Fall Risk Assessment Tools for Elderly Living in the Community: Can We Do Better?

Background Falls are a common, serious threat to the health and self-confidence of the elderly. Assessment of fall risk is an important aspect of effective fall prevention programs. Objectives and methods In order to test whether it is possible to outperform current prognostic tools for falls, we analyzed 1010 variables pertaining to mobility collected from 976 elderly subjects (InCHIANTI study). We trained and validated a data-driven model that issues probabilistic predictions about future falls. We benchmarked the model against other fall risk indicators: history of falls, gait speed, Short Physical Performance Battery (Guralnik et al. 1994), and the literature-based fall risk assessment tool FRAT-up (Cattelani et al. 2015). Parsimony in the number of variables included in a tool is often considered a proxy for ease of administration. We studied how constraints on the number of variables affect predictive accuracy. Results The proposed model and FRAT-up both attained the same discriminative ability; the area under the Receiver Operating Characteristic (ROC) curve (AUC) for multiple falls was 0.71. They outperformed the other risk scores, which reported AUCs for multiple falls between 0.64 and 0.65. Thus, it appears that both data-driven and literature-based approaches are better at estimating fall risk than commonly used fall risk indicators. The accuracy–parsimony analysis revealed that tools with a small number of predictors (~1-5) were suboptimal. Increasing the number of variables improved the predictive accuracy, reaching a plateau at ~20-30, which we can consider as the best trade-off between accuracy and parsimony. Obtaining the values of these ~20-30 variables does not compromise usability, since they are usually available in comprehensive geriatric assessments

Low levels of a urinary biomarker of dietary polyphenol are associated with substantial cognition decline over a three-year period in older adults: the Invecchiare in Chianti (InCHIANTI) Study.

Objectives: To investigate the association of total urinary polyphenols (TUP) and total dietary polyphenols (TDP) with cognitive decline in an older population. Design: The Invecchiare in Chianti (InCHIANTI) study, a cohort study with a 3-year of follow-up. Setting: tuscany, italy. Participants: Non-demented adults aged 65 and older (N=652). Measurements: TUP and TDP concentrations were analysed at baseline using the Folin-Ciocalteu assay and a validated food frequency questionnaire, respectively. Cognition was assessed using the Mini-Mental State Examination (MMSE) and Trail Making Test (TMT) at baseline and after three years of follow-up. A substantial cognitive decline was defined as a reduction in the MMSE score of 3 or more points and as an increase of at least 29 seconds on the TMT A and 68 seconds on the TMT B (these thresholds represent the worst 10% of the distribution of decline) or as test discontinued due to multiple mistakes in TMT A and B at follow-up. Results: Higher TUP levels were associated with lower risk of substantial cognitive decline on the MMSE (odds ratio [OR] comparing extreme tertiles = 0.53; 95% confidence interval [CI] = 0.340.85; P-trend = 0.008) and on the TMT-A (OR = 0.52; 95 % CI = 0.280.96; P-trend = 0.03), but not on TMT-B in a logistic regression model that adjusted for baseline cognitive score and potential confounding factors. TDP did not affect the developing substantial cognitive decline in both tests. Conclusion: High concentrations of polyphenols, a nutritional biomarker of polyphenol intake, were associated with a lower risk of substantial cognitive decline in the older population studied over a three-year period, suggesting a protective effect against cognitive impairment

Aging and the burden of multimorbidity: Associations with inflammatory and anabolic hormonal biomarkers

open9siThe InCHIANTI study baseline (1998–2000) was supported as a “targeted project” (ICS110.1/RF97.71) by the Italian Ministry of Health and in part by the U.S. National Institute on Aging (contracts: 263 MD 9164 and 263 MD 821336); the InCHIANTI Follow-up 1 (2001–2003) was funded by the U.S. National Institute on Aging (contracts: N.1-AG-1-1 and N.1-AG-1-2111); the InCHIANTI Follow-ups 2 and 3 studies (2004–2010) were financed by the U.S. National Institute on Aging (contract: N01-AG-5-0002); supported in part by the Intramural Research Program of the National Institute on Aging, National Institutes of Health, Baltimore, MarylandBackground. Multimorbidity increases with aging, but risk factors beyond age are unknown. Objective. To investigate the association of inflammatory and anabolic hormonal biomarkers with presence and prospective development of multimorbidity. Methods. Nine-year longitudinal study of 1018 participants aged 60 years or older (InCHIANTI Study). Multimorbidity was evaluated at baseline and follow-up visits as number of diagnosed diseases from a predefined list of 15 candidate chronic conditions, defined according to standard clinical criteria. Linear mixed models were used to test cross-sectional and longitudinal associations between candidate biomarkers and multimorbidity. Results. At baseline, multimorbidity was significantly higher in older participants (p <. 001) and higher IL-6, IL-1ra, TNF-α receptor II (TNFAR2), and lower dehydroepiandrosterone sulfate were associated with higher number of diseases, independent of age, sex, body mass index, and education. The rate of longitudinal increase in number of chronic diseases was significantly steeper in participants who were older at baseline (p <. 001). In addition, higher baseline IL-6 and steeper increase of IL-6 levels were significantly and independently associated with a steeper increase in multimorbidity over time (p <. 001 and p =. 003, respectively). Sensitivity analyses, performed using 15 different models obtained by removing each of 15 conditions included in the original list of candidate diseases, confirmed that results were not driven by any specific condition. Conclusions. Accumulation of chronic diseases accelerates at older ages and in persons with higher baseline levels and steeper increase over time of IL-6. High IL-6 and increase in IL-6 may serve as early warning sign to better target interventions aimed at reducing the burden of multimorbidity.openFabbri, Elisa; An, Yang; Zoli, Marco; Simonsick, Eleanor M.; Guralnik, Jack M.; Bandinelli, Stefania; Boyd, Cynthia M.; Ferrucci, LuigiFabbri, Elisa; An, Yang; Zoli, Marco; Simonsick, Eleanor M.; Guralnik, Jack M.; Bandinelli, Stefania; Boyd, Cynthia M.; Ferrucci, Luig

