BACKGROUND/OBJECTIVES
Population‐based incidence estimates of dementia and Alzheimer disease (AD) provide important information for public health policy and resource allocation. We conducted a ...meta‐analysis of published studies that reported age‐specific incidence rates of dementia and AD to determine whether dementia and AD incidence rates are changing over time.
DESIGN
PubMed and MEDLINE were searched for publications through June 30, 2017, using key words “dementia”, “Alzheimer”, and “incidence.” Inclusion criteria for the meta‐analysis are: (1) population‐based studies using personal interviews and direct examinations of the study subjects, (2) standardized clinical diagnosis criteria, (3) reporting age‐specific incidence rates, (4) published in English, and (5) sample size of 500 or greater and length of follow‐up of 2 years or greater. Mixed‐effects models were used to determine the association between birth year and incidence rates.
MEASUREMENTS
Age‐specific dementia/AD incidence rates and their standard errors reported in each study.
RESULTS
Thirty‐eight articles with 53 cohorts on dementia incidence and 31 articles with 35 cohorts on AD incidence met the inclusion criteria. There were significant associations between later birth years and decreased dementia incidence rates in all three age groups (65‐74, 75‐84, and 85 years and older). There were no significant associations between birth year and AD incident rates in any of the three age groups. In particular, AD incidence rates reported from Western countries stayed steady in all age groups, while studies in non‐Western countries showed significantly increased AD incidence rates for the 65 to 74 years age group (odds ratio = 2.78; P = .04), but a nonsignificant association for the 75 to 84 or 85 years and older groups.
CONCLUSION
Dementia incidence declined over the past four decades, but AD incidence did not decline. Further research, especially from non‐Western countries, is needed to elucidate the mechanism underlying the trends in dementia and AD incidence over time.
See related editorial by Skoog et al.
Eukaryotic genes are packed into a dynamic but stable nucleoprotein structure called chromatin. Chromatin-remodeling and modifying complexes generate a dynamic chromatin environment that ensures ...appropriate DNA processing and metabolism in various processes such as gene expression, as well as DNA replication, repair, and recombination. The INO80 and SWR1 chromatin remodeling complexes (INO80-c and SWR1-c) are ATP-dependent complexes that modulate the incorporation of the histone variant H2A.Z into nucleosomes, which is a critical step in eukaryotic gene regulation. Although SWR1-c has been identified in plants, plant INO80-c has not been successfully isolated and characterized. In this review, we will focus on the functions of the SWR1-c and putative INO80-c (SWR1/INO80-c) multi-subunits and multifunctional complexes in
. We will describe the subunit compositions of the SWR1/INO80-c and the recent findings from the standpoint of each subunit and discuss their involvement in regulating development and environmental responses in
.
Both delirium duration and delirium severity are associated with adverse patient outcomes. Serum biomarkers associated with delirium duration and delirium severity in ICU patients have not been ...reliably identified. We conducted our study to identify peripheral biomarkers representing systemic inflammation, impaired neuroprotection, and astrocyte activation associated with delirium duration, delirium severity, and in-hospital mortality.
Observational study.
Three Indianapolis hospitals.
Three-hundred twenty-one critically ill delirious patients.
None.
We analyzed the associations between biomarkers collected at delirium onset and delirium-/coma-free days assessed through Richmond Agitation-Sedation Scale/Confusion Assessment Method for the ICU, delirium severity assessed through Confusion Assessment Method for the ICU-7, and in-hospital mortality. After adjusting for age, gender, Acute Physiology and Chronic Health Evaluation II score, Charlson comorbidity score, sepsis diagnosis and study intervention group, interleukin-6, -8, and -10, tumor necrosis factor-α, C-reactive protein, and S-100β levels in quartile 4 were negatively associated with delirium-/coma-free days by 1 week and 30 days post enrollment. Insulin-like growth factor-1 levels in quartile 4 were not associated with delirium-/coma-free days at both time points. Interleukin-6, -8, and -10, tumor necrosis factor-α, C-reactive protein, and S-100β levels in quartile 4 were also associated with delirium severity by 1 week. At hospital discharge, interleukin-6, -8, and -10 retained the association but tumor necrosis factor-α, C-reactive protein, and S-100β lost their associations with delirium severity. Insulin-like growth factor-1 levels in quartile 4 were not associated with delirium severity at both time points. Interleukin-8 and S-100β levels in quartile 4 were also associated with higher in-hospital mortality. Interleukin-6 and -10, tumor necrosis factor-α, and insulin-like growth factor-1 were not found to be associated with in-hospital mortality.
