COVID-19 and Cognitive Decline in Older Adults with High-Cardiovascular Risk: A Post Hoc Analysis.

Cognitive decline has been reported as a short-term sequela in patients hospitalized for coronavirus disease-19 (COVID-19). Whether COVID-19 is associated with late cognitive impairment in older free-living individuals with high cardiovascular risk, a group at greater risk of cognitive decline, is unknown. We determined this association of COVID-19 through a longitudinal evaluation of post-COVID-19 cognitive performance and impairment as post hoc analysis in 5,179 older adults (48% female) with mean (SD) age 68.5 (5.0) years, body mass index 31.7 (3.7) kg/m2, harboring ≥ 3 criteria for metabolic syndrome (e.g., hypertension, hyperlipidemia, hyperglycemia etc.) enrolled in PREDIMED-Plus trial. Pre- and post-COVID-19 cognitive performance was ascertained from scheduled assessments conducted using a battery of neuropsychological tests, including 5 domains: Global Cognitive Function, General Cognitive Function, Execution Function, Verbal Fluency and Attention domains, which were standardized for the cohort. Cognitive impairment was defined as the bottom 10 percentile of the sample. Multivariable linear and logistic regression models assessed the association of COVID-19 with cognitive decline and impairment, respectively. After a mean 50-week follow-up, no significant associations were observed between COVID-19 status and post-COVID-19 scores of all tapped neuropsychological domains, except Global Cognitive Function (GCF). When fully adjusted, COVID-19 was marginally associated with higher (better) post-pandemic GCF score (ßadj (95% CI): 0.06 (0.00, 0.13) p=.05). However, the odds for post-COVID-19 cognitive impairment in GCF domain were not associated with the disease (ORadj (95% CI): 0.90 (0.53, 1.51) p=.68). In the PREDIMED-Plus cohort, COVID-19 status and cognitive impairment determined 50 weeks post-infection showed no association in older adults at high cardiovascular risk. This suggests that cognitive changes observed shortly after COVID-19 revert over time. However, cautious interpretation is warranted as these data were obtained within the framework of a clinical trial encouraging a healthy lifestyle.

Coronavirus disease 2019 is associated with long-term depressive symptoms in Spanish older adults with overweight/obesity and metabolic syndrome.

BACKGROUND: The coronavirus disease 2019 (COVID-19) has serious physiological and psychological consequences. The long-term (>12 weeks post-infection) impact of COVID-19 on mental health, specifically in older adults, is unclear. We longitudinally assessed the association of COVID-19 with depression symptomatology in community-dwelling older adults with metabolic syndrome within the framework of the PREDIMED-Plus cohort. METHODS: Participants (n = 5486) aged 55-75 years were included in this longitudinal cohort. COVID-19 status (positive/negative) determined by tests (e.g. polymerase chain reaction severe acute respiratory syndrome coronavirus 2, IgG) was confirmed via event adjudication (410 cases). Pre- and post-COVID-19 depressive symptomatology was ascertained from annual assessments conducted using a validated 21-item Spanish Beck Depression Inventory-II (BDI-II). Multivariable linear and logistic regression models assessed the association between COVID-19 and depression symptomatology. RESULTS: COVID-19 in older adults was associated with higher post-COVID-19 BDI-II scores measured at a median (interquartile range) of 29 (15-40) weeks post-infection [fully adjusted ß = 0.65 points, 95% confidence interval (CI) 0.15-1.15; p = 0.011]. This association was particularly prominent in women (ß = 1.38 points, 95% CI 0.44-2.33, p = 0.004). COVID-19 was associated with 62% increased odds of elevated depression risk (BDI-II ≥ 14) post-COVID-19 when adjusted for confounders (odds ratio; 95% CI 1.13-2.30, p = 0.008). CONCLUSIONS: COVID-19 was associated with long-term depression risk in older adults with overweight/obesity and metabolic syndrome, particularly in women. Thus, long-term evaluations of the impact of COVID-19 on mental health and preventive public health initiatives are warranted in older adults.

Association of adiposity and its changes over time with COVID-19 risk in older adults with overweight/obesity and metabolic syndrome: a longitudinal evaluation in the PREDIMED-Plus cohort.

