Macronutrients modified dietary intervention in the management of overweight/obese children and adolescents: a systematic review.

The prevalence of obesity in adults and children is rapidly increasing worldwide. Obesity is among the main causes of chronic diseases and various problems, including economic consequences and they can also be affected by genetic, environmental, psychological, and socioeconomic factors. Dietary modification is a well-known and important factor in weight control, in particular, dietary macronutrient composition, food selection, dietary patterns, and energy restriction can affect weight reduction. Therefore, this systematic review aims to provide basic evidence for identifying the optimal macronutrient composition for managing obesity in Korean children and adolescents. We searched literature through an international database, studies were selected using our eligibility criteria and quality was assessed via a risk of bias tool. In our results, several studies have demonstrated that dietary macronutrient modifications affect body composition and metabolic markers in children and adolescents. In contrast, hypocaloric diets, regardless of macronutrient composition, are reportedly effective for weight loss in obese children. However, these findings were based on intervention studies that examined the association between dietary macronutrient composition and obesity in non-Korean children and adolescents. Therefore, in the future, more intervention studies are needed to elucidate this relationship and evidence between macronutrients and obesity in Korean children and adolescents.

Important roles of linoleic acid and α-linolenic acid in regulating cognitive impairment and neuropsychiatric issues in metabolic-related dementia.

Metabolic syndrome (MetS), which is characterized by insulin resistance, high blood glucose, obesity, and dyslipidemia, is known to increase the risk of dementia accompanied by memory loss and depression. The direct pathways and specific mechanisms in the central nervous system (CNS) for addressing fatty acid imbalances in MetS have not yet been fully elucidated. Among polyunsaturated acids, linoleic acid (LA, n6-PUFA) and α-linolenic acid (ALA, n3-PUFA), which are two essential fatty acids that should be provided by food sources (e.g., vegetable oils and seeds), have been reported to regulate various cellular mechanisms including apoptosis, inflammatory responses, mitochondrial biogenesis, and insulin signaling. Furthermore, inadequate intake of LA and ALA is reported to be involved in neuropathology and neuropsychiatric diseases as well as imbalanced metabolic conditions. Herein, we review the roles of LA and ALA on metabolic-related dementia focusing on insulin resistance, dyslipidemia, synaptic plasticity, cognitive function, and neuropsychiatric issues. This review suggests that LA and ALA are important fatty acids for concurrent treatment of both MetS and neurological problems.

Oligonol ameliorates liver function and brain function in the 5 × FAD mouse model: transcriptional and cellular analysis.

Alzheimer's disease (AD) is a common neurodegenerative disease worldwide and is accompanied by memory deficits, personality changes, anxiety, depression, and social difficulties. For treatment of AD, many researchers have attempted to find medicinal resources with high effectiveness and without side effects. Oligonol is a low molecular weight polypeptide derived from lychee fruit extract. We investigated the effects of oligonol in 5 × FAD transgenic AD mice, which developed severe amyloid pathology, through behavioral tests (Barnes maze, marble burying, and nestle shredding) and molecular experiments. Oligonol treatment attenuated blood glucose levels and increased the antioxidant response in the livers of 5 × FAD mice. Moreover, the behavioral score data showed improvements in anxiety, depressive behavior, and cognitive impairment following a 2-month course of orally administered oligonol. Oligonol treatment not only altered the circulating levels of cytokines and adipokines in 5 × FAD mice, but also significantly enhanced the mRNA and protein levels of antioxidant enzymes and synaptic plasticity in the brain cortex and hippocampus. Therefore, we highlight the therapeutic potential of oligonol to attenuate neuropsychiatric problems and improve memory deficits in the early stage of AD.

The Synergistic Effect of Dietary Acid Load Levels and Cigarette Smoking Status on the Risk of Chronic Obstructive Pulmonary Disease (COPD) in Healthy, Middle-Aged Korean Men.

