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Phenotype-specific omic expression patterns in people with frailty could provide invaluable insight into the underlying multi-systemic pathological processes and targets for intervention. Classical approaches to frailty have not considered the potential for different frailty phenotypes. We characterized associations between frailty (with/without disability) and sets of omic factors (genomic, proteomic, and metabolomic) plus markers measured in routine geriatric care. This study was a prevalent case control using stored biospecimens (urine, whole blood, cells, plasma, and serum) from 1522 individuals (identified as robust (R), pre-frail (P), or frail (F)] from the Toledo Study of Healthy Aging (R=178/P=184/F=109), 3 City Bordeaux (111/269/100), Aging Multidisciplinary Investigation (157/79/54) and InCHIANTI (106/98/77) cohorts. The analysis included over 35,000 omic and routine laboratory variables from robust and frail or pre-frail (with/without disability) individuals using a machine learning framework. We identified three protective biomarkers, vitamin D3 (OR: 0.81 [95% CI: 0.68–0.98]), lutein zeaxanthin (OR: 0.82 [95% CI: 0.70–0.97]), and miRNA125b-5p (OR: 0.73, [95% CI: 0.56–0.97]) and one risk biomarker, cardiac troponin T (OR: 1.25 [95% CI: 1.23–1.27]). Excluding individuals with a disability, one protective biomarker was identified, miR125b-5p (OR: 0.85, [95% CI: 0.81–0.88]). Three risks of frailty biomarkers were detected: pro-BNP (OR: 1.47 [95% CI: 1.27–1.7]), cardiac troponin T (OR: 1.29 [95% CI: 1.21–1.38]), and sRAGE (OR: 1.26 [95% CI: 1.01–1.57]). Three key frailty biomarkers demonstrated a statistical association with frailty (oxidative stress, vitamin D, and cardiovascular system) with relationship patterns differing depending on the presence or absence of a disability. [ABSTRACT FROM AUTHOR]

Introduction: The evidence that blood levels of the soluble receptor for advanced glycation end products (sRAGE) predict mortality in people with cardiovascular diseases (CVD) is inconsistent. To clarify this matter, we investigated if frailty status influences this association. Methods: We analysed data of 1,016 individuals (median age, 75 years) from 3 population-based European cohorts, enrolled in the FRAILOMIC project. Participants were stratified by history of CVD and frailty status. Mortality was recorded during 8 years of follow-up. Results: In adjusted Cox regression models, baseline serum sRAGE was positively associated with an increased risk of mortality in participants with CVD (HR 1.64, 95% CI 1.09–2.49, p = 0.019) but not in non-CVD. Within the CVD group, the risk of death was markedly enhanced in the frail subgroup (CVD-F, HR 1.97, 95% CI 1.18–3.29, p = 0.009), compared to the non-frail subgroup (CVD-NF, HR 1.50, 95% CI 0.71–3.15, p = 0.287). Kaplan-Meier analysis showed that the median survival time of CVD-F with high sRAGE (>1,554 pg/mL) was 2.9 years shorter than that of CVD-F with low sRAGE, whereas no survival difference was seen for CVD-NF. Area under the ROC curve analysis demonstrated that for CVD-F, addition of sRAGE to the prediction model increased its prognostic value. Conclusions: Frailty status influences the relationship between sRAGE and mortality in older adults with CVD. sRAGE could be used as a prognostic marker of mortality for these individuals, particularly if they are also frail. [ABSTRACT FROM AUTHOR]

