The role of dietary fats on cognition and sarcopenia in the elderly.

BACKGROUND AND OBJECTIVES: To elucidate the role of dietary fats on the relationship between mild cognitive impairment and sarcopenia and help identifying and preventing the decline of cognitive and muscle function in elderly individuals. METHODS AND STUDY DESIGN: The study conducted involving a group of 1812 individuals between the ages of 61 and 92. Body composition and BMR were assessed by bioelectrical impedance analysis. Cognitive function and dietary nutrition were evaluated by neuropsychological assessments and questionnaire of food intake frequency. Lipidomics analysis was performed using UHPLC-Qtrap-MS/MS. RESULTS: MCI and SA are mutual influencing factors, lower intake of MUFA, PUFA and higher intake of fat was associated with cognitive dysfunction and/or SA (p < 0.05). PUFA was important for MCI combined with SA (Compared with Q1, Q4 OR: 0.176, 95%CI: 0.058,0.533). Lipidomics analysis revealed that triacylglycerol (TAG) contain more carbon chains with saturated double bonds may be closely related to cognitive impairment and the progression of SA (p < 0.05). While, DAG with carbon chains of unsaturated double bonds is opposite. CONCLUSIONS: Insufficient intake of unsaturated fatty acids was associated with the development of cognitive decline and the progression of SA. MUFA affecting muscle health, fats and PUFA has a greater impact on MCI combined with SA. Less MUFA intake and increasing saturated double-bonded fatty acid intake might be the key factors on promoting cognitive impairment and SA in the elderly. They have the potential to serve as prospective biomarkers indicating a higher risk of cognitive decline and/or SA in the elderly population.

Association between sodium and potassium intake levels and body compositions of Chinese college students.

BACKGROUND AND OBJECTIVES: To investigate the relationship between sodium (Na) and potassium (K) nutritional condition and body compositions in youth aiming to give target population reasonable diet recommendations. METHODS AND STUDY DESIGN: The cross-sectional study was conducted involving 512 healthy youth aged 18 to 31 years from universities in Beijing. Food frequency questionnaire (FFQ) and bioelectrical impedance analyzer (BIA) were used to collect dietary intake information and body compositions. RESULTS: There was an increasing tendency in fat-related indicators and muscle-related indicators of the dietary Na tertile group (p <0.05). Additionally, Weight, body mass index (BMI), waist circumference (WC), and muscle-related indicators increased with the dietary K tertile group (p <0.05). Across increasing tertiles of dietary Na intake, the odds ratio (OR) was increased significantly (p < 0.05) in fat-related indicators. On the contrary, with the increased dietary Na intake, the OR decreased (p < 0.05) in appendicular skeletal muscle mass index (ASMI) and body lean mass. As tertiles of dietary K intake increased, the OR in both skeletal muscle mass index (SMMI) and lean mass index (LMI) decreased. CONCLUSIONS: High dietary Na is a risk factor for abnormal lipid distribution in college students. High dietary K can maintain skeletal muscle mass and reduce the risk of obesity. Na in the diet has a greater impact on the body composition of young people than K. Low dietary Na and high dietary K still need to be strengthened in science popularization and practice among more college students.

[Relationship between geratic frailty and cognitive dysfunction in the eldly].

