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Lifestyle and vascular risk effects on MRI-based biomarkers of Alzheimer's disease: a cross-sectional study of middle-aged adults from the broader New York City area.
Mosconi, L, Walters, M, Sterling, J, Quinn, C, McHugh, P, Andrews, RE, Matthews, DC, Ganzer, C, Osorio, RS, Isaacson, RS, et al
BMJ open. 2018;8(3):e019362
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Alzheimer’s disease (AD) is the most common form of dementia, affecting nearly 34 million people worldwide. It has been estimated that one in every three cases of AD may be attributable to diet and lifestyle factors. The aim of this study was to investigate the effects of lifestyle and vascular-related risk factors for AD. Researchers studied the brain scans of 116 healthy adults aged 30-60 years. They collected information on factors related to lifestyle, such as diet, physical activity and intellectual enrichment. They also looked at markers for vascular risk such as body mass index (BMI), cholesterol and homocysteine, as well as cognitive function. The researchers found that a Mediterranean-style diet and good insulin sensitivity were both associated with a healthier brain structure. A better score for intellectual enrichment and lower BMI were both associated with better cognition. They concluded that adopting a Mediterranean-style diet and maintaining a healthy weight might reduce the risk of developing AD.
Abstract
OBJECTIVE To investigate the effects of lifestyle and vascular-related risk factors for Alzheimer's disease (AD) on in vivo MRI-based brain atrophy in asymptomatic young to middle-aged adults. DESIGN Cross-sectional, observational. SETTING Broader New York City area. Two research centres affiliated with the Alzheimer's disease Core Center at New York University School of Medicine. PARTICIPANTS We studied 116 cognitively normal healthy research participants aged 30-60 years, who completed a three-dimensional T1-weighted volumetric MRI and had lifestyle (diet, physical activity and intellectual enrichment), vascular risk (overweight, hypertension, insulin resistance, elevated cholesterol and homocysteine) and cognition (memory, executive function, language) data. Estimates of cortical thickness for entorhinal (EC), posterior cingulate, orbitofrontal, inferior and middle temporal cortex were obtained by use of automated segmentation tools. We applied confirmatory factor analysis and structural equation modelling to evaluate the associations between lifestyle, vascular risk, brain and cognition. RESULTS Adherence to a Mediterranean-style diet (MeDi) and insulin sensitivity were both positively associated with MRI-based cortical thickness (diet: βs≥0.26, insulin sensitivity βs≥0.58, P≤0.008). After accounting for vascular risk, EC in turn explained variance in memory (P≤0.001). None of the other lifestyle and vascular risk variables were associated with brain thickness. In addition, the path associations between intellectual enrichment and better cognition were significant (βs≥0.25 P≤0.001), as were those between overweight and lower cognition (βs≥-0.22, P≤0.01). CONCLUSIONS In cognitively normal middle-aged adults, MeDi and insulin sensitivity explained cortical thickness in key brain regions for AD, and EC thickness predicted memory performance in turn. Intellectual activity and overweight were associated with cognitive performance through different pathways. Our findings support further investigation of lifestyle and vascular risk factor modification against brain ageing and AD. More studies with larger samples are needed to replicate these research findings in more diverse, community-based settings.
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Effectiveness of a childhood obesity prevention programme delivered through schools, targeting 6 and 7 year olds: cluster randomised controlled trial (WAVES study).