Biomarkers of systemic inflammation and those for astrocyte and glial activation were associated with longer delirium duration, higher delirium severity, and in-hospital mortality. Utility of these biomarkers early in delirium onset to identify patients at a higher risk of severe and prolonged delirium, and delirium related complications during hospitalization needs to be explored in future studies.
The identification of metal ion binding sites is important for protein function annotation and the design of new drug molecules. This study presents an effective method of analyzing and identifying ...the binding residues of metal ions based solely on sequence information. Ten metal ions were extracted from the BioLip database: Zn2+, Cu2+, Fe2+, Fe3+, Ca2+, Mg2+, Mn2+, Na+, K+ and Co2+. The analysis showed that Zn2+, Cu2+, Fe2+, Fe3+, and Co2+ were sensitive to the conservation of amino acids at binding sites, and promising results can be achieved using the Position Weight Scoring Matrix algorithm, with an accuracy of over 79.9% and a Matthews correlation coefficient of over 0.6. The binding sites of other metals can also be accurately identified using the Support Vector Machine algorithm with multifeature parameters as input. In addition, we found that Ca2+ was insensitive to hydrophobicity and hydrophilicity information and Mn2+ was insensitive to polarization charge information. An online server was constructed based on the framework of the proposed method and is freely available at http://60.31.198.140:8081/metal/HomePage/HomePage.html.
•Tau deposition is associated with white-matter (WM) degeneration along connecting tracts.•Tau-related WM degeneration demonstrates distinct spatial pattern, similar to Braak staging.•WM degeneration ...is characterized by increased mean diffusivity and decreased axon density.•WM plays an important role in the deposition of tau pathology.
Progressive accumulation of tau neurofibrillary tangles in the brain is a defining pathologic feature of Alzheimer's disease (AD). Tau pathology exhibits a predictable spatiotemporal spreading pattern, but the underlying mechanisms of this spread are poorly understood. Although AD is conventionally considered a disease of the gray matter, it is also associated with pronounced and progressive deterioration of the white matter (WM). A link between abnormal tau and WM degeneration is suggested by findings from both animal and postmortem studies, but few studies demonstrated their interplay in vivo. Recent advances in diffusion magnetic resonance imaging and the availability of tau positron emission tomography (PET) have made it possible to evaluate the association of tau and WM degeneration (tau-WM) in vivo. In this study, we explored the spatial pattern of tau-WM associations across the whole brain to evaluate the hypothesis that tau deposition is associated with WM microstructural alterations not only in isolated tracts, but in continuous structural connections in a stereotypic pattern. Sixty-two participants, including 22 cognitively normal subjects, 22 individuals with subjective cognitive decline, and 18 with mild cognitive impairment were included in the study. WM characteristics were inferred by classic diffusion tensor imaging (DTI) and a complementary diffusion compartment model – neurite orientation dispersion and density imaging (NODDI) that provides a proxy for axonal density. A data-driven iterative searching (DDIS) approach, coupled with whole-brain graph theory analyses, was developed to continuously track tau-WM association patterns. Without applying prior knowledge of the tau spread, we observed a distinct spatial pattern that resembled the typical propagation of tau pathology in AD. Such association pattern was not observed between diffusion and amyloid-β PET signal. Tau-related WM degeneration is characterized by an increase in the mean diffusivity (with a dominant change in the radial direction) and a decrease in the intra-axonal volume fraction. These findings suggest that cortical tau deposition (as measured in tau PET) is associated with a lower axonal packing density and greater diffusion freedom. In conclusion, our in vivo findings using a data-driven method on cross-sectional data underline the important role of WM alterations in the AD pathological cascade with an association pattern similar to the postmortem Braak staging of AD. Future studies will focus on longitudinal analyses to provide in vivo evidence of tau pathology spreads along neuroanatomically connected brain areas.
