Hearing Loss is Associated With Risk of Alzheimer’s Disease: A Case-Control Study in Older People

Background

It remains unknown whether hearing loss increases the risk of Alzheimer’s disease. This study aimed to examine the association between hearing loss and risk of Alzheimer’s disease in older people in Taiwan.

Methods

Analyzing the database from Taiwan’s National Health Insurance Program, this case-control study enrolled 488 subjects ≥65 years old with newly diagnosed Alzheimer’s disease as a case group and 1952 subjects without Alzheimer’s disease as a control group from 1998–2011. Patients with Alzheimer’s disease and other comorbidities were identified by analyzing ICD-9 coding in claims data. The association of hearing loss, other comorbidities, and risk of Alzheimer’s disease were compared between groups.

Results

After controlling for confounders, multivariable logistic regression showed an adjusted odds ratio of Alzheimer’s disease of 1.39 in people with hearing loss (95% CI, 1.05–1.84) versus those without. Parkinson’s disease (OR 4.44; 95% CI, 2.54–7.78), head injury (OR 2.31; 95% CI, 1.46–3.66), depression (OR 1.68; 95% CI, 1.19–2.39), hypertension (OR 1.40; 95% CI, 1.10–1.79), and age (each year, OR 1.03; 95% CI, 1.01–1.05) also showed strong links with Alzheimer’s.

Conclusions

Hearing loss is associated with increased risk of Alzheimer’s disease in older people in Taiwan.Key words: Alzheimer’s disease, head injury, depression, hearing loss, Parkinson’s disease     

Nutritional Therapy Strategies in Pediatric Crohn’s Disease

The increase in incidences of pediatric Crohn’s Disease (CD) worldwide has been strongly linked with dietary shifts towards a Westernized diet, ultimately leading to altered gut microbiota and disturbance in intestinal immunity and the metabolome. Multiple clinical studies in children with CD have demonstrated the high efficacy of nutritional therapy with exclusive enteral nutrition (EEN) to induce remission with an excellent safety profile. However, EEN is poorly tolerated, limiting its compliance and clinical application. This has spiked an interest in the development of alternative and better-tolerated nutritional therapy strategies. Several nutritional therapies have now been designed not only to treat the nutritional deficiencies seen in children with active CD but also to correct dysbiosis and reduce intestinal inflammation. In this review, we report the most recent insights regarding nutritional strategies in children with active CD: EEN, partial enteral nutrition (PEN), Crohn’s disease exclusion diet (CDED), and CD treatment-with-eating diet (CD-TREAT). We describe their setup, efficacy, safety, and (dis)advantages as well as some of their potential mechanisms of action and perspectives. A better understanding of different nutritional therapeutic options and their mechanisms will yield better and safer management strategies for children with CD and may address the barriers and limitations of current strategies in children.     

Administration of Bifidobacterium breve Improves the Brain Function of Aβ1-42-Treated Mice via the Modulation of the Gut Microbiome

Psychobiotics are used to treat neurological disorders, including mild cognitive impairment (MCI) and Alzheimer’s disease (AD). However, the mechanisms underlying their neuroprotective effects remain unclear. Herein, we report that the administration of bifidobacteria in an AD mouse model improved behavioral abnormalities and modulated gut dysbiosis. Bifidobacterium breve CCFM1025 and WX treatment significantly improved synaptic plasticity and increased the concentrations of brain-derived neurotrophic factor (BDNF), fibronectin type III domain-containing protein 5 (FNDC5), and postsynaptic density protein 95 (PSD-95). Furthermore, the microbiome and metabolomic profiles of mice indicate that specific bacterial taxa and their metabolites correlate with AD-associated behaviors, suggesting that the gut–brain axis contributes to the pathophysiology of AD. Overall, these findings reveal that B. breve CCFM1025 and WX have beneficial effects on cognition via the modulation of the gut microbiome, and thus represent a novel probiotic dietary intervention for delaying the progression of AD.     