Background: Review findings on the role of dietary patterns in preventing depression are inconsistent, possibly due to variation in assessment of dietary exposure and depression. We studied the association between dietary patterns and depressive symptoms in six population-based cohorts and meta-analysed the findings using a standardised approach that defined dietary exposure, depression assessment and covariates. Methods: Included were cross-sectional data from 23 026 participants in six cohorts: InCHIANTI (Italy), LASA, NESDA, HELIUS (the Netherlands), ALSWH (Australia) and Whitehall II (UK). Analysis of incidence was based on three cohorts with repeated measures of depressive symptoms at 5–6 years of follow-up in 10 721 participants: Whitehall II, InCHIANTI, ALSWH. Three a priori dietary patterns, Mediterranean diet score (MDS), Alternative Healthy Eating Index (AHEI-2010), and the Dietary Approaches to Stop Hypertension (DASH) diet were investigated in relation to depressive symptoms. Analyses at the cohort-level adjusted for a fixed set of confounders, meta-analysis used a random-effects model. Results: Cross-sectional and prospective analyses showed statistically significant inverse associations of the three dietary patterns with depressive symptoms (continuous and dichotomous). In cross-sectional analysis, the association of diet with depressive symptoms using a cut-off yielded an adjusted OR of 0.87 (95% confidence interval 0.84–0.91) for MDS, 0.93 (0.88–0.98) for AHEI-2010, and 0.94 (0.87–1.01) for DASH. Similar associations were observed prospectively: 0.88 (0.80–0.96) for MDS; 0.95 (0.84–1.06) for AHEI-2010; 0.90 (0.84–0.97) for DASH. Conclusion: Population-scale observational evidence indicates that adults following a healthy dietary pattern have fewer depressive symptoms and lower risk of developing depressive symptoms. [ABSTRACT FROM AUTHOR]

Background: The aims of this study were to evaluate the relationship between anticholinergic drug burden (ACB) cognitive impairment, physical frailty, and cognitive frailty, and to determine if ACB is predictive of these phenotypes when modeled with biological and genomic biomarkers.Methods: In a retrospective cohort study, a total of 1,453 adults aged 20-102 years were used to examine ACB as a predictor for cognitive impairment, physical frailty, and cognitive frailty. Anticholinergic burden is examined as a predictor for all phenotypes in a cross-sectional analysis using logistic, ordinal regression models, and Extreme Gradient Boosting for population predictive modeling.Results: A significant association was found between ACB and cognitive decline (p = .02), frailty (p < .001), and cognitive frailty (p < .001). The odds of cognitive impairment increased by 1.21 (95% confidence interval [CI] = 1.06-1.37, p < .001), odds of being frail increased by 1.33 (95% CI = 1.18-1.50, p < .001), and odds of having cognitive frailty increased by 1.36 (95% CI = 1.21-1.54, p < .001). Population modeling results indicated ACB score as one of the stronger predictors for cognitive impairment, physical frailty, and cognitive frailty with area under the curves ranging from 0.81 to 0.88.Conclusions: Anticholinergic medications are a potentially modifiable risk factor for the prevention of cognitive and physical decline. Identification of reversible causes for cognitive and physical impairment is critical for the aging population. These findings encourage new research that may lead to effective interventions for deprescribing programs for the prevention of cognitive and physical decline in older adults. [ABSTRACT FROM AUTHOR]

This study investigated bidirectional associations between intake of food groups and depressive symptoms in 1058 Italian participants (aged 20–102 years) of the Invecchiare in Chianti study. Dietary intake, assessed with a validated FFQ, and depressive symptoms, measured with the Center for Epidemiologic Studies Depression scale (CES-D), were assessed at baseline and after 3, 6 and 9 years. Associations of repeated measurements of intakes of thirteen food groups with 3-year changes in depressive symptoms, and vice versa, were analysed using linear mixed models and logistic generalised estimating equations. Fish intake was inversely (quartile (Q)4 v. Q1, B= –0·97, 95 % CI –1·74, –0·21) and sweet food intake positively (Q4 v. Q1, B= 1·03, 95 % CI 0·25, 1·81) associated with subsequent CES-D score. In the other direction, higher CES-D scores were associated with decreases in intakes of vegetables (ratio: 0·995, 95 % CI 0·990, 0·999) and red and processed meat (B= –0·006, 95 % CI –0·010, –0·001), an increase in dairy product intake (ratio: 1·008, 95 % CI 1·004, 1·013), and increasing odds of eating savoury snacks (OR: 1·012, 95 % CI 1·000, 1·024). Fruit, nuts and legumes, potatoes, wholegrain bread, olive oil, sugar-sweetened beverages, and coffee and tea were not significantly associated in either direction. Our study confirmed bidirectional associations between food group intakes and depressive symptoms. Fish and sweet food intakes were associated with 3-year improvement and deterioration in depressive symptoms, respectively. Depressive symptoms were associated with 3-year changes in vegetable, meat, dairy product and savoury snack intakes. Trials are necessary to examine the causal associations between food groups and depression. [ABSTRACT FROM AUTHOR]