BACKGROUND: Cross-sectionally, older age and obesity are associated with increased coronavirus disease-2019 (COVID-19) risk. We assessed the longitudinal associations of baseline and changes in adiposity parameters with COVID-19 incidence in older adults at high cardiovascular risk. METHODS: This analysis included 6874 men and women (aged 55-75 years) with overweight/obesity and metabolic syndrome in the PREDIMED-Plus lifestyle intervention trial for cardiovascular risk reduction. Body weight, body-mass-index (BMI), waist circumference, waist-to-height ratio (WHtR), and a body shape index (ABSI) were measured at baseline and annual follow-up visits. COVID-19 was ascertained by an independent Event Committee until 31 December 2021. Cox regression models were fitted to evaluate the risk of COVID-19 incidence based on baseline adiposity parameters measured 5-6 years before the pandemic and their changes at the visit prior to censoring. RESULTS: At the time of censoring, 653 incident COVID-19 cases occurred. Higher baseline body weight, BMI, waist circumference, and WHtR were associated with increased COVID-19 risk. During the follow-up, every unit increase in body weight (HRadj (95%CI): 1.01 (1.00, 1.03)) and BMI (HRadj: 1.04 (1.003, 1.08)) was associated with increased COVID-19 risk. CONCLUSIONS: In older adults with overweight/obesity, clinically significant weight loss may protect against COVID-19. TRIAL REGISTRATION: This study is registered at the International Standard Randomized Controlled Trial (ISRCT; http://www.isrctn.com/ISRCTN89898870 ).

Association of monetary diet cost of foods and diet quality in Spanish older adults.

Background: A major barrier to a healthy diet may be the higher price of healthy foods compared to low-quality foods. Objectives: This study aimed to assess the association between the monetary cost of food and diet quality in Spanish older adults at high risk of cardiovascular disease. Methods: Cross-sectional analysis was carried out in Spanish older adults (n = 6,838; 48.6% female). A validated food frequency questionnaire was used to assess dietary intake. Metabolic syndrome severity, adherence to the Mediterranean diet (MedDiet), adherence to a provegetarian dietary pattern, and dietary inflammatory index were assessed. The economic cost of the foods was obtained from the Spanish Ministry of Agriculture Fisheries and Food database (2015-2017, the period of time when the participants were recruited). The total cost of diet adjusted per 1,000 kcal was computed. Results: The healthier dietary pattern was associated with a higher cost of the diet. Higher adherence to the MedDiet, anti-inflammatory diet, and the healthy version of the provegetarian dietary pattern were related to higher costs of the diet. Conclusion: Higher diet quality was associated with a higher dietary cost of the diet per 1,000 kcal/day. Food prices can be an important component of interventions and policies aimed at improving people's diets and preventing diet-related chronic diseases. Clinical trial registry number: The trial was registered in 2014 at the International Standard Randomized Controlled Trial (ISRCT; http://www.isrctn.com/ISRCTN89898870) with the number 89898870.

Metabolic syndrome criteria and severity and carbon dioxide (CO2) emissions in an adult population.

BACKGROUND: Metabolic syndrome (MetS) has become a growing risk factor of some non-communicable diseases. Increase of greenhouse gas emissions affects the planet. AIMS: To assess the association between MetS severity and amount of carbon dioxide (CO2) emitted in an adult population. DESIGN: Cross-sectional study (n = 6646; 55-76-year-old-men; 60-75-year-old-women with MetS). METHODS: Dietary habits were assessed using a pre-validated semi quantitative 143-item food frequency questionnaire. The amount of CO2 emitted due to the production of food consumed by person and day was calculated using a European database, and the severity of the MetS was calculated with the MetS Severity Score. RESULTS: Higher glycaemia levels were found in people with higher CO2 emissions. The risk of having high severe MetS was related to high CO2 emissions. CONCLUSIONS: Low CO2 emissions diet would help to reduce MetS severity. Advantages for both health and the environment were found following a more sustainable diet. TRIAL REGISTRATION: ISRCTN, ISRCTN89898870 . Registered 05 September 2013.

Carbon dioxide (CO2) emissions and adherence to Mediterranean diet in an adult population: the Mediterranean diet index as a pollution level index.

