20 results match your criteria: "MA (I.J.D.); Harvard Stem Cell Institute[Affiliation]"
Assessing the representativeness of cluster randomized trials: Evidence from two large pragmatic trials in United States nursing homes.
Clin Trials
December 2023
CAUSALab, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Background/aims: When the randomized clusters in a cluster randomized trial are selected based on characteristics that influence treatment effectiveness, results from the trial may not be directly applicable to the target population. We used data from two large nursing home-based pragmatic cluster randomized trials to compare nursing home and resident characteristics in randomized facilities to eligible non-randomized and ineligible facilities.
Methods: We linked data from the high-dose influenza vaccine trial and the Music & Memory Pragmatic TRIal for Nursing Home Residents with ALzheimer's Disease (METRICaL) to nursing home assessments and Medicare fee-for-service claims.
Multivariate genetic analysis of personality and cognitive traits reveals abundant pleiotropy.
Nat Hum Behav
September 2023
NORMENT Centre, Institute of Clinical Medicine, University of Oslo and Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
Personality and cognitive function are heritable mental traits whose genetic foundations may be distributed across interconnected brain functions. Previous studies have typically treated these complex mental traits as distinct constructs. We applied the 'pleiotropy-informed' multivariate omnibus statistical test to genome-wide association studies of 35 measures of neuroticism and cognitive function from the UK Biobank (n = 336,993).
View Article and Find Full Text PDFChallenges in Estimating the Effectiveness of COVID-19 Vaccination Using Observational Data.
Ann Intern Med
May 2023
Population Health Sciences, University of Bristol; NIHR Bristol Biomedical Research Centre; and Health Data Research UK South West Better Care Partnership, Bristol, United Kingdom (J.A.C.S.).
The COVID-19 vaccines were developed and rigorously evaluated in randomized trials during 2020. However, important questions, such as the magnitude and duration of protection, their effectiveness against new virus variants, and the effectiveness of booster vaccination, could not be answered by randomized trials and have therefore been addressed in observational studies. Analyses of observational data can be biased because of confounding and because of inadequate design that does not consider the evolution of the pandemic over time and the rapid uptake of vaccination.
View Article and Find Full Text PDFMutant-RB1 circulating tumor DNA in the blood of unilateral retinoblastoma patients: What happens during enucleation surgery: A pilot study.
PLoS One
February 2023
Department of Surgery, Ophthalmic Oncology Service, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America.
Cell free DNA (cfDNA) and circulating tumor cell free DNA (ctDNA) from blood (plasma) are increasingly being used in oncology for diagnosis, monitoring response, identifying cancer causing mutations and detecting recurrences. Circulating tumor RB1 DNA (ctDNA) is found in the blood (plasma) of retinoblastoma patients at diagnosis before instituting treatment (naïve). We investigated ctDNA in naïve unilateral patients before enucleation and during enucleation (6 patients/ 8 mutations with specimens collected 5-40 minutes from severing the optic nerve) In our cohort, following transection the optic nerve, ctDNA RB1 VAF was measurably lower than pre-enucleation levels within five minutes, 50% less within 15 minutes and 90% less by 40 minutes.
View Article and Find Full Text PDFCirculating Metabolome and White Matter Hyperintensities in Women and Men.
Circulation
April 2022
The Hospital for Sick Children (E.S., J.S., Z.P.), University of Toronto, Canada.
Background: White matter hyperintensities (WMH), identified on T2-weighted magnetic resonance images of the human brain as areas of enhanced brightness, are a major risk factor of stroke, dementia, and death. There are no large-scale studies testing associations between WMH and circulating metabolites.
Methods: We studied up to 9290 individuals (50.
DNA Methylation and Protein Markers of Chronic Inflammation and Their Associations With Brain and Cognitive Aging.