Background: Early identification of people at risk of functional decline is essential for delivering targeted preventive interventions.Objective: The aim of this study is to identify and predict trajectories of functional decline over 9 years in males and females aged 60-70 years.Methods: We included 403 community-dwelling participants from the InCHIANTI study and 395 from the LASA study aged 60-70 years at baseline, of whom the majority reported no functional decline at baseline (median 0, interquartile range 0-1). Participants were included if they reported data on ≥2 measurements of functional ability during a 9-year follow-up. Functional ability was scored with 6 self-reported items on activities of daily living. We performed latent class growth analysis to identify trajectories of functional decline and applied multinomial regression models to develop prediction models of identified trajectories. Analyses were stratified for sex.Results: Three distinct trajectories were identified: no/little decline (219 males, 241 females), intermediate decline (114 males, 158 females), and severe decline (36 males, 30 females). Higher gait speed showed decreased risk of functional limitations in males (intermediate limitations, odds ratio [OR] 0.74, 95% CI 0.57-0.97; severe limitations, OR 0.42, 95% CI 0.26-0.66). The final model in males further included the predictors fear of falling and alcohol intake (no/little decline, area under the receiver operating curve [AUC] 0.68, 95% CI 0.62-0.73; intermediate decline, AUC 0.63, 95% CI 0.56-0.69; severe decline, AUC 0.79, 95% CI 0.71-0.87). In females, higher gait speed showed a decreased risk of intermediate limitations (OR 0.51, 95% CI 0.38-0.68) and severe limitations (OR 0.18, 95% CI 0.07-0.44). Other predictors in females were age, living alone, economic satisfaction, balance, physical activity, BMI, and cardiovascular disease (no/little decline, AUC 0.80, 95% CI 0.75-0.85; intermediate decline, AUC 0.74, 95% CI 0.69-0.79; severe decline, AUC 0.95, 95% CI 0.91-0.99).Conclusion: Already in people aged 60-70 years, 3 distinct trajectories of functional decline were identified in these cohorts over a 9-year follow-up. Predictors of trajectories differed between males and females, except for gait speed. Identification of people at risk is the basis for targeting interventions. [ABSTRACT FROM AUTHOR]

Introduction: Biomarker discovery of dementia and cognitive impairment is important to gather insight into mechanisms underlying the pathogenesis of these conditions., Methods: In 997 adults from the InCHIANTI study, we assessed the association of 1301 plasma proteins with dementia and cognitive impairment. Validation was conducted in two Alzheimer's disease (AD) case-control studies as well as endophenotypes of AD including cognitive decline, brain amyloid burden, and brain volume., Results: We identified four risk proteins that were significantly associated with increased odds (peptidase inhibitor 3 (PI3), trefoil factor 3 (TFF3), pregnancy associated plasma protein A (PAPPA), agouti-related peptide (AGRP)) and two protective proteins (myostatin (MSTN), integrin aVb5 (ITGAV/ITGB5)) with decreased odds of baseline cognitive impairment or dementia. Of these, four proteins (MSTN, PI3, TFF3, PAPPA) were associated cognitive decline in subjects that were cognitively normal at baseline. ITGAV/ITGB5 was associated with lower brain amyloid burden, MSTN and ITGAV/ITGB5 were associated with larger brain volume and slower brain atrophy, and PI3, PAPPA, and AGRP were associated with smaller brain volume and/or faster brain atrophy., Discussion: These proteins may be useful as non-invasive biomarkers of dementia and cognitive impairment., Competing Interests: None to declare., (Published 2020. This article is a U.S. Government work and is in the public domain in the USA. Alzheimer's & Dementia: Translational Research & Clinical Interventions published by Wiley Periodicals, Inc on behalf of Alzheimer's Association.)