Multi-Domain Interventions for Dementia Prevention - A Systematic Review.

OBJECTIVES: There is a growing incidence of cognitive decline and dementia associated with the ageing population. Lifestyle factors such as diet, physical activity, and cognitive activities may individually or collectively be undertaken to increase one's odds of preventing cognitive decline and future dementia. This study will examine whether clinical trials using multidomain lifestyle intervention can significantly decrease the risk of cognitive decline and therefore dementia. DESIGN, SETTING AND PARTICIPANTS: This systematic literature review of multidomain lifestyle interventions for the prevention of cognitive decline and dementia followed the PRISMA guidelines. Clinical trials involving multidomain intervention (i.e., diet and physical activity, or without cognitive training) in older adults (≥ 49 years old) at higher risk of dementia were identified through 5 electronic databases (EMBASE, MEDLINE, CINAHL, Cochrane, and Scopus). A comprehensive search was performed to identify and retrieve publications until 15 November 2022. Trials were published in English. RESULTS: The included studies (n=15) assessed change in cognition in response to a multidomain lifestyle intervention. However, the cognitive outcome measures used in these studies were heterogeneous. Despite this heterogeneity, two thirds of the studies showed improvement in cognition following a multidomain intervention (n=10 with a total of 9,439 participants). However, five studies reported no improvement in cognition following the multidomain intervention. The most common form of dietary intervention included higher amount of fruit and vegetable intake; whole-grain cereal products instead of refined; low fat options in milk and meat products; and limiting sucrose intake to less than 50 g/day. Most clinical trial studies were powered to examining the effects of multidomain interventions in cognition but were not designed to test the contribution of individual domains (i.e., dietary changes, increased physical activity, or increased cognitive stimulation alone). CONCLUSION: This systematic review aimed to determine the effect of multimodal lifestyle interventions on cognitive outcomes in older adults at risk of dementia. We found that participants with conditions that may increase the risk of dementia, (e.g., hypertension, cardiovascular fragility) do benefit from multi-modal lifestyle changes including diet, physical activity, and cognitive training. Two thirds of studies using multidomain lifestyle interventions showed improvements in cognitive function. Trials with a focus on cognitive training, dietary improvement, and physical activity may prevent or delay cognitive decline in older adults including those at risk of developing dementia. Future studies should consider longer follow-up periods and adequate power to be able to examine the effects of each lifestyle component in the context of multimodal interventions.

DHA-enriched fish oil reduces insulin resistance in overweight and obese adults.

Adipose tissue inflammation is major factor in the development of insulin resistance (IR). Long-chain omega-3 polyunsaturated fatty acids (LCn-3PUFA) docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are anti-inflammatory bioactive lipids, thus may protect against type 2 diabetes (T2D) development. Previous research has demonstrated a sex-dependent association between LCn-3PUFA and T2D, and evidence suggests LCn-3PUFA may improve IR in a sex-dependent manner. This double-blind, randomized, parallel-arm placebo-controlled study aimed to determine whether DHA-enriched fish oil (FO) supplementation improves IR. Sex-dependent effects were assessed by testing for an interaction between sex and treatment in the multiple regression models. Men and women with abdominal obesity (waist circumference: males, ≥102 cm; females, ≥88 cm) and without diabetes were recruited from the community. Participants (age: 50.9 ± 12.7 years, female: 63.7%, BMI: 32.4 ± 6.6 kg/m2) were randomly allocated to either 2 g FO (860 mg DHA + 120 mg EPA) (intervention, n = 38) or 2 g corn oil (CO) /day (control, n = 35) for 12 weeks in a double-blind randomised controlled trial. A fasting blood sample was collected at 0 and 12 weeks for assessment of IR, glucose and blood lipid profile. Sixty-eight participants completed the intervention. Compared with CO (n = 32), FO (n = 36) significantly reduced fasting insulin by -1.62 µIU/L (95%CI: -2.99, -0.26,) (p = 0.021) and HOMA-IR by -0.40 units (95%CI: -0.78, -0.02, p = 0.038). Higher insulin and HOMA-IR at baseline were associated with greater reductions in the FO group (p < 0.001). There was no interaction between sex and treatment for the change in insulin (p-interactionsex*treatment = 0.816) or HOMA-IR (p-interactionsex*treatment = 0.825). DHA-enriched FO reduces IR in adults with abdominal obesity, however, sex-dependent differences were not evident in this study.

