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Background: Like other parts of the body, the retina and its neurovascular system are also affected by age-related changes. The rising age of populations worldwide makes it important to study the pathologies related to age and their potential risk factors, such as diet and eating habits. The aim of this study was to investigate the predictive power of food groups versus retinal features among noninstitutionalized older adults from Southern Italy using a machine learning approach. Methods: We recruited 530 subjects, with a mean age of 74 years, who were drawn from the large population of the Salus in Apulia Study. In the present cross-sectional study, eating habits were assessed with a validated food frequency questionnaire. For the visual assessment, a complete ophthalmic examination and optical coherence tomography-angiography analyses were performed. Results: The analyses identified 13 out of the 28 food groups as predictors of all our retinal variables: grains, legumes, olives-vegetable oil, fruiting vegetables, other vegetables, fruits, sweets, fish, dairy, low-fat dairy, red meat, white meat, and processed meat. Conclusions: Eating habits and food consumption may be important risk factors for age-related retinal changes. A diet that provides the optimal intake of specific nutrients with antioxidant and anti-inflammatory powers, including carotenoids and omega-3 fatty acids, could have beneficial effects.

Frailty is a multidisciplinary public health issue and nutrition is key concern. Given the scientific consistency about inflammation as shared pathway to poor nutrition and frailty, food processing seems a suitable target to gain evidence in frailty prevention nutrition settings. This study aimed to assess diet in relation to nutritional frailty using the NOVA classification. Browsing the dataset of the Salus in Apulia, 2185 older adults were found to have completed the nutritional assessment, providing eligible data for this study goal. A validated construct, based on the co-presence of physical frailty by CHS criteria plus nutritional imbalance, was applied to characterize nutritional frailty phenotypes. Using the NOVA classification, daily food and beverage intakes from an 85-item self-administered FFQ were assigned to three categories, and effect sizes were tested among groups according to nutritional frailty status (presence/absence). Raw and adjusted logistic regression models were run to assess associations between NOVA food categories by quintiles of daily exposure (very-low, low, mild, moderate, high) and nutritional frailty. Nutritional frailty prevalence was 27%, being more frequent in males. Eating more unprocessed or minimally processed foods was inversely related to nutritional frailty, even after adjustment (OR: 0.10, 95%CI 0.07–0.16), showing a downward ORs behavior toward lower consumption quintiles. Listing in the quintile of moderate consumption of processed foods meant a nearly 50% increase in nutritional frailty probability (OR: 1.46, 95%CI 1.03–2.06), while the probability was double for the highest quintile against the lowest (OR: 3.22, 95%CI 2.27–4.58). A growing probability of nutritional frailty was found for increasing consumption of ultra-processed foods, but significance was lacking. The contribution of food processing to poor nutrition needs to be considered when promoting a better understanding of effective nutritional screening in aging. Therefore, food processing should be accounted for when composing diet guidelines for the older population within the framework of multidisciplinary efforts to ease the frailty healthcare burden.

Very low-calorie ketogenic diets (VLCKD) are widely employed in successful weight-loss strategies. Herein, we evaluated the efficacy and safety of a VLCKD on non-alcoholic fatty liver disease (NAFLD) and parameters commonly associated with this condition in overweight and obese subjects who did not take any drugs. This prospective, real-life study included thirty-three participants who followed a VLCKD for 8 weeks. NAFLD was diagnosed using transient elastography (FibroScan). Data on anthropometric measurements, bioimpedance analysis, and biochemical assays were gathered both before and after the dietary intervention. BMI (kg/m2) (from 33.84 ± 6.55 to 30.89 ± 6.38, p < 0.01), waist circumference (cm) (from 106.67 ± 15.51 to 98.64 ± 16.21, p < 0.01), and fat mass (Kg) (from 38.47 ± 12.59 to 30.98 ± 12.39, p < 0.01) were significantly lower after VLCKD. CAP (db/m), the FibroScan parameter quantifying fatty liver accumulation, showed a significant reduction after VLCKD (from 266.61 ± 67.96 to 223 ± 64.19, p < 0.01). After VLCKD, the fatty liver index (FLI), a benchmark of steatosis, also revealed a significant decline (from 62.82 ± 27.46 to 44.09 ± 31.24, p < 0.01). Moreover, fasting blood glucose, insulin, triglycerides, total cholesterol, LDL-cholesterol, ALT, γGT, and FT3 blood concentrations, as well as insulin resistance (quantified by HOMAIR) and systolic and diastolic blood pressure levels, were significantly lower after VLCKD (p < 0.01 for all the parameters). By contrast, HDL-cholesterol, 25 (OH) vitamin D, and FT4 blood concentrations were higher after VLCKD (p < 0.01 for all parameters). The variation (δ) of CAP after VLCKD did not show a correlation with the δ of any other parameter investigated in this study. We conclude that VLCKD is a helpful approach for NAFLD independent of changes in factors commonly associated with NAFLD (obesity, fat mass, insulin resistance, lipids, and blood pressure) as well as vitamin D and thyroid hormone levels.

Epidemiological and public health resonance of sarcopenia in late life requires further research to identify better clinical markers useful for seeking proper care strategies in preventive medicine settings. Using a machine-learning approach, a search for clinical and fluid markers most associated with sarcopenia was carried out across older populations from northern and southern Italy. A dataset of adults >65 years of age (n = 1971) made up of clinical records and fluid markers from either a clinical-based subset from northern Italy (Pavia) and a population-based subset from southern Italy (Apulia) was employed (n = 1312 and n = 659, respectively). Body composition data obtained by dual-energy X-ray absorptiometry (DXA) were used for the diagnosis of sarcopenia, given by the presence of either low muscle mass (i.e., an SMI < 7.0 kg/m2 for males or

(1) Background: We investigated the differences in the neuropsychological profile as well as the pneumological and motor functions in two groups of patients admitted to rehabilitation who received different respiratory support during their COVID-19 infection. (2) Methods: Group-1 (n = 18; 15 male, median age 67.5) consisted of patients who received non-invasive mechanical ventilation; Group-2 (n = 19; 16 male, median age 63) consisted of patients who received invasive mechanical ventilation. All patients underwent a neuropsychological assessment including Mini-Mental State Examination (MMSE), Frontal Assessment Battery (FAB), and the Repeatable Battery for the Assessment of Neuropsychological Status (R-BANS) to evaluate the patients’ cognition. Depression and anxiety were also measured at admission and discharge to rehabilitation. (3) Results: At admission, patients impaired at MMSE were 44% in Group-1 and 5% in Group-2, while patients impaired at FAB were 88% in Group-1 and 26% in Group-2. Wilcoxon’s effect size revealed meaningful differences between groups for FAB, R-BANS global score, immediate and delayed memory, and attention-coding task, with Group-2 performing better than Group-1 across all measures. At discharge, 52% of the 25 patients re-assessed still had mild to moderate cognitive deficits, while 19% had depression and 35% had anxiety. (4) Conclusions: Patients who received oxygen therapy experienced higher levels of acute and chronic stress compared to those who benefitted from invasive mechanical ventilation. Despite patients showing a meaningful improvement at discharge, cognitive impairment persisted in a great number of patients; therefore, long-term neuropsychological follow-up and treatment for COVID-19 patients are recommended.

