.9%) compared with those without the condition (6.1%). After an adjusted Cox Regression analysis, the hazard ratio for death in people with osteosarcopenia was 2.48. Falls, fractures, and functional impairment were significantly more frequent in osteosarcopenic patients. CONCLUSIONS AND IMPLICATIONS: Osteosarcopenia is a common condition among older adults and is associated with an increased risk of falls, fractures, functional impairment, and mortality. Considering the high proportion of sarcopenia among osteoporotic patients and vice versa, screening for the second condition when the first is suspected should be advised.

Genome-wide association study identifying novel variant for fasting insulin and allelic heterogeneity in known glycemic loci in Chilean adolescents: The Santiago Longitudinal Study.

BACKGROUND: The genetic underpinnings of glycemic traits have been understudied in adolescent and Hispanic/Latino (H/L) populations in comparison to adults and populations of European ancestry. OBJECTIVE: To identify genetic factors underlying glycemic traits in an adolescent H/L population. METHODS: We conducted a genome-wide association study (GWAS) of fasting glucose (FG) and fasting insulin (FI) in H/L adolescents from the Santiago Longitudinal Study. RESULTS: We identified one novel variant positioned in the CSMD1 gene on chromosome 8 (rs77465890, effect allele frequency = 0.10) that was associated with FI (ß = -0.299, SE = 0.054, p = 2.72×10-8 ) and was only slightly attenuated after adjusting for body mass index z-scores (ß = -0.252, SE = 0.047, p = 1.03×10-7 ). We demonstrated directionally consistent, but not statistically significant results in African and Hispanic adults of the Population Architecture Using Genomics and Epidemiology Consortium. We also identified secondary signals for two FG loci after conditioning on known variants, which demonstrate allelic heterogeneity in well-known glucose loci. CONCLUSION: Our results exemplify the importance of including populations with diverse ancestral origin and adolescent participants in GWAS of glycemic traits to uncover novel risk loci and expand our understanding of disease aetiology.

Software for the Diagnosis of Sarcopenia in Community-Dwelling Older Adults: Design and Validation Study.

BACKGROUND: The usual diagnosis of sarcopenia requires a dual-energy x-ray absorptiometry (DXA) exam, which has low accessibility in primary care for Latin American countries. OBJECTIVE: The aim of this study is to design and validate software for mobile devices (Android, IOS) and computers, based on an adapted version of the diagnostic algorithm of sarcopenia proposed by the European Working Group on Sarcopenia in Older People (EWGSOP). METHODS: Follow-up exams were conducted on 430 community-dwelling Chileans 60 years and older (mean 68.2 years, SD 4.9) participating in the IsaMayor and Alexandros cohorts designed to study sarcopenia and disability associated with obesity, respectively. All the participants from the cohorts were randomly selected from the registries of primary health care centers and, for this study, must have a DXA scan at baseline. The software (HTSMayor) was designed according to an adapted version of the algorithm proposed by the EWGSOP and was divided into four phases: longitudinal validation of diagnostic algorithm of sarcopenia, alpha version, beta version, and release version. The software estimates appendicular skeletal muscle mass (ASM) using an anthropometric equation or DXA measurements with Chilean cut-off points. The predictive validation of the algorithm was estimated, comparing functional limitations (at least one activity of daily living, two instrumental activities of daily living, or three mobility limitations), falls, and osteoporosis at follow-ups in patients with and without sarcopenia at baseline, using adjusted logistic models. RESULTS: After a median follow-up of 4.8 years (2078.4 person-years), 37 (9.9%) new cases of sarcopenia, out of the 374 patients without sarcopenia at baseline, were identified (incidence density rate=1.78 per 100 person-years). ASM estimated with the anthropometric equation showed both a high sensitivity and specificity as compared with those estimated by DXA measurements, yielding a concordance of 0.96. The diagnostic algorithm of sarcopenia considered in the software with the equation showed both a high sensitivity (82.1%) and specificity (94.9%) when compared with DXA (reference standard). Adults without sarcopenia (at baseline) showed better physical performance (after approximately 5 years) than adults with sarcopenia. Loss of functionality was greater in adults with sarcopenia (OR 5.0, 95% CI 2.2-11.4) than in adults without sarcopenia. In addition, the risks of falls (OR 2.2, 95% CI 1.1-4.3) and osteoporosis (OR 2.8, 95% CI 1.2-6.6) were higher in older persons with sarcopenia than those without sarcopenia. The measurements and results were completed for the beta and release tests with a mean time of 10 minutes and 11 minutes, respectively. CONCLUSIONS: We developed and validated a software for the diagnosis of sarcopenia in older Chilean adults that can be used on a mobile device or a computer with good sensitivity and specificity, thus allowing for the development of programs for the prevention, delay, or reversal of this disease. To our knowledge, HTSMayor is the first software to diagnose sarcopenia. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/13657.

