Assessing the Global Impact of Brain Small Vessel Disease on Cognition: The Multi-Ethnic Study of Atherosclerosis.

Introduction: We aimed to examine the global impact of brain small vessel disease (SVD) on cognitive performance.

Methods: In 892 participants from the Multi-Ethnic Study of Atherosclerosis (MESA), we derived perivascular spaces (PVS), white matter hyperintensities (WMH), microbleeds (MB), and white matter fractional anisotropy (FA) and trace (TR). Cognitive function was assessed with a comprehensive neuropsychological battery.

Plasma TAR DNA-binding protein 43 (TDP-43) levels in a population-based cohort of older adults: The cardiovascular health study.

Brain deposition of transactive response DNA-binding protein 43 (TDP-43) is a feature of neurodegenerative syndromes. We evaluated TDP-43 plasma concentrations in 1058 participants in the Cardiovascular Health Study (CHS), a population-based longitudinal cohort. The cohort was 38% male, 11% Black, had a mean age 75 years, and 261 people developed dementia over a mean of 5.

Mapping the relationships between structural brain MRI characteristics and sleep electroencephalography patterns: the Multi-Ethnic Study of atherosclerosis.

While brain morphology is well-established as a key factor influencing overall brain function, little is known about how brain structural properties are associated with oscillatory activity, particularly during sleep. In this study, we analyzed whole-night sleep electroencephalography (EEG) and brain structural MRI data from a subset of 621 individuals in the Multi-Ethnic Study of Atherosclerosis to explore the relationship between brain structure and sleep EEG properties. We found that larger total white matter (WM) volume was associated with higher absolute broad-band power, regardless of sleep stage, likely reflecting WM contribution to enhanced synchronization across cortical regions and reduced activation attenuation via long-range myelinated fibers.

Whole genome sequencing analysis of body mass index identifies novel African ancestry-specific risk allele.

Obesity is a major public health crisis associated with high mortality rates. Previous genome-wide association studies (GWAS) investigating body mass index (BMI) have largely relied on imputed data from European individuals. This study leveraged whole-genome sequencing (WGS) data from 88,873 participants from the Trans-Omics for Precision Medicine (TOPMed) Program, of which 51% were of non-European population groups.

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.

Methylome-wide association analyses of lipids and modifying effects of behavioral factors in diverse race and ethnicity participants.

Circulating lipid concentrations are clinically associated with cardiometabolic diseases. The phenotypic variance explained by identified genetic variants remains limited, highlighting the importance of searching for additional factors beyond genetic sequence variants. DNA methylation has been linked to lipid concentrations in previous studies, although most of the studies harbored moderate sample sizes and exhibited underrepresentation of non-European ancestry populations.

Polygenic risk scores for incident dementia in the Multi-Ethnic Study of Atherosclerosis.

Over 75 Alzheimer's disease (AD) and dementia-associated variants have been identified through genome-wide association studies, but the utility of polygenic risk scores (PRS) for predicting AD and dementia in diverse and admixed populations remains unclear. We compared how PRS approaches differing in -value thresholds, variant weights, and source ancestry perform in predicting dementia in 6,338 African American, Chinese, Hispanic, and White individuals from the Multi-Ethnic Study of Atherosclerosis. We tested clumping and thresholding (C+T) methods with varying parameters against Bayesian approaches (PRS-CS, PRS-CSx).

Protocol for improving equity in quantitative big data cleaning: lessons from longitudinal analysis of electronic health records from underrepresented and marginalized communities.

Background: Large biomedical datasets, including electronic health records (EHRs), are a significant source of epidemiologic data. To prepare an EHR for analysis, there are several data-cleaning approaches; here, we focus on data filtering. Common data-filtering methods employ rules that rely on data from socially constructed dominant populations but are inappropriate for marginalized populations, leading to the loss of valuable data and neglect of underrepresented communities.

A Large-Scale Genome-wide Association Study of Blood Pressure Accounting for Gene-Depressive Symptomatology Interactions in 564,680 Individuals from Diverse Populations.

Background: Gene-environment interactions may enhance our understanding of hypertension. Our previous study highlighted the importance of considering psychosocial factors in gene discovery for blood pressure (BP) but was limited in statistical power and population diversity. To address these challenges, we conducted a multi-population genome-wide association study (GWAS) of BP accounting for gene-depressive symptomatology (DEPR) interactions in a larger and more diverse sample.

Plasma proteome-wide analysis of cerebral small vessel disease identifies novel biomarkers and disease pathways.

Cerebral small vessel disease (SVD), as defined by neuroimaging characteristics such as white matter hyperintensities (WMHs), cerebral microhemorrhages (CMHs), and lacunar infarcts, is highly prevalent and has been associated with dementia risk and other clinical sequelae. Although conditions such as hypertension are known to contribute to SVD, little is known about the diverse set of subclinical biological processes and molecular mediators that may also influence the development and progression of SVD. To better understand the mechanisms underlying SVD and to identify novel SVD biomarkers, we used a large-scale proteomic platform to relate 4,877 plasma proteins to MRI-defined SVD characteristics within 1,508 participants of the Atherosclerosis Risk in Communities (ARIC) Study cohort.