BACKGROUND: Research related to sustainable diets is is highly relevant to provide better understanding of the impact of dietary intake on the health and the environment. AIM: To assess the association between the adherence to an energy-restricted Mediterranean diet and the amount of CO2 emitted in an older adult population. DESIGN AND POPULATION: Using a cross-sectional design, the association between the adherence to an energy-reduced Mediterranean Diet (erMedDiet) score and dietary CO2 emissions in 6646 participants was assessed. METHODS: Food intake and adherence to the erMedDiet was assessed using validated food frequency questionnaire and 17-item Mediterranean questionnaire. Sociodemographic characteristics were documented. Environmental impact was calculated through greenhouse gas emissions estimations, specifically CO2 emissions of each participant diet per day, using a European database. Participants were distributed in quartiles according to their estimated CO2 emissions expressed in kg/day: Q1 (≤2.01 kg CO2), Q2 (2.02-2.34 kg CO2), Q3 (2.35-2.79 kg CO2) and Q4 (≥2.80 kg CO2). RESULTS: More men than women induced higher dietary levels of CO2 emissions. Participants reporting higher consumption of vegetables, fruits, legumes, nuts, whole cereals, preferring white meat, and having less consumption of red meat were mostly emitting less kg of CO2 through diet. Participants with higher adherence to the Mediterranean Diet showed lower odds for dietary CO2 emissions: Q2 (OR 0.87; 95%CI: 0.76-1.00), Q3 (OR 0.69; 95%CI: 0.69-0.79) and Q4 (OR 0.48; 95%CI: 0.42-0.55) vs Q1 (reference). CONCLUSIONS: The Mediterranean diet can be environmentally protective since the higher the adherence to the Mediterranean diet, the lower total dietary CO2 emissions. Mediterranean Diet index may be used as a pollution level index.

PPARγ Gene as a Possible Link between Acquired and Congenital Lipodystrophy and its Modulation by Dietary Fatty Acids.

Lipodystrophy syndromes are rare diseases that could be of genetic or acquired origin. The main complication of lipodystrophy is the dysfunction of adipose tissue, which leads to an ectopic accumulation of triglycerides in tissues such as the liver, pancreas and skeletal muscle. This abnormal fat distribution is associated with hypertriglyceridemia, insulin resistance, liver steatosis, cardiomyopathies and chronic inflammation. Although the origin of acquired lipodystrophies remains unclear, patients show alterations in genes related to genetic lipodystrophy, suggesting that this disease could be improved or aggravated by orchestrating gene activity, for example by diet. Nowadays, the main reason for adipose tissue dysfunction is an imbalance in metabolism, caused in other pathologies associated with adipose tissue dysfunction by high-fat diets. However, not all dietary fats have the same health implications. Therefore, this article aims to summarize the main genes involved in the pathophysiology of lipodystrophy, identify connections between them and provide a systematic review of studies published between January 2017 and January 2022 of the dietary fats that can modulate the development of lipodystrophy through transcriptional regulation or the regulation of protein expression in adipocytes.

Does Consumption of Ultra-Processed Foods Matter for Liver Health? Prospective Analysis among Older Adults with Metabolic Syndrome.

Non-alcoholic fatty liver disease (NAFLD) includes a spectrum of liver alterations that can result in severe disease and even death. Consumption of ultra-processed foods (UPF) has been associated with obesity and related comorbidities. However, the link between UPF and NAFLD has not been sufficiently assessed. We aimed to investigate the prospective association between UPF consumption and liver health biomarkers. Methods: We followed for 1 year 5867 older participants with overweight/obesity and metabolic syndrome (MetS) from the PREDIMED-Plus trial. A validated 143-item semi-quantitative food frequency questionnaire was used to evaluate consumption of UPF at baseline, 6, and 12 months. The degree of processing for foods and beverages (g/day) was established according to the NOVA classification system. The non-invasive fatty liver index (FLI) and hepatic steatosis index (HSI) were used to evaluate liver health at three points in time. The associations between changes in UPF consumption (percentage of total daily dietary intake (g)) and liver biomarkers were assessed using mixed-effects linear models with repeated measurements. Results: In this cohort, UPF consumption at baseline was 8.19% (SD 6.95%) of total daily dietary intake in grams. In multivariable models, each 10% daily increment in UPF consumption in 1 year was associated with significantly greater FLI (ß 1.60 points, 95% CI 1.24;1.96 points) and HSI (0.43, 0.29; 0.57) scores (all p-values < 0.001). These associations persisted statistically significant after adjusting for potential dietary confounders and NAFLD risk factors. Conclusions: A higher UPF consumption was associated with higher levels of NAFLD-related biomarkers in older adults with overweight/obesity and MetS.