OBJECTIVE: To analyze the current situation and correlation between frailty and cognitive dysfunction in the old patients of orthopedic emergency. METHODS: Enrolling 248 elderly people( ≥65 years old) in orthopedic emergency department of Beijing Jishuitan Hospital from September to December 2018, the cognitive function of the subjects was assessed by Mini-mental State Examination( MMSE). The frailty situation was assessed by FRAIL Scale. In addition, ADL, exercise tolerance assessment, gripping power and geriatric nutritional risk index( GNRI) were also tested in this study. RESULTS: In this research, 58( 23. 4%) were the elderly with normal cognitive function, 69( 27. 8%) were MCI, and 86( 34. 7%) were dementia and 35( 14. 1%) were severe dementia. The prevalence of seniors over 76 years old was significantly higher than that of the younger age group( χ~2= 39. 300, P < 0. 001), the prevalence of seniors below primary school was significantly higher than that of junior middle school and above( χ~2= 117. 082, P<0. 001), and the prevalence of dementia in patients with chronic obstructive pulmonary disease( COPD) was higher( χ~2= 11. 685, P = 0. 009). The study subjects were strong elderly, accounting for 69( 27. 8%), 114( 46. 0%) and 65( 26. 2%)were in prefrailty and frailty. The prevalence of prefrailty in 75-85 years old people was significantly higher than that in other groups, and the prevalence of prefrailty and frailty in85 years old people was both higher( χ~2= 45. 247, P<0. 001). In addition, education level( χ~2= 13. 909, P = 0. 008), hypertension( χ~2= 6. 892, P = 0. 032), COPD( χ~2= 8. 411, P =0. 015), cerebral infarction( χ~2= 7. 477, P = 0. 024) and GNRI( χ~2= 22. 942, P = 0. 001)were all the influencing factors of frailty. There were also significant differences in ADL, exercise tolerance and gripping power among the above factors. There were significant differences in cognitive function among subjects with different levels of frailty( χ~2=61. 259, P = 0. 000), ADL( χ~2= 54. 652, P<0. 001), exercise tolerance( χ~2= 77. 001, P =0. 000) and grip strength( χ~2= 54. 778, P < 0. 001). After adjusting for demographic characteristics and chronic diseases such as age, sex, education, BMI, coronary heart disease, hypertension and et al. Logistic regression analysis showed that the OR values of prefrailty, frailty, ADL and exercise tolerance affect cognition are 1. 918( 95% CI 0. 990-3. 716), 2. 732( 95%CI 1. 063-7. 023), 3. 217( 95% CI 1. 421-7. 285), 6. 440( 95% CI1. 803-22. 997). CONCLUSION: Prefrailty and frailty are closely related to cognitive dysfunction in the elderly.

Sex-specific nonlinear associations between serum lipids and different domains of cognitive function in middle to older age individuals.

To examine how serum lipids relates to specific cognitive ability domains between the men and women in Chinese middle to older age individuals. A complete lipid panel was obtained from 1444 individuals, ages 50-65, who also underwent a selection of cognitive tests. Participants were 584 men and 860 women from Linyi city, Shandong province. Multiple linear regression analyses examined serum lipids level as quadratic predictors of sex-specific measure of performance in different cognitive domains, which were adjusted for sociodemographic and lifestyle characteristics. In men, a significant quadratic effect of total cholesterol (TC) was identified for Digit Symbol (B = -0.081, P = 0.044) and also quadratic effect of low density lipoprotein-cholesterol (LDL-C) was identified for Trail Making Test B (B = -0.082, P = 0.045). Differently in women, there were significant quadratic associations between high density lipoprotein-cholesterol (HDL-C) and multiple neuropsychological tests. The nonlinear lipid-cognition associations differed between men and women and were specific to certain cognitive domains and might be of potential relevance for prevention and therapy of cognitive decline.

Genistein Inhibits Aß25-35-Induced Synaptic Toxicity and Regulates CaMKII/CREB Pathway in SH-SY5Y Cells.

Genistein (Gen), as a functional food in human diet, has shown many beneficial effects on neurodegenerative diseases such as Alzheimer's disease (AD). But the neuroprotective mechanism of Gen is not clear. Because synaptic failure is considered as the earliest phase in the pathogenesis of AD, we try to validate our hypothesis that synapse may be one target of Gen on protecting neurons. In this study, SH-SY5Y cells were pre-incubated with or without Gen for 2 h followed by the incubation with Aß25-35 (25 µmol/L) for another 24 h. Flow cytometry, Western Blots, and RT-PCR analysis were used to test the synaptic factors. The data showed that Gen pre-treatment could reverse the Aß25-35-induced down-regulation of synaptophysin and postsynaptic marker postsynaptic density-95. In addition, the down-regulation of NR1 and NR2B induced by Aß25-35 which are subunits of N-methyl-D-aspartate receptor also could be antagonized by pre-treatment of Gen. Moreover, the factors of CaMKII/CREB signaling pathway were detected. The results showed that mRNA and protein expressions of (Ca(2+))/calmodulin(CaM), CaMKII/pCaMKII, and CREB/pCREB were significantly down-regulated by Aß25-35, but they were all restored by the pre-treatment of Gen. Furthermore, Gen also maintained the intracellular Ca(2+) concentration which was disturbed by Aß25-35. In conclusion, these results suggested that Gen could protect synaptic dysfunction induced by Aß, and the mechanism might be associated with the regulation of synaptic markers and Ca(2+) level through activating CaM/CaMK/CREB signaling pathway.