Adab, P, Pallan, MJ, Lancashire, ER, Hemming, K, Frew, E, Barrett, T, Bhopal, R, Cade, JE, Canaway, A, Clarke, JL, et al
BMJ (Clinical research ed.). 2018;360:k211
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Excess weight in childhood is a global problem affecting around 41 million children under the age of 5 years. In addition to physical and psychosocial health consequences in these early years, childhood excess weight is an important predictor of obesity in adulthood. The aim of the study is to assess the effectiveness of a school and family based healthy lifestyle programme (WAVES intervention) compared with usual practice, in preventing childhood obesity. The primary outcome for clinical effectiveness was the difference in BMI z scores between arms at 15 and 30 months. The study was a school based, cluster randomised, controlled trial where 200 schools were randomly selected from all state run primary schools within 35miles of the study centre (n=980). 144 eligible schools were approached to achieve the target recruitment of 54 schools. The intervention components were delivered over a period of 12 months and targeted the home and school environment. The results show that there was no overall evidence of improvement in the primary outcomes of reduction in body mass index (BMI) z scores at 15 and 30 months after a childhood obesity prevention programme was delivered through schools and targeting 6 and 7-year olds. The intervention did not have any effects on secondary anthropometric, behavioural, or clinical outcomes. A clinically significant difference in BMI z score in favour of the intervention was seen in the first cohort of schools recruited. However, post hoc analysis suggested that this outcome may have been a cohort effect as no effect was seen in group 2 schools at any time point. Authors conclude that the study intervention did not result in a statistically significant difference in BMI z score overall, and there was no evidence of effect on measured diet or physical activity levels in children. However, the lower cost components of the intervention could be considered by schools to fulfil their mandated responsibilities for education on health and wellbeing.
Abstract
OBJECTIVE To assess the effectiveness of a school and family based healthy lifestyle programme (WAVES intervention) compared with usual practice, in preventing childhood obesity. DESIGN Cluster randomised controlled trial. SETTING UK primary schools from the West Midlands. PARTICIPANTS 200 schools were randomly selected from all state run primary schools within 35 miles of the study centre (n=980), oversampling those with high minority ethnic populations. These schools were randomly ordered and sequentially invited to participate. 144 eligible schools were approached to achieve the target recruitment of 54 schools. After baseline measurements 1467 year 1 pupils aged 5 and 6 years (control: 28 schools, 778 pupils) were randomised, using a blocked balancing algorithm. 53 schools remained in the trial and data on 1287 (87.7%) and 1169 (79.7%) pupils were available at first follow-up (15 month) and second follow-up (30 month), respectively. INTERVENTIONS The 12 month intervention encouraged healthy eating and physical activity, including a daily additional 30 minute school time physical activity opportunity, a six week interactive skill based programme in conjunction with Aston Villa football club, signposting of local family physical activity opportunities through mail-outs every six months, and termly school led family workshops on healthy cooking skills. MAIN OUTCOME MEASURES The protocol defined primary outcomes, assessed blind to allocation, were between arm difference in body mass index (BMI) z score at 15 and 30 months. Secondary outcomes were further anthropometric, dietary, physical activity, and psychological measurements, and difference in BMI z score at 39 months in a subset. RESULTS Data for primary outcome analyses were: baseline, 54 schools: 1392 pupils (732 controls); first follow-up (15 months post-baseline), 53 schools: 1249 pupils (675 controls); second follow-up (30 months post-baseline), 53 schools: 1145 pupils (621 controls). The mean BMI z score was non-significantly lower in the intervention arm compared with the control arm at 15 months (mean difference -0.075 (95% confidence interval -0.183 to 0.033, P=0.18) in the baseline adjusted models. At 30 months the mean difference was -0.027 (-0.137 to 0.083, P=0.63). There was no statistically significant difference between groups for other anthropometric, dietary, physical activity, or psychological measurements (including assessment of harm). CONCLUSIONS The primary analyses suggest that this experiential focused intervention had no statistically significant effect on BMI z score or on preventing childhood obesity. Schools are unlikely to impact on the childhood obesity epidemic by incorporating such interventions without wider support across multiple sectors and environments. TRIAL REGISTRATION Current Controlled Trials ISRCTN97000586.
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Systemic and vascular inflammation in an in-vitro model of central obesity.