Neurology
December 2021
From the Lothian Birth Cohorts Group, Department of Psychology (E.L.S.C., S.M.M., S.E.H., M.d.C.V.H., M.A.H., J.M.W., I.J.D., R.E.M., S.R.C.), Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer (E.L.S.C., A.J.S., R.E.M.), Centre for Clinical Brain Sciences (E.L.S.C., S.M.M., M.d.C.V.H., M.E.B., J.M.W., H.C.W.), UK Dementia Research Institute, Edinburgh Medical School (A.J.S., V.E.M.), Division of Psychiatry, Royal Edinburgh Hospital (C.G., M.A.H., H.C.W.), and The Queen's Medical Research Institute, Edinburgh BioQuarter (V.E.M.), University of Edinburgh, UK.
Background And Objectives: To investigate chronic inflammation in relation to cognitive aging by comparison of an epigenetic and serum biomarker of C-reactive protein and their associations with neuroimaging and cognitive outcomes.
Methods: At baseline, participants (n = 521) were cognitively normal, around 73 years of age (mean 72.4, SD 0.
Association of common genetic variants with brain microbleeds: A genome-wide association study.
Neurology
December 2020
From the Departments of Epidemiology (M.J.K., H.H.H.A., D.V., S.J.v.d.L., P.Y., M.W.V., N.A., C.M.v.D., M.A.I.), Radiology and Nuclear Medicine (H.H.H.A., P.Y., A.v.d.L., M.W.V.), and Clinical Genetics (H.H.H.A.), Erasmus MC University Medical Center, Rotterdam, the Netherlands; Stroke Research Group, Department of Clinical Neurosciences (D.L., M.T., J.L., D.J.T., H.S.M.), University of Cambridge, UK; Department of Neurology (J.R.J.R., C.L.S., J.J.H., A.S.B., C.D., S. Seshadri), Boston University School of Medicine; The Framingham Heart Study (J.R.J.R., C.L.S., J.J.H., A.S.B., S. Seshadri), MA; Department of Biostatistics (A.V.S.), University of Michigan, Ann Arbor; Icelandic Heart Association (A.V.S., S. Sigurdsson, V.G.), Kopavogur, Iceland; Brown Foundation Institute of Molecular Medicine, McGovern Medical School (M.F.), and Human Genetics Center, School of Public Health (M.F.), University of Texas Health Science Center at Houston; Clinical Division of Neurogeriatrics, Department of Neurology (E.H., L.P., R.S.), Institute for Medical Informatics, Statistics and Documentation (E.H.), and Gottfried Schatz Research Center, Department of Molecular Biology and Biochemistry (Y.S., H.S.), Medical University of Graz, Austria; Center of Cerebrovascular Diseases, Department of Neurology (J.L.), West China Hospital, Sichuan University, Chengdu; Stroke Research Centre, Queen Square Institute of Neurology (I.C.H., D.W., H.H., D.J.W.), University College London, UK; Department of Neurosurgery (I.C.H.), Klinikum rechts der Isar, University of Munich, Germany; Centre for Cognitive Ageing and Cognitive Epidemiology, Psychology (M.L., D.C.M.L., M.E.B., I.J.D., J.M.W.), and Centre for Clinical Brain Sciences, Edinburgh Imaging, UK Dementia Research Institute (M.E.B., J.M.W.), University of Edinburgh, UK; Department of Internal Medicine, Section of Gerontology and Geriatrics (S.T.), Department of Cardiology (S.T., J.v.d.G., J.W.J.), Section of Molecular Epidemiology, Biomedical Data Sciences (E.B.v.d.A., M.B., P.E.S.), Leiden Computational Biology Center, Biomedical Data Sciences (E.B.v.d.A.), Department of Radiology (J.v.d.G.), and Einthoven Laboratory for Experimental Vascular Medicine (J.W.J.), Leiden University Medical Center, the Netherlands; Department of Neurology (A.-K.G., N.S.R.), Massachusetts General Hospital, Harvard Medical School, Boston; Memory Aging and Cognition Center (S.H., C.C.), National University Health System, Singapore; Department of Pharmacology (S.H., C.C.) and Saw Swee Hock School of Public Health (S.H.), National University of Singapore and National University Health System, Singapore; Pattern Recognition & Bioinformatics (E.B.v.d.A.), Delft University of Technology, the Netherlands; Department of Biostatistics (S.L., J.J.H., Q.Y., A.S.B.), Boston University School of Public Health, MA; Department of Radiology (C.R.J., K.K.), Mayo Clinic, Rochester, MN; Glenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases (C.L.S., S. Seshadri), UT Health San Antonio, TX; Department of Medicine, Division of Geriatrics (B.G.W., T.H.M), and Memory Impairment and Neurodegenerative Dementia (MIND) Center (T.H.M.), University of Mississippi Medical Center, Jackson; Singapore Eye Research Institute (C.Y.C., J.Y.K., T.Y.W.); Department of Neuroradiology (Z.M., J.M.W.), NHS Lothian, Edinburgh; Institute of Cardiovascular and Medical Sciences (D.J.S.), College of Medical, Veterinary and Life Sciences, University of Glasgow, UK; Division of Cerebrovascular Neurology (R.F.G.), Johns Hopkins University, Baltimore, MD; Department of Neuroradiology (A.D.M.), Atkinson Morley Neurosciences Centre, St George's NHS Foundation Trust, London, UK; Department of Neurology (C.D.), University of California at Davis; Nuffield Department of Population Health (C.M.v.D.), University of Oxford, UK; Laboratory of Epidemiology and Population Sciences (L.J.L.), National Institute on Aging, Baltimore, MD; and Faculty of Medicine (V.G.), University of Iceland, Reykjavik, Iceland.
Objective: To identify common genetic variants associated with the presence of brain microbleeds (BMBs).
Methods: We performed genome-wide association studies in 11 population-based cohort studies and 3 case-control or case-only stroke cohorts. Genotypes were imputed to the Haplotype Reference Consortium or 1000 Genomes reference panel.
Whole Blood DNA Methylation Signatures of Diet Are Associated With Cardiovascular Disease Risk Factors and All-Cause Mortality.
Circ Genom Precis Med
August 2020
Population Sciences Branch, National Heart, Lung, and Blood Institute, NIH, Bethesda, MD & the Framingham Heart Study, Framingham, MA (J.M., T.H., C.L., M.M.M., R.J., D.L.).
Background: DNA methylation patterns associated with habitual diet have not been well studied.
Methods: Diet quality was characterized using a Mediterranean-style diet score and the Alternative Healthy Eating Index score. We conducted ethnicity-specific and trans-ethnic epigenome-wide association analyses for diet quality and leukocyte-derived DNA methylation at over 400 000 CpGs (cytosine-guanine dinucleotides) in 5 population-based cohorts including 6662 European ancestry, 2702 African ancestry, and 360 Hispanic ancestry participants.
Common Genetic Variation Indicates Separate Causes for Periventricular and Deep White Matter Hyperintensities.
Stroke
July 2020
GeneSTAR Research Program (L.R.Y., B.G.K., L.C.B., P.A.N.), Johns Hopkins University School of Medicine, Baltimore, MD.
Background And Purpose: Periventricular white matter hyperintensities (WMH; PVWMH) and deep WMH (DWMH) are regional classifications of WMH and reflect proposed differences in cause. In the first study, to date, we undertook genome-wide association analyses of DWMH and PVWMH to show that these phenotypes have different genetic underpinnings.
Methods: Participants were aged 45 years and older, free of stroke and dementia.
Hypertension Development by Midlife and the Roles of Premorbid Cognitive Function, Sex, and Their Interaction.
Hypertension
April 2019
From the Department of Psychology (D.M.A., C.W., I.J.D.), University of Edinburgh, United Kingdom.
Higher early-life cognitive function is associated with better later-life health outcomes, including hypertension. Associations between higher prior cognitive function and less hypertension persist even when accounting for socioeconomic status, but socioeconomic status-hypertension gradients are more pronounced in women. We predicted that differences in hypertension development between sexes might be associated with cognitive function and its interaction with sex, such that higher early-life cognitive function would be associated with lower hypertension risk more in women than in men.
View Article and Find Full Text PDFMetabolic Maturation of Human Pluripotent Stem Cell-Derived Cardiomyocytes by Inhibition of HIF1α and LDHA.
Circ Res
October 2018
From the Cardiovascular Research Center, Massachusetts General Hospital, Boston (D.H., A.L., A.Y., L.X., D.J.M., I.J.D.).