Comprehensive screening for non-alcoholic fatty liver disease (NAFLD) may help prompt clinical management of fatty liver disease. A family history, especially of diabetes, has been little studied as a predictor for NAFLD. We characterized the cross-sectional relationship between a family history of type 2 diabetes (FHT2D) and NAFLD probability in 1185 diabetes-free Apulian (Southern-Italy) subjects aged > 20 years with overweight or obesity not receiving any drug or supplementation. Clinical data and routine biochemistry were analysed. NAFLD probability was defined using the fatty liver index (FLI). A first-degree FHT2D was assessed by interviewing subjects and assigning a score of 0, 1, or 2 if none, only one, or both parents were affected by type 2 diabetes mellitus (T2DM). Our study population featured most females (70.9%, N = 840), and 48.4% (N = 574) of the sample had first-degree FHT2D. After dividing the sample by a FHT2D, we found a higher BMI, Waist Circumference (WC), and diastolic blood pressure shared by FHT2D subjects; they also showed altered key markers of glucose homeostasis, higher triglyceride levels, and worse liver function. FLI scores were significantly lower in subjects without a first-degree FHT2D. After running logistic regression models, a FHT2D was significantly associated with the NAFLD probability, even adjusting for major confounders and stratifying by age (under and over 40 years of age). A FHT2D led to an almost twofold higher probability of NAFLD, regardless of confounding factors (OR 2.17, 95% CI 1.63 to 2.89). A first-degree FHT2D acts as an independent determinant of NAFLD in excess weight phenotypes, regardless of the age group (younger or older than 40 years). A NAFLD risk assessment within multidimensional screening might be useful in excess weight subjects reporting FHT2D even in the absence of diabetes.

Introduction: Preventive nutritional management of frailty, a multidimensional intermediate status in the ageing process, may reduce the risk of adverse health-related outcomes. We investigated the ability of a measure combining physical frailty with nutritional imbalance, defined as nutritional frailty, to predict all-cause mortality over a period of up to 8 years. Methods: We analysed data on 1,943 older adults from the population-based ‘Salus in Apulia Study’. Physical frailty was operationalized using Cardiovascular Health Study criteria and cognitive frailty by combining physical frailty with cognitive impairment. A novel five-item construct was built to assess the extent of nutritional imbalance identified with a machine learning algorithm. Cox models and Kaplan–Meier survival probability analyses of physical frailty, nutritional imbalance (two or more of the following: low body mass index, low skeletal muscle index, ≥2.3 g/day sodium intake

Background: Possible relationships between suicidal ideation and biopsychosocial predictors in older age are unclear. In the population-based Salus in Apulia Study, we investigated the relationships among biomarkers, socio-demographic, psychopathological, inflammatory and metabolic characteristics and suicidal ideation in 1252 older subjects. Methods: Suicidal ideation was evaluated with the brief version of the Columbia-Suicide Severity Rating Scale. Apolipoprotein E (APOE) genotype and inflammatory profile [interleukin (IL)-6, tumor necrosis factor (TNF)-α, C-reactive protein (CRP)] were evaluated. A machine learning algorithm, the Random Forest (RF), selected potential biopsychosocial factors associated to suicidal ideation. Results: Suicidal ideators accounted for 2.32 % of subjects, were female, smokers, and obese with multimorbidity. After adjusting for age, gender, education and social dysfunction, logistic regression analyses revealed that suicidal ideation was associated to late-life depression (LLD) (odds ratio:21.71,95 % confidence interval:9.22–51.14). In the full RF model, asthma was the most important contributor to suicidal ideation. In the final RF model, education, age, and mild cognitive impairment followed by gender and global cognition were considered the most important contributors. Among biomarkers, in the final RF model, IL-6 followed by TNF-α, APOE ε4 allele presence, CRP and high-density lipoprotein cholesterol contributed most to suicidal ideation. Limitations: A relatively small number of older subjects with suicidal ideation (2.3 %); we did not distinguish between active and passive suicidal ideation. Conclusions: Although LLD is a strong determinant of suicidal ideation, other non-psychiatric factors, i.e., serum inflammation biomarkers, APOE ε4 allele, and multimorbidity, should be taken into account when evaluating a suicidal ideation phenotype in older age.

BackgroundAge is a leading contributor to the liver fibrosis rate and a gradual deterioration of optical function, but this association in older populations is still under-explored. The present study aimed to explore the link between vascular and neural retinal characteristics and the risk of liver fibrosis in 731 older adults from the population-based Salus in Apulia study.MethodsRetinal features were obtained using optical coherence tomography (OCT) and OCT-angiography (OCT-A). Liver fibrosis risk was taken as the fibrosis-4 (FIB-4) score. Generalized linear models (logistic regression) were used to estimate the association effect between each unit increase of OCT and OCT-A parameters as independent variables and a FIB-4 ≥ 2.67 score as an outcome. Generalized additive models were used to assess the non-linear association between OCT-A features and the linear FIB-4 score.ResultsIncreased gangliar cell complex (GCC) thickness was inversely associated with a FIB-4 score above the cut-off in both the raw model (OR: 0.98; 95% CI: 0.96–0.99; SE: 0.01) and after adjustment for age, sex, education, hypertension, diabetes, total cholesterol, and triglycerides (OR: 0.98; 95% CI: 0.97–0.99; SE: 0.01).ConclusionOur findings add to the growing volume of scientific literature demonstrating that liver fibrosis is associated with retinal neurodegeneration. This study raises a number of new questions, including whether OCT-A may be used to track the progression of metabolic abnormalities and define exact thresholds for predicting and classifying liver disease.

ObjectiveTo explore the linear association between inner retinal layers thickness and macular capillary density compared to variations of global cognition evaluated by psychometric measures in a cohort of Mediterranean subjects aged 65+ years.Materials and methodsWe performed a cross-sectional analysis of 574 participants aged 65 years+ drawn from a population-based Southern Italian study. All subjects underwent neurological evaluations, including global cognitive screening, the Mini-Mental State Examination (MMSE) and frontal assessment battery (FAB), together with an ophthalmic examination including optical coherence tomography (OCT) and OCT-Angiography. We assessed the average thickness of the ganglion cell complex (GCC) and the retinal nerve fiber layer (RNFL), the foveal avascular zone area, and vascular density (VD) of superficial (SVD) and deep (DVD) capillary plexi at the foveal and parafoveal area. Linear regression was applied to assess associations of ocular measurements with MMSE and FAB scores.ResultsIn the linear regression model, foveal DVD (beta = 0.01, 95% CI:0.004–0.052), whole DVD (beta = 0.04, 95% CI:0.02–0.08), and whole SVD (beta = 0.04, 95% CI:0.02–0.07) showed a positive association with MMSE. In addition, foveal SVD (beta = 0.01, 95% CI:0.003–0.05) and whole SVD (beta = 0.03, 95% CI:0.004–0.08) were positively associated with the FAB score. We found no further significant association between the MMSE score or the FAB score and the average thickness of the GCC and RNFL, and FAZ area.ConclusionA direct linear association between the VD of the macular capillary plexi with global and frontal cognitive functions was observed in elderly subjects.