Ahluwalia, A, Misto, A, Vozzi, F, Magliaro, C, Mattei, G, Marescotti, MC, Avogaro, A, Iori, E
PloS one. 2018;13(2):e0192824
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Overweight and obesity are major risk factors for a number of chronic diseases, including diabetes, cardiovascular disease and cancer. Obese individuals often have excess fat around the middle, known as central adiposity, a condition known to contribute to an increase in blood levels of compounds such as glycerol and triglycerides. This study builds on a series of studies in which it has been demonstrated that circulation of these compounds reduces glucose uptake and increases lactate availability in all cells. The aim of the study was to challenge the system in-vitro with increasing levels of adiposity to determine the impact this had on compounds in the blood and the extent to which this reflects obesity-related vascular and systemic stress observed in humans. The focus of the study was primarily on lipid-related molecules and pro-inflammatory markers. Visceral adipose tissue was obtained from 9 donors undergoing liver resection for metastatic/benign liver lesions without any underlying chronic liver disease or diabetic complications and body mass index ranging from 20-25. The study outlines that an increase of adiposity in-vitro determines a pro-inflammatory state and results in endothelial stress.
Abstract
Metabolic disorders due to over-nutrition are a major global health problem, often associated with obesity and related morbidities. Obesity is peculiar to humans, as it is associated with lifestyle and diet, and so difficult to reproduce in animal models. Here we describe a model of human central adiposity based on a 3-tissue system consisting of a series of interconnected fluidic modules. Given the causal link between obesity and systemic inflammation, we focused primarily on pro-inflammatory markers, examining the similarities and differences between the 3-tissue model and evidence from human studies in the literature. When challenged with high levels of adiposity, the in-vitro system manifests cardiovascular stress through expression of E-selectin and von Willebrand factor as well as systemic inflammation (expressing IL-6 and MCP-1) as observed in humans. Interestingly, most of the responses are dependent on the synergic interaction between adiposity and the presence of multiple tissue types. The set-up has the potential to reduce animal experiments in obesity research and may help unravel specific cellular mechanisms which underlie tissue response to nutritional overload.
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Dietary carbohydrates: role of quality and quantity in chronic disease.
Ludwig, DS, Hu, FB, Tappy, L, Brand-Miller, J
BMJ (Clinical research ed.). 2018;361:k2340
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Human populations have thrived on diets with widely varying carbohydrate content. Dietary carbohydrates comprise compounds that can be digested or metabolically transformed directly into glucose, or that undergo oxidation into pyruvate, including some sugar alcohols. This study is a review that examines the links between different types of carbohydrates and health, with special focus on obesity, diabetes, cardiovascular disease, cancer and early death. Evidence suggests that the type of carbohydrates may have a greater effect on health outcomes than total amount for the general population. A strong case can be made for consumption of high glycaemic load grains, potato products, and added sugars namely sugary drinks, being causally related to obesity, diabetes, cardiovascular disease, and some cancers. Whereas non-starchy vegetables, whole fruits, legumes, and whole kernel grains appear to protective. Authors conclude that the recent influx of rapidly digestible, high glycaemic index carbohydrates in developed nations has contributed to the epidemics of obesity and cardiometabolic disease.
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Effects of green tea supplementation on elements, total antioxidants, lipids, and glucose values in the serum of obese patients.
Suliburska, J, Bogdanski, P, Szulinska, M, Stepien, M, Pupek-Musialik, D, Jablecka, A
Biological trace element research. 2012;149(3):315-22
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Obesity is associated with low-grade inflammation and oxidative stress, both of which play roles in the development of many obesity-related diseases and metabolic imbalances. Previous studies show that green tea (GT) supplementation may have favourable effects on body weight and body composition, and there’s growing evidence for its use in the prevention of obesity and coexisting diseases. The aim of this randomised double-blind trial was to assess the effects of supplementation with GT extract on body mass, glucose levels, mineral concentrations, lipid profile and antioxidant status in obese patients. The study included 46 obese participants, who received either 379 mg GT extract or placebo daily for three months. The study found that 3-month supplementation with GT extract significantly decreased body mass index, waist circumference, total cholesterol, LDL cholesterol, triglycerides, glucose and iron levels, while the levels of HDL cholesterol, total anti-oxidants, magnesium and zinc were increased. The authors conclude that GT extract may be beneficial in improving antioxidant and mineral status, body mass index, lipid profile and glucose levels in obese people.
