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Abstract Background Chronic inflammation might play a major role in the pathogenesis linking diabetes mellitus (DM) to cognition. In addition, DM might be the main driver of dementia risk. The purpose of the present study was to evaluate whether inflammation, glycation, or both are associated with the risk of developing all-cause dementia (ACD). Methods A nationwide population-based cohort study was conducted with 4113 participants. The data were obtained from the Taiwanese Survey on Prevalence of Hypertension, Hyperglycemia, and Hyperlipidemia (TwSHHH) in 2007, which was linked with the Taiwan National Health Insurance Research Database (NHIRD). The markers of inflammation, expressed as hs-CRP, and glycation, presented as HbA1c, were measured. High levels of hs-CRP and HbA1c were defined as values greater than or equal to the 66th percentile. Developed ACD was identified based on the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes. Results During 32,926.90 person-years, 106 individuals developed ACD in up to 8 years of follow-up. The study participants were separated into four categories by the top tertiles of hs-CRP and HbA1c based on the 66th percentile: high levels of both hs-CRP and HbA1c, only high levels of hs-CRP, only high levels of HbA1c, and non-high levels of hs-CRP nor HbA1c. Those who with a high level of only hs-CRP had the higher hazard for developing ACD (adjusted HR = 2.58; 95% CI = 1.29 ~ 5.17; P = 0.007), followed by the group with a high level of only HbA1c (adjusted HR = 2.52; 95% CI = 1.34 ~ 4.74; P = 0.004) and the group with high levels of both hs-CRP and HbA1c (adjusted HR = 2.36; 95% CI = 1.20 ~ 4.62; P = 0.012). Among those aged less than 65 years, hs-CRP was the only significant predictor of ACD risk (P = 0.046), whereas it did not yield any significant result in the elderly. Conclusions A higher risk of developing ACD was found not only in patients with high levels of inflammation but also high levels of glycated hemoglobin. Future studies should focus on the clinical implementation of hs-CRP or HbA1c to monitor cognitive deficits.

BackgroundPrevious studies have demonstrated that C-reactive protein (CRP) and glycated hemoglobin (HbA1c) levels are independently associated with neurodegenerative diseases, which can be improved by altering dietary patterns. This study investigates the combined effect of CRP and HbA1c, as well as the influence of dietary patterns, on the risk of dementia.MethodsA cross-sectional study was conducted with 536 participants aged ≥65 years who were recruited from the Nutrition and Health Survey in Taiwan between 2014 and 2016. The high levels of inflammation and glycation were defined as a CRP level of >0.21 mg/dl and a HbA1c level of ≥6.50%, respectively. Mild cognitive impairment (MCI) was evaluated using the Mini-Mental State Examination (MMSE) score. The dietary patterns associated with CRP and HbA1c levels were assessed using the reduced rank regression (RRR). Multivariate logistic regression analysis of both complete and imputed datasets was performed.ResultsParticipants with high levels of both CRP and HbA1c were associated with the highest odds ratio (OR) of MCI (adjusted OR [aOR] = 3.52; 95% CI = 3.48, 3.56; p < 0.001), followed by a high level of only HbA1c (aOR = 1.73; p < 0.001) and a high level of CRP (aOR = 1.49; p < 0.001). Using the reduced rank regression, an inverse relationship between higher consumption nuts and seeds and lower levels of CRP and HbA1c was found (both factors loading < −0.2). Concerning the combined effect of tertiles among the factor 1 and factor 2 analyzed by dietary patterns, group 1 with both T3 (high tertiles) was associated with the greatest OR of MCI (aOR = 4.38; 95% CI = 4.34, 4.42; p < 0.001) using multiple imputation.ConclusionsThe combined effect of high levels of inflammation and hyperglycemia was associated with an increased likelihood of MCI. Moreover, dietary patterns positively related to inflammation and hyperglycemia were associated with MCI, while eating nuts and seeds promoted better cognition.