BRAHMA (BRM), a SWI/SNF chromatin remodeling ATPase, is essential for the transcriptional reprogramming associated with development and cell differentiation in Arabidopsis thaliana. In this study, we ...show that loss-of-function mutations in BRM led to defective maintenance of the root stem cell niche, decreased meristematic activity, and stunted root growth. Mutations of BRM affected auxin distribution by reducing local expression of several PIN-FORMED (PIN) genes in the stem cells and impaired the expression of the stem cell transcription factor genes PLETHORA (PLT1) and PLT2. Chromatin immunoprecipitation assays showed that BRM could directly target to the chromatin of PIN1, PIN2, PIN3, PIN4, and PIN7. In addition, genetic interaction assays indicate that PLTs acted downstream of BRM, and overexpression of PLT2 partially rescued the stem cell niche defect of brm mutants. Taken together, these results support the idea that BRM acts in the PLT pathway to maintain the root stem cell niche by altering the expression of PINs.
Abstract
Objectives:
To explore the possible association of childhood residence, education levels, and occupation with declining incidence rates of dementia in 2 cohorts of elderly African Americans.
...Methods
African Americans residing in Indianapolis without dementia were enrolled in 1992 and 2001 and evaluated every 2–3 years. The cohorts consist of 1,440 participants in 1992 and 1,835 participants in 2001 aged 70 years and older. Cox proportional hazard regression models were used to compare cohort differences in dementia and Alzheimer’s disease (AD) risk.
Results
The 2001 cohort had significantly decreased risk of both incident dementia and AD (hazard ratio HR: 0.62/0.57 for dementia/AD). Years of education was associated with decreased risk of dementia (HR = 0.93; p = .0011). A significant interaction (p = .0477) between education and childhood rural residence was found for the risk of AD that higher education level is significantly associated with reduced AD risk (HR = 0.87) in participants with childhood rural residence, but no association in those with urban upbringing. The cohort difference for dementia rates were attenuated by adjusting for the 3 risk factors but remained significant (HR = 0.75; p = .04).
Discussion
These results emphasize the importance of early life factors including rural residence and education for the risk for dementia later in life.
Se is an antioxidant micronutrient and has been studied for its potential role in CVD prevention. The purpose of the present study was to conduct a systematic review of the literature on the ...relationship between Se and hypertension.
We conducted a systematic literature search in PubMed and OVID of studies on Se levels and hypertension or blood pressure published in English up to June 2011. Articles meeting inclusion criteria were reviewed and the following information was gathered from each publication: study setting, participant demographics, exclusion criteria, intervention if applicable, medium of Se measure, mean level of Se, outcome definition, relationship between Se and the outcome variable, significance of this relationship, and covariates. In studies that also reported glutathione peroxidase levels, we extracted results on the relationship between glutathione peroxidase and hypertension.
Twenty-five articles were included. Approximately half of the studies reported no significant relationship between Se and hypertension. Of the remaining studies, about half found that higher Se levels were associated with lower blood pressure and the other half found the opposite relationship. The studies varied greatly in terms of study population, study design and Se levels measured in participants.
Based on the present systematic review, there is no conclusive evidence supporting an association between Se and hypertension. Randomized controlled trials and prospective studies with sufficient sample size in populations with different Se levels are needed to fully investigate the relationship between Se and hypertension.
The purpose of this study was to conduct a systematic review of the literature of cardiovascular factors pertaining to incident Alzheimer disease (AD).
A systematic literature review was conducted of ...all studies of cardiovascular risk factors for incident AD listed in PubMed in English from 2000 to 2007. Risk factors included hypertension, diabetes, exercise, alcohol intake, smoking, B complex vitamins, homocysteine, stroke, atrial fibrillation, apolipoprotein E (APOE), lipids, and diet. Inclusion criteria consisted of diagnoses of incident AD and longitudinal studies with cohorts of 500 or more.
Individual clinically defined risk factors such as hypertension and diabetes were not significantly associated with increased risk for AD. The strength of the association for hypertension could be considerably strengthened by changing criteria such as midlife measurements or using higher cutoffs for systolic blood pressure. APOE epsilon4 was the most consistent risk factor. Interactions between risk factors modify risk particularly for hypertension and diabetes. Interactions modifying risk were also found for exercise and physical function, APOE epsilon4, diabetes, and cholesterol.
In this review, the evidence that single clinically defined cardiovascular risk factors are significantly associated with incident AD is inconsistent at best. The strength of the association of cardiovascular risk factors and AD can be influenced greatly by changing the parameters of measurement of risk factors and by identifying interactions between the factors.
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