Comparing methods for glomerular filtration rate estimation.

Background: The glomerular filtration rate (GFR), estimated from serum creatinine (SCr), is widely used in clinical practice for kidney function assessment, but SCr-based equations are limited by non-GFR determinants and may introduce inaccuracies across racial groups. Few studies have evaluated whether advanced modeling techniques enhance their performance.

Methods: Using multivariable fractional polynomials (MFP), generalized additive models (GAM), random forests (RF), and gradient boosted machines (GBM), we developed four SCr-based GFR-estimating equations in a pooled data set from four cohorts ( = 4665).

Selected social and lifestyle correlates of brain health markers: the Cross-Cohort Collaboration Consortium.

Introduction: To investigate the associations of education level, marital status, and physical activity with dementia risk and brain MRI markers.

Methods: Data from six community-based samples from the Cross-Cohort Collaboration Consortium were analyzed. Self-reported education level, marital status, and physical activity at age 60 to 75 years were harmonized.

Clinical and Imaging Markers of Cardiac Function and Brain Health: A Meta-Analysis of Community-Based Studies.

Background And Objectives: Cardiac dysfunction and heart failure are linked to cognitive impairment, but the underlying brain pathology remains undetermined. We investigated associations between cardiac function (measured by echocardiography or cardiac MRI), clinical heart failure, and structural markers on brain MRI, including volumes of gray and white matter (WM), the hippocampus, and white matter hyperintensities (WMHs).

Methods: We leverage data from 7 prospective, community-based cohorts across Europe and the United States, all part of the Cross-Cohort Collaboration.

Lung Function and Brain MRI Outcomes in the Atherosclerosis Risk in Communities Neurocognitive Study.

Background: Brain imaging studies may provide etiologic insight into observed links between lung function and dementia and stroke.

Objective: We evaluated associations of lung function measures with brain MRI markers of vascular and neurodegenerative disease in the ARIC Neurocognitive Study, as few studies have examined the associations.

Methods: Lung function was measured at participants' midlife in 1990-1992 (mean age = 56±5 years) and later-life in 2011-2013 (mean age = 76±5 years), and brain MRI was performed in 2011-2013.

Association of Plasma Aβ/Aβ Ratio and Late-Onset Epilepsy: Results From the Atherosclerosis Risk in Communities Study.

Background And Objectives: The objective of this study was to determine the relationship between plasma β-amyloid (Aβ), specifically the ratio of 2 Aβ peptides (the Aβ/Aβ ratio, which correlates with increased accumulation of Aβ in the CNS), and late-onset epilepsy (LOE).

Methods: We used Medicare fee-for-service claims codes from 1991 to 2018 to identify cases of LOE among 1,424 Black and White men and women enrolled in the Atherosclerosis Risk in Communities (ARIC) study cohort. The Aβ/Aβ ratio was calculated from plasma samples collected from ARIC participants in 1993-1995 (age 50-71 years) and 2011-2013 (age 67-90 years).

Associations of Pulmonary Function with MRI Brain Volumes: A Coordinated Multi-Study Analysis.

Background: Previous studies suggest poor pulmonary function is associated with increased burden of cerebral white matter hyperintensities and brain atrophy among elderly individuals, but the results are inconsistent.

Objective: To study the cross-sectional associations of pulmonary function with structural brain variables.

Methods: Data from six large community-based samples (N = 11,091) were analyzed.

Genetic Risk, Midlife Life's Simple 7, and Incident Dementia in the Atherosclerosis Risk in Communities Study.

Background And Objectives: Higher scores in Life's Simple 7 (LS7), a metric for cardiovascular and brain health, have been associated with lower risk of dementia. It is uncertain whether this association holds among those with high genetic risk of dementia. Our objective is to evaluate the extent that LS7 may offset dementia risk across the range of genetic risk.

Education and Cardiovascular Health as Effect Modifiers of APOE ε4 on Dementia: The Atherosclerosis Risk in Communities Study.

Background: Both education and cardiovascular risk factors are strongly associated with dementia risk. However, it is not clear whether these associations persist or vary among individuals with high genetic risk for Alzheimer's disease. We examined the interactive relationship between lifestyle and genetic dementia risk factors in a prospective cohort study.

Association of Midlife Plasma Amyloid-β Levels With Cognitive Impairment in Late Life: The ARIC Neurocognitive Study.

Background And Objectives: To evaluate the association between midlife plasma amyloid-β (Aβ, Aβ, Aβ:Aβ) and risk of mild cognitive impairment (MCI) and dementia.

Methods: Plasma Aβ and Aβ were retrospectively measured with a fluorometric bead-based immunoassay in a subsample of the Atherosclerosis Risk in Communities cohort study. We investigated the relationship of plasma Aβ, Aβ, and Aβ:Aβ ratio measured in midlife and late life and the change from midlife to late life to risk of MCI, dementia, and combined MCI/dementia outcomes in late life (from 2011-2019).

Plasma amyloid β levels are driven by genetic variants near APOE, BACE1, APP, PSEN2: A genome-wide association study in over 12,000 non-demented participants.