We investigated whether cigarette smoking and dietary acid load (DAL) are associated with a risk of chronic obstructive pulmonary disease (COPD) in healthy, middle-aged Korean men. Healthy men without diagnosed chronic disease (aged 40-64 years) from the KNHANES-VI (2013-2015) were included in the analysis (n = 774) and were subdivided by smoking status and DAL levels, as estimated using the quartile of net endogenous acid production (NEAP). The current smokers tended to have a higher risk of COPD than the never-smokers before and after adjustment. When divided by the DAL quartile, the Q4 group tended to have a higher risk of COPD than the Q1 group. Additionally, the current smokers with lower (Q2), modest (Q3), and the highest NEAP scores (Q4) showed risks of COPD that were more than fourfold higher than those of the never-smokers with the lowest NEAP scores (Q1). The ex-smokers with higher NEAP scores (Q3 and Q4) showed risks of COPD that were more than fourfold higher than those of the Q1 group. Interestingly, the risk of COPD was also more than sixfold higher in the never-smokers with the highest NEAP scores compared to that in the Q1 group. The NEAP scores and smoking status synergistically increased the risk of COPD in healthy, middle-aged Korean men. This suggests that DAL levels are an important factor in the prevention and management of COPD.

The association between dietary sodium intake and obesity in adults by sodium intake assessment methods: a review of systematic reviews and re-meta-analysis.

BACKGROUND/OBJECTIVES: The scientific evidence of a sodium-obesity association is limited by sodium intake assessments. Our specific aim is to synthesize the association between dietary sodium intake and obesity across the sodium intake assessments as evidenced by systematic reviews in adults. SUBJECTS/METHODS: A systematic search identified systematic reviews comparing the association of dietary sodium intakes with obesity-related outcomes such as body mass index (BMI), body weight, waist circumference, and risk of (abdominal) obesity. We searched PubMed on October 24, 2022. To assess the Risk of Bias in Systematic Reviews (ROBIS), we employed the ROBIS tool. RESULTS: This review included 3 systematic reviews, consisting of 39 unique observational studies (35 cross-sectional studies and 4 longitudinal studies) and 15 randomized controlled trials (RCTs). We found consistently positive associations between dietary sodium intake and obesity-related outcomes in cross-sectional studies. Studies that used 24-h urine collection indicated a greater BMI for those with higher sodium intake (mean difference = 2.27 kg/m2; 95% confidence interval [CI], 1.59-2.51; P < 0.001; I2 = 77%) compared to studies that used spot urine (mean difference = 1.34 kg/m2; 95% CI, 1.13-1.55; P < 0.001; I2 = 95%) and dietary methods (mean difference = 0.85 kg/m2; 95% CI, 0.1-1.51; P < 0.05; I2 = 95%). CONCLUSIONS: Quantitative synthesis of the systematic reviews has shown that cross-sectional associations between dietary sodium intake and obesity outcomes were substantially different across the sodium intake assessments. We need more high-quality prospective cohort studies and RCTs using 24-h urine collection to examine the causal effects of sodium intake on obesity.

Minor alleles in the FTO SNPs contributed to the increased risk of obesity among Korean adults: meta-analysis from nationwide big data-based studies.

BACKGROUND/OBJECTIVES: Many studies have revealed an association between fat mass and the obesity-related gene (FTO) and obesity. On the other hand, no meta-analysis was conducted with data from only Koreans. Therefore, this study performed a meta-analysis using Korean data to provide evidence for the association between FTO single nucleotide polymorphisms (SNPs) and the risk of obesity among Korean adults. SUBJECT/METHODS: Meta-analysis was finally conducted with data extracted from seven datasets of four studies performed on Korean adults after the screening passed. Five kinds of FTO SNPs (rs9939609, rs7193144, rs9940128, rs8050136, and rs9926289) were included, and the relationship between FTO SNPs and body mass index (BMI) was investigated using linear regression with an additive model adjusted for covariants, such as age, sex, and area. RESULTS: The minor alleles of FTO SNPs were associated with increased BMI (odds ratio [OR], 1.31; 95% confidence interval [CI], 1.21-1.42). In sub-group analysis, FTO rs9939609 T>A was significantly associated with BMI (OR, 1.23; 95% CI, 1.06-1.42). The other FTO SNPs together were significantly associated with BMI (OR, 1.37; 95% CI, 1.25-1.49). The publication bias was not observed based on Egger's test. CONCLUSIONS: This meta-analysis showed that minor alleles in the FTO SNPs were significantly associated with an increased BMI among Korean adults. This meta-analysis is the first to demonstrate that minor alleles in the FTO SNPs contribute significantly to the increased risk of obesity among Korean adults using data from a Korean population.

Erratum: Effect of Breakfast Consumption and Meal Time Regularity on Nutrient Intake and Cardiometabolic Health in Korean Adults.