The effect of soybean isoflavone on the dysregulation of NMDA receptor signaling pathway induced by ß-amyloid peptides 1-42 in rats.

Synaptic damage is the key factor of cognitive impairment. The purpose of this study was to understand the effect of soybean isoflavone (SIF) on synaptic damage induced by ß-amyloid peptide 1-42 (Aß1-42) in rats. Adult male Wistar rats were randomly divided into control, Aß1-42, SIF, and SIF + Aß1-42 (SIF pretreatment) groups according to body weight. SIF was treated orally by gavage in SIF and SIF + Aß1-42 groups. After 14 days pretreatment with SIF or vehicle, Aß1-42 was injected into the lateral cerebral ventricle of rats in Aß1-42 and SIF + Aß1-42 groups using miniosmotic pump. The level of Aß1-42 and the expression of N-methyl-D-aspartic-acid receptor (NMDAR) were observed by immunohistochemistry. Reverse transcriptase polymerase chain reaction was used to detect the mRNA levels of NMDAR, calmodulin (CaM), calcium/CaM-dependent protein kinase II (CaMKII), cAMP-response element binding protein (CREB), and brain-derived neurotrophic factor (BDNF). The results showed that Aß1-42 down-regulated mRNA and protein expression of the NR1 and NR2B subunits of NMDAR, SIF pretreatment could reverse these changes. The mRNA expression of CaM, CaMKII, CREB, and BDNF were down-regulated by Aß1-42, but they were all regulated by SIF pretreatment. These results suggest that SIF pretreatment could antagonize the neuron damage in rats induced by Aß1-42, and its mechanism might be associated with the NMDA receptor and CaM/CaMKII/CREB/BDNF signaling pathway, which are the synaptic plasticity-related molecules.

The oxysterol 27-hydroxycholesterol increases oxidative stress and regulate Nrf2 signaling pathway in astrocyte cells.

The disturbance in cholesterol metabolism has been considered as a cause of alzheimer's disease (AD), which dues to the oxidative damage and cell apoptosis in the brain. We aimed to investigate the toxicity and mechanism of AD-like pathology caused by cholesterol oxidation metabolite 27-hydroxycholesterol (27-OHC) in astrocyte cells. C6 cells were treated with 0, 5, 10, 20 µM 27-OHC for 24 h (h). The cell viability was monitored by using methyl thiazolyl tetrazolium test, generation of reactive oxygen species (ROS) was measured by using 2', 7'-dichlorodihydrofluorescein diacetate fluorescent probe under flow cytometry. The concentrations of 8-hydroxyl deoxyguanosine, the anti-oxidative enzymes such as total superoxide dismutase (tSOD), reduced glutathione (rGSH) and glutathione peroxidase (GSH-Px) were tested by using enzyme-linked immunosorbent assay and enzymic method, respectively. The gene and protein expression of nuclear factor E2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), NAD(P)H dehydrogenase quinone 1 (NQO1) and γ-glutamylcysteine synthetase (γ-GCS) in C6 cells were detected by quantitative western blot analysis and real-time PCR analysis. Moreover, the Nrf2 expressions in both of the cytoplasm and nucleus were detected with western blot analysis, and the localization of Nrf2 was performed by immunocytochemistry and confocal microscopy. 27-OHC increased the levels of ROS and decreased the levels of tSOD, rGSH, GSH-Px in C6 cells dose-dependently. In addition, 27-OHC down regulated the expressions of Nrf2, HO-1, NQO1 and γ-GCS at both of gene and protein levels, while Nrf2 expression in the cytoplasm showed decreased trend after incubated for 24 h with 27-OHC. The cholesterol metabolite 27-OHC is toxic to C6 cells and contributed to oxidative damage via regulating the Nrf2 signaling pathway. Our results suggest that 27-OHC may represent a common pathogenic factor in AD.

Global DNA methylation was changed by a maternal high-lipid, high-energy diet during gestation and lactation in male adult mice liver.