Objectives: Individuals with late-life depression (LLD) may have shorter survival, but there is a lack of findings in population-based settings about health-related outcomes of LLD and its subtypes: early-onset depression (EOD) and late-onset depression (LOD). We aimed to evaluate the risk of all-cause mortality of individuals with LLD and its subtypes in an older population-based cohort. Moreover, we investigated whether inflammatory, cognitive, genetic features and multimorbidity could modify the effect of this association. Design: Longitudinal population-based study with 8-year follow-up. Setting and Participants: We analyzed data on a sample of 1479 participants, all aged >65 years, in the Salus in Apulia Study. Methods: LLD was diagnosed through DSM-IV-TR criteria and LOD and EOD according to the age of onset. Multimorbidity status was defined as the copresence of 2 or more chronic diseases. Results: The overall prevalence of LLD in this older sample from Southern Italy was 10.2%, subdivided into 3.4% EOD and 6.8% LOD. In multivariable Cox models adjusted for age, gender, education, global cognition, apolipoprotein E ε4 allele, physical frailty, interleukin-6, and multimorbidity, LLD showed a greater risk of all-cause mortality. LOD differed from EOD regarding gender, education, cognitive dysfunctions, and diabetes mellitus. There was a significantly increased risk of all-cause mortality for participants with LOD (hazard ratio:1.99; 95% CI 1.33–2.97) in the time of observation between enrollment date and death date (7.31 ± 2.17 months). Conclusions and Implication: In older age, individuals with LOD but not with EOD had a significantly decreased survival, probably related to increased inflammation, multimorbidity, and cognitive impairments.

BackgroundTransient elastography is an ultrasound-based method to detect non-alcoholic fatty liver disease (NAFLD). Despite the simultaneously rising prevalence of fatty liver and metabolic disease, further information about metabolic risk indicators of fatty liver is still necessary.MethodsA Southern Italian population sample with obesity (N = 87) was cross-sectionally explored for associations among the presence of NAFLD, assessed by FibroScan, and clinical, biochemical and anthropometric parameters. Inclusion criteria were age >18 years, BMI ≥ 25 kg/m2, no ongoing supplemental or drug therapy, including oral contraceptives or osteoporosis medications; exclusion criteria were pregnancy, endocrinological diseases, cardiovascular diseases, neoplasia, renal or hepatic failure, hereditary thrombocytopenia, hepatitis B (HBV) or hepatitis C virus (HCV) infection, and excess alcohol consumption.ResultsThe study sample featured a female predominance (67%, N = 60), age range 18–64 years, and 40% prevalence of NAFLD, in accordance with the fibroscan-measured controlled attenuation parameter (CAP) threshold value above 302 dB/m. Males were slightly more frequently affected by NAFLD (51.4% vs. 48.6%, p = 0.01). Insulin levels, insulin resistance (quantified by HOMA-IR), diastolic blood pressure, BMI, visceral adipose tissue (VAT), and waist circumference were significantly higher in the NAFLD subset compared to their counterparts (p < 0.01, p < 0.01, p = 0.05, p < 0.01, p < 0.01, p < 0.01, respectively). Uric acid (p < 0.01) also showed a positive trend in the NAFLD group. Other liver steatosis parameters, measured by stiffness (p < 0.01), fatty liver index (FLI) (p < 0.01) and FibroScan-AST (FAST) (p < 0.01), were also significantly greater in the NAFLD group. In three nested linear regression models built to assess associations between CAP values and serum uric acid levels, a single unit increase in uricemia indicated a CAP increase by 14 dB/m, after adjusting for confounders (coefficient: 14.07, 95% CI 0.6–27.54).ConclusionsClinical-metabolic screening for NAFLD cannot ignore uricemia, especially in patients with obesity.

Introduction In subjects with nonalcoholic fatty liver disease (NAFLD), advanced fibrosis (AF) carries the highest risk of adverse liver-related events. To reduce the number of unnecessary biopsies, several noninvasive tools (NITs) for the risk stratification of fibrosis have been developed. We conducted this meta-analysis to assess the performance of the fibrosis-4 index (FIB-4) and NAFLD fibrosis scores (NFS), the 2 most common NITs, for the appropriate selection of subjects with AF for biopsy. Methods Four databases were searched until December 2020 (CRD42021224766). Original articles reporting data on the performance of FIB-4 and NFS, interpreted according to standard cutoffs in subjects with biopsy-proven NAFLD, were included. Separate data extractions were performed according to the lower cutoff, the higher cutoff, and the dual threshold approach. The numbers of subjects classified as true-negative, true-positive, false-negative, and false-positive were extracted. Summary operating points were estimated using a random-effects model. Results Eighteen studies evaluating 12,604 subjects were included. Participants were adult outpatients with biopsy-proven NAFLD or nonalcoholic steatohepatitis. Overall, a weak-to-moderate performance was found for both scores. The head-to-head comparison showed FIB-4 to be associated with a higher performance in ruling in and NFS in ruling out AF in the single threshold approach, whereas, with the dual threshold approach, a lower prevalence of indeterminate findings was found for FIB-4. Discussion This meta-analysis suggested that currently available NITs have a limited performance in identifying AF among subjects with NAFLD. Further studies are needed to optimize existing thresholds or develop new NITs.

Although the pathophysiological bases of Alzheimer's disease (AD) remain incompletely understood and disease-modifying therapies are not available, intervention on modifiable risk factors is warranted. Research on nutrition and dietary components is challenging and controversies still persist about the role of micro- and macronutrients and health outcomes in dementia. Importantly, results of preclinical investigations have shown that vitamin D triggers different neural pathways that may be protective against these neurodegenerative mechanisms, including the deposition of amyloid plaques, inflammatory processes, neurofibrillary degeneration, glutamatergic excitotoxicity, excessive intraneuronal calcium influx, and oxidative stress, although its relationship with AD still needs to be fully understood.The authors analyzed the recent evidence about the effects of vitamin D insufficiency on AD and the role of supplementation.Both insufficient (25-49.9 ng/ml) and deficient levels (25 ng/ml) of vitamin D may contribute to an increased susceptibility to AD. However, further well-designed prospective studies are needed for a better understanding of the involvement of low vitamin D concentrations in the AD natural history. Randomized clinical trials will also be necessary to address the issue of causality and determine whether vitamin D supplementation may be effective for the prevention or treatment of AD.

Consistency among population-based studies investigating the relationship between diet and cognition in older inhabitants in the Mediterranean area is poor. The present study investigated whether diet changes over 12 years were associated with cognitive function in older people in Southern-Italy.From the 'Salus in Apulia Study', that includes the MICOL and GreatAGE Studies, 584 participants were selected, firstly enrolled in MICOL3 (M3) and later in the GreatAGE Study (MICOL4, M4). Foods and micronutrients intake were recorded in both studies, and global cognitive function in M4, assessed with the Mini Mental State Examination.Plant-based foods, particularly coffee and vegetables, as well as vitamin A sources, were inversely associated to age-related cognitive impairment. Alcohol consumption showed a detrimental role on cognition, while red meat appeared to be beneficial in the present study, although its role is traditionally considered harmful for cognitive function.Our study confirmed that a traditional Mediterranean dietary pattern based on agricultural products and low alcohol consumption may help to prevent/delay age-related cognitive impairment.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has affected the entire planet. The objectives of our study were to compare responses to the vaccine (Pfizer-Biontech COMIRNATY) in a population of patients with intestinal bowel syndrome undergoing different biological therapies or conventional therapy. The study recruited 390 patients who received the first vaccination dose during the dedicated vaccination campaign for inflammatory bowel disease (IBD) patients. The inclusion criteria were a diagnosis of CD or UC and complete vaccination with the Pfizer–BioNTech COVID-19 (Comirnaty) vaccine. The exclusion criteria were other significant diseases or important therapies under way or contraindications to vaccination according to the European drug surveillance recommendations. Linear rank models were run to assess the association between the different therapies and S1/S2 antibodies at three different times. The models showed that in patients with IBD receiving Vedolizumab a significant increase in mean IgG levels was observed, independently of other therapies and confounding factors (β: 57.45, 95% CI 19.62 to 19.00). This study confirmed the complete antibody response to vaccination against COVID-19 in patients with IBD undergoing biological therapy—particularly Vedolizumab treatment—but also a reduced immune response due to concomitant steroid therapy.