[This corrects the article on p. 240 in vol. 10, PMID: 34095015.].

A narrative review on the application of doubly labeled water method for estimating energy requirement for Koreans.

Research articles were reviewed to validate the estimated energy requirements (EERs) equations developed by the Institute of Medicine of the National Academies (IOM). These equations are based on total energy expenditure (TEE) measured by the doubly labeled water (DLW) method. We subsequently aimed to provide the basis for the suitability to apply the IOM equations as EER equations for Koreans, and develop relevant equations for EER in the Dietary Reference Intake for Koreans (KDRI). Additionally, besides the EER(IOM) equations, other equations were examined for EER estimation. Research papers demonstrating the validation of the EER(IOM) equations based on TEE(DLW) were searched through PubMed (up to September 2019). Of the 637 potentially relevant articles identified, duplicates and unsuitable titles and abstracts were excluded. Furthermore, papers with irrelevant subject and inappropriate study design were also excluded. Finally, 11 papers were included in the review. Among the reviewed papers, 8 papers validated the application of the EER(IOM) equations for EER based on TEE(DLW). These included 3 studies for children (USA 1, Korea 2), 1 for adolescents (Portugal), 2 for adults (Korean), and 2 for the elderly (Korea, USA). EER(IOM) equations were found to be generally acceptable for determining EER by using the DLW method, except for Korean boys at 9-11 yrs (overestimated) and female athletes at 19-24 yrs (underestimated). Additionally, 5 papers include the validation of other EER equations, beside EER(IOM) for EER based on TEE(DLW). In Japanese dietary reference intake and recommended dietary allowance, EER equations are acceptable for determining EER based on TEE(DLW). The EER(IOM) equations is generally acceptable for determining EER using the DLW method in Koreans as well as several populations, although certain defined groups were found to be unfit for the estimation. Additionally, the concept of healthy body mass index of Koreans and physical activity levels need to be considered, thereby providing the basis for developing relevant equations of EER in KDRI.

Timing of Adiposity Rebound and Determinants of Early Adiposity Rebound in Korean Infants and Children Based on Data from the National Health Insurance Service.

Adiposity rebound (AR) is defined as the second rise in the body mass index (BMI) usually occurring in early childhood. This study aimed to investigate the timing of AR and the factors determining early AR (EAR) by tracking BMI patterns using large-scale longitudinal nationwide data (n = 142,668; 73,389 boys and 69,279 girls) over seven time periods (4-6, 9-12, 18-24, 30-36, 42-48, 54-60, and 66-71 months). The average BMI rebound indicating AR was found before the age of 5 years (6th time period, 54-60 months). Interestingly, children experiencing BMI rebound during the 4th to 6th time periods showed a small increase in the proportion of underweight in the 2nd time period, but a dramatically higher proportion of underweight during the corresponding time period, similar to M-shaped patterns. In contrast, overweight or obese children in the above group showed opposite W-shaped patterns. The parameters predicting the risk of EAR are diverse for each time period by sex. Adequate breastfeeding before the age of 1 year, adequate diet, and reduced sugar-sweetened beverage consumption after the age of 1 year were important for reducing EAR. This study presents for the first time, the timing of AR and the major determinants of EAR among Korean infants and children based on large-scale nationwide data.

Short-term Effects of Eating Behavior Modification on Metabolic Syndrome-Related Risks in Overweight and Obese Korean Adults.

Background: We investigated whether eating behavior modification improves metabolic syndrome (MetS)-related risks in overweight/obese Korean adults, and identified dietary factors that improve metabolic status. Methods: Among 159 volunteers, 71 with a body mass index ≥23 kg/m2 and without other chronic diseases participated in the 8-week intervention, among which 54 participants who completed the intervention were included in the analyses. At baseline, patients were categorized either metabolically healthy obese (MHO; <3 MetS risk factors, n=42) or metabolically unhealthy obese (MUHO; ≥3 MetS risk factors, n=12), and then educated regarding how to choose healthy foods and meals. Results: Lipid profiles and anthropometric and glycemic parameters were significantly improved among all participants after the intervention. Changes in waist circumference (P= 0.025), and glycemic parameters (glucose, P=0.046, insulin, P=0.005, C-peptide, P=0.041) were positively correlated with changes in calorie intake from snacks. Changes in visceral fat area were negatively correlated with changes in total calorie intake (P=0.046), and positively correlated with those in calorie intake from dietary fats (P=0.039). In addition, changes in insulin (P=0.013) and C-peptide (P=0.008) concentrations were negatively correlated with changes in dietary fiber intake at dinner. After the intervention, 83.3% of initially MUHO participants became MHO and 16.7% of MHO participants became MUHO. Conclusion: Eating behavior modification may be an important strategy to improve metabolic factors in overweight/obese people.

