Invecchiare In Chianti Research Articles

Moving towards the detection of frailty with biomarkers: A population health study.

Aging adults experience increased health vulnerability and compromised abilities to cope with stressors, which are the clinical manifestations of frailty. Frailty is complex, and efforts to identify biomarkers to detect frailty and pre-frailty in the clinical setting are rarely reproduced across cohorts. We developed a predictive model incorporating biological and clinical frailty measures to identify robust biomarkers across data sets. Data were from two large cohorts of older adults: "Invecchiare in Chianti (Aging in Chianti, InCHIANTI Study") (n = 1453) from two small towns in Tuscany, Italy, and replicated in the Atherosclerosis Risk in Communities Study (ARIC) (n = 6508) from four U.S. communities. A complex systems approach to biomarker selection with a tree-boosting machine learning (ML) technique for supervised learning analysis was used to examine biomarker population differences across both datasets. Our approach compared predictors with robust, pre-frail, and frail participants and examined the ability to detect frailty status by race. Unique biomarker features identified in the InCHIANTI study allowed us to predict frailty with a model accuracy of 0.72 (95% confidence interval (CI) 0.66-0.80). Replication models in ARIC maintained a model accuracy of 0.64 (95% CI 0.66-0.72). Frail and pre-frail Black participant models maintained a lower model accuracy. The predictive panel of biomarkers identified in this study may improve the ability to detect frailty as a complex aging syndrome in the clinical setting. We propose several concrete next steps to keep research moving toward detecting frailty with biomarker-based detection methods.

Metabolomic markers mediate erythrocyte anisocytosis in older adults: Results from three independent aging cohorts.

Anisocytosis reflects unequal-sized red blood cells and is quantified using red blood cell distribution width (RDW). RDW increases with age and has been consistently associated with adverse health outcomes, such as cardiovascular disease and mortality. Why RDW increases with age is not understood. We aimed to identify plasma metabolomic markers mediating anisocytosis with aging. We performed mediation analyses of plasma metabolomics on the association between age and RDW using resampling techniques after covariate adjustment. We analyzed data from adults aged 70 or older from the main discovery cohort of the Baltimore Longitudinal Study of Aging (BLSA, n=477, 46% women) and validation cohorts of the Health, Aging and Body Composition Study (Health ABC, n=620, 52% women) and Invecchiare in Chianti, Aging in the Chianti Area (InCHIANTI) study (n=735, 57% women). Plasma metabolomics was assayed using the Biocrates MxP Quant 500 kit in BLSA and Health ABC and liquid chromatography with tandem mass spectrometry in InCHIANTI. In all three cohorts, symmetric dimethylarginine (SDMA) significantly mediated the association between age and RDW. Asymmetric dimethylarginine (ADMA) and 1-methylhistidine were also significant mediators in the discovery cohort and one validation cohort. In the discovery cohort, we also found choline, homoarginine, and several long-chain triglycerides significantly mediated the association between age and RDW. This metabolomics study of three independent aging cohorts identified a specific set of metabolites mediating anisocytosis with aging. Whether SDMA, ADMA, and 1-methylhistidine are released by the damaged erythrocytes with high RDW or they affect the physiology of erythrocytes causing high RDW should be further investigated.

Apolipoprotein E gene variants shape the association between dietary fibre intake and cognitive decline risk in community-dwelling older adults.

healthy dietary patterns have been associated with lower risk for age-related cognitive decline. However, little is known about the specific role of dietary fibre on cognitive decline in older adults. this study aimed to examine the association between dietary fibre and cognitive decline in older adults and to assess the influence of genetic, lifestyle and clinical characteristics in this association. the Invecchiare in Chianti, aging in the Chianti area study is a cohort study of community-dwelling older adults from Italy. Cognitive function, dietary and clinical data were collected at baseline and years 3, 6, 9 and 15. Our study comprised 848 participants aged ≥ 65years (56% female) with 2,038 observations. cognitive decline was defined as a decrease ≥3units in the Mini-Mental State Examination score during consecutive visits. Hazard ratios for cognitive decline were estimated using time-dependent Cox regression models. energy-adjusted fibre intake was not associated with cognitive decline during the 15-years follow-up (P > 0.05). However, fibre intake showed a significant interaction with Apolipoprotein E (APOE) haplotype for cognitive decline (P = 0.02). In participants with APOE-ɛ4 haplotype, an increase in 5g/d of fibre intake was significantly associated with a 30% lower risk for cognitive decline. No association was observed in participants with APOE-ɛ2 and APOE-ɛ3 haplotypes. dietary fibre intake was not associated with cognitive decline amongst older adults for 15years of follow-up. Nonetheless, older subjects with APOE-ɛ4 haplotype may benefit from higher fibre intakes based on the reduced risk for cognitive decline in this high-risk group.