Abstract
The consumption of green tea has been associated with cardiovascular and metabolic diseases. There have been some studies on the influence of green tea on the mineral status of obese subjects, but they have not yielded conclusive results. The aim of the present study is to examine the effects of green tea extract on the mineral, body mass, lipid profile, glucose, and antioxidant status of obese patients. A randomized, double-blind, placebo-controlled study was conducted. Forty-six obese patients were randomly assigned to receive either 379 mg of green tea extract, or a placebo, daily for 3 months. At baseline, and after 3 months of treatment, the anthropometric parameters, blood pressure, and total antioxidant status were assessed, as were the levels of plasma lipids, glucose, calcium, magnesium, iron, zinc, and copper. We found that 3 months of green tea extract supplementation resulted in decreases in body mass index, waist circumference, and levels of total cholesterol, low-density cholesterol, and triglyceride. Increases in total antioxidant level and in zinc concentration in serum were also observed. Glucose and iron levels were lower in the green tea extract group than in the control, although HDL-cholesterol and magnesium were higher in the green tea extract group than in the placebo group. At baseline, a positive correlation was found between calcium and body mass index, as was a negative correlation between copper and triglycerides. After 3 months, a positive correlation between iron and body mass index and between magnesium and HDL-cholesterol, as well as a negative correlation between magnesium and glucose, were observed. The present findings demonstrate that green tea influences the body's mineral status. Moreover, the results of this study confirm the beneficial effects of green tea extract supplementation on body mass index, lipid profile, and total antioxidant status in patients with obesity.
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Serum levels of IGF-I, IGFBP-3 and colorectal cancer risk: results from the EPIC cohort, plus a meta-analysis of prospective studies.
Rinaldi, S, Cleveland, R, Norat, T, Biessy, C, Rohrmann, S, Linseisen, J, Boeing, H, Pischon, T, Panico, S, Agnoli, C, et al
International journal of cancer. 2010;126(7):1702-15
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Insulin-like growth factor-I (IGF-1) plays an important role in growth and development as a function of available energy and essential nutrients from body reserves and diet. The aim of the study was to examine the relationships of colorectal cancers with serum levels of IGF-I, and with 2 measures of IGF-binding protein (IGFBP)-3. The study also examined whether relative risks associated to IGF-I levels were modified by anthropometric and dietary factors. A meta-analysis was performed where the study results were combined with the results from previously published prospective studies. For the study, 1,121 case sets with IGF-1 and total IGFBP-3 measurements were observed. For each case participant with colon or rectum cancer, 1 control participant was selected randomly. Control were matched to cases depending on a set criteria. The study found no association between colorectal cancer risk and serum levels of IGF-1 or IGFBP-3. However, the results from the meta-analysis showed only a very mild significant positive association. Overall, findings from the study together with those from the prospective cohort studies indicate a modest role for elevated circulating IGF-I levels in the development of colorectal cancer.
Abstract
Several prospective studies have shown a moderate positive association between increasing circulating insulin-like growth factor-I (IGF-I) levels and colorectal cancer risk. However, the associations were often statistically nonsignificant, and the relationship of cancer risk with IGF-I's major binding protein, IGFBP-3, showed major discrepancies between studies. We investigated the association of colorectal cancer risk with serum IGF-I, total and intact IGFBP-3, in a case-control study nested within the EPIC cohort (1,121 cases of colorectal cancer and 1,121 matched controls). Conditional logistic regression was used to adjust for possible confounders. Our present study results were combined in a meta-analysis with those from 9 previous prospective studies to examine the overall evidence for a relationship of prediagnostic serum IGF-I with colorectal cancer risk. In the EPIC study, serum concentrations of IGF-I and IGFBP-3 showed no associations with risk of colorectal cancer overall. Only in subgroup analyses did our study show moderate positive associations of IGF-I levels with risk, either among younger participants only (and only for colon cancer) or among participants whose milk intakes were in the lowest tertile of the population distribution (RR for an increase of 100 ng/ml = 1.43 [95% CI = 1.13-1.93]). Nevertheless, in the meta-analysis a modest positive association remained between serum IGF-I and colorectal cancer risk overall (RR = 1.07 [1.01-1.14] for 1 standard deviation increase in IGF-I). Overall, data from our present study and previous prospective studies combined indicate a relatively modest association of colorectal cancer risk with serum IGF-I.