Background: Minimally invasive methods in colorectal surgery offer unquestionable advantages, especially in the context of obesity. The current study addresses the lack of scientific evidence on the long-term oncologic safety of video-laparoscopic (VL) approaches in excess-weight CRC patients undergoing surgery. Methods: We retrospectively analyzed a surgical database consisting of 138 CRC patients undergoing VL (n = 87, 63%) and open CRC surgery (n = 51, 37%). To reduce selection bias, a propensity score matching was applied as a preliminary step to balance the comparison between the two surgery groups, i.e., VL and open surgery. Data from patients treated by the same surgeon were used.to minimize bias. Additional Cox regression models were run on the matched sample (N = 98) to explore the observed benefits of VL surgery in terms of overall and cancer-free survival. The nonparametric Kaplan-Meier method was used to compare the two surgical approaches and assess the likelihood of survival and cancer relapse. Results: The study sample was mostly male (N = 86, 62.3%), and VL outnumbered open surgery (63% versus 37%). Both before and after the matching, the VL-allocated group showed better overall survival (p < 0.01) with comparable cancer-free survival over more than five years of median observation time (66 months). Kaplan Meier survival probability curves corroborated the VL significant protective effect on survival (HR of 0.32; 95% CI: 0.13 to 0.81) even after adjusting for major confounding factors (age, gender, comorbidity index, BMI, tumor localization, tumor staging, tumor grading, clearance, CRM). Findings on oncologic performance by tumor relapse were comparable but lacked significance due to the small number of events observed. Conclusions: Comparing CRC surgical approaches, VL allocation showed comparable cancer-free survival but also a better performance on overall mortality than open surgery over more than five years of median observation.

Introduction: There is scientific consistency in the concept of ultra-processed foods (UPFs) as a descriptor of an unhealthy diet. The most recent literature points to troubling evidence that policies adopted to address the SARS-CoV-2 pandemic may have contributed to diverting eating habits toward a poorer diet. Considering the historically unique SARS-CoV-2 pandemic lockdown scenario, and the health burden imposed by UPFs on human health, it is critical to investigate how the epidemic has influenced UPF intake directly. Reviewing the literature, we aimed to assess the changes in the consumption of UPFs during the pandemic lockdown compared to previous habits in the general population. Methods: Consulting six databases, we examined articles investigating the consumption of UPFs according to the NOVA classification both before the SARS-CoV-2 pandemic and during lockdowns. In total, 28 reports were included in the final analysis. Results: A clear trend of an increasing consumption of sweets (chocolate, candy, cookies, pastries, cakes, desserts, and confectionery, 31.75% increase vs. 21.06% decrease), packaged fatty or salty snacks (23.71% increase vs. 20.73% decrease), and baked goods (bread products, pizza, and sandwiches, 28.03% increase vs. 13.5% decrease) emerged, versus a decrease in ready-to-eat dishes (16.2% increase vs. 22.62% decrease) and ready-made meals (10.6% increase vs. 31.43% decrease), such as instant soups, canned foods, fast food, and chips, as well as sugary drinks in general (14.55% increase vs. 22.65% decrease). No trend was observed for processed meat consumption. Conclusion: The current pandemic scenario raises concerns about the increased consumption of UPFs, especially sweets, snacks, and baked goods, and points to an urgent need to implement policy strategies to manage the trade in these foods from a preventive perspective.

Background Age-related hearing loss (ARHL) and retinal vessel changes have both been associated to neurodegeneration/dementia, suggesting a possible link between these 2 conditions in older age. We aimed to determine whether superficial and deep vascular density (SVD and DVD) of the capillary plexi of macular vasculature can be associated with peripheral ARHL and age-related central auditory central processing (CAPD). Method We analyzed data on 886 older participants (65 years+, age range: 65–92 years) in the cross-sectional population-based Salus in Apulia Study. Optical coherence tomography angiography was used to measure SVD and DVD of the capillary plexi of the macula at the 3-mm circle area centered on the fovea (whole retina), the parafoveal quadrant, and foveal quadrant. Disabling peripheral ARHL was defined as >40 dB hearing level of pure tone average on the frequencies from 0.5, 1, 2, and 4 KHz in the better ear, and age-related CAPD as Results DVD at the whole retina and at the parafoveal quadrant were inversely associated only with age-related CAPD (odds ratio [OR]: 0.93, 95% confidence interval [CI]: 0.88–0.96 and OR: 0.94, 95 CI: 0.90–0.99, respectively). No further associations with peripheral ARHL were evident. Conclusions Retinal vasculature is associated with central auditory processing pathology, possibly playing an important role in early detection and intervention. The association of retinal vascular density with age-related CAPD may bring us a further step forward in understanding the biological mechanisms underlying the links between neurodegeneration/dementia and ARHL.

Purpose Growing awareness of the biological and clinical value of nutrition in frailty settings calls for further efforts to investigate dietary gaps to act sooner to achieve focused management of aging populations. We cross-sectionally examined the eating habits of an older Mediterranean population to profile dietary features most associated with physical frailty. Methods Clinical and physical examination, routine biomarkers, medical history, and anthropometry were analyzed in 1502 older adults (65 +). CHS criteria were applied to classify physical frailty, and a validated Food Frequency Questionnaire to assess diet. The population was subdivided by physical frailty status (frail or non-frail). Raw and adjusted logistic regression models were applied to three clusters of dietary variables (food groups, macronutrients, and micronutrients), previously selected by a LASSO approach to better predict diet-related frailty determinants. Results A lower consumption of wine (OR 0.998, 95% CI 0.997–0.999) and coffee (OR 0.994, 95% CI 0.989–0.999), as well as a cluster of macro and micronutrients led by PUFAs (OR 0.939, 95% CI 0.896–0.991), zinc (OR 0.977, 95% CI 0.952–0.998), and coumarins (OR 0.631, 95% CI 0.431–0.971), was predictive of non-frailty, but higher legumes intake (OR 1.005, 95%CI 1.000–1.009) of physical frailty, regardless of age, gender, and education level. Conclusions Higher consumption of coffee and wine, as well as PUFAs, zinc, and coumarins, as opposed to legumes, may work well in protecting against a physical frailty profile of aging in a Mediterranean setting. Longitudinal investigations are needed to better understand the causal potential of diet as a modifiable contributor to frailty during aging.