An objective metric of individual health and aging for population surveys

BackgroundWe have previously developed and validated a biomarker-based metric of overall health status using Mahalanobis distance (DM) to measure how far from the norm of a reference population (RP) an individual’s biomarker profile is. DM is not particularly sensitive to the choice of biomarkers; however, this makes comparison across studies difficult. Here we aimed to identify and validate a standard, optimized version of DM that would be highly stable across populations, while using fewer and more commonly measured biomarkers.MethodsUsing three datasets (the Baltimore Longitudinal Study of Aging, Invecchiare in Chianti and the National Health and Nutrition Examination Survey), we selected the most stable sets of biomarkers in all three populations, notably when interchanging RPs across populations. We performed regression models, using a fourth dataset (the Women’s Health and Aging Study), to compare the new DM sets to other well-known metrics [allostatic load (AL) and self-assessed health (SAH)] in their association with diverse health outcomes: mortality, frailty, cardiovascular disease (CVD), diabetes, and comorbidity number.ResultsA nine- (DM9) and a seventeen-biomarker set (DM17) were identified as highly stable regardless of the chosen RP (e.g.: mean correlation among versions generated by interchanging RPs across dataset of r = 0.94 for both DM9 and DM17). In general, DM17 and DM9 were both competitive compared with AL and SAH in predicting aging correlates, with some exceptions for DM9. For example, DM9, DM17, AL, and SAH all predicted mortality to a similar extent (ranges of hazard ratios of 1.15–1.30, 1.21–1.36, 1.17–1.38, and 1.17–1.49, respectively). On the other hand, DM9 predicted CVD less well than DM17 (ranges of odds ratios of 0.97–1.08, 1.07–1.85, respectively).ConclusionsThe metrics we propose here are easy to measure with data that are already available in a wide array of panel, cohort, and clinical studies. The standardized versions here lose a small amount of predictive power compared to more complete versions, but are nonetheless competitive with existing metrics of overall health. DM17 performs slightly better than DM9 and should be preferred in most cases, but DM9 may still be used when a more limited number of biomarkers is available.

The Plasma Proteome Fingerprint Associated with Circulating Carotenoids and Retinol in Older Adults

BackgroundAlthough diets rich in carotenoids are associated with reduced risks of cardiovascular disease, age-related macular degeneration, disability, and other adverse aging outcomes, the underlying biological mechanisms are not fully elucidated. ObjectivesTo characterize the plasma proteome fingerprint associated with circulating carotenoid and retinol concentrations in older adults. MethodsIn 728 adults ≥65 y participating in the Invecchiare in Chianti (InCHIANTI) Study, plasma α-carotene, β-carotene, β-cryptoxanthin, lutein, zeaxanthin, and lycopene were measured using HPLC. The SOMAscan assay was used to measure 1301 plasma proteins. Multivariable linear regression models were used to examine the relationship of individual carotenoids and retinol with plasma proteins. A false discovery rate approach was used to deal with multiple comparisons using a q-value < 0.05. ResultsPlasma β-carotene, β-cryptoxanthin, lutein, zeaxanthin, and lycopene were associated with 85, 39, 4, 2, and 5 plasma proteins, respectively, in multivariable linear regression models adjusting for potential confounders (q < 0.05). No proteins were associated with α-carotene or retinol. Two or more carotenoids were positively associated with ferritin, 6-phosphogluconate dehydrogenase (decarboxylating), hepcidin, thrombospondin-2, and choline/ethanolamine kinase. The proteins associated with circulating carotenoids were related to energy metabolism, sirtuin signaling, inflammation and oxidative stress, iron metabolism, proteostasis, innate immunity, and longevity. ConclusionsThe plasma proteomic fingerprint associated with elevated circulating carotenoids in older adults provides insight into the mechanisms underlying the protective role of carotenoids on health.