A new paradigm in sarcopenia: Cognitive impairment caused by imbalanced myokine secretion and vascular dysfunction.

Sarcopenia characterized by reduced skeletal muscle mass and decreased muscle strength is increasing in prevalence globally. The pathophysiology of sarcopenia is related to various factors including hormonal imbalance, increased intracellular oxidative stress, reduction of food intake, advanced age, low body mass index, and low physical activity. Recently, sarcopenia has been reported to be associated with cognitive decline, and the common risk factors between sarcopenia and memory loss were observed in cohort studies. Many researchers suggested that the prevalence of sarcopenia is associated with vascular disorder, such as atherosclerosis and alteration of intracellular mechanisms caused by changes in myokine secretion. We herein review the emerging evidence on the strong link between cognitive impairment and sarcopenia, focusing on myokine secretion and vascular dysfunction, and provide an understanding of the relevant mechanisms and crucial determinants in cognitive decline caused by sarcopenia.

Role of ketone bodies in diabetes-induced dementia: sirtuins, insulin resistance, synaptic plasticity, mitochondrial dysfunction, and neurotransmitter.

Patients with type 2 diabetes can have several neuropathologies, such as memory deficits. Recent studies have focused on the association between metabolic imbalance and neuropathological problems, and the associated molecular pathology. Diabetes triggers neuroinflammation, impaired synaptic plasticity, mitochondrial dysfunction, and insulin resistance in the brain. Glucose is a main energy substrate for neurons, but under certain conditions, such as fasting and starvation, ketone bodies can be used as an energy fuel for these cells. Recent evidence has shed new light on the role of ketone bodies in regulating several anti-inflammation cellular pathways and improving glucose metabolism, insulin action, and synaptic plasticity, thereby being neuroprotective. However, very high amount of ketone bodies can be toxic for the brain, such as in ketoacidosis, a dangerous complication that may occur in type 1 diabetes mellitus or alcoholism. Recent findings regarding the relationship between ketone bodies and neuropathogenesis in dementia are reviewed in this article. They suggest that the adequately low amount of ketone bodies can be a potential energy source for the treatment of diabetes-induced dementia neuropathology, considering the multifaceted effects of the ketone bodies in the central nervous system. This review can provide useful information for establishing the therapeutic guidelines of a ketogenic diet for diabetes-induced dementia.

Relationship between Adipose Tissue Derived Hormones and Cardiometabolic Risk according to Obesity Status.

Adiponectin, and leptin are adipose tissue derived hormones affecting metabolic status. This study aimed to investigate the relationship between circulating adiponectin and leptin levels, and cardiometabolic parameters by obesity status among healthy women without metabolic disease. Finally 141 participants were included in the analyses and categorized into three groups by their body mass index (kg/m2) (normal weight: 18.5 ≤ body mass index [BMI] < 23.0, n=65; overweight: 23.0 ≤ BMI < 25.0, n=26; obesity: 25.0 ≤ BMI, n=50). Overweight and obesity groups were older, and had significantly higher levels of adiposity, blood pressure, fasting glucose, triglyceride, and high sensitivity C-reactive protein (hs-CRP), and lower levels of high density lipoprotein (HDL)-cholesterol than normal weight group. Circulating leptin levels, and leptin to adiponectin ratio were highest in obesity group, but circulating adiponectin levels were not statistically different among the three groups. Circulating leptin levels were negatively correlated with adiponectin levels, and leptin to adiponectin ratio. In addition, leptin levels were positively correlated with waist circumference, systolic blood pressure, insulin resistance, and hs-CRP, and negatively with HDL-cholesterol. However, circulating adiponectin levels were negatively correlated only with waist circumference, and hs-CRP. These patterns were retained after adjusted for confounding factors such as age, smoking and drinking habits, menopausal status and total calorie intake. In conclusion, circulating adiponectin and leptin levels according to obesity status were differently observed among healthy women, and circulating leptin levels may be a more sensitive parameter for cardiometabolic risk in healthy women.