An epigenetic mechanism has been suggested to explain the effects of the maternal diet on the development of disease in offspring. The present study aimed to observe the effects of a maternal high-lipid, high-energy (HLE) diet on the DNA methylation pattern of male offspring in mice. Female C57BL/6J mice were fed an HLE diet during gestation and lactation. The genomic DNA methylations at promoter sites of genes in the liver, mRNA and protein levels of selected genes related to lipid and glucose metabolism were measured by microarray, real-time PCR and Western blot. The results indicated that the percentage of methylated DNA in offspring from dams that were fed an HLE diet was significantly higher than that from dams that were fed a chow diet, and most of these genes were hypermethylated in promoter regions. The nuclear protein content and mRNA levels of hypermethylated genes, such as PPARγ and liver X receptor α (LXRα), were decreased significantly in offspring in the HLE group. The results suggested that the DNA methylation profile in adult offspring livers was changed by the maternal HLE diet during gestation and lactation.

Soy isoflavone antagonizes the oxidative cerebrovascular injury induced by ß-amyloid peptides 1-42 in rats.

Numerous evidences have shown that the antioxidative properties of soy isoflavone (SIF) have beneficial effects on prophylaxis of neurodegeneration, however, the mechanism is still not fully illustrated. As cerebrovascular dysfunction could initiate a cascade of events leading to pathogenesis of Alzheimer's disease, we tried to investigate whether SIF could protect the cerebrovascular system due to antagonizing oxidative damage induced by Aß1-42 in present study. In addition, NF-E2-related factor 2 (Nrf2) signaling pathways in the cerebrovascular tissue of Wistar rats were investigated to identify the potential cerebrovascular protective targets of SIF. Research results showed that SIF reduced the excessive production of nitrotyrosine in cerebrovascular tissue induced by Aß1-42, and maintained redox homeostasis by increasing the level of GSH and GSH/GSSG. Moreover, SIF could alleviate the down-regulation of Nrf2, γ-glutamylcysteine synthetase, Heme oxygenase-1 expressions in cerebrovascular tissue induced by Aß1-42 and suppress the increase of Kelch like ECH protein-1 (Keap1). These data suggested that SIF might reduce the cerebrovascular oxidative damage induced by Aß1-42 through regulating the Nrf2 signaling pathway. The mechanisms of SIF modulating the potential target Nrf2 might be associated with Keap1 expression.

Association of habitual physical activity with depression and anxiety: a multicentre cross-sectional study.

OBJECTIVE: Despite the known benefits of physical activity, the effect of habitual physical activity (HPA) on depression and anxiety remains unclear. This study aimed to investigate the association of HPA with the risk of depression and anxiety among Chinese adults, with the consideration of disease severity. METHODS: The participants in this multicentre cross-sectional study were from the nationwide survey of the psychology and behaviour of Chinese residents. Depression and anxiety were measured using the nine-item Patient Health Questionnaire and seven-item Generalised Anxiety Disorder scale. HPA was assessed by the short form of the International Physical Activity Questionnaire. Crude and adjusted ORs with their 95% CIs were estimated by using ordinal logistic regression. RESULTS: Of the 19 798 participants, 3901 (19.7%) had anxiety and 8914 (45.02%) had depression. Compared with inactive participants, depression risk in individuals reporting low, median and high volume HPA was reduced by 23% (OR 0.77, 95% CI 0.66 to 0.89), 21% (OR 0.79, 95% CI 0.68 to 0.90) and 13% (OR 0.87, 95% CI 0.78 to 0.98), respectively, after adjustment for confounder. No significant association of HPA with anxiety risk was observed. CONCLUSION: Participation in HPA, whether low, median or high volume, was associated with a lower risk of depression compared with inactive participation, while no significant association was observed between HPA and anxiety.

Adaptive responses by mouse fetus to a maternal HLE diet by downregulating SREBP1: a microarray- and bio-analytic-based study.

Maternal diet has long been recognized as a significant factor affecting offspring development and health, but the target genes affected by a maternal high-lipid diet are currently unknown. In this study, the gene expression profile of neonatal mouse liver was analyzed using gene chips to identify genes with significant up- or downregulated expression levels due to maternal high-fat diet during gestation. Real-time PCR and Western blotting were used to measure key genes selected using microarray. Serum lipid, glucose, and insulin levels in adult offspring from dams fed with chow or a high-lipid diet were measured using commercial kits. Results indicate that the expression of genes involved in cholesterol and fatty acid synthesis were significantly inhibited, while the expression of genes involved in glycolysis were significantly decreased by maternal high-lipid diet during gestation. SREBP1 might be the key gene regulating genes involved in fatty acid, glucose, and cholesterol metabolism in response to a maternal high-fat diet.