Sex-specific 25-hydroxyvitamin D threshold concentrations for functional outcomes in older adults: PRoject on Optimal VItamin D in Older adults (PROVIDO)

Threshold serum 25-hydroxyvitamin D [25(OH)D] concentrations for extraskeletal outcomes are uncertain and could differ from recommendations (20-30 ng/mL) for skeletal health. We aimed to identify and validate sex-specific threshold 25(OH)D concentrations for older adults' physical function. Using 5 large prospective, population-based studies-Age, Gene/Environment Susceptibility-Reykjavik (n=4858, Iceland); Health, Aging, and Body Composition (n=2494, United States); Invecchiare in Chianti (n=873, Italy); Osteoporotic Fractures in Men (n=2301, United States); and Study of Osteoporotic Fractures (n=5862, United States)-we assessed 16,388 community-dwelling adults (10,376 women, 6012 men) aged≥65 y. We analyzed 25(OH)D concentrations with the primary outcome (incident slow gait: women <0.8 m/s; men <0.825 m/s) and secondary outcomes (gait speed, incident self-reported mobility, and stair climb impairment) at median 3.0-y follow-up. We identified sex-specific 25(OH)D thresholds that best discriminated incident slow gait using machine learning in training data (2/3 cohort-stratified random sample) and validated using the remaining (validation) data and secondary outcomes. Mean age in the cohorts ranged from 74.4 to 76.5 y in women and from 73.3 to 76.6 y in men. Overall, 1112/6123 women (18.2%) and 494/3937 men (12.5%) experienced incident slow gait, 1098/7011 women (15.7%) and 474/3962 men (12.0%) experienced incident mobility impairment, and 1044/6941 women (15.0%) and 432/3993 men (10.8%) experienced incident stair climb impairment. Slow gait was best discriminated by 25(OH)D<24.0 ng/mL compared with 25(OH)D≥24.0 ng/mL in women (RR: 1.29; 95% CI: 1.10, 1.50) and 25(OH)D<21.0 ng/mL compared with 25(OH)D≥21.0 ng/mL in men (RR: 1.43; 95% CI: 1.01, 2.02). Most associations between 25(OH)D and secondary outcomes were modest; estimates were similar between validation and training datasets. Empirically identified and validated sex-specific threshold 25(OH)D concentrations for physical function for older adults, 24.0 ng/mL for women and 21.0 ng/mL for men, may inform candidate reference concentrations or the design of vitamin D intervention trials.

Elevated Plasma Growth and Differentiation Factor 15 Predicts Incident Anemia in Older Adults Aged 60 Years and Older.

Anemia is common in older adults and associated with greater morbidity and mortality. The causes of anemia in older adults have not been completely characterized. Although elevated circulating growth and differentiation factor 15 (GDF-15) has been associated with anemia in older adults, it is not known whether elevated GDF-15 predicts the development of anemia. We examined the relationship between plasma GDF-15 concentrations at baseline in 708 nonanemic adults, aged 60 years and older, with incident anemia during 15 years of follow-up among participants in the Invecchiare in Chianti (InCHIANTI) Study. During follow-up, 179 (25.3%) participants developed anemia. The proportion of participants who developed anemia from the lowest to highest quartile of plasma GDF-15 was 12.9%, 20.1%, 21.2%, and 45.8%, respectively. Adults in the highest quartile of plasma GDF-15 had an increased the risk of developing anemia (hazards ratio 1.15, 95% confidence interval 1.09, 1.21, p < .0001) compared to those in the lower 3 quartiles in a multivariable Cox proportional hazards model adjusting for age, sex, serum iron, soluble transferrin receptor, ferritin, vitamin B12, congestive heart failure, diabetes mellitus, and cancer. Circulating GDF-15 is an independent predictor for the development of anemia in older adults.

Plasma proteomic signature of the risk of developing mobility disability: A 9-year follow-up.

