Amorphous silica particles, such as nanoparticles (<100 nm diameter particles), are used in a wide variety of products, including pharmaceuticals, paints, cosmetics, and food. Nevertheless, the immunotoxicity of these particles and the relationship between silica particle size and pro-inflammatory activity are not fully understood. In this study, we addressed the relationship between the size of amorphous silica (particle dose, diameter, number, and surface area) and the inflammatory activity (macrophage phagocytosis, inflammasome activation, IL-1β secretion, cell death and lung inflammation). Irrespective of diameter size, silica particles were efficiently internalized by mouse bone marrow-derived macrophages via an actin cytoskeleton-dependent pathway, and induced caspase-1, but not caspase-11, activation. Of note, 30 nm-1000 nm diameter silica particles induced lysosomal destabilization, cell death, and IL-1β secretion at markedly higher levels than did 3000 nm-10000 nm silica particles. Consistent with in vitro results, intra-tracheal administration of 30 nm silica particles into mice caused more severe lung inflammation than that of 3000 nm silica particles, as assessed by measurement of pro-inflammatory cytokines and neutrophil infiltration in bronchoalveolar lavage fluid of mice, and by the micro-computed tomography analysis. Taken together, these results suggest that silica particle size impacts immune responses, with submicron amorphous silica particles inducing higher inflammatory responses than silica particles over 1000 nm in size, which is ascribed not only to their ability to induce caspase-1 activation but also to their cytotoxicity.

Although several studies have demonstrated a potential correlation of dietary patterns with cognitive function, the relationship between tooth loss and dietary patterns and cognitive function have not been identified. In this cross-sectional study, we used a reduced rank regression (RRR) analysis, a technique used previously to observe dietary patterns based on the intakes of nutrients or levels of biomarkers associated with the condition of interest, to identify tooth loss-related dietary patterns and investigate the associations of such patterns with cognitive impairment in 334 community-dwelling Japanese subjects aged ≥ 60 years. According to Pearson correlation coefficients, the intakes of six nutrients (ash content, sodium, zinc, vitamin B1, α- and β-carotene) correlated significantly with the number of remaining teeth. Using RRR analysis, we extracted four dietary patterns in our subject population that explained 86.67% of the total variation in the intakes of these six nutrients. Particularly, dietary pattern 1 (DP1) accounted for 52.2% of the total variation. Food groups with factor loadings of ≥ 0.2 included pickled green leafy vegetables, lettuce/cabbage, green leaves vegetables, cabbage, carrots/squash; by contrast, rice had a factor loading of <−0.2. In a multivariate regression analysis, the adjusted odds ratios regarding the prevalence of cognitive impairment for the lowest, middle and highest tertiles of the DP1 score were 1.00 (reference), 1.224 (95% confidence interval [CI]: 0.611–2.453) and 0.427 (95% CI: 0.191–0.954), respectively. To our knowledge, this is the first report to show that tooth loss-related dietary patterns are associated with a high prevalence of cognitive impairment. These results may motivate changes in dental treatment and the dietary behaviours and thereby lower the risk of cognitive impairment.

Our results demonstrate significant beneficial effects of vitamins C and E in reducing the risk of cognitive decline in women with APOE E4 and men without APOE E4, respectively.

Background: Glucose dysmetabolism is an important risk factor for dementia. Objective: We investigated the associations of diabetes mellitus, the levels of glycemic measures, and insulin resistance and secretion measures with dementia and its subtypes in a cross-sectional study. Methods: In this study, 10,214 community-dwelling participants were enrolled. Hemoglobin A1c (HbA1c), the homeostasis model assessment (HOMA) for insulin resistance (HOMA-IR), the HOMA of percent β-cell function (HOMA-β), and the glycated albumin (GA) was evaluated. The associations of each measure with Alzheimer’s disease (AD) and vascular dementia (VaD) were investigated. Results: The multivariable-adjusted odds ratios (ORs) of AD were significantly higher in participants with diabetes mellitus than in those without diabetes (1.46 [95% CI: 1.08–1.97]). Higher HbA1c levels were significantly associated with AD at diabetes (≥6.5%) and even at prediabetes (5.7 %–6.4 %) levels; multivariable-adjusted ORs for AD in participants at the diabetes level were 1.72 (95% CI: 1.19–2.49), and those in participants at the prediabetes level were 1.30 (95% CI: 1.00–1.68), compared with those in normal participants. Moreover, higher GA levels were associated with AD. No associations were observed between the diabetic status or the levels of glycemic measures and VaD. In addition, no significant relationships were observed between insulin resistance and secretion measurements and AD and VaD. Conclusion: Our findings indicate that diabetes mellitus and hyperglycemia are significantly associated with AD, even in individuals at the prediabetes level.

Apolipoprotein E E4 (APOE4) is a risk factor for cognitive decline. A high blood vitamin C (VC) level reduces APOE4-associated risk of developing cognitive decline in women. In the present study, we aimed to examine the effects of functional variants of VC transporter genes expressed in the brain (SLC2A1, SLC2A3, and SLC23A2) on APOE4-associated risk of developing cognitive decline. This case–control study involved 393 Japanese subjects: 252 cognitively normal and 141 cognitively impaired individuals (87 mild cognitive impairment and 54 dementia). Database searches revealed that rs1279683 of SLC23A2, and rs710218 and rs841851 of SLC2A1 are functional variants that are significantly associated with the altered expression of the respective genes and genotyped as three single nucleotide variants (SNVs). When stratified by SNV genotype, we found a significant association between APOE4 and cognitive decline in minor allele carriers of rs1279683 (odds ratio [OR] 2.02, 95% CI, 1.05–3.87, p = 0.035) but not in the homozygote carriers of the major allele. Significant associations between APOE4 and cognitive decline were also observed in participants with major allele homozygotes of rs710218 (OR 2.35, 95% CI, 1.05–5.23, p = 0.037) and rs841851 (OR 3.2, 95% CI, 1.58–6.46, p = 0.0012), but not in minor allele carriers of the respective SNVs. In contrast, the three functional SNVs showed no significant effect on cognitive decline. Our results imply that functional SNVs of VC transporter genes can affect APOE4-associated risk of developing cognitive decline via altered VC levels in the brain.