Midlife Type 2 Diabetes Mellitus (T2DM) is associated with a greater risk of dementia in later life. Peripheral inflammation and its impact on cognition is proposed as one of the pathological mechanisms mediating this link. However, studies have primarily focused on older individuals with established cognitive impairment and a long duration of T2DM. Importantly, knowledge of which individuals with midlife T2DM who are at greatest risk of later cognitive decline is lacking. We examined the cross-sectional relationship between serum levels of 8 pro-inflammatory markers (IL-1β, IL-6, TNF-α, IL-8, MCP-1, CXCL10, IL-12p70, CRP) and performance on a detailed neuropsychological assessment battery in middle-aged adults with uncomplicated T2DM (N = 89; 52 ± 8.1 years, 47% female) and matched healthy controls (N = 50; 52 ± 8.3 years, 59% female). Linear regression was used to analyze associations between serum markers and cognitive performance in the overall cohort, followed by a T2DM∗protein concentration interaction analysis to identify any T2DM-specific effects. We observed a significant T2DM-specific association between serum TNF-α levels and scores on the Paired Associates Learning (PAL) task (β -3.16, SE 1.32, p = 0.01, Std. Beta -0.94), a task with significant working memory demands previously implicated in T2DM-related cognitive dysfunction. However, this did not persist on controlling for multiple testing. We provide exploratory evidence for a significant T2DM-specific relationship between serum TNF-α and memory performance. These findings require further replication and longitudinal analysis with the aim of selecting-out individuals with midlife T2DM at risk of future cognitive decline for potential preventative interventions.This study aimed to investigate the effect of 12 weeks of dual-task training on cognitive status, physical performance, and brain oscillation of patients with Alzheimer's disease (AD). Twenty-six AD patients were randomly assigned to two groups, the training group (TG) and control group (CG). TG executed progressive combined exercises with visual stimulation twice a week for 12 weeks. Training included muscle endurance, balance, flexibility, and aerobic exercises with eyes closed and opened. Brain oscillation on electroencephalography (EEG) and a series of physical, cognitive, and mental tests were taken before and post-intervention. There was a significant improvement after training protocol in cognitive function, particularly in short-term and working memory, attention, and executive function (p less then 0.01). Besides, there were substantial improvements in depression status (GDS scale), aerobic fitness (6 min walking), flexibility (chair sit and reach) functional ability (chair stand, timed up and go test), strength (knee extensions, preacher biceps curl, handgrip) in TG compared to CG. These signs of progress were associated with a significant increase (p less then 0.05) in the frequency of brain oscillation and a decrease in the theta/alpha ratio. In addition to physical performance, the regular combined training with visual stimulation improves brain health as indicated by improving cognitive function and reducing the theta/alpha ratio. Clinical Trial Registration Iranian Registry of Clinical Trials (IRCT) https//www.irct.ir/, identifier IRCT20190504043468N1-August 5, 2020.Background Alzheimer's disease (AD) and Parkinson's disease (PD) are two major neurodegenerative diseases worldwide. Demographic aging is in rapid progress in China. Up-to-date estimates of AD and PD prevalence have not been provided. Methods Studies that reported the prevalence of AD and PD in China were identified via a systematic database search from 1985 to 2018. Meta-analysis, local polynomial regression and autoregressive integrated moving average model were used for analyses. Results A total of 99 studies were included in the study with populations of 385,312 and 227,228, respectively for AD and PD. The overall prevalence of AD and PD following age standardization was 3.20% [95% confidence interval (CI) = 3.17-3.23] and 1.06% (95% CI = 1.02-1.10), respectively in individuals over 60 years old. The rates increased drastically for every 10-years increment of age. The yearly prevalence of AD was predicted to increase from 3.81 to 6.17% in the next 5 years. Significant differences were observed between genders [male to female odds ratio (OR) for AD = 0.57, 95% CI = 0.51-0.64; OR for PD = 1.25, 95% CI = 1.06-1.46], and between education