circRNAs expressed in human peripheral blood are associated with human aging phenotypes, cellular senescence and mouse lifespan.

Circular RNAs (circRNAs) are an emerging class of non-coding RNA molecules that are thought to regulate gene expression and human disease. Despite the observation that circRNAs are known to accumulate in older organisms and have been reported in cellular senescence, their role in aging remains relatively unexplored. Here, we have assessed circRNA expression in aging human blood and followed up age-associated circRNA in relation to human aging phenotypes, mammalian longevity as measured by mouse median strain lifespan and cellular senescence in four different primary human cell types. We found that circRNAs circDEF6, circEP300, circFOXO3 and circFNDC3B demonstrate associations with parental longevity or hand grip strength in 306 subjects from the InCHIANTI study of aging, and furthermore, circFOXO3 and circEP300 also demonstrate differential expression in one or more human senescent cell types. Finally, four circRNAs tested showed evidence of conservation in mouse. Expression levels of one of these, circPlekhm1, was nominally associated with lifespan. These data suggest that circRNA may represent a novel class of regulatory RNA involved in the determination of aging phenotypes, which may show future promise as both biomarkers and future therapeutic targets for age-related disease

Comparison of 24-h volume and creatinine-corrected total urinary polyphenol as a biomarker of total dietary polyphenols in the InCHIANTI Study

Polyphenols have beneficial effects on several chronic diseases but assessing polyphenols intake from self-reported dietary questionnaires tends to be inaccurate and not very reliable. A promising alternative is to use urinary excretion of polyphenols as a proxy measure of intake. The best method to assess urinary excretion is to collect 24-h urine. However, since collecting 24-h urine method is expensive, time consuming and may be difficult to implement in large population-based studies, measures obtained from spot urine normalized by creatinine are commonly used. The purpose of the study was to evaluate the correlation between polyphenols dietary intake and total urinary polyphenol excretion (TPE), expressed by both 24-h volume and urinary creatinine normalization in 928 participants from the InCHIANTI study. Dietary intake data were collected using a validated food frequency questionnaire. Urinary TPE was analyzed by Folin-Ciocalteau assay. Both urinary TPE expression models were statistically correlated (r=0.580), and the partial correlation coefficient improved (pr=0.722) after adjusting for the variables that modify the urinary creatinine excretion (i.e. gender, age, BMI, physical activity and renal function). In crude models, polyphenol intake was associated with TPE corrected by 24-h volume (r=0.211; P<0.001), but not with creatinine normalization (r=0.014; P=0.692). However, urinary TPE expressed by creatinine correction was significantly correlated with dietary polyphenols after adjusting for covariates (pr=0.113; P=0.002). We conclude that urinary TPE expressed by 24-h volume is a better biomarker of polyphenol dietary intake than by urinary creatinine normalization. After covariate adjustment, both can be used for studying the relationships between polyphenol intake and health in large-scale epidemiological studies

The relationship between urinary total polyphenols and the frailty phenotype in a community-dwelling older population: the InCHIANTI study.

Background. Frailty, an age-related state of increased vulnerability, is associated with a higher risk of multiple adverse events. Studies have suggested that the quality of dietary intake may affect the development of frailty. We hypothesized that frailty in older subjects would be associated with dietary total polyphenols (DTP) intake and its biomarker, urinary total polyphenols (UTP). Methods. The Invecchiare in Chianti (InCHIANTI) Study is a prospective cohort study set in the Chianti area (Italy). We used data at baseline from 811 participants aged 65 years and older. UTP was determined using the Folin-Ciocalteu assay after solid-phase extraction. DTP was estimated using a validated Food Frequency Questionnaire and our own polyphenol database. The frailty, prefrailty, and nonfrailty states were defined according to the Fried and colleagues' criteria. Multinomial logistic regressions adjusted for potential confounders were used to assess the relationship between polyphenols and frailty. Results. Both DTP and UTP concentrations progressively decrease from nonfrail to frail participants. Participants in the highest UTP tertile compared to those in the lowest tertile were significantly less likely to be both frail (odds ratio [OR] = 0.36 [0.14-0.88], p = .025) and prefrail (OR = 0.64 [0.42-0.98], p = .038). Exhaustion and slowness were the only individual frailty criteria significantly associated with UTP tertiles. No significant association was observed between frailty and DTP, after adjustment for covariates. Conclusions. High concentrations of UTP were associated with lower prevalence of frailty and prefrailty in an older community-dwelling population. A polyphenol-rich diet may protect against frailty in older persons. Our findings should be confirmed in longitudinal studies