Copper-2 Ingestion,Plus Increased Meat Eating Leading to Increased Copper Absorption,Are Major Factors Behind the Current Epidemic of Alzheimer’s Disease

It has become clear that copper toxicity is playing a major role in Alzheimer’s disease; but why is the brain copper toxicity with cognition loss in Alzheimer’s disease so much different clinically than brain copper toxicity in Wilson’s disease, which results in a movement disorder? Furthermore, why is the inorganic copper of supplement pills and in drinking water so much more damaging to cognition than the organic copper in food? A recent paper, which shows that almost all food copper is copper-1, that is the copper-2 of foods reverts to the reduced copper-1 form at death or harvest, gives new insight into these questions. The body has an intestinal transport system for copper-1, Ctr1, which channels copper-1 through the liver and into safe channels. Ctr1 cannot absorb copper-2, and some copper-2 bypasses the liver, ends up in the blood quickly, and is toxic to cognition. Humans evolved to handle copper-1 safely, but not copper-2. Alzheimer’s is at least in part, a copper-2 toxicity disease, while Wilson’s is a general copper overload disease. In this review, we will show that the epidemiology of the Alzheimer’s epidemic occurring in developed, but not undeveloped countries, fits with the epidemiology of exposure to copper-2 ingestion leached from copper plumbing and from copper supplement pill ingestion. Increased meat eating in developed countries is also a factor, because it increases copper absorption, and thus over all copper exposure.     

Nutrigenomic Studies on the Ameliorative Effect of Enzyme-Digested Phycocyanin in Alzheimer’s Disease Model Mice

Alzheimer’s disease (AD) is the most common form of dementia, and the cognitive impairments associated with this degenerative disease seriously affect daily life. Nutraceuticals for the prevention or delay of AD are urgently needed. It has been increasingly observed that phycocyanin (PC) exerts neuroprotective effects. AD model mice intracerebroventricularly injected with amyloid beta-peptide 25–35 (Aβ_25–35) at 10 nmol/head displayed significant cognitive impairment in the spontaneous alternation test. Cognitive impairment was significantly ameliorated in mice treated with 750 mg/kg of enzyme-digested (ED) PC by daily oral administration for 22 consecutive days. Application of DNA microarray data on hippocampal gene expression to nutrigenomics studies revealed that oral EDPC counteracted the aberrant expression of 35 genes, including Prnp, Cct4, Vegfd (Figf), Map9 (Mtap9), Pik3cg, Zfand5, Endog, and Hbq1a. These results suggest that oral administration of EDPC ameliorated cognitive impairment in AD model mice by maintaining and/or restoring normal gene expression patterns in the hippocampus.     

Fatty Acid Metabolism in Carriers of Apolipoprotein E Epsilon 4 Allele: Is It Contributing to Higher Risk of Cognitive Decline and Coronary Heart Disease?

Apolipoprotein E (ApoE) is a protein playing a pivotal role in lipid homeostasis since it regulates cholesterol, triglyceride and phospholipid metabolism in the blood and the brain. APOE gene regulates the expression of this protein and has three different alleles: ε2, ε3 and ε4. Carrying an APOE4 allele is recognised as a genetic risk factor of late-onset Alzheimer’s disease (LOAD) and coronary heart disease (CHD). Consuming fatty fish, rich in long chain omega-3 fatty acids (LC omega-3), seems to be associated with risk reduction of developing LOAD and CHD but this link seems not to hold in APOE4 carriers, at least in LOAD. In CHD trials, APOE4 carriers supplemented with LC omega-3 were categorized as differential responders to the treatment with regards to CHD risk markers. This is potentially because fatty acid metabolism is disturbed in APOE4 carriers compared to the non-carriers. More specifically, homeostasis of LC omega-3 is disrupted in carriers of APOE4 allele and this is potentially because they β-oxidize more LC omega-3 than the non-carriers. Therefore, there is a potential shift in fatty acid selection for β-oxidation towards LC omega-3 which are usually highly preserved for incorporation into cell membranes.     