IntroductionMobility disability is a powerful indicator of poor health in older adults. The biological and pathophysiological mechanism underlying the development of mobility disability remains unknown. This study conducted a data‐driven discovery phase investigation to identify plasma proteins that predict the incidence of mobility disability in community‐dwelling older adults without mobility disability at baseline.MethodsWe investigated 660 women and men, aged 71.9 ± 6.0 (60–94) years, who participated in the Invecchiare in Chianti, “Aging in the Chianti Area” study and completed the 400‐m walk at fast pace (400‐m walk) at enrollment. Median follow‐up time was 8.57 [interquartile, 3.20–9.08] years. SOMAscan technology was used to measure 1,301 plasma proteins at enrollment. The incident of mobility disability was defined as inability to complete the 400‐m walk. Protein‐specific Cox proportional hazard model was adjusted for sex, age, and other important covariates.ResultsPlasma levels of 75 proteins predicted mobility disability (p < .05). Significant proteins were enriched for the KEGG “PI3K‐Akt signaling,” “phagosomes,” and “cytokine–cytokine receptor interaction” pathways. After multiple comparison adjustment, plasma cathepsin S (CTSS; hazard ratio [HR] 1.33, 95% CI: 1.17, 1.51, q = 0.007), growth/differentiation factor 15 (GDF15; HR: 1.45, 95% CI: 1.23, 1.72, q = 0.007), and thrombospondin‐2 (THBS2; HR: 1.44, 95% CI: 1.22, 1.69, q = 0.007) remained significantly associated with high risk of losing mobility.ConclusionCTSS, GDF15, and THBS2 are novel blood biomarkers associated with new mobility disability in community‐dwelling individuals. Overall, our analysis suggests that cellular senescence and inflammation should be targeted for prevention of mobility disability.

Interaction Between Vitamin D and Interleukin 6 on Slow Gait Speed: 6-Year Follow-up Data of Older Adults From InCHIANTI.

Whereas the independent effects of biomarkers, including 25-hydroxy vitamin D (25(OH)D), insulin-like growth factor 1, C-reactive protein, and interleukin 6 (IL-6), on gait speed in older adults have been evaluated, their joint effects on gait speed are not well understood. Study subjects aged at least 65 at baseline (N = 970) were enrolled in the population-based Invecchiare in Chianti (InCHIANTI) study from 1998 to 2000 and were followed up at 3 and 6 years. All above biomarkers and gait speed data were measured at each of the three time points. Using a generalized estimating equation approach, we determined if slow gait speed (<0.8 m/s) was associated with the biomarkers. Further investigation was conducted for interactions between high IL-6 (≥.87 pg/mL) and other biomarkers focusing on low 25(OH)D (<20 ng/mL). After controlling for other biomarkers and potential confounders, IL-6 emerged as the only biomarker independently associated with gait speed. The association between high IL-6 and slow gait speed was enhanced by low 25(OH)D, with significant interaction between high IL-6 and low 25(OH)D (p = .038). The odds ratio of slow gait speed for low 25(OH)D and high IL-6 was 1.63 (95% confidence interval [CI]: 1.15, 2.32) compared with the reference groups with both biomarker levels at the other ends. The association of low vitamin D with slow gait speed statistically interacts with high IL-6. Coexisting vitamin D insufficiency and inflammation may provide a better biomarker for identifying those at risk of developing impairments in gait speed than either factor alone.

Predictive Capacity of Frailty Phenotype Toward Patterns of Disability Identified Using Latent Class Analysis

ObjectivesFrailty phenotype (FP) has low sensitivity toward the identification of older people who will lose 1 or more activities of daily living. Nevertheless, the definition of disability in terms of activities of daily living may not resemble the pattern of functional impairment occurring during aging. The aim of this study was to examine the discriminative capacity of the FP toward the identification of patterns of disabilities in an extended list of tasks, identified among community-dwelling older people. DesignLongitudinal cohort study. Setting and participantsWe included 997 persons age 65 years and older selected from the Invecchiare in Chianti (InCHIANTI) Study population. MeasuresUsing latent class analysis, we assessed the pattern of 3-year changes in 24 functional tasks. Then, we calculated the discriminative capacity of the FP for each pattern of disability. Analyses were stratified by sex. ResultsIn both men and women, we recognized 3 classes: stable function; disability in complex tasks; and global functional disability. Among women, ability of FP to identify persons in global functional disability showed sensitivity = 0.42, specificity = 0.98, positive and negative predictive values 0.75 and 0.91; the corresponding values for prediction of disability in complex tasks were 0.13, 0.98, 0.68, and 0.75. Similar results were obtained among men. Conclusions/ImplicationsOver 3 years, older people of the InCHIANTI population remained largely functional stable, some persons developed deficiency in complex tasks, and a minority developed global functional disability. Trying to predict these 3 patterns may be useful for the care of older people in order to promote individualized interventions to reduce the burden of disabilities and their consequences. To this purpose, FP showed a fairly good capacity to identify people at risk of functional decline, but further studies are needed to identify instruments with better prognostic capacity.