Elevated plasma ferritin in elderly individuals with high neocortical amyloid-ß load.

Ferritin, an iron storage and regulation protein, has been associated with Alzheimer's disease (AD); however, it has not been investigated in preclinical AD, detected by neocortical amyloid-ß load (NAL), before cognitive impairment. Cross-sectional analyses were carried out for plasma and serum ferritin in participants in the Kerr Anglican Retirement Village Initiative in Aging Health cohort. Subjects were aged 65-90 years and were categorized into high and low NAL groups via positron emission tomography using a standard uptake value ratio cutoff=1.35. Ferritin was significantly elevated in participants with high NAL compared with those with low NAL, adjusted for covariates age, sex, apolipoprotein E ɛ4 carriage and levels of C-reactive protein (an inflammation marker). Ferritin was also observed to correlate positively with NAL. A receiver operating characteristic curve based on a logistic regression of the same covariates, the base model, distinguished high from low NAL (area under the curve (AUC)=0.766), but was outperformed when plasma ferritin was added to the base model (AUC=0.810), such that at 75% sensitivity, the specificity increased from 62 to 71% on adding ferritin to the base model, indicating that ferritin is a statistically significant additional predictor of NAL over and above the base model. However, ferritin's contribution alone is relatively minor compared with the base model. The current findings suggest that impaired iron mobilization is an early event in AD pathogenesis. Observations from the present study highlight ferritin's potential to contribute to a blood biomarker panel for preclinical AD.

Induction of Metallothionein in Rat Liver by Zinc Exposure: A Dose and Time Dependent Study.

Metallothioneins (MTs) are low molecular weight ubiquitous metalloproteins with high cysteine (thiol) content. The intracellular concentration of zinc (Zn) is tightly regulated and MT plays a crucial role in it. The present study investigates the relationship between the Zn status (as a function of Zn concentration and time) in the rat liver and the occurrence of hepatic MT. For dose dependent study, four experimental groups, one control and three receiving different levels of metal supplementation, were chosen [Group 1 control and Group 2, Group 3, Group 4 receiving subcutaneous dose of 10, 50 and 100 mg of Zn/kg body weight (in the form of ZnSO4·7H2O), respectively]. For the time dependent expression of MT, again four experimental groups, i.e. Group 5 control and Group 6, Group 7, Group 8 receiving 50 mg of Zn/kg body weight (in the form of ZnSO4·7H2O) subcutaneously and sacrificed at different time intervals after last injection i.e. 6, 18, 48 h, respectively were chosen. Isolation of MT was done by using combination of gel filtration and ion exchange chromatography while characterization of MT fraction was carried in the wavelength range 200-400 nm. Expression of MT was studied by using Western blot analysis. The results revealed that the MT expression increases with increasing the dose of Zn administered and maximum at 18 h after last Zn injection. Accumulation of MT with increase dose would help in maintaining the intracellular Zn concentration by its sequestration which further reduces the possibility of undesirable binding of Zn to other proteins significantly and maintains Zn homeostasis. The maximum expression of MT at 18 h is indicative of its half life.

Effect of diets rich in either saturated fat or n-6 polyunsaturated fatty acids and supplemented with long-chain n-3 polyunsaturated fatty acids on plasma lipoprotein profiles.

