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

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

Leukocyte CCR2 expression is associated with mini-mental state examination score in older adults

This is a copy of an article published in Rejuvenation Research © 2012 Mary Ann Liebert, Inc.; Rejuvenation Research is available online at: http://online.liebertpub.com.Circulating inflammatory markers may play an important role in cognitive impairment at older ages. Mice deficient for the chemokine (C-C motif) receptor 2 (CCR2) develop an accelerated Alzheimer-like pathology. CCR2 is also important in neurogenesis. To identify human gene transcripts most closely associated with Mini-Mental State Examination (MMSE) scores, we undertook a genome-wide and inflammation specific transcriptome screen in circulating leukocytes from a population-based sample

Whole-genome sequencing to understand the genetic architecture of common gene expression and biomarker phenotypes.

Initial results from sequencing studies suggest that there are relatively few low-frequency (<5%) variants associated with large effects on common phenotypes. We performed low-pass whole-genome sequencing in 680 individuals from the InCHIANTI study to test two primary hypotheses: (i) that sequencing would detect single low-frequency-large effect variants that explained similar amounts of phenotypic variance as single common variants, and (ii) that some common variant associations could be explained by low-frequency variants. We tested two sets of disease-related common phenotypes for which we had statistical power to detect large numbers of common variant-common phenotype associations-11 132 cis-gene expression traits in 450 individuals and 93 circulating biomarkers in all 680 individuals. From a total of 11 657 229 high-quality variants of which 6 129 221 and 5 528 008 were common and low frequency (<5%), respectively, low frequency-large effect associations comprised 7% of detectable cis-gene expression traits [89 of 1314 cis-eQTLs at P < 1 × 10(-06) (false discovery rate ∼5%)] and one of eight biomarker associations at P < 8 × 10(-10). Very few (30 of 1232; 2%) common variant associations were fully explained by low-frequency variants. Our data show that whole-genome sequencing can identify low-frequency variants undetected by genotyping based approaches when sample sizes are sufficiently large to detect substantial numbers of common variant associations, and that common variant associations are rarely explained by single low-frequency variants of large effect

Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition

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 &lt;. 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 &lt;. 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 &lt;. 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