Dietary behaviour is a core element in diabetes self-management. There are no remarkable differences between nutritional guidelines for people with type 2 diabetes and healthy eating recommendations for the general public. This study aimed to evaluate dietary differences between subjects with and without diabetes and to describe any emerging dietary patterns characterizing diabetic subjects. In this cross-sectional study conducted on older adults from Southern Italy, eating habits in the “Diabetic” and “Not Diabetic” groups were assessed with FFQ, and dietary patterns were derived using an unsupervised learning algorithm: principal component analysis. Diabetic subjects (n = 187) were more likely to be male, slightly older, and with a slightly lower level of education than subjects without diabetes. The diet of diabetic subjects reflected a high-frequency intake of dairy products, eggs, vegetables and greens, fresh fruit and nuts, and olive oil. On the other hand, the consumption of sweets and sugary foods was reduced compared to non-diabetics (23.74 ± 35.81 vs. 16.52 ± 22.87; 11.08 ± 21.85 vs. 7.22 ± 15.96). The subjects without diabetes had a higher consumption of red meat, processed meat, ready-to-eat dishes, alcoholic drinks, and lower vegetable consumption. The present study demonstrated that, in areas around the Mediterranean Sea, older subjects with diabetes had a healthier diet than their non-diabetic counterparts.

Background: Epidemiological studies have shown that food is a compelling means of maintaining a state of well-being and preventing diseases. Many malignant diseases are related to nutrition, and the nutrient-organism interaction could define the balance between health and disease. Nutrients and dietary components influence epigenetic phenomena and modify drug response so that food-organism interactions may influence individual predisposition to disease and its potential therapeutic response. Aim: In this review, we highlighted emerging opinions and data on a large cluster of nutraceuticals, as well as functional foods and specific dietary patterns, with respect to cancer, including breast, pancreas, prostate, and colorectal. Only those nutraceuticals and nutritional supplements yielding sufficient and convincing data have been reported in this review; molecules with inconclusive clinical evidence will not be discussed. Conclusions: Growing and accumulating evidence is validating the use of nutraceuticals in cancer settings. However, a knowledge gap remains in terms of causal evidence for several compounds where a window for further clinical studies is left.

Background: Retinal microvasculature assessment at capillary level may potentially aid the evaluation of early microvascular changes due to hypertension. We aimed to investigate associations between the measures obtained using optical coherence tomography (OCT) and OCT-angiography (OCT-A) and hypertension, in a southern Italian older population. Methods: We performed a cross-sectional analysis from a population-based study on 731 participants aged 65 years+ subdivided into two groups according to the presence or absence of blood hypertension without hypertensive retinopathy. The average thickness of the ganglion cell complex (GCC) and the retinal nerve fiber layer (RNFL) were measured. The foveal avascular zone area, vascular density (VD) at the macular site and of the optic nerve head (ONH) and radial peripapillary capillary (RPC) plexi were evaluated. Logistic regression was applied to assess the association of ocular measurements with hypertension. Results: GCC thickness was inversely associated with hypertension (odds ratio (OR): 0.98, 95% confidence interval (CI): 0.97–1). A rarefaction of VD of the ONH plexus at the inferior temporal sector (OR: 0.95, 95% CI: 0.91–0.99) and, conversely, a higher VD of the ONH and RPC plexi inside optic disc (OR: 1.07, 95% CI: 1.04–1.10; OR: 1.04, 95% CI: 1.02–1.06, respectively) were significantly associated with hypertension. Conclusion: A neuroretinal thinning involving GCC and a change in capillary density at the peripapillary network were related to the hypertension in older patients without hypertensive retinopathy. Assessing peripapillary retinal microvasculature using OCT-A may be a useful non-invasive approach to detect early microvascular changes due to hypertension.

Background the possible relationship between dietary habits and the incidence of late-onset depression (LOD), defined as first depression onset at later age, is unclear. Objective to investigate the relationship between consumption of different food groups and incident LOD. Design longitudinal population-based study with a 12-year follow-up. Setting Castellana Grotte, Bari, Italy. Subjects five hundred and forty-six older subjects from the Salus in Apulia Study. Methods baseline data were recorded in 2003–06, and diagnostic data were recorded in 2013–18 at follow-up. Dietary intake was assessed with a food frequency questionnaire. Depressive disorders were assessed with the Structured Clinical Interview for DSM-IV Axis I Disorders. Subjects who already suffered from depression or other psychiatric disorders at baseline were excluded from the analysis. The association between LOD and single dietary determinants was examined by Cox regression analysis and then applying the hazard ratio (HR). Results subjects with incident LOD (n = 34) had lower global cognition and total cholesterol levels and a higher body mass index (BMI) at baseline. Only processed meat significantly increased the risk of incident LOD of about 10% by 5 g/day intake (HR adjusted for age, sex, education, multimorbidity and BMI: 1.13, 95% confidence intervals: 1.04–1.22). A similar relationship was found for single foods in the processed meat food group such as sausages, salami and mortadella and baked ham, but not for raw ham. Conclusions in midlife, a higher intake of processed meat was not only associated with an increased risk of cardiovascular- and metabolic-related chronic diseases in older age but also with an increased risk of developing LOD.

Hepatic steatosis, often known as fatty liver, is the most common hepatic disease in Western countries. The latest guidelines for the treatment of nonalcoholic fatty liver disease emphasize lifestyle measures, such as changing unhealthy eating patterns. Using a propensity score-matching approach, this study investigated the effect of adhering to a Mediterranean diet (MedDiet) on fatty liver risk in an older population (≥65 years) from Southern Italy. We recruited 1.403 subjects (53.6% men, ≥65 years) who completed a food frequency questionnaire (FFQ) and underwent clinical assessment between 2015 and 2018. For the assessment of the liver fat content, we applied the Fatty Liver Index (FLI). To evaluate the treatment effect of the MedDiet, propensity score matching was performed on patients with and without FLI > 60. After propensity score-matching with the MedDiet pattern as treatment, we found a higher consumption of red meat (p = 0.04) and wine (p = 0.04) in subjects with FLI > 60. Based on the FLI, the inverse association shown between adherence to the MedDiet and the risk of hepatic steatosis shows that the MedDiet can help to prevent hepatic steatosis. Consuming less red and processed meat, as well as alcoholic beverages, may be part of these healthy lifestyle recommendations.