Rationale: Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) are a readily available, robustly reproducible, and physiologically appropriate human cell source for cardiac disease modeling, drug discovery, and toxicity screenings in vitro. However, unlike adult myocardial cells in vivo, hPSC-CMs cultured in vitro maintain an immature metabolic phenotype, where majority of ATP is produced through aerobic glycolysis instead of oxidative phosphorylation in the mitochondria. Little is known about the underlying signaling pathways controlling hPSC-CMs' metabolic and functional maturation.
View Article and Find Full Text PDFExome Chip Analysis Identifies Low-Frequency and Rare Variants in MRPL38 for White Matter Hyperintensities on Brain Magnetic Resonance Imaging.
Stroke
August 2018
From the Institute of Molecular Medicine, McGovern Medical School at The University of Texas Health Science Center at Houston (M.F., X.J.).
Article Synopsis
- White matter hyperintensities (WMH) on brain MRIs are indicators of small vessel disease and preclinical neurological disorders, but current knowledge on their genetic influences is limited, especially regarding low-frequency and rare coding variants.
- A study involving over 20,000 stroke and dementia-free adults explored the genetic contributions to WMH by analyzing a mix of common and low-frequency variants across different ethnic backgrounds.
- The research found significant associations with common variants in several genes (like TRIM65) and identified novel low-frequency variants in MRPL38, suggesting that both common and rare genetic factors play a role in WMH burden, despite limitations in replication of findings.
Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function.
Nat Commun
May 2018
Centre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology, School of Philosophy, Psychology and Language Sciences, The University of Edinburgh, Edinburgh, EH8 9JZ, UK.
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.
View Article and Find Full Text PDFNovel Mutation in (Filamin C) Causes Familial Restrictive Cardiomyopathy.
Circ Cardiovasc Genet
December 2017
From the Cardiovascular Research Center, Massachusetts General Hospital, Charlestown (N.R.T., M.A.M., D.H., J.Y., V.A.P., R.W.M., S.C., E.D., D.J.M., M.L., S.A.L., I.J.D., P.T.E.); Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA (N.R.T., J.Y., V.A.P., S.A.L., H.L., P.T.E.); Department of Medicine I, Klinikum Grosshadern, University of Munich (LMU), Germany (S.C.); German Centre for Cardiovascular Research, Partner site Munich, Germany (S.C.); Division of Cardiology (M.A.S., D.J.M., N.S.S., M.L., S.A.L., I.J.D., P.T.E.) and Department of Pathology, Center for Systems Biology (J.R.S.), Massachusetts General Hospital, Boston; and Computational Biomedicine Section, Department of Medicine, Boston University School of Medicine, MA (H.L.).
Background: Restrictive cardiomyopathy (RCM) is a rare cardiomyopathy characterized by impaired diastolic ventricular function resulting in a poor clinical prognosis. Rarely, heritable forms of RCM have been reported, and mutations underlying RCM have been identified in genes that govern the contractile function of the cardiomyocytes.
Methods And Results: We evaluated 8 family members across 4 generations by history, physical examination, electrocardiography, and echocardiography.
Novel Blood Pressure Locus and Gene Discovery Using Genome-Wide Association Study and Expression Data Sets From Blood and the Kidney.
Hypertension
September 2017
Center for Complex Disease Genomics, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD (D.E.A., P.N., A. Chakravarti, G.B.E.).
Elevated blood pressure is a major risk factor for cardiovascular disease and has a substantial genetic contribution. Genetic variation influencing blood pressure has the potential to identify new pharmacological targets for the treatment of hypertension. To discover additional novel blood pressure loci, we used 1000 Genomes Project-based imputation in 150 134 European ancestry individuals and sought significant evidence for independent replication in a further 228 245 individuals.
View Article and Find Full Text PDFEpigenetic Patterns in Blood Associated With Lipid Traits Predict Incident Coronary Heart Disease Events and Are Enriched for Results From Genome-Wide Association Studies.