Soy isoflavone attenuates brain mitochondrial oxidative stress induced by ß-amyloid peptides 1-42 injection in lateral cerebral ventricle.

The aim of this study is to investigate whether soy isoflavone (SIF) reduces oxidative stress and improves the antioxidant ability in mitochondria of rat brain damaged by injection of beta-amyloid peptides 1-42 (Aß1-42). Forty Wistar rats were randomly divided into control, Aß1-42, SIF + Aß1-42, and SIF groups according to body weight. The rats in the SIF + Aß1-42 group and SIF group were intragastrically administered SIF suspension in 0.5% CMC-Na for 28 days, whereas the rats in control group and Aß1-42 group were administered the same volume of 0.5% CMC-Na. On day 14, the rats in the Aß1-42 group and SIF + Aß1-42 group were injected with Aß1-42 into the lateral cerebral ventricle with physiological saline. The rat brains were then sampled, and brain mitochondria were isolated. After this, the mitochondrial membrane potential (MMP) and mitochondrial redox state were measured. The contents of brain nuclear factor E2-related factor (Nrf2) and heme oxygenase-1 (HO-1) protein in brain tissue were quantitated by Western blot. The results showed that SIF maintained the MMP, elevated the reduced glutathione/oxidized glutathione (GSH/GSSG) ratio, and increased glutathione peroxidase (GPx) and manganese superoxide dismutase (MnSOD) protein expression in brain mitochondria. Additionally, SIF reversed the Aß1-42-induced downregulation of the protein expression of Nrf2 and HO-1 in brain tissue. These results indicated that SIF could alleviate the oxidative damage and maintain the redox imbalance in brain mitochondria damaged by Aß1-42. This might result from regulation of the Nrf2/HO-1 pathway.

Soybean isoflavone ameliorates ß-amyloid 1-42-induced learning and memory deficit in rats by protecting synaptic structure and function.

This research aims to investigate whether soybean isoflavone (SIF) could alleviate the learning and memory deficit induced by ß-amyloid peptides 1-42 (Aß 1-42) by protecting the synapses of rats. Adult male Wistar rats were randomly allocated to the following groups: (1) control group; (2) Aß 1-42 group; (3) SIF group; (4) SIF + Aß 1-42 group (SIF pretreatment group) according to body weight. The 80 mg/kg/day of SIF was administered orally by gavage to the rats in SIF and SIF+Aß 1-42 groups. Aß 1-42 was injected into the lateral cerebral ventricle of rats in Aß 1-42 and SIF+Aß 1-42 groups. The ability of learning and memory, ultramicrostructure of hippocampal synapses, and expression of synaptic related proteins were investigated. The Morris water maze results showed the escape latency and total distance were decreased in the rats of SIF pretreatment group compared to the rats in Aß1-42 group. Furthermore, SIF pretreatment could alleviate the synaptic structural damage and antagonize the down-regulation expressions of below proteins induced by Aß1-42: (1) mRNA and protein of the synaptophysin and postsynaptic density protein 95 (PSD-95); (2) protein of calmodulin (CaM), Ca(2+) /calmodulin-dependent protein kinase II (CaMK II), and cAMP response element binding protein (CREB); (3) phosphorylation levels of CaMK II and CREB (pCAMK II, pCREB). These results suggested that SIF pretreatment could ameliorate the impairment of learning and memory ability in rats induced by Aß 1-42, and its mechanism might be associated with the protection of synaptic plasticity by improving the synaptic structure and regulating the synaptic related proteins.

Genistein alleviates the mitochondria-targeted DNA damage induced by ß-amyloid peptides 25-35 in C6 glioma cells.

