Publications by authors named "Launer L"

Article Synopsis
  • Smoking affects levels of good and bad cholesterol and fat in the blood, but we don't know if genetics play a role in how smoking influences these levels.
  • Researchers studied a lot of people (over 133,000) to see if genes and smoking together affect cholesterol and triglycerides, finding 13 new gene locations related to these fats.
  • It's important to include different groups of people in research, especially when looking at how lifestyle choices like smoking interact with genes, to discover new things.
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Animal models support a role for the gut microbiota in the development of hypertension. There has been a lack of epidemiological cohort studies to confirm these findings in human populations. We examined cross-sectional associations between measures of gut microbial diversity and taxonomic composition and blood pressure (BP) in 529 participants of the biracial (black and white) CARDIA study (Coronary Artery Risk Development in Young Adults).

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Article Synopsis
  • The study explores a new method to identify genetic factors associated with cerebral small vessel disease in older adults by analyzing MRI data on white matter hyperintensities and brain infarcts.
  • It uses whole exome sequencing from multiple population-based cohorts and focuses on specific candidate genes linked to Mendelian small vessel disease, such as HTRA1 and NOTCH3.
  • The findings reveal significant genetic associations that suggest common mechanisms between rare and common forms of small vessel disease, highlighting the potential of using extreme phenotypes for gene mapping.
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Introduction: Many consequences of cerebrovascular disease are identifiable by magnetic resonance imaging (MRI), but variation in methods limits multicenter studies and pooling of data. The European Union Joint Program on Neurodegenerative Diseases (EU JPND) funded the HARmoNizing Brain Imaging MEthodS for VaScular Contributions to Neurodegeneration (HARNESS) initiative, with a focus on cerebral small vessel disease.

Methods: Surveys, teleconferences, and an in-person workshop were used to identify gaps in knowledge and to develop tools for harmonizing imaging and analysis.

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Article Synopsis
  • Late-onset Alzheimer's disease (LOAD) is the most common type of dementia and is influenced by genetics.
  • Researchers studied a lot of people (94,437) to find specific genes that may increase the risk of developing LOAD, confirming 20 known ones and discovering 5 new ones.
  • They also found that certain genetic traits related to the immune system and how the brain processes proteins are linked to a higher risk of LOAD, suggesting there are more rare genes yet to be identified that could also play a role.
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Background: Performance on complex walking tasks may provide a screen for future cognitive decline.

Objective: To identify walking tasks that are most strongly associated with subsequent cognitive decline.

Methods: Community-dwelling older adults with Modified Mini-Mental State (3MS) >85 at baseline (n = 223; mean age = 78.

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Background: We investigated whether carotid intima-media thickness is associated with measures of cerebral blood flow (CBF), white matter hyperintensities, and brain volume in a biracial cohort of middle-aged individuals.

Methods: We performed a cross-sectional cohort study based on data from a multicenter, population-based study Coronary Artery Risk Development in Young Adults. Using linear and logistic regression, we estimated the association of the composite intima-media thickness measured in three segments of carotid arteries (common carotid artery, carotid artery bulb, and internal carotid artery) with volume (cm3) and CBF (mL/100 g/min) in the total brain and gray matter as well as volume of white matter hyperintensities (cm3).

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Objective: To determine whether classes of diabetes medications are associated with cognitive health and dementia risk, above and beyond their glycemic control properties.

Research Design And Methods: Findings were pooled from 5 population-based cohorts: the Framingham Heart Study, the Rotterdam Study, the Atherosclerosis Risk in Communities (ARIC) Study, the Aging Gene-Environment Susceptibility-Reykjavik Study (AGES) and the Sacramento Area Latino Study on Aging (SALSA). Differences between users and non-users of insulin, metformin and sulfonylurea were assessed in each cohort for cognitive and brain MRI measures using linear regression models, and cognitive decline and dementia/AD risk using mixed effect models and Cox regression analyses, respectively.

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Cigarette smoking has been associated with dementia and dementia-related brain changes, notably gray matter (GM) volume atrophy. These associations are thought to reflect the co-morbidity of smoking and vascular, respiratory, and substance use/psychological conditions. However, the extent and localization of the smoking-GM relationship and the degree to which vascular, respiratory, and substance use/psychological factors influence this relationship remain unclear.

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Objective: We investigated differences in the anatomical distribution of cerebral microbleeds (CMBs) on MRI, hypothesized to indicate the type of underlying cerebral small vessel disease (SVD), between Eastern and Western general populations.

Methods: We analyzed data from 11 studies identified by a PubMed search between 1996 and April 2014 according to the Preferred Reporting Items for a Systematic Review and Meta-analysis of Individual Participant Data. Study quality measures indicated low or medium risk of bias.

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A person's lipid profile is influenced by genetic variants and alcohol consumption, but the contribution of interactions between these exposures has not been studied. We therefore incorporated gene-alcohol interactions into a multiancestry genome-wide association study of levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. We included 45 studies in stage 1 (genome-wide discovery) and 66 studies in stage 2 (focused follow-up), for a total of 394,584 individuals from 5 ancestry groups.

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Importance: There are currently no proven treatments to reduce the risk of mild cognitive impairment and dementia.