Longitudinal association of dietary acid load with kidney function decline in an older adult population with metabolic syndrome.

Background: Diets high in acid load may contribute to kidney function impairment. This study aimed to investigate the association between dietary acid load and 1-year changes in glomerular filtration rate (eGFR) and urine albumin/creatinine ratio (UACR). Methods: Older adults with overweight/obesity and metabolic syndrome (mean age 65 ± 5 years, 48% women) from the PREDIMED-Plus study who had available data on eGFR (n = 5,874) or UACR (n = 3,639) at baseline and after 1 year of follow-up were included in this prospective analysis. Dietary acid load was estimated as potential renal acid load (PRAL) and net endogenous acid production (NEAP) at baseline from a food frequency questionnaire. Linear and logistic regression models were fitted to evaluate the associations between baseline tertiles of dietary acid load and kidney function outcomes. One year-changes in eGFR and UACR were set as the primary outcomes. We secondarily assessed ≥ 10% eGFR decline or ≥10% UACR increase. Results: After multiple adjustments, individuals in the highest tertile of PRAL or NEAP showed higher one-year changes in eGFR (PRAL, ß: -0.64 ml/min/1.73 m2; 95% CI: -1.21 to -0.08 and NEAP, ß: -0.56 ml/min/1.73 m2; 95% CI: -1.13 to 0.01) compared to those in the lowest category. No associations with changes in UACR were found. Participants with higher levels of PRAL and NEAP had significantly higher odds of developing ≥10% eGFR decline (PRAL, OR: 1.28; 95% CI: 1.07-1.54 and NEAP, OR: 1.24; 95% CI: 1.03-1.50) and ≥10 % UACR increase (PRAL, OR: 1.23; 95% CI: 1.04-1.46) compared to individuals with lower dietary acid load. Conclusions: Higher PRAL and NEAP were associated with worse kidney function after 1 year of follow-up as measured by eGFR and UACR markers in an older Spanish population with overweight/obesity and metabolic syndrome.

One-year longitudinal association between changes in dietary choline or betaine intake and cardiometabolic variables in the PREvención con DIeta MEDiterránea-Plus (PREDIMED-Plus) trial.

BACKGROUND: Choline and betaine intakes have been related to cardiovascular health. OBJECTIVES: We aimed to explore the relation between 1-y changes in dietary intake of choline or betaine and 1-y changes in cardiometabolic and renal function traits within the frame of the PREDIMED (PREvención con DIeta MEDiterránea)-Plus trial. METHODS: We used baseline and 1-y follow-up data from 5613 participants (48.2% female and 51.8% male; mean ± SD age: 65.01 ± 4.91 y) to assess cardiometabolic traits, and 3367 participants to assess renal function, of the Spanish PREDIMED-Plus trial. Participants met ≥3 criteria of metabolic syndrome and had overweight or obesity [BMI (in kg/m2) ≥27 and ≤40]. These criteria were similar to those of the PREDIMED parent study. Dietary intakes of choline and betaine were estimated from the FFQ. RESULTS: The greatest 1-y increase in dietary choline or betaine intake (quartile 4) was associated with improved serum glucose concentrations (-3.39 and -2.72 mg/dL for choline and betaine, respectively) and HbA1c levels (-0.10% for quartile 4 of either choline or betaine intake increase). Other significant changes associated with the greatest increase in choline or betaine intake were reduced body weight (-2.93 and -2.78 kg, respectively), BMI (-1.05 and -0.99, respectively), waist circumference (-3.37 and -3.26 cm, respectively), total cholesterol (-4.74 and -4.52 mg/dL, respectively), and LDL cholesterol (-4.30 and -4.16 mg/dL, respectively). Urine creatinine was reduced in quartile 4 of 1-y increase in choline or betaine intake (-5.42 and -5.74 mg/dL, respectively). CONCLUSIONS: Increases in dietary choline or betaine intakes were longitudinally related to improvements in cardiometabolic parameters. Markers of renal function were also slightly improved, and they require further investigation.This trial was registered at https://www.isrctn.com/ as ISRCTN89898870.

Desired weight loss and its association with health, health behaviors and perceptions in an adult population with weight excess: One-year follow-up.