levels (Illiterate to non-illiterate OR for AD = 2.99, 95% CI = 2.38-3.75), but not between urban and rural settings. Conclusion Our results provide an updated insight into the epidemiology of AD and PD in China and their associated rates and ratios. The findings may facilitate China policy makers and health professionals mitigate the related health issues.Circular RNAs (circRNAs) have recently been discovered as a novel type of endogenous non-coding RNA that may regulate gene expression in mammals. In the central nervous system (CNS), circRNAs are relevant to many neurological disorders such as Alzheimer's disease (AD). In this study, we attempted to identify an aberrant circRNA, hsa_circ_0003391, which is significantly downregulated in the peripheral blood of patients with AD, and to explore the relationship between hsa_circ_0003391 and the clinical manifestation of AD. The expression of hsa_circ_0003391 had a specific decrease in the peripheral blood of patients with AD compared to those with other types of dementia. To evaluate the potential diagnostic value of the circRNA, we performed a receiver operating characteristic (ROC) curve analysis. The area under the curve (AUC) value was 0.7283 for hsa_circ_0003391, which was statistically significant. https://www.selleckchem.com/products/dmx-5084.html The natural form of hsa_circ_0003391 in the peripheral blood was a loop structure with good stability. We found a potential correlation between the expression of hsa_circ_0003391 and the clinical manifestations of AD. Bioinformatic analysis was carried out to predict the latent target microRNAs (miRNA) of hsa_circ_0003391. Furthermore, microRNAs targeted by hsa_circ_0003391 were successfully detected, and miR-574-5p had an expected elevation in the AD groups, suggesting that miR-574-5p might be a potential microRNA target for hsa_circ_0003391. Our results suggest that the downregulation of hsa_circ_0003391 in the peripheral blood has a potential relationship with AD. Our findings not only provide an important latent biomarker but also highlight an important perspective for the following study into AD pathogenesis. This may promote the process of novel therapeutics targeting non-coding RNA.
Midlife Type 2 Diabetes Mellitus (T2DM) is associated with a greater risk of dementia in later life. Peripheral inflammation and its impact on cognition is proposed as one of the pathological mechanisms mediating this link. However, studies have primarily focused on older individuals with established cognitive impairment and a long duration of T2DM. Importantly, knowledge of which individuals with midlife T2DM who are at greatest risk of later cognitive decline is lacking. We examined the cross-sectional relationship between serum levels of 8 pro-inflammatory markers (IL-1β, IL-6, TNF-α, IL-8, MCP-1, CXCL10, IL-12p70, CRP) and performance on a detailed neuropsychological assessment battery in middle-aged adults with uncomplicated T2DM (N = 89; 52 ± 8.1 years, 47% female) and matched healthy controls (N = 50; 52 ± 8.3 years, 59% female). Linear regression was used to analyze associations between serum markers and cognitive performance in the overall cohort, followed by a T2DM∗protein concentration interaction analysis to identify any T2DM-specific effects. We observed a significant T2DM-specific association between serum TNF-α levels and scores on the Paired Associates Learning (PAL) task (β -3.16, SE 1.32, p = 0.01, Std. Beta -0.94), a task with significant working memory demands previously implicated in T2DM-related cognitive dysfunction. However, this did not persist on controlling for multiple testing. We provide exploratory evidence for a significant T2DM-specific relationship between serum TNF-α and memory performance. These findings require further replication and longitudinal analysis with the aim of selecting-out individuals with midlife T2DM at risk of future cognitive decline for potential preventative interventions.This study aimed to investigate the effect of 12 weeks of dual-task training on cognitive status, physical performance, and brain oscillation of patients with Alzheimer's disease (AD). Twenty-six AD patients were randomly assigned to two groups, the training group (TG) and control group (CG). TG executed progressive combined exercises with visual stimulation twice a week for 12 weeks. Training included muscle endurance, balance, flexibility, and aerobic exercises with eyes closed and opened. Brain oscillation on