Conceptual frameworks for the integration of genetic and social epidemiology in complex diseases.

Uncovering the root causes of complex diseases requires complex approaches, yet many studies continue to isolate the effects of genetic and social determinants of disease. Epidemiologic efforts that under-utilize genetic epidemiology methods and findings may lead to incomplete understanding of disease. Meanwhile, genetic epidemiology studies are often conducted without consideration of social and environmental context, limiting the public health impact of genomic discoveries.

The power of representation: Statistical analysis of diversity in US Alzheimer's disease genetics data.

Introduction: Alzheimer's disease (AD) is a complex disease influenced by genetics and environment. More than 75 susceptibility loci have been linked to late-onset AD, but most of these loci were discovered in genome-wide association studies (GWAS) exclusive to non-Hispanic White individuals. There are wide disparities in AD risk across racially stratified groups, and while these disparities are not due to genetic differences, underrepresentation in genetic research can further exacerbate and contribute to their persistence.

Development and External Validation of Models to Predict Persistent Hypoxemic Respiratory Failure for Clinical Trial Enrichment.

Objectives: Improving the efficiency of clinical trials in acute hypoxemic respiratory failure (HRF) depends on enrichment strategies that minimize enrollment of patients who quickly resolve with existing care and focus on patients at high risk for persistent HRF. We aimed to develop parsimonious models predicting risk of persistent HRF using routine data from ICU admission and select research immune biomarkers.

Design: Prospective cohorts for derivation ( n = 630) and external validation ( n = 511).

The Association of Upper Airway Anatomy with Brain Structure: The Multi-Ethnic Study of Atherosclerosis.

Sleep apnea, affecting an estimated 1 in 4 American adults, has been reported to be associated with both brain structural abnormality and impaired cognitive function. Obstructive sleep apnea is known to be affected by upper airway anatomy. To better understand the contribution of upper airway anatomy to pathways linking sleep apnea with impaired cognitive function, we investigated the association of upper airway anatomy with structural brain abnormalities.

Proteome Network Analysis Identifies Potential Biomarkers for Brain Aging.

Background: Alzheimer's disease and related dementias (ADRD) involve biological processes that begin years to decades before onset of clinical symptoms. The plasma proteome can offer insight into brain aging and risk of incident dementia among cognitively healthy adults.

Objective: To identify biomarkers and biological pathways associated with neuroimaging measures and incident dementia in two large community-based cohorts by applying a correlation-based network analysis to the plasma proteome.

Identification of circulating proteins associated with general cognitive function among middle-aged and older adults.

Identifying circulating proteins associated with cognitive function may point to biomarkers and molecular process of cognitive impairment. Few studies have investigated the association between circulating proteins and cognitive function. We identify 246 protein measures quantified by the SomaScan assay as associated with cognitive function (p < 4.

The association of upper airway anatomy with cognitive test performance: the Multi-Ethnic Study of Atherosclerosis.

Background: Numerous upper airway anatomy characteristics are risk factors for sleep apnea, which affects 26% of older Americans, and more severe sleep apnea is associated with cognitive impairment. This study explores the pathophysiology and links between upper airway anatomy, sleep, and cognition.

Methods: Participants in the Multi-Ethnic Study of Atherosclerosis underwent an upper airway MRI, polysomnography to assess sleep measures including the apnea-hypopnea index (AHI) and completed the Cognitive Abilities Screening Instrument (CASI).

Serum NfL and GFAP are associated with incident dementia and dementia mortality in older adults: The cardiovascular health study.

Introduction: Circulating neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) have been independently associated with dementia risk. Their additive association, and their associations with dementia-specific mortality, have not been investigated.

Methods: We associated serum NfL, GFAP, total tau ,and ubiquitin carboxyl-terminal hydrolase-L1, measured in 1712 dementia-free adults, with 19-year incident dementia and dementia-specific mortality risk, and with 3-year cognitive decline.

Beyond the Individual: Community-Centric Approaches to Increase Diversity in Biomedical Research.

Community-centric approaches to engage underrepresented populations-including community engagement, community-level consent practices, and capacity development for research-are means to enhance diversity in biomedical research populations in a more ethical way. Low diversity is a known problem in biomedical research that presents challenges in translating the benefits of research to the global population. Through long-term partnerships built on trust and collaboration, communities who would otherwise avoid research may be more willing to participate.

Association of immune cell subsets with incident heart failure in two population-based cohorts.

Aims: Circulating inflammatory markers are associated with incident heart failure (HF), but prospective data on associations of immune cell subsets with incident HF are lacking. We determined the associations of immune cell subsets with incident HF as well as HF subtypes [with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF)].

Methods And Results: Peripheral blood immune cell subsets were measured in adults from the Multi-Ethnic Study of Atherosclerosis (MESA) and Cardiovascular Health Study (CHS).