The association of VDR polymorphisms and type 2 diabetes in older people living in community in Santiago de Chile.

INTRODUCTION: Several polymorphisms have been associated with obesity and type 2 diabetes in different populations. OBJECTIVE: To investigate the frequencies of a genetic polymorphism of vitamin D receptor (FokI and BsmI) in patients with T2D. METHODS: The case-control study was conducted in 138 patients with T2D and 172 control subjects, men and women (60-79 years old). The genotype and allele frequency determination of VDR polymorphisms were determined in these subjects. RESULTS: The frequency of the C allele of the FokI polymorphism was significantly higher in the T2D group than in healthy subjects (p = 0.025). The frequencies of the BsmI variant were similar in subjects with and without T2D (p = 0.747). Consistent with these data, there was an association of the C allele with T2D (OR = 1.74, 95% CI = 1.003-3.084, p = 0.036), but not the AG + GG variants for BsmI (OR = 1.02, 95% CI = 0.635-1.649, p = 0.916). We can observe a significant association between carrier of the T > C variant of FokI and type 2 diabetes, adjusted for vitamin D, age, obesity (overweight and obesity), seasonality, sex and Homa-IR. Here, we show a significant association between the FokI polymorphisms (TC + CC) and T2D with an odds ratio of 1.9001 (95% CI (1.0970-3.6838), p = 0.041). CONCLUSION: Our study suggests that the C allele (TC + CC) of the VDR-FokI gene is a possible risk factor for T2D in older people living in a community in Santiago de Chile.

Gender, nutritional status and disability-free life expectancy among older people in Santiago, Chile.

BACKGROUND: This study was aimed to estimate life expectancy (LE), disability-free life expectancy (DFLE) and disabled life expectancy (DLE) among older adults from Santiago, Chile, and to determine the existence of differences by gender and by body mass index (BMI) categories in these indicators. METHODS: A sample of 1216 people aged 60 or more, from the Chilean cohort of the Study of Health, Ageing and Well-Being was recruited in 2000; two follow-up assessments were carried out in a 10-year period. Functional limitation was assessed through self-report of difficulties in activities of daily living, instrumental activities of daily living and mobility. BMI was determined with measured weight and height. Multistate life tables were employed to estimate LE and healthy life expectancy (HLE). RESULTS: At 60 years, women could expect to live on average an additional 20.4 years (95% CI 19.0-21.6), and men an additional 16.4 years (95% CI 14.9-17.7). Total LE was longer among women at all ages, but they had a higher proportion of disabled years to be lived compared to men, with a difference of 14% at 60 years, and 10% at 90 years. There were no significant differences in LE, DFLE and DLE between BMI categories. DISCUSSION: Despite a longer LE, Chilean older women expect to live a higher proportion of years with disabilities, compared to men. Public health programs should address factors affecting LE of older men, and those associated with disability among older women.

Reference values of hand-grip dynamometry and the relationship between low strength and mortality in older Chileans.