Reactive oxygen species (ROS) are mainly produced by mitochondria which can cause oxidative stress. It has been considered that mitochondrial damage induced by oxidative stress is related to Alzheimer's disease (AD). Besides, mitochondrial DNA (mtDNA) is more vulnerable to oxidative damage than other biomacromolecules, causing serious dysfunction to mitochondria. ß-amyloid peptides (Aß) is a main factor responsible for the occurrence and development of AD. Astrocytes is an important target cell for Aß' toxicity and can be activated to neglect their normal fountain in the central nervous system. Genistein (Gen), a main active ingredient of soybean isoflavone, has been shown to have neuroprotective effects by antagonizing oxidative damage induced by Aß. Thus, in the present study, we evaluated Aß25-35 induced mitochondrial DNA (mtDNA) damage and the protective effect of Gen in C6 glioma cells (C6 cells). The study design was consisted of four groups: control group (vehicle), Aß group treated with Aß25-35, Gen + Aß group treated with Gen + Aß25-35 and Gen group treated with Gen only. C6 cells were pre-incubated with or without Gen (50 µM) for 2 h followed by the incubation with Aß25-35 (25 µM) for another 24 h. Then the cells were harvested and processed to perform the analysis according to protocols. The mitochondrial ROS in C6 cells were measured by fluorescence spectrometer. Enzyme-linked immunosorbent assay (ELISA) was used to detect the mitochondrial reduced glutathione (GSH) and oxidized glutathione (GSSG) in C6 cells, then the ratio of GSH and GSSG was calculated. The levels of 8-hydroxydeoxyguanosine (8-OHdG) in C6 cells was also detected by ELISA. In addition, mtDNA deletion was detected by polymerase chain reaction (PCR). The mRNA and protein expression of 8-oxoguanine DNA glycosylase (OGG1) in both C6 cells and its mitochondria, and manganese superoxide dismutase (MnSOD) in mitochondria were detected by using reverse transcription-PCR and Western blot. The results showed that the increased mitochondrial ROS accumulation in C6 cells induced by Aß was profoundly reversed by pre-treaded with Gen (p < 0.05). The ratio of GSH and GSSG in mitochondria was significantly increased in both Gen + Aß group and Gen group compared with Aß group (p < 0.05). The levels of 8-OHdG in C6 cells and mtDNA deletion were decreased after pre-treated with Gen (p < 0.05). Gen could also up-regulate the mRNA and protein expression of OGG1 in both C6 cells and its mitochondria and mitochondrial MnSOD compared with the Aß group (p < 0.05). These results confirmed that Gen could alleviate the mitochondria-targeted oxidative damage induced by ß-amyloid 25-35 in C6 cells which might be useful for the treatment of neurodegenerative diseases.

The effects of phytosterol supplementation on serum LDL-C levels and learning ability in mice fed a high-fat, high-energy diet from gestation onward.

A high-fat, high-energy (HFE) diet may be deleterious to the cardiovascular system and mental health. We previously reported that serum cholesterol levels and escape latency were significantly increased in mice by feeding them an HFE diet from gestation onward. In this study, we examined whether an HFE diet supplemented with phytosterols fed to pregnant C57BL/6j dams and their offspring would protect the HFE-diet-induced compromise of the offspring's learning capability. We measured serum cholesterol levels, brain N-methyl-D-aspartate receptor (NMDAR1) mRNA and protein expression and liver sterol 27-hydroxylase (Cyp27a1) mRNA expression, as well as a Morris water maze performance. The results showed that, compared to mice consuming the HFE diet alone, those also consuming phytosterols (the HFE + PS diet) significantly decreased mean serum low-density lipoprotein cholesterol levels and altered brain NMDAR1 mRNA and protein expression and liver Cyp27a1 mRNA expression. The Morris water maze experiments indicated that dietary phytosterol supplementation slightly decreased the escape latency (p = 0.07). Collectively, these observations suggest that consumption of phytosterols from early in life may help alleviate the detrimental effects of HFE diets in mice.

Role of soy lecithin combined with soy isoflavone on cerebral blood flow in rats of cognitive impairment and the primary screening of its optimum combination.