BACKGROUND/OBJECTIVES: Abnormalities in lipoprotein profiles (size, distribution and concentration) play an important role in the pathobiology of atherosclerosis and coronary artery disease. Dietary fat, among other factors, has been demonstrated to modulate lipoprotein profiles. We aimed to investigate if background dietary fat (saturated, SFA versus omega-6 polyunsaturated fatty acids, n-6PUFA) was a determinant of the effects of LCn-3PUFA supplementation on lipoprotein profiles. SUBJECTS/METHODS: A randomized controlled clinical intervention trial in a parallel design was conducted. Healthy subjects (n=26) were supplemented with 400 mg eicosapentaenoic acid plus 2000 mg docosahexaenoic acid daily and randomized to consume diets rich in either SFA or n-6PUFA for a period of 6 weeks. Blood samples, collected at baseline and after 6 weeks of intervention, were assessed for plasma lipoprotein profiles (lipoprotein size, concentration and distribution in subclasses) determined using nuclear magnetic resonance spectroscopy. RESULTS: Study participants receiving the SFA or the n-6PUFA enriched diets consumed similar percentage energy from fat (41 and 42% respectively, P=0.681). However, subjects on the SFA diet consumed 50% more energy as saturated fat and 77% less as linoleic acid than those consuming the n-6PUFA diet (P<0.001). The diets rich in SFA and n-6PUFA reduced the concentration of total very-low-density lipoprotein (VLDL) particles (P<0.001, both), and their subclasses and increased VLDL (P=0.042 and P=0.007, respectively) and LDL (P=0.030 and 0.027, respectively) particle size. In addition, plasma triglyceride concentration was significantly reduced by LCn-3PUFA supplementation irrespective of the dietary fat. CONCLUSIONS: LCn-3PUFA modulated lipoprotein profiles in a similar fashion when supplemented in diets rich in either SFA or n-6PUFA.

Protective role of Aloe vera against X-ray induced testicular dysfunction.

The present investigation was carried out to evaluate the possible radioprotective potential of an Aloe vera extract against whole-body X-ray irradiation-induced testicular alterations in mice. Male balb/c mice were divided into four groups: control, A. vera, X-ray and A. vera pre-treated + X-ray irradiated. Histopathological examination revealed significant structural alterations in testes after X-ray exposure, which was also associated with the presence of apoptotic cells as assessed by TUNEL assay. X-ray irradiation resulted in elevation in the levels of reactive oxygen species, lipid peroxidation, a reduction in glutathione concentration and enhanced activities of antioxidant enzymes such as glutathione reductase, glutathione peroxidase, catalase, superoxide dismutase and glutathione-S-transferase. Sperm count/motility and testosterone levels were significantly decreased in the irradiated group. Irradiated animals pre-treated with A. vera extract revealed an improvement in antioxidant status, inhibition of lipid peroxides, apoptotic cell formation and enhanced testicular parameters when compared to the X-ray-exposed group. These findings suggest that A. vera extract could ameliorate X-ray-induced damage due to its free radical scavenging properties and its potential to boost cellular antioxidant defence machinery.

Sex hormones and systemic inflammation are modulators of the obese-asthma phenotype.

BACKGROUND: Both systemic inflammation and sex hormones have been proposed as potential mediators of the obese-asthma phenotype. The aim of this study was to examine the associations between sex hormones, oral contraceptive pill (OCP) use, systemic inflammation and airway inflammation in adults with asthma. METHODS: Obese (n = 39) and nonobese (n = 42) females and obese (n = 24) and nonobese (n = 25) males with asthma were recruited. Females were further categorized as reproductive-aged (<50 years old; n = 36) or older (>50 years old; n = 45). Thirteen (36.1%) reproductive-aged females were using the OCP. Participants had induced sputum cell counts measured and blood analysed for sex hormones and inflammatory markers. RESULTS: Obese reproductive-aged females had higher sputum %neutrophils than nonobese reproductive-aged females (45.4 ± 24.3% vs 27.5 ± 17.5%, P = 0.016); however, there was no difference in sputum neutrophils in obese compared with nonobese males (P = 0.620) or older females (P = 0.087). Multiple linear regression analysis found testosterone and OCP use to be negative predictors of sputum %neutrophils, while C-reactive protein and IL-6 were positive predictors of sputum %neutrophils. BMI and age were not significant predictors in the multivariate model. Reproductive-aged females using the OCP had significantly lower sputum %neutrophils than those not using the OCP (23.2 ± 12.6% vs 42.1 ± 23.8%, P = 0.015). CONCLUSIONS: This study suggests that sex hormones and systemic inflammation may be mediating the obese-asthma phenotype. The observation that OCP use was associated with lower sputum %neutrophils in reproductive-aged females warrants further investigation.

Circulating CD36+ microparticles are not altered by docosahexaenoic or eicosapentaenoic acid supplementation.