Circ Cardiovasc Genet
January 2017
From the Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory (Å.K.H., S.G., E.I.) and Department of Medical Sciences, Molecular Medicine and Science for Life Laboratory (J.K.S.), Uppsala University, Sweden; Cardiovascular Medicine unit, Department of Medicine Solna, Karolinska Institute, Stockholm, Sweden (Å.K.H.) Framingham Heart Study, MA (M.M.M., R.J., C.Y., C.L., T.H., S.D., L.A.C., D.L.); Department of Biostatistics (C.L., L.A.C., S.D.), Boston University, MA; Boston University, MA (M.M.M.); Department of Cardiology, Boston Children's Hospital, MA (M.M.M.); Population Sciences Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD (M.M.M., R.J., C.Y., C.L., T.H., D.L.); Centre for Cognitive Ageing and Cognitive Epidemiology (R.E.M., J.M.S., I.J.D.), Medical Genetics Section, Centre for Genomics and Experimental Medicine, Institute of Genetics and Molecular Medicine (R.E.M.), Alzheimer Scotland Dementia Research Centre (J.M.S.), and Department of Psychology (I.J.D.), University of Edinburgh, United Kingdom; Queensland Brain Institute, The University of Queensland, Brisbane, Australia (R.E.M., A.F.M., S.S.); Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia (S.S., A.F.M.); Hebrew Senior Life, Harvard Medical School, Boston, MA (R.J.); Department of Epidemiology, School of Public Health (M.R.I.) and Department of Biostatistics, Section on Statistical Genetics (D.Z.), University of Alabama at Birmingham; Department of Biostatistics, Harvard School of Public Health, Boston, MA (L. Liang); William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, United Kingdom (P.D.); Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders (PACER-HD), King Abdulaziz University, Jeddah, Saudi Arabia (P.D.); Department of Twin Research and Genetic Epidemiology, King's College London, United Kingdom (T.D.S.); Deparment of Medical Sciences, Cardiovascular Epidemiology, Uppsala University Hospital, Sweden (J.S., L.L.); Children's Hospital Oakland Research Institute, CA (R.M.K.); College of Public Health, University of Kentucky, Lexington (D.K.A.); and Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, CA (E.I.).
Background: Genome-wide association studies have identified loci influencing circulating lipid concentrations in humans; further information on novel contributing genes, pathways, and biology may be gained through studies of epigenetic modifications.
Methods And Results: To identify epigenetic changes associated with lipid concentrations, we assayed genome-wide DNA methylation at cytosine-guanine dinucleotides (CpGs) in whole blood from 2306 individuals from 2 population-based cohorts, with replication of findings in 2025 additional individuals. We identified 193 CpGs associated with lipid levels in the discovery stage (<1.
Polygenic risk of ischemic stroke is associated with cognitive ability.
Neurology
February 2016
From the Centre for Cognitive Ageing and Cognitive Epidemiology (S.E.H., R. Marioni, C.L.M.S., M.E.B., J.M.S., D.J.P., J.M.W., I.J.D.), Centre for Clinical Brain Sciences (C.L.M.S., M.E.B., J.M.W.), Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine (C.H.), Alzheimer Scotland Dementia Research Centre (J.M.S.), and Department of Psychology (I.J.D.), University of Edinburgh; Medical Genetics Section (S.E.H., R. Marioni, A.C., C.L.M.S., D.J.P.), University of Edinburgh Centre for Genomic and Experimental Medicine and MRC Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, UK; Institute for Stroke and Dementia Research (R. Malik), Klinikum der Universität München, Ludwig-Maximilians-Universität, Munich, Germany; Queensland Brain Institute (R. Marioni), The University of Queensland, Brisbane, Australia; Department of Neurology (S.S.), Boston University School of Medicine, Framingham; The Framingham Heart Study (S.S.), Framingham, MA; and Departments of Neurology and Public Health Sciences (B.B.W.), University of Virginia, Charlottesville.
Objectives: We investigated the correlation between polygenic risk of ischemic stroke (and its subtypes) and cognitive ability in 3 relatively healthy Scottish cohorts: the Lothian Birth Cohort 1936 (LBC1936), the Lothian Birth Cohort 1921 (LBC1921), and Generation Scotland: Scottish Family Health Study (GS).