Introduction: There is increasing interest in plasma amyloid beta (Aβ) as an endophenotype of Alzheimer's disease (AD). Identifying the genetic determinants of plasma Aβ levels may elucidate important biological processes that determine plasma Aβ measures.

Methods: We included 12,369 non-demented participants from eight population-based studies.

Author Correction: Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function.

Christina M. Lill, who contributed to analysis of data, was inadvertently omitted from the author list in the originally published version of this article. This has now been corrected in both the PDF and HTML versions of the article.

Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function.

General cognitive function is a prominent and relatively stable human trait that is associated with many important life outcomes. We combine cognitive and genetic data from the CHARGE and COGENT consortia, and UK Biobank (total N = 300,486; age 16-102) and find 148 genome-wide significant independent loci (P < 5 × 10) associated with general cognitive function. Within the novel genetic loci are variants associated with neurodegenerative and neurodevelopmental disorders, physical and psychiatric illnesses, and brain structure.

Meta-analysis of epigenome-wide association studies of cognitive abilities.

Cognitive functions are important correlates of health outcomes across the life-course. Individual differences in cognitive functions are partly heritable. Epigenetic modifications, such as DNA methylation, are susceptible to both genetic and environmental factors and may provide insights into individual differences in cognitive functions.

The PPARG Pro12Ala Polymorphism and 20-year Cognitive Decline: Race and Sex Heterogeneity.

Previous reports suggest race/ethnic and sex heterogeneity in the association between the Pro12Ala polymorphism of the peroxisome proliferator-activated receptor gamma (PPARG) gene and cognitive decline. Tests of verbal memory, processing speed, and verbal fluency and a composite global Z-score were used to assess cognitive performance longitudinally in a large (n=11,620) biracial cohort of older adults in the Atherosclerosis Risk in Communities Neurocognitive Study from midlife to older age. Linear mixed models were used to estimate associations between the Ala12 allele and cognitive performance over 20 years of follow-up.

Neuroimaging Correlates of Cerebral Microbleeds: The ARIC Study (Atherosclerosis Risk in Communities).

Background And Purpose: Cerebral microbleed (CMB) location (deep versus strictly lobar) may elucidate underlying pathology with deep CMBs being more associated with hypertensive vascular disease and lobar CMBs being more associated with cerebral amyloid angiopathy. The objective of this study was to determine whether neuroimaging signs of vascular disease and Alzheimer pathology are associated with different types of CMBs.

Methods: Among 1677 nondemented ARIC (Atherosclerosis Risk in Communities) participants (mean age=76±5 years; 40% men; 26% black) with 3-Tesla MRI scans at the fifth examination (2011-2013), we fit multinomial logistic regression models to quantify relationships of brain volumes (Alzheimer disease signature regions, total gray matter, frontal gray matter, and white matter hyperintensity volumes), infarct frequencies (lacunar, nonlacunar, and total), and apolipoprotein E (number of ε4 alleles) with CMB location (none, deep/mixed, or strictly lobar CMBs).

Whole exome sequence-based association analyses of plasma amyloid-β in African and European Americans; the Atherosclerosis Risk in Communities-Neurocognitive Study.

Objective: We performed single-variant and gene-based association analyses of plasma amyloid-β (aβ) concentrations using whole exome sequence from 1,414 African and European Americans. Our goal was to identify genes that influence plasma aβ42 concentrations and aβ42:aβ40 ratios in late middle age (mean = 59 years), old age (mean = 77 years), or change over time (mean = 18 years).

Methods: Plasma aβ measures were linearly regressed onto age, gender, APOE ε4 carrier status, and time elapsed between visits (fold-changes only) separately by race.

snpGeneSets: An R Package for Genome-Wide Study Annotation.

Genome-wide studies (GWS) of SNP associations and differential gene expressions have generated abundant results; next-generation sequencing technology has further boosted the number of variants and genes identified. Effective interpretation requires massive annotation and downstream analysis of these genome-wide results, a computationally challenging task. We developed the snpGeneSets package to simplify annotation and analysis of GWS results.

The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape: A Large-Scale Genome-Wide Interaction Study.

Genome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age- and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320,485 individuals of European descent) with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium.

Genetic association and gene-smoking interaction study of carotid intima-media thickness at five GWAS-indicated genes: the Bogalusa Heart Study.

Objectives: To examine the associations of five GWAS-identified genes with carotid intima-media thickness (IMT) in a biracial sample from the Bogalusa Heart Study, and evaluate their participation in gene-smoking interactions.

Methods: Far wall IMTs of common carotid arteries were measured using high-resolution B-mode ultrasound. Both the gene-smoking interactions and single-marker associations were evaluated by linear models of carotid IMT levels, while the gene-based analyses were assessed through the truncated product method.

Gene-smoking interactions identify several novel blood pressure loci in the Framingham Heart Study.

Background: Cardiovascular diseases are among the most significant health problems in the United States. Blood pressure (BP) variability has a genetic component, and most of the genetic variance remains to be identified. One promising strategy for gene discovery is genome-wide analysis of interactions between single nucleotide polymorphisms (SNPs) and environmental factors related to cardiovascular diseases.