Hearing loss is one of the top contributors to years lived with disability and is a risk factor for dementia. Molecular evidence on the cellular origins of hearing loss in humans is growing. Here, we performed a genome-wide association meta-analysis of clinically diagnosed and self-reported hearing impairment on 723,266 individuals and identified 48 significant loci, 10 of which are novel. A large proportion of associations comprised missense variants, half of which lie within known familial hearing loss loci. We used single-cell RNA-sequencing data from mouse cochlea and brain and mapped common-variant genomic results to spindle, root, and basal cells from the stria vascularis, a structure in the cochlea necessary for normal hearing. Our findings indicate the importance of the stria vascularis in the mechanism of hearing impairment, providing future paths for developing targets for therapeutic intervention in hearing loss. publishedVersion

Introduction: For Alzheimer’s disease (AD) treatment, US FDA granted accelerated approval for aducanumab due to its amyloid-β (Aβ)-lowering effects, notwithstanding the reported poor correlation between amyloid plaque reduction and clinical change for this drug. The diversification of drug targets appears to be the future of the AD field and from this perspective, drugs modulating microglia dysfunction and combination treatment regimens offer some promise. Areas covered: The aim of the present article was to provide a comprehensive review of ALZT-OP1 (cromolyn sodium plus ibuprofen), an experimental combination treatment regimen for AD, discussing their mechanisms of action targeting Aβ and neuroinflammation, examining the role of microglia in AD and offering our own insights on the role of present and alternative approaches directed toward neuroinflammation. Expert opinion: Enrolling high-risk participants with elevated brain amyloid could help to slow cognitive decline in secondary prevention trials during AD preclinical stages. Long-term follow-up indicated that non-steroidal anti-inflammatory drugs use begun when the brain was still normal may benefit these patients, suggesting that the timing of therapy could be crucial. However, previous clinical failures and the present incomplete understanding of the Aβ pathophysiological role in AD put this novel experimental combination regimen at substantial risk of failure.

Background: In 2010, the European Working Group on Sarcopenia in Older People (EWGSOP1) issued its first operational definition to diagnose sarcopenia. This was updated in 2019 with a revised sequence of muscle mass and muscle strength (EWGSOP2). The aim of the study was to investigate the impact of these different operational definitions on sarcopenia prevalence in a representative population-based sample. Methods: For each algorithm, the prevalence of sarcopenia-related categories was calculated and related to sociodemographic and lifestyle variables, anthropometric parameters, and laboratory biomarkers. The present analysis used data from the Salus in Apulia Study (Italy, 740 subjects, mean age 75.5 ± 5.9 years, 54% women). Results: The application of the EWGSOP1 adapted algorithm resulted in 85% [95% confidence intervals (CI): 82–88%] non-sarcopenic subjects, 10% (95% CI: 8–12%) pre-sarcopenic subjects, and 5% (95% CI: 3–7%) sarcopenic/severe sarcopenic subjects. The sarcopenia-related categories were inversely related to weight and body mass index (BMI), particularly in overweight/obese subjects, and these categories showed favorable metabolic biomarkers. The EWGSOP2 algorithm yielded 73% (95% CI: 69–76%) non-sarcopenic subjects, 24% (95% CI: 21–27%) probably sarcopenic subjects, and 4% (95% CI: 2–5%) sarcopenic subjects. Conclusions: The present study identified BMI as a potential confounder of the prevalence estimates of sarcopenia-related categories in population-based settings with different EWGSOP operational definitions.

Objectives: Non-alcoholic fatty liver disease (NAFLD) currently affects a quarter of the global population. Systemic inflammation, metabolic syndrome, and coronary artery disease, all conditions associated with NAFLD, have also been related to cognitive dysfunction in older age. The present study aimed to investigate the relationship between NAFLD risk and a dementia diagnosis in a large population-based sample aged > 65 years.Methods: We selected 1,542 participants (723 men) from the Salus in Apulia Study. To assess the risk of fat distribution in the liver, we used the Fatty Liver Index (FLI). Dementia was diagnosed according to the American Psychiatric Association criteria (DSM-5).Results: The overall prevalence of dementia was 8.5% [95% confidence interval (CI): 7–10%]. Subjects with dementia were older [effect size (ES): −0.89, 95% CI: −1.07 to −0.70], had a lower level of education (ES:0.88, 95% CI:0.69–1.06), higher levels of gamma-glutamyl transferase (ES: −0.21, 95% CI: −0.39 to −0.03), lower levels of total cholesterol (ES: −0.24, 95% CI: −0.42 to −0.06) and low-density lipoprotein cholesterol (ES: −0.20, 95% CI: −0.38 to 0.02), and a higher FLI (ES: −0.22, 95% CI: −0.39 to −0.04). In the logistic regression model adjusted for age, sex, education, hypertension, diabetes mellitus, alcohol consumption, smoking habits, stroke, cholesterol, and Apo-E, a dementia diagnosis was positively associated with FLI > 60 [odds ratio (OR):1.81; standard error (SE): 0.53; 95% CI: 1.02–3.21].Conclusion: Our findings suggested that an increased NAFLD risk may be associated to dementia and cognitive decline in older age. Considering the high NAFLD prevalence, the possible adverse disease effects on cognitive performance pose a health problem with significant social and economic implications.

BackgroundDiet and social determinants influence the state of human health. In older adults, the presence of social, physical and psychological barriers increases the probability of deprivation. This study investigated the relationship between social deprivation and eating habits in non-institutionalized older adults from Southern Italy, and identified foods and dietary habits associated with social deprivation.MethodsWe recruited 1,002 subjects, mean age 74 years, from the large population based Salus in Apulia Study. In this cross-sectional study, eating habits and the level of deprivation were assessed with FFQ and DiPCare-Q, respectively.ResultsDeprived subjects (n = 441) included slightly more females, who were slightly older and with a lower level of education. They consumed less fish (23 vs. 26 g), fruiting vegetables (87 vs. 102 g), nuts (6 vs. 9 g) and less “ready to eat” dishes (29 vs. 33 g). A Random Forest (RF) model was used to identify a dietary pattern associated with social deprivation. This pattern included an increased consumption of low-fat dairy products and white meat, and a decreased consumption of wine, leafy vegetables, seafood/shellfish, processed meat, red meat, dairy products, and eggs.ConclusionThe present study showed that social factors also define diet and eating habits. Subjects with higher levels of deprivation consume cheaper and more readily available food.

Age is a major contributor to the liver fibrosis rate and its adverse health-related outcomes, including mortality, but older populations are still under-explored. We investigated multimorbidity and inflammatory biomarkers in relation to the increasing liver fibrosis risk to delineate 8-year all-cause mortality trajectories in 1929 older adults from the population-based Salus in Apulia Study. Liver fibrosis risk was assumed using the fibrosis-4 (FIB-4) score, assigned to three liver fibrosis risk groups (low, intermediate, high). In the secondary analyses, the APRI score was also calculated to allow for comparisons. Male subjects (prevalence difference: −13.49, 95% confidence interval (CI): −18.96 to −8.03), a higher multimorbidity burden (effect size, ES: −0.14, 95% CI: −0.26 to −0.02), a higher prevalence of physical frailty (ES: 6.77, 95% CI: 0.07 to 13.47), and a more pronounced inflammatory pattern as indicated by tumor growth factor-α circulating levels (ES: −0.12, 95% CI: −0.23 to −0.01) were significantly more common in the highest-risk FIB-4 score group. Liver function characterized by lipid profile and platelet levels worsened with increasing FIB-4 risk score. The 8-year risk of death was nearly double in subjects in the highest-risk FIB-4 score group, even after controlling for possible confounders. Furthermore, a steeper mortality curve was clearly observed for FIB-4 scores as compared with the APRI scoring system with respect to liver fibrosis risk. In conclusion, using a scoring tool based on simple routine biomarkers to detect liver fibrosis risk may enhance biological knowledge of age-related outcomes of chronic liver disease and be helpful in the clinical setting to identify subjects at risk for adverse health-related outcomes, including mortality.