AIM: This study was aimed to set reference values of hand-grip strength by age and sex and validate cut points for risk of functional limitation and mortality in older Chileans. METHODS: This was a pooled analysis of four studies including 6,426 people ≥60 years of nondependent community-dwelling Chileans. After exclusion criteria, the final sample included 5,250 subjects, from whom 2,193 were followed to study all-cause mortality associated with low hand-grip strength. Face-to-face interviews registering sociodemographic characteristics, self-reported chronic diseases, and functional limitations were conducted. Anthropometric measurements and observed mobility were performed by trained professionals. Hand-grip strength was measured with a hand dynamometer T-18 (Country Technology, Inc.) before 2008 or with JAMAR brand from 2008 onwards. Percentiles were calculated through descriptive analysis and quantile regression models for specific groups of age and sex. Adjusted Cox regression hazard models for mortality risk according to low dynamometry condition and covariates were developed. RESULTS: We deliver reference values of hand-grip strength for older Chileans proposing the 25th percentile as the cut-off point for low dynamometry risk: men ≤27 kg, women ≤15 kg. Low hand-grip strength was associated with Instrumental Activities of Daily Living limitations (p=0.001), and altered physical performance evaluated through the Timed Up and Go test (p=0.0001), grasping (p=0.001), bending (p<0.0001), and lifting (p<0.0001). After Cox proportional hazard regression models were assessed with a median follow-up of 9.2 years, the adjusted risk of all-cause mortality associated with a hand-grip strength lower than the 25th percentile in older Chileans showed a hazard ratio of 1.39 (95% confidence interval: 1.13-1.71). CONCLUSION: The cut-off points of dynamometry validated for the older Chileans allow the incorporation in the geriatric evaluation in primary health care of an easy-to-use, inexpensive indicator to identify older adults at risk of sarcopenia, frailty, and dismobility. In addition this also helps to optimize the evaluation of intervention strategies focused on the maintenance of functionality.

Frequency of frailty and its association with cognitive status and survival in older Chileans.

BACKGROUND: Age-associated brain physiologic decline and reduced mobility are key elements of increased age-associated vulnerability. OBJECTIVE: To study the frequency of frailty phenotype and its association with mental health and survival in older Chileans. METHODS: Follow-up of ALEXANDROS cohorts designed to study disability associated with obesity in community-dwelling people 60 years and older living in Santiago, Chile. At baseline, 2,098 (67% women) of 2,372 participants had the necessary measurements for the identification of the frailty phenotype: weak handgrip dynamometry, unintentional weight loss, fatigue/exhaustion, five chair-stands/slow walking speed and difficulty walking (low physical activity). After 10-15 years, 1,298 people were evaluated and 373 had died. Information regarding deaths was available for the whole sample. RESULTS: The prevalence of frailty at baseline (≥3 criteria) in the whole sample was 13.9% (women 16.4%; men 8.7%) and the pre-frailty prevalence (1-2 criteria) was 63.8% (65.0% vs 61.4%), respectively. Frailty was associated with cognitive impairment (frail 48.1%; pre-frail 21.7%; nonfrail 20.5%, P<0.001) and depression (frail 55.1%; pre-frail 27.3%; nonfrail 18.8%, P<0.001). Logistic regression models for frailty adjusted for sex and age showed a strong association between frailty and mild cognitive impairment (MCI) (odds ratio [OR] =3.93; 95% CI: 1.41-10.92). Furthermore, an important association was found for depression and frailty (OR =2.36; 95% CI 1.82-3.06). Age- and sex-adjusted hazard ratios (HRs) for death showed an increased risk with increasing frailty: pre-frail HR =1.56 (95% CI: 1.07-2.29), frail HR =1.91 (95% CI: 1.15-3.19); after adjustment by age and sex, a higher risk of death was observed for people identified as frail (HR =1.56, P=0.014) and pre-frail (HR =1.30, P=0.065). MCI and dementia were also risk factors for death (MCI: HR =1.69, P<0.027; dementia: HR =1.66, P=0.016). CONCLUSION: Frailty is highly prevalent and strongly associated with cognitive impairment and depression in older Chileans. The risk for death was higher for frail people, but underlying cognitive impairment is a key component of the lower survival rate.

Low Leptin Availability as a Risk Factor for Dementia in Chilean Older People.