Adherence to COVID-19 Nutrition Guidelines Is Associated with Better Nutritional Management Behaviors of Hospitalized COVID-19 Patients

Good nutritional support is crucial for the immune system to fight against coronavirus disease 2019 (COVID-19). However, in the context of a pandemic with a highly transmissible coronavirus, implementation of nutrition practice may be difficult. A multicenter electronic survey involving 62 dieticians was conducted, in order to understand barriers associated with dieticians’ adherence to nutrition guidelines for hospitalized COVID-19 patients in Indonesia. 69% of dieticians felt under stress when performing nutrition care, and 90% took supplements to boost their own immunity against the coronavirus. The concerns related to clinical practice included a lack of clear guidelines (74%), a lack of access to medical records (55%), inadequate experience or knowledge (48%), and a lack of self-efficacy/confidence (29%) in performing nutritional care. Half (52%) of the dieticians had performed nutrition education/counseling, 47% had monitored a patient’s body weight, and 76% had monitored a patient’s dietary intake. An adjusted linear regression showed that guideline adherence independently predicted the dieticians’ nutrition care behaviors of nutrition counselling (ß: 0.24 (0.002, 0.08); p = 0.04), and monitoring of body weight (ß: 0.43 (0.04, 0.11); p = 0.001) and dietary intake (ß: 0.47(0.03, 0.10); p = 0.001) of COVID-19 patients. Overall, adherence to COVID-19 nutrition guidelines is associated with better nutritional management behaviors in hospitalized COVID-19 patients.     

Effects of Supplementation with Folic Acid and Its Combinations with Other Nutrients on Cognitive Impairment and Alzheimer’s Disease: A Narrative Review

Cognitive impairment and Alzheimer’s Disease, among other cognitive dysfunctions, has been recognized as a major public health problem. Folic acid is a well-known essential nutrient whose deficiency has been linked to neurocognitive dysfunctions, owing to hyperhomocysteinemia, an independent risk factor for cardio- and cerebrovascular diseases, including cognitive impairment, Alzheimer’s Disease, and vascular dementia. However, to date, there is certain controversy about the efficacy of vitamin supplementation in patients with these pathologies. Therefore, we have reviewed the available dietary intervention studies based on folic acid, either alone or in combination with different vitamins or nutrients into the progression of Alzheimer’s Disease and Cognitive impairment, highlighting the cognition and biochemical markers employed for the evaluation of the disease progression. Undeniably, the compiled information supports the potential benefits of vitamin supplementation in these pathologies, especially relevant to the aging process and quality of life, although more research is urgently needed to confirm these positive findings.     

Dopamine Transporter Genetic Variants and Pesticides in Parkinson’s Disease

Background

Research suggests that independent and joint effects of genetic variability in the dopamine transporter (DAT) locus and pesticides may influence Parkinson’s disease (PD) risk.

Materials

Methods: In 324 incident PD patients and 334 population controls from our rural California case–control study, we genotyped rs2652510, rs2550956 (for the DAT 5′ clades), and the 3′ variable number of tandem repeats (VNTR). Using geographic information system methods, we determined residential exposure to agricultural maneb and paraquat applications. We also collected occupational pesticide use data. Employing logistic regression, we calculated odds ratios (ORs) for clade diplotypes, VNTR genotype, and number of susceptibility (A clade and 9-repeat) alleles and assessed susceptibility allele–pesticide interactions.

Results

PD risk was increased separately in DAT A clade diplotype carriers [AA vs. BB: OR = 1.66; 95% confidence interval (CI), 1.08–2.57] and 3′ VNTR 9/9 carriers (9/9 vs. 10/10: OR = 1.8; 95% CI, 0.96–3.57), and our data suggest a gene dosing effect. Importantly, high exposure to paraquat and maneb in carriers of one susceptibility allele increased PD risk 3-fold (OR = 2.99; 95% CI, 0.88–10.2), and in carriers of two or more alleles more than 4-fold (OR = 4.53; 95% CI, 1.70–12.1). We obtained similar results for occupational pesticide measures.

Discussion

Using two independent pesticide measures, we a) replicated previously reported gene–environment interactions between DAT genetic variants and occupational pesticide exposure in men and b) overcame previous limitations of nonspecific pesticide measures and potential recall bias by employing state records and computer models to estimate residential pesticide exposure.

Conclusion

Our results suggest that DAT genetic variability and pesticide exposure interact to increase PD risk.     