Cardiovascular Health Is Associated With Disability Among Older Community Dwelling Men and Women.

Objective: The aim of this study was to investigate whether an index of overall cardiovascular health (CVH) is associated with disability in older individuals. Method: Data on 925 participants of the InCHIANTI study (Invecchiare in Chianti, aging in the Chianti area, ≥65 years, 55% women) with median follow-up of 9 years were used. CVH score was assessed by smoking status, physical activity, body mass index, diet quality, blood pressure, plasma cholesterol, and fasting blood glucose. Disability was examined using instrumental activities of daily living (IADL disabilities >0 vs. 0) and activities of daily living (ADL disabilities >0 vs. 0). Generalized estimating equations and Cox models assessed relationships between baseline CVH with disability and worsening over 9 years. Results: A 1-point increase in the CVH score was associated with 23% and 17% of lower odds of ADL (p < .001) and IADL (p < .001) disability and was protective of worsening of disability over 9 years. Cox models demonstrated that a 1-point increase in CVH score was associated with lower hazards of both ADL (hazard ratio [HR] = 0.86, p = .005) and IADL (HR = 0.91, p = .007) disability. Discussion: Among older individuals, better CVH was associated with lower risk of disability and worsening over 9 years.

Gait Speed and Mobility Disability: Revisiting Meaningful Levels in Diverse Clinical Populations

To investigate the heterogeneity of clinically meaningful levels of gait speed relative to self-reported mobility disability (SR-MD). Five longitudinal studies with older adults in different health states (onset of acute event, presence of chronic condition, sedentary, community living) were used to explore the relationship between gait speed and SR-MD. Lifestyle Interventions and Independence for Elders Pilot (LIFE-P), LIFE, Trial of Angiotensin-Converting Enzyme Inhibition and Novel Cardiovascular Risk Factors (TRAIN), Baltimore Hip Fracture Study (BHS2), Invecchiare in Chianti (InCHIANTI). Individuals aged 65 and older (N=3,540): sedentary, community dwelling (LIFE-P/LIFE), with hip fracture (BHS2), random population-based sample (InCHIANTI), high cardiovascular risk (TRAIN). Usual-pace gait speed across 3 to 4 m and SR-MD, defined as inability to walk approximately 1 block or climb 1 flight of stairs. The mean gait speed of participants without SR-MD was greater than 1.0 m/s in InCHIANTI and TRAIN, 0.79 m/s in LIFE-P/LIFE, and 0.46 m/sec in BHS2. Of individuals with SR-MD, mean gait speed was 0.08 m/s slower in LIFE-P/LIFE, 0.19 m/s slower in TRAIN, 0.22 m/s slower in BHS2, and 0.36 m/s slower in InCHIANTI. The optimal gait speed cutpoint for minimizing SR-MD misclassification rates ranged from 0.3 m/s in BHS2 to 1.0 m/s in TRAIN. In longitudinal analyses, development of SR-MD was dependent on initial gait speed and change in gait speed (p<.001). The relationship between absolute levels of gait speed and SR-MD may be context specific, and there may be variations between populations. Across diverse clinical populations, clinical interpretations of how change in usual pace gait speed relates to development of SR-MD depend on where on the gait speed continuum change occurs.

Clusters of functional domains to identify older persons at risk of disability.