Little study has yet been made of the effect of different beverages on oral health outcomes in the aging population. The purpose of this systematic review is to evaluate the association between different beverages, including alcohol intake, coffee, milk, tea, and sugary drinks, and a cluster of oral health outcomes, including periodontal disease, oral dysbiosis, and tooth loss in older adults. The literature was screened from the inception up to May 2021 using six different electronic databases. Two independent researchers assessed the eligibility of 1308 retrieved articles regarding inclusion criteria; only 12 fitted the eligibility requirements, representing 16 beverage entries. A minimum age of 60 was the inclusion criterion. No exclusion criteria were applied to outcomes assessment tools, recruiting facilities (hospital or community), general health status, country, and study type (longitudinal or cross-sectional). The consumption of alcoholic beverages was expressed as alcohol intake in all eligible studies, thereby replacing alcoholic beverages in the analysis. The quality of evidence was judged as moderate for alcohol and low or very low for beverages. In regard to oral health in the elderly, the review identified information on alcohol (56.25%), followed by coffee (18.75%), milk (12.50%), tea (6.25%), and sugary drinks (6.25%). Alcohol, sugary drinks, and coffee were found to be related to tooth loss. Periodontal disease was inversely related to coffee and milk, but fostered by alcohol consumption. In one article, tea but not coffee seemed to improve oral microbiota. In summary, alcohol seems to be a driver for tooth loss and periodontal disease in the aging population. However, more research is needed to gain a more solid knowledge in this research area.Systematic Review Registration:https://www.crd.york.ac.uk/prospero/, PROSPERO, Identifier: CRD42021256386.

Background. Hepatocellular carcinoma (HCC) is most commonly considered as a complication of cirrhosis. However, an increasing number of HCC in subjects with non-alcoholic fatty liver disease (NAFLD) without cirrhosis is being reported. We conducted a meta-analysis to assess the prevalence of the absence of cirrhosis in NAFLD-associated HCC. Methods. Four databases were searched until March 2021 (CRD42021242969). The original articles included were those reporting data on the presence or absence of cirrhosis among at least 50 subjects with NAFLD-associated HCC. The number of subjects with absent cirrhosis in each study was extracted. For statistical pooling of data, a random-effects model was used. Subgroup analyses according to the continent, target condition and reference standard for the diagnosis of cirrhosis were conducted. Results. Thirty studies were included, evaluating 13,371 subjects with NAFLD-associated HCC. The overall prevalence of cases without cirrhosis was 37% (95%CI 28 to 46). A higher prevalence was reported in Asia versus Europe, North America and South America (45, 36, 37 and 22%, respectively) as well as in studies adopting histology only as the reference standard for the diagnosis of cirrhosis versus histology and other modalities (e.g., radiology, endoscopy, biochemistry or overt clinical findings) (53 and 27%, respectively). No difference was found between studies including subjects with non-alcoholic steatohepatitis (NASH) only, versus NAFLD with or without NASH (p = 0.385). One in three subjects with NAFLD-associated HCC presented without cirrhosis. This should be reflected in future guidelines and surveillance programs adapted to allow for the early detection of these cancers too.

Background: Aging is the main negative prognostic factor for various chronic diseases, such as liver fibrosis, and clinical disorders such as hearing loss. This study aimed to investigate the association between age-related hearing loss (ARHL) and age-related central auditory processing disorder (CAPD), and the risk for liver fibrosis in a cross-sectional study on an aging population. Methods: Liver fibrosis risk was judged on the fibrosis-4 (FIB-4) score. Peripheral ARHL was evaluated with pure tone audiometry using a calibrated audiometer. The pure tone average (PTA), calculated as a threshold ≤ 40 dB (HL) in the better ear, was measured at the frequencies 0.5–4 kHz. For age-related CAPD assessment, we employed the Synthetic Sentence Identification with an Ipsilateral Competitive Message test (SSI-ICM). General linear Logistic regression models were used to estimate the association. Results: The increase in the PTA 0.5–2 kHz (coefficient: 0.02, SE: 0.01, CI 95%: 0.01 to 0.03) was directly associated with a higher risk of liver fibrosis (FIB-4 ≥ 2.67). Moreover, the reduction in SSI (coefficient: −0.02, SE: 0.01, CI 95%: −0.03 to −0.01) was inversely associated with FIB-4 values < 2.67. Conclusion: Our results show an association between liver fibrosis and both ARHL and CAPD, linked by the typical consequence of aging. We also assume a role of inflammatory responses and oxidative stress.

The liver contribution to the biological network underlying physical frailty in aging is underestimated. How best to measure this contribution magnitude and impact on health risk trajectories in frail individuals is not yet entirely clear. We analyzed the association of a novel liver frailty phenotype with the risk of death in older participants of the Salus in Apulia Study cohort. Clinical and physical examination, routine biomarkers, medical history, and anthropometry were analyzed in 1929 older adults (65 +). Physical frailty was classified by Cardiovascular Health Study criteria, and liver fibrosis risk by fibrosis-4 (FIB-4). The liver frailty phenotype was defined as physical frailty plus high-risk liver fibrosis (score > 2.67). Physical frailty, high-risk liver fibrosis, and liver frailty subjects were compared to subjects without these conditions (non-frail). Proportional Cox regression tested the adjusted association between liver frailty and all-cause mortality for each category. The liver frailty prevalence was relatively low (3.8%), but higher in men (58.1%). Compared to non-frail older subjects, liver frailty subjects were significantly older (effect size (ES) − 1.11, 95% confidence interval (CI) − 1.35 to − 0.87), with a lower education (ES 0.48, 95%CI 0.24 to 0.71) and higher multimorbidity (ES 15.81, 95%CI 4.20 to 27.41). Cox multivariate analyses showed a two-fold increased risk of overall mortality (hazard ratio 2.09, 95%CI 1.16–3.74) even after the adjustment for age, sex, education, and alcohol consumption. The liver frailty phenotype runs twice the risk of overall mortality compared with the non-frail population. This clinical tool, validated in a Southern Italian population, is based on simple sets of measures that can conveniently be assessed also in the primary care setting. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11357-021-00434-x.

Malabsorptive disorders are closely associated with micronutrient deficiencies. In inflammatory bowel disease (IBD), trace element deficiencies pose a clinical burden from disease onset throughout its course, contributing to morbidity and poor quality of life. We aimed to conduct a systematic review and meta-analysis of the prevalence of zinc deficiency in IBD. Literature screening was performed on six electronic databases until 1 May 2022. Two independent investigators assessed the 152 retrieved articles for inclusion criteria, met by only nine, that included 17 prevalence entries for Crohn’s disease (CD) (n = 9) and ulcerative colitis (UC) (n = 8). No exclusion criteria were applied to language, deficiency cut-offs, population age, general health status, country, or study setting (cohort or cross-sectional). The prevalence of zinc deficiency in blood was scored positive if due to a single disease, not cumulative factors. Zinc deficiency prevalence across selected studies showed higher values in CD than in UC. Pooled analyses by the IBD subgroup showed a total population of 1677 with CD, for an overall mean zinc deficiency prevalence of 54% and 95% confidence intervals (CI) ranging from 0.51 to 0.56, versus 41% (95%CI 0.38–0.45) in the UC population (n = 806). The overall prevalence at meta-analysis was estimated at 50% (95%CI 0.48–0.52), but with high heterogeneity, I2 = 96%. The funnel plot analysis failed to show any evidence of publication bias. The risk of bias across selected studies was moderate to low. In IBD contexts, one of two patients suffers from zinc deficiency. Mismanagement of micronutrient deficiencies plays a role in inflammation trajectories and related cross-pathways. Clinicians in the field are advised to list zinc among trace elements to be monitored in serum.