Background: Metabolic syndrome (MetS) worsens quality of life and increases mortality. Dissatisfaction with weight in patients with MetS may modify the effect of lifestyle interventions to achieve changes in health-related behaviors. Objective: To assess 1-year changes in cardiovascular risk scores, self-perceived general health and health-related behaviors according to observed changes in desired weight loss during the first year of intervention in a large cardiovascular prevention trial. Design: Prospective analysis of the PREDIMED-PLUS trial, including 5,499 adults (55-75 years old) with overweight or obesity at baseline. Methods: The desired weight loss was the difference between ideal and measured weight. Tertiles of change in desired weight loss (1 year vs. baseline) were defined by the following cut-off points: ≥0.0 kg (T1, n = 1,638); 0.0 to -4.0 kg (T2, n = 1,903); ≤-4.0 kg (T3, n = 1,958). A food frequency questionnaire assessed diet and the Minnesota-REGICOR questionnaire assessed physical activity. The Framingham equation assessed cardiovascular risks. The changes in the severity of MetS were also assessed. The Beck Depression Inventory assessed depressive symptoms and the SF-36 assessed health-related quality of life. Data were analyzed using general linear models. Results: BMI decreased at T2 and T3 (T1: 0.3, T2: -0.7, T3: -1.9). The most significant improvement in diet quality was observed at T3. Cardiovascular risk decreased at T2 and T3. Mean reductions in MetS severity score were: -0.02 at T1, -0.39 at T2 and -0.78 at T3. The perception of physical health increases in successive tertiles. Conclusions: In older adults with MetS, more ambitious desired weight loss goals were associated with improvements in diet, cardiovascular health and perceived physical health during the first year of a healthy lifestyle intervention programme. Weight dissatisfaction needs to be considered by health professionals. Clinical trial registration: http://www.isrctn.com/ISRCTN89898870, identifier 89898870.

Differential Immunometabolic Effects of High-Fat Diets Containing Coconut, Sunflower, and Extra Virgin Olive Oils in Female Mice.

SCOPE: To compare the effects of three high-fat diets (HFDs) based on coconut, sunflower, or extra virgin olive oils (EVOOs) on adipose tissue, metabolism, and inflammation. METHODS AND RESULTS: Mice are fed for 16 weeks on their respective HFD. HFD based on coconut oil produces significantly lower body weight than EVOO- or sunflower oil-based HFDs. Furthermore, the coconut oil HFD leads to metabolic disturbances such as reduction of circulating leptin and adiponectin concentrations, hypertriglyceridemia, hepatomegaly, and liver triglyceride accumulation. Likewise, this diet produces an increase in serum pro-inflammatory cytokines (interleukin 6 [IL-6] and tumor necrosis factor-α [TNF-α]). In white (WAT) and brown (BAT) adipose tissue, the HFD based on coconut oil does not cause significant changes in the expression of studied proteins related to thermogenesis (uncoupling protein 1 [UCP-1]), mitochondrial biogenesis, and browning (peroxisome proliferator-activated receptor-γ coactivator 1α [PGC-1α] and nuclear factor E2-related factor 2 [Nrf2]). However, the HFD based on EVOO induces upregulation of UCP-1, PGC-1α, and Nrf2 expression in BAT, increases the expression of UCP-1 and PGC-1α in inguinal WAT, and enhances the expression of PGC-1α in epididymal WAT. CONCLUSIONS: An HFD based on coconut oil could reduce circulating leptin and adiponectin concentrations, increase the liver fat content, raise serum triglycerides, and promote inflammation by increasing circulating pro-inflammatory cytokines, while an EVOO-based HFD could increase thermogenic activity.

Dairy Product Consumption and Changes in Cognitive Performance: Two-Year Analysis of the PREDIMED-Plus Cohort.

SCOPE: Dairy consumption has been suggested to impact cognition; however, evidence is limited and inconsistent. This study aims to longitudinally assess the association between dairy consumption with cognitive changes in an older Spanish population at high cardiovascular disease risk. METHODS AND RESULTS: Four thousand six hundred sixty eight participants aged 55-75 years, completed a validated food frequency questionnaire at baseline and a neuropsychological battery of tests at baseline and 2-year follow-up. Multivariable linear regression models are used, scaled by 100 (i.e., the units of ß correspond to 1 SD/100), to assess associations between baseline tertile daily consumption and 2-year changes in cognitive performance. Participants in the highest tertile of total milk and whole-fat milk consumption have a greater decline in global cognitive function (ß: -4.71, 95% CI: -8.74 to -0.69, p-trend = 0.020 and ß: -6.64, 95% CI: -10.81 to -2.47, p-trend = 0.002, respectively) compared to those in the lowest tertile. No associations are observed between low fat milk, yogurt, cheese or fermented dairy consumption, and changes in cognitive performance. CONCLUSION: Results suggest there are no clear prospective associations between consumption of most commonly consumed dairy products and cognition, although there may be an association with a greater rate of cognitive decline over a 2-year period in older adults at high cardiovascular disease risk for whole-fat milk.