BackgroundCentral obesity is known to be associated with diabetes. Increasing lower extremity circumference was hypothesized in association with lower risk of diabetes.ObjectiveThis study determined which anthropometric patterns correlates the best with pre-diabetic and diabetic status among healthy adults.DesignCross-sectional study with nationwide population sampling of participants was designed.ParticipantsIn total, 1,358 ethnic Chinese adult participants were recruited from the Nutrition and Health Survey in Taiwan 2013-2016; the whole-body composition was measured through dual-energy X-ray absorptiometry.Main outcome measuresFat and lean mass in whole and specific parts of body among heathy Asian adults with normal glycemic, pre-diabetic, and diabetic states were measured, separately.Statistical analyses performedThe generalized linear model was used to investigate the association between body composition (lean and fat mass) and hyperglycemic status. The reduced rank regression (RRR) was used to confirm the correlation between glycemic status and predicting factors (body composition parameters).ResultsTrunk fat positively correlated with the fasting glucose level (r = 0.327, P < 0.001) and HbA1c (r = 0.329, P < 0.001), whereas limb fat negatively correlated with the fasting glucose level (r = -0.325, P < 0.001) and HbA1c (ρ = -0.342, P < 0.001), respectively. In RRR analyses, fasting glucose and HbA1c exhibited a high positive association on fat amount per lean mass of the trunk (factor loading = 0.5319 and 0.5599, respectively) and of android area (0.6422 and 0.6104) and a high negative association fat amount per lean mass of the legs (-0.3863 and -0.3083) and gynoid area (-0.3414 and -0.3725).ConclusionsFor healthy community participants, increasing trunk fat had a greater risk of hyperglycemic status. Increasing lower extremity mass may confer lower risk of diabetes.

BackgroundThe relationship of alteration of metabolic syndrome (MetS) with dementia remains unclear. The purpose of study was to evaluate the association between dynamic change in MetS status around a 5‐year period and dementia. Methods and ResultsThe cohort study was conducted from the Taiwanese Survey on Prevalence of Hypertension, Hyperglycemia, and Hyperlipidemia in 2002, with follow‐up in 2007. The sample was subsequently linked to the National Health Insurance Research Database. Participants were divided into 3 groups: persistent MetS (MetS both in 2002 and 2007); nonpersistent MetS (MetS either in 2002 or 2007); and non‐MetS (MetS neither in 2002 nor 2007). Furthermore, the individuals with nonpersistent MetS were categorized as improved MetS (MetS in 2002 but not in 2007) and worsened MetS (MetS not in 2002 but in 2007). Each participant was tracked until the end of 2011 to identify the development of dementia. In total, 3458 participants aged 40 to 80 years were included. Up to 10 years and 31 741 person‐years of follow‐up, 76 patients developed dementia. Only a relationship was found between the nonpersistent MetS and dementia (adjusted hazard ratio=1.93; 95% confidence interval =1.17–3.19; P=0.010). Moreover, a significantly higher dementia risk was observed in patients with worsened MetS (adjusted hazard ratio=2.22; 95% confidence interval=1.32–3.72; P=0.003), but not those with persistent (P=0.752) or improved (P=0.829) MetS. Similar results were detected in participants aged ≥65 years. ConclusionsPatients with worsened MetS had an increased dementia risk during the 10‐year follow‐up period in a population‐based sample.

Cardiovascular disease is the leading cause of mortality in hemodialysis patients and is associated with chronic inflammation. Elevation of uremic toxins, particular protein-bound uremic toxins, is a possible cause of hyper-inflammation in hemodialysis patients. But the association between uremic toxins and inflammatory markers in hemodialysis is still unclear.We conducted a cross-sectional study to evaluate the association of the serum uremic toxins and inflammatory markers in hemodialysis patients.The uremic toxins were not associated with inflammatory markers--including high sensitivity C-reactive protein, IL(Interleukin) -1β, IL-6, tumor necrosis factor-α. In multiple linear regression, serum levels of total p-cresol sulfate (PCS) were independently significantly associated with serum total indoxyl sulfate (IS) (standardized coefficient: 0.274, p

The prevalence of coronary vasospasm and also the factors associated with coronary vasospasm in CKD is still unclear. In this cross-sectional study of 859 consecutive CKD patients with angina pectoris received coronary catheterization, we evaluated the factors associated with coronary vasospasm. Patients with vasospasm were older and had higher peripheral blood white cell counts, higher peripheral blood monocyte cell counts, higher haemoglobin levels, higher hs-CRP levels, and lower levels of serum creatinine than patients without vasospasm. The results of multivariate logistic regression analysis revealed that peripheral blood monocyte count and hs-CRP level were independently associated with coronary vasospasm in patients with stage 1 CKD. Only peripheral blood monocyte count but not hs-CRP was independently associated with coronary vasospasm in patients with stages 2 and 3 of CKD. In conclusion, peripheral blood monocyte count is independently associated with coronary vasospasm in patients with stage 1–3 CKD, whereas hs-CRP is only independently associated with coronary vasospasm in patients with stage 1 CKD.