Declining physical functioning covers a prominent span of later life and, as a modifiable driver to be leveraged, lifestyle plays a critical role. This research aimed to undertake a systematic review investigating the association between levels of coffee consumption and declining conditions of physical functioning during aging, such as sarcopenia, frailty, weakness, falls, and disability, while trying to explain the underlying mechanisms, both from a metabolic and social angle. The literature was reviewed from inception to May 2022 using different electronic databases, not excluding the grey literature. Two independent researchers assessed the eligibility of 28 retrieved articles based on inclusion criteria; only 10 met the eligibility requirements. Different levels of coffee consumption were considered as exposure(s) and comparator(s) according to PECO concepts, while middle age was an inclusion criterion (40+ years). No limitations were set on the tool(s) assessing physical functioning, type of dietary assessment(s), study setting, general health status, country, and observational study design (cohort, cross-sectional). The cross-sectional design outnumbered the longitudinal (90%, n = 9/10). The overall quality rating was judged poor (70%) to good (30%). It was found that higher exposure to coffee drinking is strongly associated with better physical functioning outcomes, and the findings showed consistency in the direction of association across selected reports. Countering physical decline is a considerable challenge in easing the burden of population aging. For preventive models that aim to allow a better lifestyle, it has to be kept in mind that increased coffee consumption does not lead to poor physical functioning.

Importance: The association between age-related hearing loss (ARHL) and physical or cognitive frailty has been poorly explored. These associations could define new perspectives for delaying frailty-related processes in older age. Objective: To examine whether peripheral ARHL and age-related central auditory processing disorder (CAPD) are independently associated with physical or cognitive frailty. Design, Setting, and Participants: This cross-sectional study analyzed registry data from December 31, 2014, on 1929 older (≥65 years) participants of the Salus in Apulia Study (Southern Italy) who underwent audiologic, physical, and neuropsychological assessment. Data analysis was performed from December 12, 2019, to January 4, 2020. Main Outcomes and Measures: Prevalence of peripheral ARHL in older individuals with physical and/or cognitive frailty and those without frailty assessed using the Fried criteria (physical) and the Mini-Mental State Examination (cognitive). Multivariable logistic regression models were used to assess associations of audiologic variables with frailty phenotype. Results: Data from 1929 participants (mean [SD] age, 73.6 [6.3] years; 974 male [50.5%]) were eligible for the analyses. The prevalence of peripheral ARHL was higher in the physical frailty group (96 [26.6%]) than in the nonfrail group (329 [21.0%]) (difference, 5.61 percentage points; 95% CI, 0.63-10.59 percentage points) and in the cognitive frailty group (40 [38.8%]) than in the nonfrail group (385 [21.1%]) (difference, 17.75 percentage points; 95% CI, 8.2-27.3 percentage points). Age-related CAPD was more prevalent in the physical frailty group (62 [17.2%]) than in the nonfrail group (219 [14.0%]) (difference, 3.21 percentage points; 95% CI, -1.04 to 7.46 percentage points) and in the cognitive frailty group (28 [27.2%]) than in the nonfrail group (253 [13.9%]) (difference, 13.33 percentage points; 95% CI, 4.10-22.21 percentage points). In the multivariable models, age-related CAPD was associated with cognitive frailty in the fully adjusted model (odds ratio [OR], 1.889; 95% CI, 1.094-3.311). There was also an inverse association between the unitary increase in Synthetic Sentence Identification With the Ipsilateral Competitive Message scores, indicating a lower likelihood of this disorder, and cognitive frailty (OR, 0.989; 95% CI, 0.988-0.999). Peripheral ARHL was associated with cognitive frailty only in the partially adjusted model (OR, 1.725; 95% CI, 1.008-2.937). Conclusions and Relevance: In this cross-sectional study of 1929 participants, age-related CAPD was independently associated with cognitive frailty. Whether the management of ARHL may help prevent the development of different frailty phenotypes or improve their clinical consequences should be addressed in longitudinal studies and, eventually, well-designed randomized clinical trials..

BACKGROUND AND PURPOSE In older age, physical and cognitive declines have been shown to occur simultaneously or consequent to one another, and several operational definitions have been proposed to consider the co-presence of the two declines; for example, "Motoric cognitive risk syndrome" (MCR) has been proposed as a definition for the coexistence of slow gait plus subjective cognitive complaints. Given the increasing interest in MCR and its potential role as both biomarker and therapeutic target, we aimed to estimate its prevalence in a large cohort of non-demented older subjects, and to examine the associations between physical status, global cognitive dysfunction, and impairment in various cognitive domains in MCR. METHODS A population-based sample of 1041 older people in Southern Italy (mean age 75.15 years) was enrolled. We defined MCR using slowness and a single question for subjective cognitive complaints. We also administered a comprehensive neuropsychological test battery, together with tests assessing physical function. RESULTS The prevalence of MCR was 9.9% (95% confidence interval 8.2-11.9). MCR was associated with decreased processing speed and executive function after adjusting for all relevant confounders. However, we found no significant association of MCR with decreased global cognition and immediate/delayed free recall of verbal memory. MCR was also associated with increased exhaustion, low muscle strength, and low physical activity, and increased levels of C-reactive protein and interleukin-6. CONCLUSIONS The present findings on MCR prevalence and associated cognitive and physical domains and inflammatory biomarkers may help to uncover altered pathways and therapeutic targets for intervention during the long preclinical phase of neurodegenerative dementia.

Aging is often associated with a decline in physical function that eventually leads to loss of autonomy in activities of daily living (ADL). Walking is a very common ADL, important for main determinants of quality of life in older age, and it requires the integration of many physiological systems. Gait speed has been described as the ‘sixth vital sign’ because it is a core indicator of health and function in aging and disease. We reviewed original studies up to June 2020 that assessed frailty in both longitudinal and cross‐sectional observational studies, paying particular attention to how gait is measured in older population and how the gait parameter adopted may influence the estimated frailty models and the health‐related outcomes of the various studies (i.e. clinical, cognitive, physical, and nutritional outcomes). Eighty‐five studies met the search strategy and were included in the present systematic review. According to the frailty tools, more than 60% of the studies used the physical phenotype model proposed by Fried and colleagues, while one‐third referred to multi‐domain indexes or models and only 5% referred to other single‐domain frailty models (social or cognitive). The great heterogeneity observed in gait measurements and protocols limited the possibility to directly compare the results of the studies and it could represent an important issue causing variability in the different outcome measures in both clinical‐and population‐based settings. Gait appeared to be an indicator of health and function also in frail older adults, and different gait parameters appeared to predict adverse health‐related outcomes in clinical, cognitive, and physical domains and, to a lesser extent, in nutritional domain. Gait has the potential to elucidate the common basic mechanisms of cognitive and motor decline. Advances in technology may extend the validity of gait in different clinical settings also in frail older adults, and technology‐based assessment should be encouraged. Combining various gait parameters may enhance frailty prediction and classification of different frailty phenotypes.