Genetic Evidence Supporting Fibroblast Growth Factor 21 Signalling as a Pharmacological Target for Cardiometabolic Outcomes and Alzheimer’s Disease

Fibroblast growth factor 21 (FGF21) is a human metabolic hormone whose effects include modification of macronutrient preference and energy homeostasis. In animal models, FGF21 has been shown to have beneficial effects on cardiometabolic outcomes, Alzheimer’s disease risk and lifespan. In this study, the single-nucleotide polymorphism rs838133 in the FGF21 gene region was leveraged to investigate the potential clinical effects of targeting FGF21. The FGF21 G allele was associated with lower intakes of total sugars and alcohol, and higher intakes of protein and fat as well as favourable with lipid levels, blood pressure traits, waist-to-hip ratio, systemic inflammation, cardiovascular outcomes, Alzheimer’s disease risk and lifespan. These findings may be used to anticipate the effects of pharmacologically increasing FGF21 signalling.     

Are Nutritional Patterns among Polish Hashimoto Thyroiditis Patients Differentiated Internally and Related to Ailments and Other Diseases?

There is not any diet recommended for Hashimoto’s disease, despite that those patients are often undernourished. Because of the high heterogeneity of Hashimoto’s patients, insight into dietary patterns might shed some light on the patient-tailored dietary approach, thus improving their treatment and helping to identify patients with the highest probability of particular nutritional deficiencies. The aim of this study was to identify Hashimoto’s patients’ dietary patterns and their characterization based on both socio-demographic variables and dietary self-assessment. We collected data online from patients with Hashimoto’s disease. The questionnaire formula used in the study was developed based on a validated food frequency questionnaire KomPAN^®. K-means pattern analyses were used to characterize patients into patterns based on the frequency of particular types of foods consumption and socio-demographic factors. Four patterns were identified. We labeled them as ‘Convenient’, ‘Non-meat’, ‘Pro-healthy’, and ‘Carnivores’ with participants proportions at approximately one-fourth per each pattern. The patients were mainly of the female gender (94.08%), with a female: male ratio of 15.9. Hashimoto’s patients differed in their food product choices, food choice motives, dieting experience, nutritional knowledge, smoking habits, food allergies and intolerances, and lipid disorders, and thus represent different eating patterns. However, these patterns were not determined by comorbidities or the majority of ailments.     

Microbiome Associations of Therapeutic Enteral Nutrition

One of the most effective forms of therapeutic enteral nutrition is designated as “exclusive enteral nutrition” (EEN). EEN constitutes the monotonous enteral delivery of complete liquid nutrition and has been most explored in the treatment Crohn’s disease (CD), a form of inflammatory bowel disease. While EEN’s mechanisms of action are not clearly understood, it has been shown to modify the composition of the intestinal microbiome, an important component of CD pathogenesis. The current literature on the intestinal microbiome in healthy individuals and CD patients is reviewed with respect to EEN therapy. Further investigations in this field are needed to better understand the role and potential for EEN in chronic human disorders.     

Nutrition, démences vasculaires et maladie d’Alzheimer

Approximately 770,000 persons in France suffer from dementia. Alzheimer’s disease is the most frequent cause of dementia, followed by the vascular and mixed forms of dementia. In mixed dementia, the vascular lesions contribute to the severity of the cognitive impairment linked to neurodegenerative lesions. In fact, although the prevalence of cerebrovascular disease and Alzheimer’s disease are both high, some data suggest that their association is not fortuitous. Some vascular risk factors, that also represent risk factors for the development of dementia, are liable to be modified, and especially by nutrition. The question is to what extent nutritional factors may de implicated in the risk of developing dementia, and thus to estimate the possibility of modulating this risk by environmental measures. Cognitively impaired patients lose weight and present many nutritional deficiencies, but transversal studies do not allow to establish a causal link between nutrition and the risk of developing dementia. Longitudinal and cohort studies show an association between diabetes, hyperhomocysteinemia, hypercholesterolemia, low intake in n-3 fatty acids and oxidative stress and the risk of dementia. These nutritional factors contribute to the process of atherosclerosis, but also seem implicated in the physiopathology of neurodegenerative lesions by complex mechanisms. On the whole, few interventional studies have been conducted. Only these studies will help propose specific nutritional recommendations for the prevention of the risk of dementia, and/or to develop a new therapeutic approach. Meanwhile, the priority seems to prevent vascular risk factors, in accordance with the objectives of the Programme National Nutrition et Santé.     