Methods: Polygenic risk scores for ischemic stroke were created in LBC1936 (n = 1005), LBC1921 (n = 517), and GS (n = 6,815) using genome-wide association study summary data from the METASTROKE collaboration. We investigated whether the polygenic risk scores correlate with cognitive ability in the 3 cohorts.
Genes from a translational analysis support a multifactorial nature of white matter hyperintensities.
Stroke
February 2015
From the Centre for Cognitive Ageing and Cognitive Epidemiology (L.M.L., M.V.H., S.M.M., M.E.B., J.S., I.J.D., J.M.W.), Division of Neuroimaging Sciences, Brain Research Imaging Centre, (M.V.H., S.M.M., M.E.B., J.M.W.) and Academic Neuropathology (C.S.), Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom; Centre for Cognitive Ageing and Cognitive Epidemiology, Medical Genetics Section, University of Edinburgh Centre for Genomics and Experimental Medicine and MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom (W.D.H., S.E.H., D.J.P.); Department of Bioengineering, Imperial College London, London, United Kingdom (E.B.); BHF Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom (M.M., J.M., D.G., A.D.); Department of Biostatistics, Boston University School of Public Health, MA (Q.Y.); The Framingham Heart Study, Boston, MA (Q.Y., S.S.); The Human Genetics Center and Institute of Molecular Medicine, The University of Texas Health Science Center, Houston (M.F.); Departments of Epidemiology, Radiology and Neurology, Erasmus Medical Center, Rotterdam, The Netherlands (M.A.I.); Netherlands Consortium for Healthy Aging, Leiden, The Netherlands (M.A.I.); 12 INSERM U740 (Paris 7 University) and U708 (Bordeaux University), Bordeaux, France (S.D.); Department of Neurology, Lariboisière Hospital, 7 University, DHU Neurovasc Paris Sorbonne, Paris, France (S.D.); University of Versailles Saint-Quentin-en-Yvelines, Versailles, France (S.D.); Department of Neurology, Boston University School of Medicine, MA (S.D., S.S.); Laboratory of Epidemiology and Population Sciences, Intramural Research Program, National Institute on Aging, National Institutes of Health, Bethesda, MD (L.L.); Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle (J.C.B.); and Clinical Division of Neurogeri
Background And Purpose: White matter hyperintensities (WMH) of presumed vascular origin increase the risk of stroke and dementia. Despite strong WMH heritability, few gene associations have been identified. Relevant experimental models may be informative.
View Article and Find Full Text PDFPersistent integration of reprogramming factors impairs the in vitro cardiogenic potential of induced pluripotent stem cells.
Circ Cardiovasc Genet
October 2014
From the Cell and Tissue Engineering Group, Institute of Bioengineering and Nanotechnology, Singapore, Singapore (N.M.); and Cardiology Division, Cardiovascular Research Center, Massachusetts General Hospital, Boston (I.J.D.); Harvard Medical School, Boston, MA (I.J.D.); Harvard Stem Cell Institute, Cambridge, MA (I.J.D.).
Vascular risk factors, large-artery atheroma, and brain white matter hyperintensities.
Neurology
April 2014
From the Centre for Clinical Brain Sciences (J.M.W., F.N.D., M.V.H., Z.M., M.B., M.S.D.) and Centre for Cognitive Ageing and Cognitive Epidemiology (M.A., M.V.H., A.J.G., M.B., J.M.S., I.J.D.), University of Edinburgh, UK.
Objective: To determine the magnitude of potentially causal relationships among vascular risk factors (VRFs), large-artery atheromatous disease (LAD), and cerebral white matter hyperintensities (WMH) in 2 prospective cohorts.
Methods: We assessed VRFs (history and measured variables), LAD (in carotid, coronary, and leg arteries), and WMH (on structural MRI, visual scores and volume) in: (a) community-dwelling older subjects of the Lothian Birth Cohort 1936, and (b) patients with recent nondisabling stroke. We analyzed correlations, developed structural equation models, and performed mediation analysis to test interrelationships among VRFs, LAD, and WMH.