Corrigendum: Liver health and dementia in an Italian older population: Findings from the Salus in Apulia study.

[This corrects the article DOI: 10.3389/fnagi.2021.748888.].

Retinal Microvasculature and Neural Changes and Dietary Patterns in an Older Population in Southern Italy.

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.

Serum levels of IL-6 are associated with cognitive impairment in the salus in apulia population-based study.

Growing evidence suggests that inflammation contributes to brain aging and neurodegeneration. This study investigates the relationship between global cognitive as well executive function and the inflammatory markers IL-6, CRP, and TNF-α in a population-based study of older adults. A population-based sample, of older people in Southern Italy, was enrolled. We measured serum levels of IL-6, CRP, and TNF-α. We also administered two neuropsychological tests: Mini-Mental State Examination and Frontal Assessment Battery. Rank-based regression models were performed to investigate the relationship between inflammatory markers and cognitive functions, including major demographic and clinical confounders for adjustment. The sample consisted of 1929 subjects aged between 65 and 95 years. Multivariate linear regression analysis revealed that higher serum levels of IL-6 were associated with lower MMSE and FAB scores even after adjustment for demographic data and cardiovascular risk factors. No significant associations were found between cognitive functioning and serum levels of CRP and TNF-α. Our results suggest that higher levels of IL-6 were associated with cognitive impairment in an older adult population of Southern Italy.

Dietary profiling of physical frailty in older age phenotypes using a machine learning approach: the Salus in Apulia Study.

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.

Liver Fibrosis and Hearing Loss in an Older Mediterranean Population: Results from the Salus in Apulia Study.

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.

Dietary Patterns Associated with Diabetes in an Older Population from Southern Italy Using an Unsupervised Learning Approach.

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.

Association of Neuroretinal Thinning and Microvascular Changes with Hypertension in an Older Population in Southern Italy.

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.

Mediterranean Diet and Fatty Liver Risk in a Population of Overweight Older Italians: A Propensity Score-Matched Case-Cohort Study.

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.

Liver frailty and all-cause mortality in the older participants of the Salus in Apulia Study.

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.

Liver fibrosis and retinal features in an older Mediterranean population: Results from the Salus in Apulia study.

Background: Age 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. Methods: Retinal 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. Results: Increased 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). Conclusion: Our 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.

Liver Health and Dementia in an Italian Older Population: Findings From the Salus in Apulia Study.

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.

Dietary Habits and Nutrient Intakes Are Associated to Age-Related Central Auditory Processing Disorder in a Cohort From Southern Italy.

OBJECTIVES: Central auditory processing disorder (CAPD) commonly occurs in older age. However, few studies of a possible link between age-related CAPD and diet in an older population have been conducted. The objective of the present study was to investigate the relationship between eating habits and age-related CAPD in a population >65 years, using cross-sectional and retrospective data obtained in the same population-based study about 12 years ago. METHODS: We selected 734 participants (403 men) from a large population-based study. For age-related CAPD assessment, we used the Synthetic Sentence Identification with Ipsilateral Competitive Message test. Dietary habits were assessed by a Food Frequency Questionnaire. Associations between age-related CAPD and food groups/macro-and micronutrients were explored using adjusted logistic regression models. RESULTS: Age-related CAPD subjects consumed more dairy (111 vs. 98 g/d), olives and vegetable oil (63 vs. 52 g/d) and spirits (2 vs.1 g/d), and less fruits (536 vs. 651 g/d) in the cross-sectional analysis. Age-related CAPD subjects had a lower intake of potassium, vitamin C, and a higher fat intake. Further analyses identified dietary fiber as being inversely related to age-related CAPD. DISCUSSION: The present study provided evidence that the dietary hypotheses proposed for explaining the development of cognitive disorders in older age might also hold for age-related CAPD. Further data from other large and prospective population-based studies are needed for confirming these findings.