Graptopetalum paraguayense Extract Ameliorates Proteotoxicity in Aging and Age-Related Diseases in Model Systems

Declines in physiological functions are the predominant risk factors for age-related diseases, such as cancers and neurodegenerative diseases. Therefore, delaying the aging process is believed to be beneficial in preventing the onset of age-related diseases. Previous studies have demonstrated that Graptopetalum paraguayense (GP) extract inhibits liver cancer cell growth and reduces the pathological phenotypes of Alzheimer’s disease (AD) in patient IPS-derived neurons. Here, we show that GP extract suppresses β-amyloid pathology in SH-SYS5Y-APP₆₉₅ cells and APP/PS1 mice. Moreover, AMP-activated protein kinase (AMPK) activity is enhanced by GP extract in U87 cells and APP/PS1 mice. Intriguingly, GP extract enhances autophagy in SH-SYS5Y-APP₆₉₅ cells, U87 cells, and the nematode Caenorhabditis elegans, suggesting a conserved molecular mechanism by which GP extract might regulate autophagy. In agreement with its role as an autophagy activator, GP extract markedly diminishes mobility decline in polyglutamine Q35 mutants and aged wild-type N2 animals in C. elegans. Furthermore, GP extract significantly extends lifespan in C. elegans.     

Association between the Sociodemographic Characteristics of Parents with Health-Related and Lifestyle Markers of Children in Three Different Spanish-Speaking Countries: An Inter-Continental Study at OECD Country Level

The purpose of this cross-cultural study was to determine the association between the sociodemographic background of a child’s parents (i.e., their socioeconomic level, marital status, and educational level) with the child’s lifestyle (i.e., Mediterranean diet (MD), physical activity (PA) and screen time (ST)), and health markers. Material: This cross-sectional study included 1273 children, from Chile (n = 496), Colombia (n = 340), and Spain (n = 437). The sociodemographic information together with the lifestyle and health markers of the children were measured. There was an inverse association between a low or medium-low socioeconomic level for the parents of Chilean children and handgrip strength (β −0.61, p < 0.001); meanwhile, for Spanish children, an inverse association between a low or medium-low socioeconomic level and PA after school (β −0.58, p = 0.016), lifestyle (β −0.74, p = 0.015), and with MD adherence (β −0.86, p = 0.004) was found. The risk (i.e., by odd ratios (OR)) of being divorced/separated parents marital status showed an inverse association with abdominal obesity (OR 0.21, p = 0.045) in Spanish children; however, the parent’s marital status and a low educational level were risk factors for the suffering of a low nutritional level in Colombian children (OR 2.02, p = 0.048; OR 2.49, p < 0.001, respectively). On the other hand, a low educational level for parents reported for Chilean children had a positive association with ST of ≥4 h per day (OR 1.82, p = 0.020). In conclusion, in Spanish-speaking children, the lifestyle and health markers of the children are affected by the sociodemographic background of their parents; however, these effects could be moderated by the socio-cultural and economic status of their countries as members of the OCDE; therefore, it is essential to develop policies that decrease these gaps, so that children who are under-resourced can reach their full potential.     

Trends and Urban-Rural Disparities of Energy Intake and Macronutrient Composition among Chinese Children: Findings from the China Health and Nutrition Survey (1991 to 2015)

The nutrition status of children is gaining more attention with a rapid nutrition transition. This study aimed to investigate trends and urban-rural differences in dietary energy and macronutrient composition among Chinese children. A total of 7565 participants aged 6 to 17 years were obtained from three rounds (1991, 2004 and 2015) of the Chinese Health and Nutrition Survey (CHNS). The individual diet was evaluated via three consecutive 24-hour dietary recalls and compared with the Chinese Dietary Reference Intakes (DRIs). From 1991 to 2015, there was a significant increase in children’s fat intake, the proportion of energy intake from fat, and the proportion of children with more than 30% of energy from fat and less than 50% of energy from carbohydrates (p < 0.001). Compared with the DRI, the proportion with higher fat and lower carbohydrate intakes were, respectively, 64.7% and 46.8% in 2015. The urban-rural disparities in fat and carbohydrate intake gradually narrowed, while the gap in protein intake increased notably over time (p < 0.001). Chinese children experienced a rapid transformation to a low-carbohydrate and high-fat diet. Urban-rural disparities persistently existed; further nutritional interventions and education were of great significance, so as to ensure a more balanced diet for Chinese children.     