BACKGROUND AND AIMS: Circulating microparticles (MP) are the source of a plasma derived form of the scavenger receptor CD36, termed soluble (s)CD36, the levels of which correlate with markers of atherosclerosis and risk of cardiovascular disease. Long chain n-3 polyunsaturated fatty acids have cardioprotective effects that we have previously reported to be gender specific. The aim of this study was to determine if dietary docosahexaenoic acid (DHA) and/or eicosapentaenoic acid (EPA) supplementation affect circulating CD36 + MP levels, and if this occurs differentially in healthy men and women. METHODS AND RESULTS: Participants (43M, 51F) aged 39.6 ± 1.7 years received 4 weeks of daily supplementation with DHA rich (200 mg EPA; 1000 mg DHA), EPA rich (1000 mg EPA; 200 mg DHA), or placebo (sunola) oil in a double-blinded, randomised, placebo controlled trial. Plasma CD36 + MP were enumerated by flow cytometry and differences between genders and treatments were evaluated by Student's or paired t-test and one way ANOVA. Males and females had similar levels of CD36 + MP at baseline (mean = 1018 ± 325 vs 980 ± 318; p = 0.577) and these were not significantly changed after DHA (M, p = 0.571; F, p = 0.444) or EPA (M, p = 0.361; F, p = 0.901) supplementation. Likewise, the overall percent change in these levels were not different between supplemented cohorts compared to placebo when all participants were combined (% change in CD36 + MP: DHA = 5.7 ± 37.5, EPA = -3.4 ± 35.4, placebo = -11.5 ± 32.9; p = 0.158) or stratified by gender (M, DHA = -2.6 ± 30.6, EPA = -15.1 ± 20.1, placebo = -21.4 ± 28.7, p = 0.187; F, DHA = 11.7 ± 41.5, EPA = 6.8 ± 42.9, placebo = -2.8 ± 34.7, p = 0.552). CONCLUSION: The cardioprotective effects of DHA and EPA do not act through a CD36 + MP mechanism.

Effects of dietary saturated and n-6 polyunsaturated fatty acids on the incorporation of long-chain n-3 polyunsaturated fatty acids into blood lipids.

BACKGROUND/OBJECTIVES: Omega-3 polyunsaturated fatty acids (n-3PUFA) are better absorbed when they are combined with high-fat meals. However, the role of different dietary fats in modulating the incorporation of n-3PUFA in blood lipids in humans has not been previously explored. Omega-6 polyunsaturated fatty acids (n-6PUFA) are known to compete with n-3PUFA in the metabolic pathways and for the incorporation into phospholipids, whereas saturated fats (SFA) may enhance n-3PUFA incorporation into tissues. SUBJECTS/METHODS: In a randomized parallel-design trial, we aimed to investigate the long-term effects of n-3PUFA supplementation in subjects consuming a diet enriched with either SFA or n-6PUFA on fatty acid incorporation into plasma and erythrocytes and on blood lipid profiles (total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides). RESULTS: Dietary supplementation with n-3PUFA co-administered with SFA for 6 weeks resulted in a significant rise in total cholesterol (0.46±0.60 mmol/L; P=0.020) and LDL-C (0.48±0.48 mmol/L; P=0.011) in comparison with combination with n-6PUFA. The diet enriched with SFA also induced a greater increase in eicosapentaenoic acid (2.07±0.79 vs 1.15±0.53; P=0.004), a smaller decrease in docosapentaenoic acid (-0.12±0.23 vs -0.30±0.20; P=0.034) and a similar increase in docosahexaenoic acid (3.85±1.14 vs 3.10±1.07; P=0.128) percentage in plasma compared with the diet enriched with n-6PUFA. A similar effect was seen in erythrocytes. N-3PUFA supplementation resulted in similar changes in HDL-C and triglyceride levels. CONCLUSIONS: The results suggest that dietary substitution of SFA with n-6PUFA, despite maintaining low levels of circulating cholesterol, hinders n-3PUFA incorporation into plasma and tissue lipids.

T2 relaxation time alterations underlying neurocognitive deficits in alcohol-use disorders (AUD) in an Indian population: A combined conventional ROI and voxel-based relaxometry analysis.