BACKGROUND/OBJECTIVES: Soy isoflavone (SIF) and soy lecithin (SL) have beneficial effects on many chronic diseases, including neurodegenerative diseases. Regretfully, there is little evidence to show the combined effects of these soy extractives on the impairment of cognition and abnormal cerebral blood flow (CBF). This study examined the optimal combination dose of SIF + SL to provide evidence for improving CBF and protecting cerebrovascular endothelial cells. MATERIALS/METHODS: In vivo study, SIF50 + SL40, SIF50 + SL80 and SIF50 + SL160 groups were obtained. Morris water maze, laser speckle contrast imaging (LSCI), and hematoxylin-eosin staining were used to detect learning and memory impairment, CBF, and damage to the cerebrovascular tissue in rat. The 8-hydroxy-2'-deoxyguanosine (8-OHdG) and the oxidized glutathione (GSSG) were detected. The anti-oxidative damage index of superoxide dismutase (SOD) and glutathione (GSH) in the serum of an animal model was also tested. In vitro study, an immortalized mouse brain endothelial cell line (bEND.3 cells) was used to confirm the cerebrovascular endothelial cell protection of SIF + SL. In this study, 50 µM of Gen were used, while the 25, 50, or 100 µM of SL for different incubation times were selected first. The intracellular levels of 8-OHdG, SOD, GSH, and GSSG were also detected in the cells. RESULTS: In vivo study, SIF + SL could increase the target crossing times significantly and shorten the total swimming distance of rats. The CBF in the rats of the SIF50 + SL40 group and SIF50 + SL160 group was enhanced. Pathological changes, such as attenuation of the endothelium in cerebral vessels were much less in the SIF50 + SL40 group and SIF50 + SL160 group. The 8-OHdG was reduced in the SIF50 + SL40 group. The GSSG showed a significant decrease in all SIF + SL pretreatment groups, but the GSH showed an opposite result. SOD was upregulated by SIF + SL pretreatment. Different combinations of Genistein (Gen)+SL, the secondary proof of health benefits found in vivo study, showed they have effective anti-oxidation and less side reaction on protecting cerebrovascular endothelial cell. SIF50 + SL40 in rats experiment and Gen50 + SL25 in cell test were the optimum joint doses on alleviating cognitive impairment and regulating CBF through protecting cerebrovascular tissue by its antioxidant activity. CONCLUSIONS: SIF+SL could significantly prevent cognitive defect induced by ß-Amyloid through regulating CBF. This kind of effect might be attributed to its antioxidant activity on protecting cerebral vessels.

Exploring cognitive trajectories and their association with physical performance: evidence from the China Health and Retirement Longitudinal Study.

OBJECTIVES: The long-term trends of cognitive function and its associations with physical performance remain unclear, particularly in Asian populations. The study objectives were to determine cognitive trajectories in middle-aged and elderly Chinese individuals, as well as to examine differences in physical performance across cognitive trajectory groups. METHODS: Data were extracted from the China Health and Retirement Longitudinal Study. A total of 5,701 participants (47.7% male) with a mean age of 57.8 (standard deviation, 8.4) years at enrollment were included. A group-based trajectory model was used to identify cognitive trajectory groups for each sex. Grip strength, repeated chair stand, and standing balance tests were used to evaluate physical performance. An ordered logistic regression model was employed to analyze differences in physical performance across cognitive trajectory groups. RESULTS: Three cognitive trajectory groups were identified for each sex: low, middle, and high. For both sexes, higher cognitive trajectory groups exhibited smaller declines with age. In the fully adjusted model, relative to the low trajectory group, the odds ratios (ORs) of better physical performance in the middle cognitive group were 1.37 (95% confidence interval [CI], 1.17 to 1.59; p<0.001) during follow-up and 1.40 (95% CI, 1.20 to 1.64; p<0.001) at the endpoint. The ORs in the high trajectory group were 1.94 (95% CI, 1.61 to 2.32; p<0.001) during follow-up and 2.04 (95% CI, 1.69 to 2.45; p<0.001) at the endpoint. CONCLUSIONS: Cognitive function was better preserved in male participants and individuals with higher baseline cognitive function. A higher cognitive trajectory was associated with better physical performance over time.

The Protective Effects of Zeaxanthin on Amyloid-ß Peptide 1-42-Induced Impairment of Learning and Memory Ability in Rats.