Background: The pathophysiology of insulin resistance-induced hypertension and hyperlipidemia might entail differences in dementia risk in cases with hypertension and hyperlipidemia without prior diabetes mellitus (DM). This study investigated whether incident hypertension, incident hyperlipidemia, or both, increased the dementia risk in patients with and without DM. Methods: A nationwide retrospective cohort study was conducted. The study sample was obtained from the National Health Insurance Research Database. We enrolled 10,316 patients with a new diagnosis of DM between 2000 and 2002 in the DM cohort. For the same period, we randomly selected 41,264 patients without DM in the non-DM cohort (matched by age and sex at a 1:4 ratio with the DM cohort). Both cohorts were then separately divided into four groups on the basis of incident hypertension or incident hyperlipidemia status. Results: In total, 51,580 patients aged between 20 and 99 years were enrolled. The dementia risk was higher in the DM cohort than in the non-DM cohort (adjusted hazard ratio (HR) = 1.47, 95% confidence interval (CI) = 1.30-1.67, p < 0.001). In the DM cohort, the dementia risk in patients with both hypertension and hyperlipidemia did not significantly increase compared with that in those without hypertension and hyperlipidemia (p = 0.529). Similar results were observed in those with either hypertension (p = 0.341) or hyperlipidemia (p = 0.189). In the non-DM cohort, patients with both hypertension and hyperlipidemia had a higher dementia risk (adjusted HR = 1.33, 95% CI = 1.09-1.63, p = 0.006). The results remained largely unchanged in patients with only hypertension (adjusted HR = 1.22, 95% CI = 1.05-1.40, p = 0.008). However, the dementia risk did not increase significantly in patients with only hyperlipidemia (p= 0.187). Conclusions: The development of hypertension, hyperlipidemia, or both, following a diagnosis of incident diabetes is secondary to diabetes onset and likely mediated through insulin resistance associated with diabetes, which does not further accentuate dementia risk. DM itself (i.e., the systemic influence of hyperglycemia) might be the main driver of increased dementia risk. [ABSTRACT FROM AUTHOR]

Background Chronic musculoskeletal (MS) pain is common in patients with chronic kidney disease (CKD) undergoing haemodialysis. However, epidemiological data for chronic MS pain and factors associated with chronic MS pain in patients with early- or late-stage CKD who are not undergoing dialysis are limited. Method A cross-sectional study to evaluate the prevalence of chronic MS pain and factors associated with chronic MS pain in patients with early- and late-stage CKD who were not undergoing dialysis, was conducted. In addition, the distribution of pain severity among patients with different stages of CKD was evaluated. Results Of the 456 CKD patients studied, 53.3% (n = 243/456) had chronic MS pain. Chronic MS pain was independently and significantly associated with hyperuricemia as co-morbidity, as well as with the calcium × phosphate product levels. In CKD patients with hyperuricemia, chronic MS pain showed a negative, independent significant association with diabetes mellitus as a co-morbidity (odds ratio: 0.413, p = 0.020). However, in the CKD patients without hyperuricemia as a co-morbidity, chronic MS pain showed an independent significant association with the calcium × phosphate product levels (odds ratio: 1.093, p = 0.027). Furthermore, stage-5 CKD patients seemed to experience more severe chronic MS pain than patients with other stages of CKD. Conclusion Chronic MS pain is common in CKD patients. Chronic MS pain was independently and significantly associated with hyperuricemia as co-morbidity, and with the calcium × phosphate product levels in early- and late-stage CKD patients who were not on dialysis. [ABSTRACT FROM AUTHOR]

Objective: Hemodialysis has an adverse impact on the immunological, nutritional, and emotional status of patients. The biochemical markers of inflammation and nutrition were studied as well as the relationship of these factors to emotional symptoms. Method: One hundred and ninety-five patients undergoing hemodialysis were enrolled. The mean age was 58.5 years. Emotional symptoms were assessed using the Mini International Neuropsychiatric Interview, Hospital Anxiety and Depression Scale, Chalder Fatigue Scale, and Short-form Health-related Quality of Life. Venus blood was collected for laboratory assessment of serum hemoglobin, albumin, ferritin, C-reactive protein, interleukin (IL) 1(3), IL-6, and tumor necrosis factor a. Results: Among the 195 subjects (92 men and 103 women), 47 (24.1%) fulfilled the criteria for a major depressive disorder (MDD). The IL-6 level in patients with a MDD was significantly higher than in the patients without a MDD. Significant correlation was observed among the following factors: IL-6, fatigue, and quality of life for both physical and mental components. The albumin levels showed a significant correlation with the IL-6 and depression scores. Conclusions: These results show that the serum levels of albumin and IL-6 might be laboratory markers associated with the expression of emotional symptoms in patients undergoing hemodialysis. Prospective studies are needed to determine the causal relationships among these variables. [ABSTRACT FROM AUTHOR]