Long-term heavy alcohol consumption has traditionally been associated with impaired cognitive abilities, such as deficits in abstract reasoning, problem solving, verbal fluency, memory, attention, and visuospatial processing. The present study aimed at exploring these neuropsychological deficits in alcohol-use disorders (AUD) in an Indian population using the Postgraduate Institute Battery of Brain Dysfunction (PGIBBD) and their possible correlation with alterations in T2 relaxation times (T2-RT), using whole-brain voxel-based relaxometry (VBR) and conventional region of interest (ROI) approach. Multi-echo T2 mapping sequence was performed on 25 subjects with AUD and 25 healthy controls matched for age, education, and socioeconomic status. Whole-brain T2-RT measurements were conducted using VBR and conventional ROI approach. The study was carried out on a 3T whole-body MR scanner. Post processing for VBR and ROI analysis was performed using SPM 8 software and vendor-provided software, respectively. A PGIBBD test battery was conducted on all subjects to assess their cognitive abilities, and the results were reported as raw scores. VBR and ROI results revealed that AUD subjects showed prolonged T2-RTs in cerebellum bilaterally, parahippocampal gyrus bilaterally, right anterior cingulate cortex, left superior temporal gyrus, left middle frontal gyrus, and left calcarine gyrus. A significant correlation was also observed between the neuropsychological test raw scores and alterations in T2-RT in AUD subjects. Our results are consistent with previous studies suggesting tissue disruption or gliosis or demyelination as a possible reason for prolonged T2-RTs. This damage to brain tissue, which is evident as prolonged T2-RT, could possibly be associated with impaired cognitive abilities noticeable in AUD subjects.

Dietary predictors of arterial stiffness in a cohort with type 1 and type 2 diabetes.

OBJECTIVE: To determine the dietary predictors of central blood pressure, augmentation index and pulse wave velocity (PWV) in subjects with type 1 and type 2 diabetes. METHODS: Participants were diagnosed with type 1 or type 2 diabetes and had PWV and/or pulse wave analysis performed. Dietary intake was measured using the Dietary Questionnaire for Epidemiological Studies Version 2 Food Frequency Questionnaire. Serum lipid species and carotenoids were measured, using liquid chromatography electrospray ionization-tandem mass spectrometry and high performance liquid chromatography, as biomarkers of dairy and vegetable intake, respectively. Associations were determined using linear regression adjusted for potential confounders. RESULTS: PWV (n = 95) was inversely associated with reduced fat dairy intake (ß = -0.01; 95% CI -0.02, -0.01; p = 0 < 0.05) in particular yoghurt consumption (ß = -0.04; 95% CI -0.09, -0.01; p = 0 < 0.05) after multivariate adjustment. Total vegetable consumption was negatively associated with PWV in the whole cohort after full adjustment (ß = -0.04; 95% CI -0.07, -0.01; p < 0.05). Individual lipid species, particularly those containing 14:0, 15:0, 16:0, 17:0 and 17:1 fatty acids, known to be of ruminant origin, in lysophosphatidylcholine, cholesterol ester, diacylglycerol, phosphatidylcholine, sphingomyelin and triacylglycerol classes were positively associated with intake of full fat dairy, after adjustment for multiple comparisons. However, there was no association between serum lipid species and PWV. There were no dietary predictors of central blood pressure or augmentation index after multivariate adjustment. CONCLUSION: In this cohort of subjects with diabetes reduced fat dairy intake and vegetable consumption were inversely associated with PWV. The lack of a relationship between serum lipid species and PWV suggests that the fatty acid composition of dairy may not explain the beneficial effect.

Impaired visual information processing in alcohol-dependent subjects: a proton magnetic resonance spectroscopy study of the primary visual cortex.