Objective: To evaluate the effect of intensive blood pressure control on risk of dementia.

Design, Setting, And Participants: Randomized clinical trial conducted at 102 sites in the United States and Puerto Rico among adults aged 50 years or older with hypertension but without diabetes or history of stroke.

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Many genetic loci affect circulating lipid levels, but it remains unknown whether lifestyle factors, such as physical activity, modify these genetic effects. To identify lipid loci interacting with physical activity, we performed genome-wide analyses of circulating HDL cholesterol, LDL cholesterol, and triglyceride levels in up to 120,979 individuals of European, African, Asian, Hispanic, and Brazilian ancestry, with follow-up of suggestive associations in an additional 131,012 individuals. We find four loci, in/near CLASP1, LHX1, SNTA1, and CNTNAP2, that are associated with circulating lipid levels through interaction with physical activity; higher levels of physical activity enhance the HDL cholesterol-increasing effects of the CLASP1, LHX1, and SNTA1 loci and attenuate the LDL cholesterol-increasing effect of the CNTNAP2 locus.

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Studies have shown that inter-individual differences in grey matter, as measured by voxel-based morphometry, are coordinated between voxels. This has been done by studying covariance maps based on a limited number of seed regions. Here, we used GPU-based (Graphics Processing Unit) accelerated computing to calculate, for the first time, the aggregated map of the total structural topographical organisation in the brain on voxel level in a large sample of 960 healthy individuals in the age range 68-83 years.

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Not much is known about brain structural change in younger populations and minorities. The cross-sectional relationship between depressive symptomatology and racial discrimination with structural measures of brain tissue volume was investigated using magnetic resonance images of 710 participants in the Coronary Artery Risk Development in Young Adults CARDIA Study in 2010. Those reporting depressive symptoms and racial discrimination had lower total brain matter volume compared with those who reported neither (-8.

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Article Synopsis
  • The study aims to investigate the genetic and lifestyle factors that contribute to MRI-defined brain infarcts (BI) using large population cohorts.
  • Researchers conducted meta-analyses on data from 18 cohorts, revealing a 17.7% prevalence of BI, particularly increasing after age 65, and identified two significant genetic loci associated with BI.
  • High blood pressure and its genetic risk factors emerged as the most significant modifiable risk factors for BI, highlighting the need for more extensive datasets to confirm the findings.
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Importance: African American individuals have higher dementia risk than individuals of white race/ethnicity. They also have higher rates of type 2 diabetes, which may contribute to this elevated risk. This study examined the association of the following 2 classes of alleles at the haptoglobin (Hp) locus that are associated with poor cognition, cardiovascular disease, and mortality: Hp 1-1 (associated with poor cognition and cerebrovascular disease) and Hp 2-1 and Hp 2-2 (associated with greater risk of myocardial infarction and mortality).

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Background: Lipids are implicated in the pathogenesis of age-related macular degeneration (AMD). The relationship between systemic lipids and AMD has not been well characterized. The objective was to investigate the relationship between serum lipids and AMD in older adults using a lipidomic approach.

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Background: Organochlorine pesticides are associated with an increased risk of Parkinson's disease. A preliminary analysis from the Honolulu-Asia Aging Study suggested that heptachlor epoxide, a metabolite from an organochlorine pesticide extensively used in Hawaii, may be especially important. This was a cross sectional analysis to evaluate the association of heptachlor epoxide and other organochlorine compounds with Lewy pathology in an expanded survey of brain organochlorine residues from the longitudinal Honolulu-Asia Aging Study.

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Article Synopsis
  • - The study investigates the genetic factors influencing plasma levels of Factor VIII (FVIII) and von Willebrand factor (VWF), which are linked to both clotting disorders and thrombosis risk, using data from over 46,000 individuals across various ethnic backgrounds.
  • - Researchers discovered 13 new genetic associations with FVIII and VWF levels, including 7 associated with FVIII and 11 with VWF, extending the knowledge beyond previously known variants. Functional tests supported most of these associations.
  • - The analysis suggests that higher plasma levels of FVIII may contribute to increased risk of venous thrombosis and coronary artery disease, while elevated VWF levels might heighten the risk of ischemic stroke, highlighting the potential for these proteins
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Article Synopsis
  • Researchers studied how thick the inside of certain arteries are and the buildup of plaque in those arteries, which are important for understanding heart problems and strokes.
  • They analyzed data from over 71,000 people for artery thickness and nearly 49,000 for plaque to find new genes related to these issues.
  • The study showed connections between the thickness of arteries, plaque buildup, different types of strokes, and heart disease, helping to understand the genetic factors behind these health problems.
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Aims: Non-ischaemic cardiomyopathies (NICM) can cause heart failure and death. Cardiac magnetic resonance (CMR) detects myocardial scar/fibrosis associated with myocardial infarction (MI) and NICM with late gadolinium enhancement (LGE). The aim of this study was to determine the prevalence and prognosis of ischaemic and non-ischaemic myocardial fibrosis in a community-based sample of older adults.

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In the version of this article originally published, the name of author Martin H. de Borst was coded incorrectly in the XML. The error has now been corrected in the HTML version of the paper.

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