Synergistic Effect of Squalene and Hydroxytyrosol on Highly Invasive MDA-MB-231 Breast Cancer Cells.

Several studies relate Mediterranean diet and virgin olive oil (VOO) intake with lower risk of several chronic diseases, including breast cancer. Many of them described antitumor properties of isolated minor compounds present in VOO, but beneficial properties of VOO arise from the effects of all its compounds acting together. The aim of the present study was to test the antitumor effects of two minor compounds from VOO (hydroxytyrosol (HT) and squalene (SQ)) on highly metastatic human breast tumor cells (MDA-MB-231) when acting in combination. Both isolated compounds were previously analyzed without showing any antitumoral effect on highly invasive MDA-MB-231 breast cancer cells, but the present results show that HT at 100 µM, combined with different concentrations of SQ, could exert antitumor effects. When they are combined, HT and SQ are able to inhibit cell proliferation, promoting apoptosis and DNA damage in metastatic breast cancer cells. Therefore, our results suggest that the health-promoting properties of VOO may be due, at least in part, to the combined action of these two minor compounds.

Polyphenol intake and cardiovascular risk in the PREDIMED-Plus trial. A comparison of different risk equations.

INTRODUCTION AND OBJECTIVES: Quantification of cardiovascular risk has been based on scores such as Framingham, Framingham-REGICOR, SCORE or Life's Simple 7 (LS7). In vitro, animal, and randomized clinical studies have shown that polyphenols may provide benefits to the vascular system and reduce the inflammatory response. However, some clinical-epidemiological studies have yielded inconsistent results. Our aim was to assess the possible association between intake of the various polyphenol classes and established cardiovascular scores. METHODS: This cross-sectional analysis involved 6633 PREDIMED-Plus study participants. Food polyphenol content was estimated by a semiquantitative food frequency questionnaire, adjusted for total energy intake according to the residual method. The association between polyphenol intake and cardiovascular risk was tested using linear regression analyses. RESULTS: Total polyphenol and flavonoid intake were directly and significantly associated only with the LS7 scale. Intake of lignans was directly and significantly associated with SCORE and LS7 scales, stilbene intake with SCORE, and phenolic acid intake with Framingham and Framingham-REGICOR scores. Other polyphenol classes were associated in a protective and significant manner in Framingham, SCORE and LS7 scores. In women, intake of all the polyphenol classes, except phenolic acids, showed a protective trend in the results of the Framingham, Framingham-REGICOR scores and LS7 scale. CONCLUSIONS: An inverse association was found between consumption of the 'other polyphenols' class and, especially among women, with estimated cardiovascular risk. The results were similar to those of Framingham, Framingham-REGICOR and LS7 (after eliminating the diet component) and differed from those of SCORE, but the predictors included were limited in the latter case.

Glycemic Dysregulations Are Associated With Worsening Cognitive Function in Older Participants at High Risk of Cardiovascular Disease: Two-Year Follow-up in the PREDIMED-Plus Study.