OBJECTIVE: The aim was to study the role of leptin in the development of dementia. METHODS: Follow-up of the ALEXANDROS cohorts, with baseline measurements in 2000. From 1,136 available subjects free of dementia at baseline, 667 subjects had frozen baseline blood samples for measuring leptin and soluble leptin receptor (sOB-R). The free leptin index (FLI) was calculated as the ratio of leptin to sOB-R. Dementia was defined as an MMSE score <22 and a score >5 in the Pfeffer Activities Questionnaire. RESULTS: After 15 years of follow-up, 42 incident cases of dementia were identified. No difference in serum leptin was observed between people with and without dementia, but sOB-R was higher in demented than in nondemented subjects (sOB-R: 44.94 ± 23.97 vs. 33.73 ± 21.13 ng/ml). The adjusted risk for dementia increased, the higher the log sOB (hazard ratio = 3.58; 95% CI 1.72-7.45, p = 0.001). CONCLUSION: Lower availability of free leptin was found in demented than in nondemented people, suggesting a role of leptin in cognition.

FokI polymorphism in vitamin D receptor gene: Differential expression of TNFα in peripheral mononuclear cells of type 2 diabetic subjects.

INTRODUCTION: FokI polymorphism has been associated with obesity and type 2 diabetes (T2D) in some populations. OBJECTIVE: To investigate the frequencies of a genetic polymorphism of Vitamin D receptor (FokI) in patients with T2D and control subjects and investigate the role of 1,25(OH)2D3 in the expression of pro-inflammatory markers in peripheral blood mononuclear cells (PBMCs). METHODS: The case-control study was conducted in 160 patients with T2D and 160 control subjects, men and women (30-74 years old). The genotype and allele frequency of FokI polymorphisms were determined in these subjects. Subsequently a subgroup of 40 subjects was included from which PBMCs were removed. In vitro, the culture medium was supplemented with two different concentrations of 1,25(OH)2D3(10- 8 M and 10- 10 M). The expression profiles of TNFα and mRNA were analysed by qPCR, and GAPDH and ß-actin were used as housekeeping genes. RESULTS: The control subjects have an increased frequency of the FF genotype. In subjects with T2D, the ff genotype was associated with higher HOMA-IR values than individuals with genotype Ff (p = 0.021). In vitro study in PBMCs showed differential expression of TNFα mRNA by FokI genotype, with a lower expression of this marker of inflammation in FF genotype subjects at a concentration of 10- 8 M of 1,25(OH)2D3. CONCLUSION: Our data suggest that VDR FokI polymorphism is associated with T2D, and the genotypes Ff and ff of this variant show a reduced response or resistance to the anti-inflammatory action of VitD, which could indicate a functional role of FokI polymorphism of VDR.

Estimación y validación de puntos de corte de índice de masa muscular esquelética para la identificación de sarcopenia en adultos mayores chilenos / Validation of cut points of skeletal muscle mass index for identifying sarcopenia in chilean older people

Objetivos: Estimar y validar puntos de corte de índice de masa muscular esquelética (IMMAE) en adultos mayores chilenos, para el diagnóstico de sarcopenia Métodos: Estimación de puntos de corte para IMMAE determinados por DEXA y por ecuación antropométrica en un análisis secundario de datos transversales de 440 Adultos Mayores (AM) chilenos, y posterior validación transversal en una muestra de 164 AM. Se realizaron pruebas de rendimiento físico, auto-reporte de salud, antropometría y DEXA. Se definió la fuerza muscular disminuida por dinamometría de mano (AU)

Objectives: To estimate and validate cut-off points of skeletal muscle mass index (SMI) in Chilean population, for using in an algorithm for a diagnosis of sarcopenia developed by European Working Group on Sarcopenia in Older People (EWGSOP). Methods: Secondary analysis of Cross-sectional data in 440 Chilean older subjects to estimate cut-off points of SMI determined by DEXA and predicted by an anthropometric equation. Afterward a cross-sectional validation in a sample of 164 older people was performed. Anthropometric measures, self-reported health status, physical performance tests and DEXA were carried out. Decreased muscle strength was defined as handgrip strength (AU)