Background: The microsatellite polymorphism of heme oxygenase (HO)-1 gene promoter has been shown to be associated with the susceptibility to ischemic event, including coronary artery disease (CAD), myocardial infarction, and peripheral vascular disease. We aimed to examine whether the length of (GT)n repeats in HO-1 gene promoter is associated with ischemic stroke in people with CAD risk factors, especially low level of HDL. Methods: A total of 183 consecutive firstever ischemic stroke inpatients and 164 non-stroke patients were screened for the length of (GT)n repeats in HO-1 promoter. The long (L) and short (S) genotype are defined as the averaged repeat number >26 and ≦26, respectively. Results: Stroke patients tended to have more proportions of hypertension, diabetics and genotype L, than those of genotype S. Patients with genotype L of HO-1 gene promoter have higher stroke risk in comparison with genotype S especially in dyslipidemia individuals. The significant differences on stroke risk in multivariate odds ratios were found especially in people with low HDL-C levels. Conclusions: Subjects carrying longer (GT)n repeats in HO-1 gene promoter may have greater susceptibility to develop cerebral ischemic only in the presence of low HDL-C, suggesting the protective effects in HO-1 genotype S in the process of ischemic stroke, particularly in subjects with poor HDL-C status. [ABSTRACT FROM AUTHOR]

Background/Aims: The prevalence ofcardiovascular disease and mortality rate is relatively low in Chinese dialysis patients. This study aimed to evaluate the predictive value of nutritional and inflammatory markers in Chinese hemodialysis patients. Methods: A total of 158 patients (70 men and 88 women, age 59.9 ± 13.2 years) were studied. Nutritional and inflammatory markers, including subjective global assessment (SGA), insulin-like growth factor-1, albumin, tumor necrosis factor-α, interleukin (IL)-1β, IL-6, serum amyloid A (SAA), and C-reactive protein (CRP), were measured. These patients were followed up until April 2004 (36 months) to determine the incidence and causes of death. Results: SGA (p = 0.001), IL-1β (p = 0.032), SAA (p = 0.031), IL-6 (p = 0.001) and CRP (p < 0.001) were found to be significant predictors of mortality. After adjusting with age, sex, diabetes, coronary artery disease, Kt/Vurea, and duration on dialysis, CRP (odds ratio = 4.58; p = 0.038) and SGA (odds ratio = 6.57; p = 0.004) remained the independent predictors of mortality. The adjusted mortality rate was highest for patients with a high CRP level and malnutrition (assessed by SGA). Conclusions: SGA and CRP levels are the most significant predictors of mortality in Chinese dialysis patients. Chinese dialysis patients with a high CRP level tend to be at higher risk of mortality only if they are malnourished. Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Orf virus (ORFV) OV20.0L is an ortholog of vaccinia virus (VACV) gene E3L. The function of VACV E3 protein as a virulence factor is well studied, but OV20.0 has received less attention. Here we show that like VACV E3L, OV20.0L encodes two proteins, a full-length protein and a shorter form (sh20). The shorter sh20 is an N-terminally truncated OV20.0 isoform generated when a downstream AUG codon is used for initiating translation. These isoforms differed in cellular localization, with full-length OV20.0 and sh20 found throughout the cell and predominantly in the cytoplasm, respectively. Nonetheless, both OV20.0 isoforms were able to bind double-stranded RNA (dsRNA)-activated protein kinase (PKR) and dsRNA. Moreover, both isoforms strongly inhibited PKR activation as shown by decreased phosphorylation of the translation initiation factor eIF2 subunit and protection of Sindbis virus infection against the activity of interferon (IFN). In spite of this apparent conservation of function in vitro, a recombinant ORFV that was able to express only the sh20 isoform was attenuated in a mouse model. [ABSTRACT FROM AUTHOR]