Introduction: Type 2 diabetes has been linked to greater cognitive decline, but other glycemic parameters such as prediabetes, diabetes control and treatment, and HOMA-IR and HbA1c diabetes-related biomarkers have shown inconsistent results. Furthermore, there is limited research assessing these relationships in short-term studies. Thus, we aimed to examine 2-year associations between baseline diabetes/glycemic status and changes in cognitive function in older participants at high risk of cardiovascular disease. Methods: We conducted a 2-year prospective cohort study (n=6,874) within the framework of the PREDIMED-Plus study. The participants (with overweight/obesity and metabolic syndrome; mean age 64.9 years; 48.5% women) completed a battery of 8 cognitive tests, and a global cognitive function Z-score (GCF) was estimated. At baseline, participants were categorized by diabetes status (no-diabetes, prediabetes, and <5 or ≥5-year diabetes duration), and also by diabetes control. Furthermore, insulin resistance (HOMA-IR) and glycated hemoglobin (HbA1c) levels were measured, and antidiabetic medications were recorded. Linear and logistic regression models, adjusted by potential confounders, were fitted to assess associations between glycemic status and changes in cognitive function. Results: Prediabetes status was unrelated to cognitive decline. However, compared to participants without diabetes, those with ≥5-year diabetes duration had greater reductions in GCF (ß=-0.11 (95%CI -0.16;-0.06)], as well as in processing speed and executive function measurements. Inverse associations were observed between baseline HOMA-IR and changes in GCF [ß=-0.0094 (95%CI -0.0164;-0.0023)], but also between HbA1c levels and changes in GCF [ß=-0.0085 (95%CI -0.0115, -0.0055)], the Mini-Mental State Examination, and other executive function tests. Poor diabetes control was inversely associated with phonologic fluency. The use of insulin treatment was inversely related to cognitive function as measured by the GCF [ß=-0.31 (95%CI -0.44, -0.18)], and other cognitive tests. Conclusions: Insulin resistance, diabetes status, longer diabetes duration, poor glycemic control, and insulin treatment were associated with worsening cognitive function changes in the short term in a population at high cardiovascular risk. Clinical Trial Registration: http://www.isrctn.com/ISRCTN89898870, identifier ISRCTN: 89898870.

Physical activity and metabolic syndrome severity among older adults at cardiovascular risk: 1-Year trends.

BACKGROUND AND AIMS: Modifiable lifestyle factors, such as physical activity (PA) and Mediterranean diet (MD), decrease metabolic syndrome (MetS). The aim was to assess 1-year changes of leisure-time physical activity (LTPA), sedentary behavior, and diet quality according to MetS severity in older population at high cardiovascular risk. METHODS AND RESULTS: Prospective analysis of 55-75-year-old 4359 overweight/obese participants with MetS (PREDIMED-Plus trial) categorized in tertiles according to 1-year changes of a validated MetS severity score (MetSSS). Anthropometrics, visceral adiposity index, triglycerides and glucose index, dietary nutrient intake, biochemical marker levels, dietary inflammatory index, and depression symptoms were measured. Diet quality was assessed by 17-item MD questionnaire. PAs were self-reported using the Minnesota-REGICOR Short Physical Activity Questionnaire and 30-s chair stand test. Sedentary behaviors were measured using the Spanish version of the Nurses' Health Study questionnaire. After 1-year follow-up, decreasing MetSSS was associated with an anti-inflammatory dietary pattern, high intake of vegetables, fruits, legumes, nuts, whole grain cereals, white fish, and bluefish and low intake of refined cereals, red and processed meat, cookies/sweets, and snacks/ready-to-eat-meals. It resulted in high intake of polyunsaturated fatty acids, omega-3 fatty acids, protein, fiber, vitamins B1, B6, B9, C, D, potassium, magnesium, and phosphorus and low glycemic index and saturated fatty acid, trans fatty acid, and carbohydrates intake. Regarding PA and sedentary behavior, decreasing MetSSS was associated with increased moderate-to-vigorous LTPA, chair stand test, and decreased sedentary and TV-viewing time. CONCLUSION: Decreasing MetSSS was associated with an anti-inflammatory dietary pattern, high LTPA, high MD adherence, low sedentary time, and low depression risk.

Use of Different Food Classification Systems to Assess the Association between Ultra-Processed Food Consumption and Cardiometabolic Health in an Elderly Population with Metabolic Syndrome (PREDIMED-Plus Cohort).