Resveratrol Levels and All-Cause Mortality in Older Community-Dwelling Adults

Importance Resveratrol, a polyphenol found in grapes, red wine, chocolate, and certain berries and roots, is considered to have antioxidant, anti-inflammatory, and anti-cancer effects in humans and is related to longevity in some lower organisms. Objective To determine whether resveratrol levels achieved with diet are associated with inflammation, cancer, cardiovascular disease, and mortality in humans. Design Prospective cohort study, the Invecchiare in Chianti (InCHIANTI) Study ("Aging in the Chianti Region"), 1998-2009. Setting Two villages in the Chianti area, Tuscany region of Italy. Participants Population-based sample of 783 community-dwelling men and women, ≥65 y Exposure 24-h urinary resveratrol metabolites Main outcomes and measures Primary outcome measure was all-cause mortality. Secondary outcomes were markers of inflammation (serum C-reactive protein [CRP], interleuki

Operationalization of a frailty index among older adults in the InCHIANTI study: predictive ability for all-cause and cardiovascular disease mortality

Background The frailty index (FI) is a sensitive instrument to measure the degree of frailty in older adults, and is increasingly used in cohort studies on aging. Aims To operationalize an FI among older adults in the "Invecchiare in Chianti" (InCHIANTI) study, and to validate its predictive capacity for mortality. Methods Longitudinal data were used from 1129 InCHIANTI participants aged >= 65 years. A 42-item FI was operationalized following a standard procedure using baseline data (1998/2000). Associations of the FI with 3- and 6-year all-cause and cardiovascular disease (CVD) mortality were studied using Cox regression. Predictive accuracy was estimated by the area under the ROC curve (AUC), for a continuous FI score and for different cut-points. Results The median FI was 0.13 (IQR 0.08-0.21). Scores were higher in women, and at advanced age. The FI was associated with 3- and 6-year all-cause and CVD mortality (HR range per 0.01 FI increase = 1.03-1.07, all p < 0.001). The continuous FI score predicted the mortality outcomes with moderate-to-good accuracy (AUC range 0.72-0.83). When applying FI cut-offs between 0.15 and 0.35, the accuracy of this FI for predicting mortality was moderate (AUC range 0.61-0.76). Overall, the predictive accuracy of the FI was higher in women than in men. Conclusions The FI operationalized in the InCHIANTI study is a good instrument to grade the risk of all-cause mortality and CVD mortality. More measurement properties, such as the responsiveness of this FI when used as outcome measure, should be investigated in future research

Effects of the diabetes linked TCF7L2 polymorphism in a representative older population

BACKGROUND: A polymorphism in the transcription factor 7-like 2 (TCF7L2) gene has been found to be associated with type 2 diabetes in case-control studies. We aimed to estimate associations of the marker rs7903146 (C/T) polymorphism with fasting glucose, lipids, diabetes prevalence and complications in an older general population. METHODS: In total, 944 subjects aged ≥ 65 years from the population representative InCHIANTI study were enrolled in this study. Those with fasting blood glucose of ≥ 7 mmol/l or physician diagnosis were considered diabetic. Cut-off points for impaired fasting glucose (IFG) were ≥ 5.6 mmol/l to < 7 mmol/l. RESULTS: In the general population sample, minor (T) allele carriers of rs7903146 had higher fasting blood glucose (FBG) (p = 0.028) but lower fasting insulin (p = 0.030) and HOMA2b scores (p = 0.001), suggesting poorer beta-cell function. T allele carriers also had smaller waist circumference (p = 0.009), lower triglyceride levels (p = 0.006), and higher high-density lipoprotein cholesterol (p = 0.008). The prevalence of diabetes or IFG was 32.4% in TT carriers and 23.3% in CC carriers; adjusted OR = 1.67 (95% confidence interval 1.05 to 2.65, p = 0.031). Within the diabetic and IFG groups, fewer T allele carriers had metabolic syndrome features (p = 0.047) or had experienced a myocardial infarction (p = 0.037). Conversely, T allele carriers with diabetes had poorer renal function (reduced 24-hour creatinine clearance, p = 0.013), and possibly more retinopathy (p = 0.067). Physician-diagnosed dementia was more common in the T carriers (in diabetes p = 0.05, with IFG p = 0.024). CONCLUSION: The TCF7L2 rs7903146 polymorphism is associated with lower insulin levels, smaller waist circumference, and lower risk lipid profiles in the general elderly population. Patients with diabetes who are carriers of the minor allele are less likely to have metabolic-syndrome features, but may experience more microvascular complications, although the number of cases was small. If replicated, these findings may have implications for developing treatment approaches tailored by genotype