electroencephalography (EEG) and a series of physical, cognitive, and mental tests were taken before and post-intervention. There was a significant improvement after training protocol in cognitive function, particularly in short-term and working memory, attention, and executive function (p less then 0.01). Besides, there were substantial improvements in depression status (GDS scale), aerobic fitness (6 min walking), flexibility (chair sit and reach) functional ability (chair stand, timed up and go test), strength (knee extensions, preacher biceps curl, handgrip) in TG compared to CG. These signs of progress were associated with a significant increase (p less then 0.05) in the frequency of brain oscillation and a decrease in the theta/alpha ratio. In addition to physical performance, the regular combined training with visual stimulation improves brain health as indicated by improving cognitive function and reducing the theta/alpha ratio. Clinical Trial Registration Iranian Registry of Clinical Trials (IRCT) https//www.irct.ir/, identifier IRCT20190504043468N1-August 5, 2020.Background Alzheimer's disease (AD) and Parkinson's disease (PD) are two major neurodegenerative diseases worldwide. Demographic aging is in rapid progress in China. Up-to-date estimates of AD and PD prevalence have not been provided. Methods Studies that reported the prevalence of AD and PD in China were identified via a systematic database search from 1985 to 2018. Meta-analysis, local polynomial regression and autoregressive integrated moving average model were used for analyses. Results A total of 99 studies were included in the study with populations of 385,312 and 227,228, respectively for AD and PD. The overall prevalence of AD and PD following age standardization was 3.20% [95% confidence interval (CI) = 3.17-3.23] and 1.06% (95% CI = 1.02-1.10), respectively in individuals over 60 years old. The rates increased drastically for every 10-years increment of age. The yearly prevalence of AD was predicted to increase from 3.81 to 6.17% in the next 5 years. Significant differences were observed between genders [male to female odds ratio (OR) for AD = 0.57, 95% CI = 0.51-0.64; OR for PD = 1.25, 95% CI = 1.06-1.46], and between education levels (Illiterate to non-illiterate OR for AD = 2.99, 95% CI = 2.38-3.75), but not between urban and rural settings. Conclusion Our results provide an updated insight into the epidemiology of AD and PD in China and their associated rates and ratios. The findings may facilitate China policy makers and health professionals mitigate the related health issues.Circular RNAs (circRNAs) have recently been discovered as a novel type of endogenous non-coding RNA that may regulate gene expression in mammals. In the central nervous system (CNS), circRNAs are relevant to many neurological disorders such as Alzheimer's disease (AD). In this study, we attempted to identify an aberrant circRNA, hsa_circ_0003391, which is significantly downregulated in the peripheral blood of patients with AD, and to explore the relationship between hsa_circ_0003391 and the clinical manifestation of AD. The expression of hsa_circ_0003391 had a specific decrease in the peripheral blood of patients with AD compared to those with other types of dementia. To evaluate the potential diagnostic value of the circRNA, we performed a receiver operating characteristic (ROC) curve analysis. The area under the curve (AUC) value was 0.7283 for hsa_circ_0003391, which was statistically significant. https://www.selleckchem.com/products/dmx-5084.html The natural form of hsa_circ_0003391 in the peripheral blood was a loop structure with good stability. We found a potential correlation between the expression of hsa_circ_0003391 and the clinical manifestations of AD. Bioinformatic analysis was carried out to predict the latent target microRNAs (miRNA) of hsa_circ_0003391. Furthermore, microRNAs targeted by hsa_circ_0003391 were successfully detected, and miR-574-5p had an expected elevation in the AD groups, suggesting that miR-574-5p might be a potential microRNA target for hsa_circ_0003391. Our results suggest that the downregulation of hsa_circ_0003391 in the peripheral blood has a potential relationship with AD. Our findings not only provide an important latent biomarker but also highlight an important perspective for the following study into AD pathogenesis. This may promote the process of novel therapeutics targeting non-coding RNA.
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