The association between ultra-processed food (UPF) and risk of cardiometabolic disorders is an ongoing concern. Different food processing-based classification systems have originated discrepancies in the conclusions among studies. To test whether the association between UPF consumption and cardiometabolic markers changes with the classification system, we used baseline data from 5636 participants (48.5% female and 51.5% male, mean age 65.1 ± 4.9) of the PREDIMED-Plus ("PREvention with MEDiterranean DIet") trial. Subjects presented with overweight or obesity and met at least three metabolic syndrome (MetS) criteria. Food consumption was classified using a 143-item food frequency questionnaire according to four food processing-based classifications: NOVA, International Agency for Research on Cancer (IARC), International Food Information Council (IFIC) and University of North Carolina (UNC). Mean changes in nutritional and cardiometabolic markers were assessed according to quintiles of UPF consumption for each system. The association between UPF consumption and cardiometabolic markers was assessed using linear regression analysis. The concordance of the different classifications was assessed with intra-class correlation coefficients (ICC3, overall = 0.51). The highest UPF consumption was obtained with the IARC classification (45.9%) and the lowest with NOVA (7.9%). Subjects with high UPF consumption showed a poor dietary profile. We detected a direct association between UPF consumption and BMI (p = 0.001) when using the NOVA system, and with systolic (p = 0.018) and diastolic (p = 0.042) blood pressure when using the UNC system. Food classification methodologies markedly influenced the association between UPF consumption and cardiometabolic risk markers.

Association between coffee consumption and total dietary caffeine intake with cognitive functioning: cross-sectional assessment in an elderly Mediterranean population.

PURPOSE: Coffee is rich in compounds such as polyphenols, caffeine, diterpenes, melanoidins and trigonelline, which can stimulate brain activity. Therefore, the possible association of coffee consumption with cognition is of considerable research interest. In this paper, we assess the association of coffee consumption and total dietary caffeine intake with the risk of poor cognitive functioning in a population of elderly overweight/obese adults with metabolic syndrome (MetS). METHODS: PREDIMED-plus study participants who completed the Mini-Mental State Examination test (MMSE) (n = 6427; mean age = 65 ± 5 years) or a battery of neuropsychological tests were included in this cross-sectional analysis. Coffee consumption and total dietary caffeine intake were assessed at baseline using a food frequency questionnaire. Logistic regression models were fitted to evaluate the association between total, caffeinated and decaffeinated coffee consumption or total dietary caffeine intake and cognitive impairment. RESULTS: Total coffee consumers and caffeinated coffee consumers had better cognitive functioning than non-consumers when measured by the MMSE and after adjusting for potential confounders (OR 0.63; 95% CI 0.44-0.90 and OR 0.56; 95% CI 0.38-0.83, respectively). Results were similar when cognitive performance was measured using the Clock Drawing Test (CDT) and Trail Making Test B (TMT-B). These associations were not observed for decaffeinated coffee consumption. Participants in the highest tertile of total dietary caffeine intake had lower odds of poor cognitive functioning than those in the reference tertile when screened by the MMSE (OR 0.64; 95% CI 0.47-0.87) or other neurophysiological tests evaluating a variety of cognitive domains (i.e., CDT and TMT-A). CONCLUSIONS: Coffee consumption and total dietary caffeine intake were associated with better cognitive functioning as measured by various neuropsychological tests in a Mediterranean cohort of elderly individuals with MetS. TRIAL REGISTRATION: ISRCTN89898870. Registration date: July 24, 2014.

Association between ankle-brachial index and cognitive function in participants in the PREDIMED-Plus study: cross-sectional assessment.

INTRODUCTION AND OBJECTIVES: The ankle-brachial index (ABI) is an indicator of peripheral artery disease (PAD). The aim of this study was to assess the association between PAD, measured with the ABI, and cognitive function in persons with overweight or obesity and metabolic syndrome. METHODS: Cross-sectional study conducted with baseline data from the PREDIMED-Plus study, which included 4898 participants (after exclusion of those without ABI measurements) aged between 55 and 75 years, and with overweight or obesity and metabolic syndrome. At the baseline assessment, we measured the ABI with a standardized protocol and assessed the presence of other cardiovascular risk factors (eg, diabetes, dyslipidemia, hypertension). Cognitive function was evaluated using several tests validated for the Spanish population (mini-mental state examination [MMSE], phonological and semantic verbal fluency test, WAIS-III working memory index [WMI], parts A and B of the trail making test (TMT), and clock drawing test). Generalized linear models were used to assess the association between the ABI and cognitive function. RESULTS: Among the participants, 3.4% had PAD defined as ABI ≤ 0.9, and 3.3% had arterial calcification defined as ABI ≥ 1.4. PAD was associated with age, systolic blood pressure and obesity indicators, while arterial calcification was also associated with obesity and diabetes. No significant associations were observed between cognitive function and ABI or PAD. CONCLUSIONS: In our sample, the presence of PAD increased with age, blood pressure, and obesity. No significant association was observed between ABI, PAD, or cognitive function.