To date, there is no consensus on which set of variables should be used to identify older persons at risk of disability in activities of daily living. The present study aimed to: (i) evaluate how different deficits cluster in a population of community-dwelling older persons; and (ii) investigate whether the discriminative capacity of physical performance measures towards the development of disability might be improved by adding psychological, social and environmental indicators. Data are from 709 non-disabled older persons participating in the "Invecchiare in Chianti" study. We carried out a cluster analysis of 12 deficits in multiple functional domains, selected from the available frailty assessment instruments. Then, participants were assigned to a group, based on the obtained clusters of variables. For each group, we measured the prognostic capacity and the predictive ability for 6-year disability. The analysis showed a "physical" cluster (including weight loss, reduced grip strength/gait speed/physical activity, impaired balance, environmental barriers) and a "psychosocial" cluster (e.g. living alone, depression, low income). Thus, participants were classified into four groups according to the presence of a physical and/or psychosocial cluster. Compared with the "fit" group, the relative risks of becoming disabled in the "physical," "psychosocial" and "mixed" deficit groups were 2.23 (95% CI 0.71-7.00), 1.52 (95% CI 0.62-3.75) and 6.37 (95% CI 2.83-14.33), respectively. The positive and negative predictive values for the "physical," "psychosocial" and "mixed" deficit groups were, respectively, 9% and 87%, 6% and 83%, and 27% and 94%. As expected, physical and psychosocial deficits cluster predominantly into different groups. Even when both are considered simultaneously, the ability to predict incident disability is still insufficient. Geriatr Gerontol Int 2018; 18: 685-691.

Association Between Sodium Excretion and Cardiovascular Disease and Mortality in the Elderly: A Cohort Study

ObjectiveHigh dietary sodium intake is a risk factor for cardiovascular events and death. Recently, a J-shaped correlation between sodium intake and adverse outcomes has been shown. The evidence on the association between sodium intake and cardiovascular outcomes in the elderly is scant. The objective of this study was to evaluate the correlation between sodium intake and cardiovascular events and mortality in an elderly population, taking into account frailty status. DesignCohort study of community dwelling older people enrolled in the InCHIANTI (Invecchiare in Chianti - Aging in the Chianti) study from 1998 to 2000 and followed-up for 9 years. SettingTwo communities in Tuscany, Italy. ParticipantsA total of 920 participants 65 years of age and older, with 24-hour urinary sodium excretion data. MeasurementsNine-year mortality and incident cardiovascular events were analyzed using Cox and nonlinear log-binomial models, stratified by frailty status. Sensitivity analysis in participants without hypertension and cardiovascular diseases was performed. ResultsMean age of the population was 74.5 years (standard deviation 6.99); 55.4% were women. There was a bi-modal association between sodium excretion and mortality, with risk increasing only below sodium excretion of 6.25 g/d [hazard ratio (HR) 1.29, 95% confidence interval (CI) 1.20-1.38], confirmed in the adjusted model (HR 1.12, 95% CI 1.04-1.22). These results were confirmed in participants without cardiovascular diseases. After stratification for frailty phenotype, the association was stronger in frail participants (adjusted HR 1.23, 95% CI 1.02-1.50 vs HR 1.11, 95% CI 1.01-1.22 in robust participants). There was no association between 24-hour sodium excretion and 9-year incidence of cardiovascular diseases (adjusted risk ratio 0.96, 95% CI 0.90-1.02). ConclusionsReduced sodium excretion is associated with increased mortality in a sample of community-dwelling older people, especially among the frail participants. High levels of sodium excretion are not associated with adverse outcomes in this population; therefore, sodium restriction might not be beneficial in older people.

Oxidized LDL, Gamma-Glutamyltransferase and Adverse Outcomes in Older Adults.

Gamma-glutamyltransferase (GGT) is a biomarker of liver disease and oxidative stress which was associated with all-cause and cardiovascular (CV) mortality in the general population and in patients with high risk conditions. This study aims at assessing whether oxLDL modifies the relationship between GGT, all-cause, and CV mortality in elderly individuals from the general population. Observational longitudinal study. Population-based cohort of older individuals (>65years) free of liver disease. One thousand and thirty-eight individuals from the Invecchiare in Chianti (InCHIANTI) study. Serum GGT level, oxidized low-density lipoprotein (oxLDL), CV comorbidities, all-cause and CV mortality. The median age of the study population (n=1,038) was 74years (inter-quartile range: 69-79), 152 individuals (15%) had past CV events. During a median follow-up of 9years, 401 individuals died, 168 of them (42%) for CV causes. In adjusted analyses, GGT predicted all-cause mortality (HR for 20U/L increase in serum GGT: 1.11, 95% CI: 1.02-1.21, P=.02) and CV mortality (HR: 1.17, 95% CI: 1.03-1.33; P=.02). Furthermore, in an analysis for interaction circulating oxLDL amplified the effect of GGT on all-cause mortality (P=.003). Circulating oxLDL amplifies the effect of GGT on mortality in the elderly. The mechanism for this association remains unknown and requires further research, including studying the potential role of GGT in oxidative stress. These results are consistent with the hypothesis of a causal role of GGT in the CV morbidity and mortality in older individuals and indicate that oxLDL plays a crucial role in the interpretation of the link between GGT and the risk of adverse clinical events in this population.