Effect of Breakfast Consumption and Meal Time Regularity on Nutrient Intake and Cardiometabolic Health in Korean Adults.

OBJECTIVE: Dietary factors are important contributors to obesity and related metabolic disorders. Few studies have evaluated the impact of dietary habits (e.g., breakfast consumption frequency and meal regularity) on metabolic health. We investigated the effects of breakfast consumption frequency and meal time regularity on nutrient intake and cardiometabolic status in Korean adults. METHODS: Participants without diagnosed diseases (n=217) were examined for anthropometric and biochemical parameters, lifestyle, dietary habits, and nutrient intake. They were categorized into 4 groups by breakfast consumption frequency (≥6 or <6 times/week) and meal time regularity (regular or irregular): breakfast ≥6 times/week and regular eating (HBRE), breakfast ≥6 times/week and irregular eating (HBIE), breakfast <6 times/week and regular eating (LBRE) and breakfast <6 times/week and irregular eating (LBIE). RESULTS: Participants in the LBIE group were the youngest, had higher waist circumference, body mass index, triglyceride levels, and inflammation, and consumed the highest daily total caloric intake (TCI), the highest proportion of fats, and the lowest proportion of carbohydrates. The LBIE group also had the lowest proportion of energy intake at breakfast and the highest proportion at dinner. The LBIE group consumed the lowest amounts of fiber, beta-carotene, vitamin K, folate, calcium and iron, and had the highest prevalence of inadequate nutrient intake for TCI, protein, vitamins A, C, B6, and B12, folate, calcium, iron, zinc, and copper. CONCLUSION: Regular breakfast consumption and meal times are related to healthy lifestyle habits and adequate nutrient intake, which affect metabolic health, thereby helping prevent obesity and related metabolic disorders.

XGBoost based machine learning approach to predict the risk of fall in older adults using gait outcomes.

This study aimed to identify the optimal features of gait parameters to predict the fall risk level in older adults. The study included 746 older adults (age: 63-89 years). Gait tests (20 m walkway) included speed modification (slower, preferred, and faster-walking) while wearing the inertial measurement unit sensors embedded in the shoe-type data loggers on both outsoles. A metric was defined to classify the fall risks, determined based on a set of questions determining the history of falls and fear of falls. The extreme gradient boosting (XGBoost) model was built from gait features to predict the factor affecting the risk of falls. Moreover, the definition of the fall levels was classified into high- and low-risk groups. At all speeds, three gait features were identified with the XGBoost (stride length, walking speed, and stance phase) that accurately classified the fall risk levels. The model accuracy in classifying fall risk levels ranged between 67-70% with 43-53% sensitivity and 77-84% specificity. Thus, we identified the optimal gait features for accurate fall risk level classification in older adults. The XGBoost model could inspire future works on fall prevention and the fall-risk assessment potential through the gait analysis of older adults.

Circulating GLP-1 Levels as a Potential Indicator of Metabolic Syndrome Risk in Adult Women.

Glucagon-like peptide-1 (GLP-1), an incretin hormone, plays an important role in regulating glucose homeostasis. In this study, the applicability of circulating GLP-1 levels as an early indicator of metabolic syndrome (MetS) risk was examined. Women without diagnosed diseases were grouped according to their number of MetS risk factors (MetS RFs) (no RFs as Super-healthy, n = 61; one or two RFs as MetS risk carriers, n = 60; 3 ≤ RFs as MetS, n = 19). The circulating GLP-1 levels and homeostasis model assessment insulin resistance (HOMA-IR) scores were significantly higher in the MetS group than in the other two groups. The GLP-1 levels correlated positively with adiposity, HOMA-IR, blood pressure, and high sensitivity C-reactive protein (hs-CRP), but not with fasting glucose and lipid profiles, whose significances were maintained after adjustments for age, smoking and drinking habits, menopausal status, and total calorie intake. The GLP-1 levels also increased proportionally with the number of MetS RFs. In the MetS group, the GLP-1 levels were much higher in individuals with obesity (body mass index ≥ 25 kg/m2). In conclusion, the circulating GLP-1 level may be applicable as a potential early indicator of MetS risk in women without diagnosed diseases. Further study with a large population is needed to confirm the conclusion.