OBJECTIVE: Chronic alcoholism is associated with impaired cognitive abilities, with a more severe deficit in visual than in verbal functions. The visual processing deficits have classically been associated with impaired function of the visual cortex, located in the occipital lobe. The present study sought to increase current understanding of the impaired visual processing abilities in alcohol-dependent subjects and their correlation with metabolic aberrations in the occipital lobe using in vivo proton magnetic resonance spectroscopy (¹H MRS). METHOD: To that end, ¹H MRS was carried out in the primary visual cortex on 35 alcohol-dependent subjects and 35 healthy controls. Neuropsychological tests for visual processing skills were performed on all the subjects, and the deficits were reported as raw dysfunction rating scores. RESULTS: The alcohol-dependent subjects showed a significant increase in choline/creatine (Cho/Cr) and myo-Inositol/creatine (mI/Cr) ratios, whereas N-acetyl-aspartate/creatine (NAA/Cr) and glutamate-glutamine/creatine (Glu-Gln)/Cr ratios were significantly decreased. Reductions in NAA levels might be attributed to neuronal loss, whereas reductions in Glu-Gln levels might reflect perturbation of the Glu-Gln system in alcohol-dependent individuals, which could represent a neuroprotective adaptation. Elevations in mI levels may reflect astrocyte proliferation as well as an osmotic response to cell shrinkage, whereas a significant increase in Cho levels indicates altered cell membrane metabolism. Also, a significant inverse correlation between NAA/Cr and raw dysfunction scores (rDyS) on the Nahor-Benson (NB) test and Glu-Gln/Cr with rDyS of the NB and the Bender-Gestalt (BG) test was observed, whereas a positive correlation between rDyS of the BG and the NB test and Cho/Cr was observed. CONCLUSIONS: The results suggest that metabolic alterations in the primary visual cortex may contribute to the neuropsychological impairment in visual information processing observed in alcohol-dependent subjects.

Saturated fat consumption may not be the main cause of increased blood lipid levels.

Consumption of foods rich in saturated fatty acids (SFA) has often been associated with elevated blood lipid levels and consequently with risk for chronic diseases, including coronary heart disease. However, epidemiological and interventional studies on this topic are contradictory. While some studies have established a positive link, other studies have failed to show a significant association between saturated fat consumption and blood lipid levels, and others have even found an inverse association. Moreover, studies using animal models have demonstrated that dietary saturated fats raise blood lipid (cholesterol and triglycerides) levels only when the diet is deficient in omega-3 polyunsaturated fatty acids (n-3PUFA). The n-3PUFA are known for their potential in the management of hyperlipidaemia for the prevention of coronary heart disease, as well as for their anti-arrhythmic, anti-aggregatory and anti-inflammatory potential. We believe that with an adequate consumption of n-3PUFA dietary saturated fat may not result in elevated blood lipid levels. Therefore, we critically evaluated the literature regarding saturated fat and blood lipid level, with an emphasis on the role of n-3PUFA on this relationship. Evidence from animal studies and few clinical trials lead to the hypothesis that there are beneficial or neutral effects of saturated fatty acids when combined with recommended levels of n-3PUFA in the diet. However, an intervention focusing on the background fat when the volunteers' diet is supplemented with n-3PUFA is yet to be done. Proving the authenticity of this hypothesis would mean a substantial change in public health messages regarding saturated fats and their health effects; and also a change in the strategies related to prevention of chronic cardiac and artery diseases.

The association between dietary patterns and type 2 diabetes: a systematic review and meta-analysis of cohort studies.

BACKGROUND: Observational studies suggest that dietary pattern intake plays an important role in the development of type 2 diabetes. A meta-analysis was performed of existing cohort studies on the association between dietary patterns and the risk of type 2 diabetes. METHODS: Pertinent studies were identified by searching MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature, PROQUEST, MEDNAR and the Joanna Briggs Institute Library of Systematic Reviews, as well as the reference lists of all identified studies up to September 2012. A random-effects meta-analysis was performed to pool relative risk (RR) estimates from individual studies to assess the relationship between dietary pattern intake and the risk of type 2 diabetes. Statistical heterogeneity was assessed using I(2) and sensitivity analyses were conducted. Publication bias was evaluated by visual inspection of funnel plots and was formally assessed using Egger's test. RESULTS: There were fifteen cohort studies that met the inclusion criteria. There was evidence of a reduction in the risk of type 2 diabetes in the highest adherence compared to the lowest adherence to healthy dietary patterns [RR = 0.79, 95% confidence interval (CI) = 0.74-0.86, P < 0.005]. An increase in the risk of type 2 diabetes was evident for the highest adherence compared to the lowest adherence to unhealthy dietary patterns (RR = 1.44, 95% CI = 1.33-1.57, P < 0.005). CONCLUSIONS: The results of this systematic review and meta-analysis indicate that dietary patterns may be associated with the risk of type 2 diabetes.