Clinical and Nutritional Impact of a Semi-Elemental Hydrolyzed Whey Protein Diet in Patients with Active Crohn’s Disease: A Prospective Observational Study

Background: Malnourishment is a common complication in patients with Crohn’s disease. Methods: An observational, prospective study was conducted to assess the nutritional status, disease activity, and stool frequency at baseline and after 12 weeks of treatment with a semi-elemental diet in patients with active Crohn’s disease. Results: A total of 144 patients with Crohn’s disease were included. The nutritional status improved after treatment, resulting in 76.1% of patients at low risk of malnourishment, 20.4% moderately malnourished, and 8.5% severely malnourished after 12 weeks of treatment. Nutritional status improvement was associated with the number of nutritional supplements. Mean albumin levels and body mass index (BMI) improved after 12 weeks of nutritional treatment (from 3.0 g/dL to 3.7 g/dL and from 20.2 kg/m² to 21.1 kg/m², respectively). A significant decrease in HBI was found after 12 weeks of nutritional treatment (from 10.2 to 3.7). The mean number of stools per day decreased with the 12 week semi-elemental diet (from 4.6 stools/day to 1.7 stools/day). Conclusion: In this observational study, the semi-elemental diet seemed effective in improving the nutritional status, disease activity, and stool frequency in patients with active Crohn’s disease.     

The Outcome of COVID-19 Lockdown on Changes in Body Mass Index and Lifestyle among Croatian Schoolchildren: A Cross-Sectional Study

Globally, the COVID-19 pandemic altered adults’ and children’s lifestyles and habits, causing an increase in body weight. Adolescents are sensitive to habit changes and, because of their insufficient capacity to deal with the unexpected COVID-19 changes, were at greater risk of noncommunicable disease development due to the consequences of adopting unhealthy habits. The survey aimed to reveal the changes in nutritional status and lifestyle habits of school children in Croatia and to assess their nutrition knowledge and emotional state and feelings about COVID-19 lockdown. Self-reported data from 1370 school children aged 10 to 15 years were obtained to examine the influence of the lockdown on their nutritional status, lifestyle and emotional status, and to assess their nutrition knowledge. The study revealed that the COVID-19 lockdown has caused an increase in the proportion of overweight and obesity among Croatian school children who changed their lifestyle habits towards being less physically active, spending more time using screen-based media and revealing potential psychological distress. However, the schoolchildren had a high adherence to the Mediterranean diet assessed with the Mediterranean Diet Quality Index for children and adolescents (KIDMED) index and had good nutrition knowledge. Public health programs promoting a healthy lifestyle and involving the whole family, in a school environment, could provide children with a healthy adulthood.     

The Modification of the Gut Microbiota via Selected Specific Diets in Patients with Crohn’s Disease

Gastrointestinal symptoms in Crohn’s disease (CD) are common and affect the quality of life of patients; consequently, a growing number of studies have been published on diet interventions in this group. The role of the gut microbiota in the pathogenesis and the progression of inflammatory bowel diseases (IBD), including CD, has been widely discussed. Mainly, a decreased abundance of Firmicutes, species of the Bifidobacterium genus, and the Faecalibacterium prausnitzii species as well as a reduced general diversity have been described. In this review article, we summarize available data on the influence of reduction diets on the microbiome of patients with CD. One of the most frequently used elimination diets in CD patients is the low-FODMAP (Fermentable Oligosaccharides, Disaccharides, Monosaccharides, and Polyols) diet. Although many papers show it may reduce abdominal pain, diarrhea, or bloating, it also reduces the intake of prebiotic substances, which can negatively affect the gut microbiota composition, decreasing the abundance of Bifidobacterium species and Faecalibacterium prausnitzii. Other elimination diets used by IBD patients, such as lactose-free or gluten-free diets, have also been shown to disturb the microbial diversity. On the other hand, CDED (Crohn’s disease exclusion diet) with partial enteral nutrition not only induces the remission of CD but also has a positive influence on the microbiota. The impact of diet interventions on the microbiota and, potentially, on the future course of the disease should be considered when nutritional guidelines for IBD patients are designed. Dietetic recommendations should be based not only on the regulation of the symptoms but also on the long-term development of the disease.