Role of Adiponectin and Brain Derived Neurotrophic Factor in Metabolic Regulation Involved in Adiposity and Body Fat Browning.

Obesity, characterized by excessive fat mass, has been emerging as a major global epidemic and contributes to the increased risk of morbidity around the world. Thus, the necessity to find effective therapy and specific regulatory mechanisms is increasing for controlling obesity. Lately, many researchers have been interested in the linkage between obesity and adipokines/myokines, particularly adiponectin and brain-derived neurotrophic factor (BDNF). However, the role of adiponectin and BDNF in adiposity has not been clearly defined yet. We examined the association of adiposity with adiponectin and BDNF through human study (observational study) with Korean women and in vitro experiments. In the human study, we found a negative relationship between adiposity and circulating adiponectins but irregular patterns in the relationship between adiposity and circulating BDNFs. In the in vitro study using 3T3-L1 adipocytes, adiponectin treatment strongly promoted adipocyte differentiation and the fat browning process, whereas BDNF treatment attenuated adipocyte differentiation and the fat browning process in differentiated adipocytes. Our results demonstrate that adiponectin and BDNF play an important role in regulating fat mass and the expression of fat-browning markers in different ways, and also suggest that circulating adiponectin may be used as an important monitoring index for obesity status.

Impacts of Dietary Macronutrient Pattern on Adolescent Body Composition and Metabolic Risk: Current and Future Health Status-A Narrative Review.

Obesity, particularly in childhood and adolescence, is one of the serious public health problems worldwide. According to the World Health Organization, 10% of young people aged 5-17 years are obese, which is rapidly increasing around the world. Furthermore, approximately 80% of adolescents who become obese develop bodyweight-related health problems in adulthood. Eating habits and lifestyles play important roles in forming body composition and metabolic status. Changes in body composition in adolescence, the period in which secondary sex characteristics begin to develop, can alter hormonal and metabolic status, can consequently affect health status and the risk of developing chronic diseases in adulthood, and moreover may have an impact on probable body composition and metabolic status in the next generation. Here, we reviewed cross-sectional and interventional studies to analyze the role of dietary patterns focusing on macronutrient intake in growth, body composition, and metabolic changes in adolescents. These findings provide insights into optimal dietary guidelines for healthy growth with accretion of adequate body composition in adolescence, and provide an effective strategy for preventing and managing the risk of obesity-related metabolic disease in adulthood, with the additional benefit of providing potential benefits for the next generation's health.

Alleviation of Depression by Glucagon-Like Peptide 1 Through the Regulation of Neuroinflammation, Neurotransmitters, Neurogenesis, and Synaptic Function.

Depression has emerged as a major cause of mortality globally. Many studies have reported risk factors and mechanisms associated with depression, but it is as yet unclear how these findings can be applied to the treatment and prevention of this disorder. The onset and recurrence of depression have been linked to diverse metabolic factors, including hyperglycemia, dyslipidemia, and insulin resistance. Recent studies have suggested that depression is accompanied by memory loss as well as depressive mood. Thus, many researchers have highlighted the relationship between depressive behavior and metabolic alterations from various perspectives. Glucagon-like peptide-1 (GLP-1), which is secreted from gut cells and hindbrain areas, has been studied in metabolic diseases such as obesity and diabetes, and was shown to control glucose metabolism and insulin resistance. Recently, GLP-1 was highlighted as a regulator of diverse pathways, but its potential as the therapeutic target of depressive disorder was not described comprehensively. Therefore, in this review, we focused on the potential of GLP-1 modulation in depression.

The importance of BDNF and RAGE in diabetes-induced dementia.

Diabetes-induced dementia is an emerging neurodisorder all over the world. The prevalence rates of dementia and diabetes have been gradually increasing worldwide. Diabetes has been known to lead to oxidative stress, inflammation aggravation, and hyperglycemia conditions in the brain. Various diabetic implications cause the lower secretion of brain-derived neurotrophic factor (BDNF) and the increase of receptor for advanced glycation end products (RAGE), ultimately leading to both cerebrovascular dysfunction and cognitive decline. Here, we summarized the significant evidences highlighting the specific mechanisms between BDNF and RAGE and cerebrovascular dysfunction and memory function and how these relate to diabetes-induced dementia. Especially, we review that the association between BDFN and RAGE in neuroinflammation, the reduction of long-term potentiation, and the vascular implications in brain.