Assessment of lexical semantic judgment abilities in alcohol-dependent subjects: an fMRI study.

Neuropsychological studies have shown that alcohol dependence is associated with neurocognitive deficits in tasks requiring memory, perceptual motor skills, abstraction and problem solving, whereas language skills are relatively spared in alcoholics despite structural abnormalities in the language-related brain regions. To investigate the preserved mechanisms of language processing in alcohol-dependents, functional brain imaging was undertaken in healthy controls (n=18) and alcohol-dependents (n=16) while completing a lexical semantic judgment task in a 3 T MR scanner. Behavioural data indicated that alcohol-dependents took more time than controls for performing the task but there was no significant difference in their response accuracy. fMRI data analysis revealed that while performing the task, the alcoholics showed enhanced activations in left supramarginal gyrus, precuneus bilaterally, left angular gyrus, and left middle temporal gyrus as compared to control subjects. The extensive activations observed in alcoholics as compared to controls suggest that alcoholics recruit additional brain areas to meet the behavioural demands for equivalent task performance. The results are consistent with previous fMRI studies suggesting compensatory mechanisms for the execution of task for showing an equivalent performance or decreased neural efficiency of relevant brain networks. However, on direct comparison of the two groups, the results did not survive correction for multiple comparisons; therefore, the present findings need further exploration.

Dietary restriction and exercise improve airway inflammation and clinical outcomes in overweight and obese asthma: a randomized trial.

BACKGROUND: Obesity and asthma are associated conditions; however, the mechanisms linking the two remain unclear. Few studies have examined the effects of weight loss on inflammation and clinical outcomes in obese-asthma. OBJECTIVE: To compare the effects of weight loss achieved by dietary restriction, exercise or combined dietary restriction and exercise on airway inflammation and clinical outcomes in overweight and obese adults with asthma. METHODS: Participants (n = 46; 54.3% female, body mass index (mean ± SD) 33.7 ± 3.5 kg/m(2) ) were randomized to complete a 10-week dietary, exercise or combined dietary and exercise intervention. Dual-energy x-ray absorptiometry was performed, the Juniper Asthma Control Questionnaire and Juniper Asthma Quality of Life Questionnaire completed and inflammatory markers, dietary intake and physical activity measured. The trial was registered with the Australian Clinical Trials Registry: ACTRN12611000235909. RESULTS: Retention was 82.6%. Mean ± SD weight loss was 8.5 ± 4.2%, 1.8 ± 2.6% and 8.3 ± 4.9% after the dietary, exercise and combined interventions respectively. Asthma control improved after the dietary (mean ± SD; -0.6 ± 0.5, P ≤ 0.001) and combined interventions (-0.5 ± 0.7, P = 0.040), whereas quality of life improved after the dietary [median (IQR); 0.9 (0.4, 1.3), P = 0.002], exercise [0.49 (0.03, 0.78), P = 0.037] and combined [0.5 (0.1, 1.0), P = 0.007] interventions. A 5-10% weight loss resulted in clinically important improvements to asthma control in 58%, and quality of life in 83%, of subjects. Gynoid adipose tissue reduction was associated with reduced neutrophilic airway inflammation in women [ß-coefficient (95% CI); 1.75 (0.02, 3.48), P = 0.047], whereas a reduction in dietary saturated fat was associated with reduced neutrophilic airway inflammation in males (r = 0.775, P = 0.041). The exercise intervention resulted in a significant reduction to sputum eosinophils [median (IQR); -1.3 (-2.0, -1.0)%, P = 0.028]. CONCLUSION AND CLINICAL RELEVANCE: This study suggests a weight-loss goal of 5-10% be recommended to assist in the clinical management of overweight and obese adults with asthma. The obese-asthma phenotype may involve both innate and allergic inflammatory pathways.

A comparative validation of a child food frequency questionnaire using red blood cell membrane fatty acids.