Agreement between Chronic Kidney Disease Epidemiological Collaboration and Berlin Initiative Study equations for estimating glomerular filtration rate in older people: The Invecchiare in Chianti (Aging in Chianti Region) study.

The aim was to investigate to what extent chronic kidney disease (CKD) can be staged interchangeably by Chronic Kidney Disease Epidemiological Collaboration (CKD-EPI) and by Berlin Initiative Study (BIS) equations, and to verify whether cystatinC can improve concordance between formulas. Our series consisted of 828 community-dwelling individuals aged 65years or older enrolled in the Invecchiare in Chianti Study ("Aging in the Chianti Region"). Estimated glomerular filtration rate was calculated using the creatinine-based CKD-EPI, creatinine/cystatinC-based CKD-EPI, creatinine-based BIS and creatinine/cystatinC-based BIS equations. Agreement and sources of discrepancy between equations in identifying people with different degrees of kidney dysfunction was investigated by κ statistic and Bland-Altman plots. Overall, CKD-EPI values were higher than that obtained with BIS equations, especially for eGFR=30-60mL/min/1.73m2 . A total of 191 out of 828 participants were classified in stage2 by the creatinine-based CKD-EPI and in stage3a by the creatinine-based BIS equation, whereas 123 participants were classified in stage2 by creatinine/cystatinC-based CKD-EPI and in stage 3a by the creatinine/cystatinC-based BIS equation. A total of 27 participants were classified in stage3a by creatinine-based CKD-EPI and in stage3b by creatinine-based BIS equation, whereas 18 were classified as stage3a by creatinine/cystatinC-based CKD-EPI and stage3b by the creatinine/cystatinC-based BIS equation. Despite a fair overall concordance, the CKD-EPI and BIS equations cannot be considered interchangeable to assess estimated glomerular filtration rate in older people, and using creatinine/cystatinC-based rather than creatinine-based equations only marginally improves the concordance between CKD-EPI and BIS. Disagreement between equations might significantly impact the applications of stage-specific measures for managing CKD among older people. Geriatr Gerontol Int 2017; 17: 1559-1567.

Self-Reported Masticatory Dysfunction and Mortality in Community Dwelling Elderly Adults: A 9-Year Follow-Up.

To evaluate the association, if any, between masticatory dysfunction (MD) and mortality in older adults. The Invecchiare in Chianti (InCHIANTI) Study, a cohort study with 9-year follow-up. Tuscany, Italy. Individuals aged 65 and older (N = 1,155). MD was self-reported; Cox regression was used to assess the association between self-reported MD and 9-year all-cause mortality. This association was also evaluated after stratifying according to use of dentures. Analyses were adjusted for potential confounders, including demographic characteristics, lifestyle habits, comorbidities, nutrient intake, medications, and objective parameters. Four hundred five (35%) participants reported MD. Over the 9-year follow-up, 475 (41%) subjects died. According to Cox regression analysis, self-reported MD was associated with higher mortality (relative risk (RR) = 1.23, 95% confidence interval (CI) = 1.02-1.48), after adjusting for potential confounders. In participants with self-reported MD, uncorrected edentulism was the condition associated with the greatest risk of mortality (RR = 2.10, 95% CI = 1.07-4.14); use of dentures seemed to blunt this association (RR = 1.12, 95% CI = 0.87-1.44). Self-reported MD, chiefly when due to uncorrected edentulism, is associated with 9-year all-cause mortality in community-dwelling elderly adults. Further studies are needed to evaluate whether the timely correction of MD using adequate dentures can increase the survival of older adults.

Peripheral Blood Transcriptomic Signatures of Fasting Glucose and Insulin Concentrations.