Background and Objectives: Zeaxanthin (ZEA) as one of the biologically active phytochemicals presents a neuroprotective effect. Since ZEA may play its anti-oxidative role in neurodegenerative diseases including Alzheimer's disease (AD), we hypothesized cognitive defects could be prevented or deferred by ZEA pre-treatment. Methods and Study Design: All the rats were randomly divided into four groups (control, Aß1-42, ZEA, and ZEA + Aß groups). Learning and memory ability of rats, cerebrovascular ultrastructure changes, the redox state, endothelin-1 (ET-1) level, and amyloid-ß peptide (Aß) level in plasma and the Aß transport receptors which are advanced glycation end products (RAGEs) and LDL receptor-related protein-1 (LRP-1) and interleukin-1ß (IL-1ß) expressions in the cerebrovascular tissue were measured in the present study. Results: The escape latency and frequency of spanning the position of platform showed significant differences between the Aß group and ZEA treatment groups. ZEA could prevent the ultrastructure changes of cerebrovascular tissue. In addition, ZEA also showed the protective effects on regulating redox state, restraining ET-1 levels, and maintaining Aß homeostasis in plasma and cerebrovascular. Moreover, the disordered expressions of RAGE and LRP-1 and IL-1ß induced by Aß1-42 could be prevented by the pre-treatment of ZEA. Conclusion: ZEA pre-treatment could prevent learning and memory impairment of rats induced by Aß1-42. This neuroprotective effect might be attributable to the anti-oxidative and anti-inflammatory effects of ZEA on maintaining the redox state and reducing the Aß level through regulating the Aß transport receptors and inflammatory cytokine of the cerebrovascular tissue.

Association between Dairy Product Intake and Risk of Fracture among Adults: A Cohort Study from China Health and Nutrition Survey.

Background: The current literature reports inconsistent associations between dairy product intake and fracture. This study assessed the association between dairy product intake and the risk of fracture among Chinese adults and examined the mediation effects of height and body mass index (BMI) on the association. Methods: Data in 1997−2015 from the China Health and Nutrition Survey were used. Dietary data were collected by a 24-hour dietary recall, and occurrences of fracture were obtained by self-report of participants. Cumulative average intake of daily dairy products was calculated by the sum of the dairy product intake and divided by the total waves of participating in the surveys before fracture. Cox proportion hazard regressions were performed to explore the associations between dairy product intake and the risk of fracture. Mediation analysis models were established to examine the mediation effects of height and BMI on the associations. Results: A total of 14,711 participants were included. Dairy product intake of 0.1−100 g/day was associated with a decreased risk of fracture, while no association was observed among participants with dairy product intake of >100 g/day. The indirect effects of dairy product intake on the fracture mediated by height and BMI were much smaller than the direct effects. Conclusions: Dairy product intake with 0.1−100 g/day is associated with a lower risk of fracture, and the association is mainly a direct result of nutrients in dairy products and much less a result of the mediation effects of height or BMI. Dairy product intake of 0.1−100 g/day might be a cost-effective measure for Chinese adults to decrease fracture incidence.

Association between dairy consumption and the risk of diabetes: A prospective cohort study from the China Health and Nutrition Survey.

Diet is closely related to the risk of diabetes; yet the relationship between dairy consumption and the risk of diabetes is unclear with conflicting evidence from previous studies. This study used data from the Chinese Health and Nutrition Survey to investigate the association between dairy consumption and diabetes. A total of 15,512 adults were included; dairy consumption at each survey was assessed by the 3-day 24-h recall and weighed food record methods, and diabetes occurrence was derived from self-reported information. The association between dairy consumption and diabetes was explored using Cox regression and further stratified with BMI and energy intake. Results indicated that 12,368 (79.7%) participants had no dairy consumption, while 2,179 (14.0%) and 947 (6.1%) consumed dairy at 0.1-100 and >100 g/day, respectively. After adjusting for potential confounders, dairy consumption of 0.1-100 g/day was associated with lower risk of diabetes in all participants (HR 0.53, 95% CI:0.38 -0.74; P < 0.001) and males (HR 0.50, 95% CI: 0.31-0.80; P = 0.004). According to the restricted cubic splines (RCS), the protective effect on diabetes was significant in the total population with dairy consumption ranging from 25 to 65 g/day (HR <1, P = 0.025). In the stratified analysis, consuming 30-80 g/day was associated with reduced diabetes risk among the ≤ 2,000 kcal/day energy intake group (HR <1, P = 0.023). In conclusion, dairy consumption was inversely associated with a reduced diabetes risk in Chinese population. Further studies are required to examine the optimal level of dairy consumption for preventing diabetes in the Chinese population.