BACKGROUND/OBJECTIVES: There are limited validated tools available for the assessment of dietary intake in pediatric populations. This report describes a comparative validation study of selected fatty acid intakes in children assessed by food frequency questionnaire (FFQ), compared with erythrocyte membrane fatty acids. SUBJECTS/METHODS: Overall, 46 overweight and 47 healthy-weight children aged 5-12 years (mean±SD, 9.1±1.3years, body mass index 20.5±4.0) were recruited; dietary fatty acid intakes assessed by parent report using a 135-item semi-quantitative FFQ, were compared with selected child erythrocyte membrane fatty acids assessed from fasting samples using gas chromatography. Spearman's rank correlation coefficients were calculated between fatty acid intake estimates (% of energy) and erythrocyte membrane concentrations (%mol/mol). RESULTS: Significant correlations were found between dietary and erythrocyte eicosapentanoic acid (EPA) concentration (r=0.24, P<0.05) with a statistical trend for total omega three (∑n-3) fatty acids (r=0.22, P=0.06) and linoleic acid (r=0.32, P=0.07) in the healthy-weight children only. CONCLUSION: Parental report of selected child fatty acid intakes using an FFQ can be used to provide an estimate of child intake of EPA, but further work is required to quantify this relationship for other fatty acids and in other populations.

Gender-specific inhibition of platelet aggregation following omega-3 fatty acid supplementation.

BACKGROUND AND AIMS: Increased platelet aggregation is a major risk factor for heart attacks, stroke and thrombosis. Long chain omega-3 polyunsaturated fatty acids (LCn-3PUFA; eicosapentaenoic acid, EPA; docosahexaenoic acid, DHA) reduce platelet aggregation; however studies in the published literature involving EPA and/or DHA supplementation have yielded equivocal results. Recent in vitro studies have demonstrated that inhibition of platelet aggregation by LCn-3PUFA is gender specific. We examined the acute effects of dietary supplementation with EPA or DHA rich oils on platelet aggregation in healthy male and females. METHODS AND RESULTS: A blinded placebo controlled trial involving 15 male and 15 female subjects. Platelet aggregation was measured at 0, 2, 5 and 24 h post-supplementation with a single dose of either a placebo or EPA or DHA rich oil capsules. The relationship between LCn-3PUFA and platelet activity at each time point was examined according to gender vs. treatment. EPA was significantly the most effective in reducing platelet aggregation in males at 2, 5 and 24 h post-supplementation (-11%, -10.6%, -20.5% respectively) whereas DHA was not effective relative to placebo. In contrast, in females, DHA significantly reduced platelet aggregation at 24 h (-13.7%) while EPA was not effective. An inverse relationship between testosterone levels and platelet aggregation following EPA supplementation was observed. CONCLUSION: Interactions between sex hormones and omega-3 fatty acids exist to differentially reduce platelet aggregation. For healthy individuals, males may benefit more from EPA supplementation while females are more responsive to DHA.

Airway inflammation is augmented by obesity and fatty acids in asthma.

Obesity and asthma are associated, but the mechanism(s) of the association have yet to be elucidated. The aim of this study was to assess airway inflammation in relation to obesity and plasma fatty acids in males and females with and without asthma. Obese (n=68) and nonobese (n=47) adults with asthma, and obese (n=16) and nonobese (n=63) healthy controls had induced sputum and venous blood samples analysed for inflammatory markers. There was a positive interaction between obesity and asthma on sputum neutrophil percentage (p=0.012) and C-reactive protein level (p=0.003). Although sputum eosinophil percentage was elevated in asthma (p=0.001), there was no effect of obesity (p=0.16). Sputum neutrophil percentage was positively associated with body mass index in females with asthma (ß=1.015, 95% CI 0.258-1.772; p=0.009) and neutrophilic asthma was present in a greater proportion of obese compared with non-obese females (42.9% versus 16.2%; p=0.017). In males with asthma, sputum neutrophil percentage was positively associated with total plasma saturated fatty acids (ß=0.108, 95% CI 0.036-0.180; p=0.004) and negatively with monounsaturated fatty acids (ß= -0.068, 95% CI -0.131- -0.005; p=0.035). This was the first study to demonstrate an increase in neutrophilic airway inflammation in obese asthma. This relationship was significant only in females with asthma. In males, saturated and monounsaturated fatty acids were important predictors of neutrophilic airway inflammation in asthma.