Genome-wide association studies (GWAS) have successfully identified genetic loci associated with glycemic traits. However, characterizing the functional significance of these loci has proven challenging. We sought to gain insights into the regulation of fasting insulin and fasting glucose through the use of gene expression microarray data from peripheral blood samples of participants without diabetes in the Framingham Heart Study (FHS) (n = 5,056), the Rotterdam Study (RS) (n = 723), and the InCHIANTI Study (Invecchiare in Chianti) (n = 595). Using a false discovery rate q <0.05, we identified three transcripts associated with fasting glucose and 433 transcripts associated with fasting insulin levels after adjusting for age, sex, technical covariates, and complete blood cell counts. Among the findings, circulating IGF2BP2 transcript levels were positively associated with fasting insulin in both the FHS and RS. Using 1000 Genomes–imputed genotype data, we identified 47,587 cis-expression quantitative trait loci (eQTL) and 6,695 trans-eQTL associated with the 433 significant insulin-associated transcripts. Of note, we identified a trans-eQTL (rs592423), where the A allele was associated with higher IGF2BP2 levels and with fasting insulin in an independent genetic meta-analysis comprised of 50,823 individuals. We conclude that integration of genomic and transcriptomic data implicate circulating IGF2BP2 mRNA levels associated with glucose and insulin homeostasis.

The association between dietary patterns derived by reduced rank regression and depressive symptoms over time: the Invecchiare in Chianti (InCHIANTI) study.

This study aimed to identify dietary patterns using reduced rank regression (RRR) and to explore their associations with depressive symptoms over 9 years in the Invecchiare in Chianti study. At baseline, 1362 participants (55·4 % women) aged 18-102 years (mean age 68 (sd 15·5) years) were included in the study. Baseline data collection started in 1998 and was repeated after 3, 6 and 9 years. Dietary intake information was obtained using a country-specific, validated FFQ with 188 food items. For baseline diet, dietary pattern scores in quartiles (Q) were derived using RRR with the nutrients EPA+DHA, folate, Mg and Zn as response variables. Continuous depression scores from the Centre for Epidemiologic Studies Depression (CES-D) scale were used for assessing depressive symptoms. The derived dietary pattern was rich in vegetables, olive oil, grains, fruit, fish and moderate in wine and red and processed meat, and was labelled as 'typical Tuscan dietary pattern'. After full adjustment, an inverse association was observed between this dietary pattern and depressive symptoms at baseline (Q1 v. Q4, B -2·77; 95 % CI -4·55, -0·98). When examining the relationship between the above-mentioned dietary pattern at baseline and depressive symptoms over 9 years, a similar association was found after full adjustment for confounding factors (Q1 v. Q4, B -1·78; 95 % CI -3·17, -0·38). A diet rich in vegetables, olive oil, grains, fruits, fish and moderate in wine and red and processed meat was consistently associated with lower CES-D scores over a 9-year period in the Tuscan population.

Association of habitual dietary resveratrol exposure with the development of frailty in older age: the Invecchiare in Chianti study

Resveratrol may play a protective role against the frailty syndrome (FS) because of its antioxidant and anti-inflammatory properties. We prospectively evaluated the association between habitual dietary resveratrol exposure and the development of FS after 3-, 6-, and 9-y follow-up periods in a community-dwelling older population. We conducted a longitudinal analysis with the use of data from 769 participants aged ≥65 y from the Invecchiare in Chianti (Aging in Chianti) study. Total dietary resveratrol (TDR) intake was estimated at baseline with the use of a validated food-frequency questionnaire, which was developed to assess participants' usual food intakes over the previous year, and an ad hoc resveratrol database. Total urinary resveratrol (TUR) was analyzed with the use of liquid chromatography-tandem mass spectrometry with a previous solid-phase extraction at baseline. The combination of both measures [total dietary resveratrol plus total urinary resveratrol (TDR+TUR)] was computed with the use of the Howe's method. FS was assessed at baseline and at 3-, 6-, and 9-y of follow-up and was defined as the presence of ≥3 of the following 5 criteria: shrinking, exhaustion, sedentariness, slowness, and weakness. TDR+TUR concentrations were inversely associated with FS risk over 3-y of follow-up (OR for comparison of extreme tertiles: 0.11; 95% CI: 0.03, 0.45; P-trend = 0.002) but not after 6- and 9-y of follow-up in multinomial logistic regression models adjusted for baseline frailty status and potential confounders. These results did not differ when analyses were further adjusted for inflammatory markers. Higher habitual dietary resveratrol exposure was associated with lower risk of older community dwellers developing FS during the first 3 y of follow-up but not after longer follow-up periods.