Publications by authors named "Clinton Wright"

Progression of cerebral small vessel disease (CSVD) is associated with cognitive decline. Blood-brain barrier disruption (BBBD) and fluid extravasation to the interstitial space may contribute to progression of white matter hyperintensities (WMH). We hypothesized that increased free water (FW) would colocalize with BBBD and relate to cognitive performance.

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Objective: Red blood cell (RBC) concentration impacts cerebrovascular disease, yet it is unclear whether RBC concentrations relate to dementia risk, particularly in racially/ethnically diverse cohorts. We investigated whether RBC concentrations associate with incident dementia risk in a diverse population of stroke-free individuals and explored whether cerebral small vessel disease (CSVD) mediates this relationship.

Methods: A longitudinal observational analysis was performed using a population-based cohort of stroke-free, older adult participants (>50 years) from the Northern Manhattan Study (NOMAS) enrolled between 2003-2008.

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Article Synopsis
  • Pulse-wave velocity (ePWV) is linked to arterial stiffness and increased cardiovascular disease risk, and this study investigated its relationship with cerebral small-vessel disease in a diverse group of 1257 participants from the NOMAS study.
  • The analysis showed a significant association between ePWV and white matter hyperintensity volume, with stronger effects observed in Hispanic and non-Hispanic Black populations, indicating racial and ethnic variations in this risk factor.
  • Findings suggest that ePWV could be a key mechanism behind adverse cerebrovascular outcomes in individuals with cerebral small-vessel disease, emphasizing the importance of monitoring this measure, especially in minority groups.
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Introduction: Arterial stiffness is linked to age-related cognitive dysfunction. Estimated pulse wave velocity (ePWV) is associated with cerebrovascular disease. We sought to determine whether ePWV was associated with cognition in a multiethnic population.

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Background And Purpose: Brain arterial luminal diameters are reliably measured with automated imaging software. Nonautomated imaging software alternatives such as a Picture Archiving Communication System are more common bedside tools used for manual measurement. This study is aimed at validating manual measurements against automated methods.

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Objective: Subclinical brain infarcts (SBI) increase the risk for stroke and dementia, but whether they should be considered equivalent to symptomatic stroke when determining blood pressure targets remains unclear. We tested whether intensive systolic blood pressure (SBP) treatment reduced the risk of new SBI or stroke and determined the association between SBI and cognitive impairment.

Methods: In this secondary analysis of SPRINT (Systolic Pressure Intervention Trial), participants ≥50 years old, with SBP 130-180mmHg and elevated cardiovascular risk but without known clinical stroke, dementia, or diabetes, were randomized to intensive (<120mmHg) or standard (<140mmHg) SBP treatment.

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Article Synopsis
  • - The study analyzed over 8,400 adults over 40 to see how the sizes of brain arteries correlate with dementia and stroke risk using MRI scans.
  • - Findings showed that larger overall and carotid artery diameters significantly increase the risk of dementia (up to 1.74 times) and stroke (up to 2.11 times for basilar arteries).
  • - The results suggest that measuring brain artery sizes through MRI could be a valuable tool for predicting dementia and stroke risk across different populations.
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Article Synopsis
  • The study investigates the link between red blood cell (RBC) concentrations, measured as hematocrit, and lacunar infarcts—small brain lesions related to ischemic stroke—using two groups: stroke-free adults and acute stroke patients.
  • Results showed that in stroke-free older adults, there is a U-shaped relationship, meaning both low and high hematocrit levels are associated with chronic covert lacunar infarcts.
  • In acute stroke patients, the study found a direct correlation where higher hematocrit levels were linked to an increased occurrence of acute lacunar strokes, suggesting that RBC concentrations might play a significant role in both chronic and acute brain injury.
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Nonvalvular atrial fibrillation is a common rhythm disorder of middle-aged to older adults that can cause ischemic strokes and systemic embolism. Lifelong use of oral anticoagulants reduces the risk of these ischemic events but increases the risk of major and clinically relevant hemorrhages. These medications also require strict compliance for efficacy, and they have nontrivial failure rates in higher-risk patients.

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Prior work in the Northern Manhattan Study (NOMAS) identified impaired cognition in cross-sectional analyses and more rapid memory decline in individuals with evidence of prior common infectious disease exposures. In this study, we sought to determine the cross-sectional relationship between prior exposure to cytomegalovirus, herpes simplex viruses 1 and 2, Chlamydia pneumoniae, and Helicobacter pylori and three magnetic resonance imaging (MRI) signatures (whole-brain cortical thickness, a previously validated AD signature, and hippocampal volume) in 455 NOMAS participants. We performed confounder-adjusted linear regression analyses between neuroimaging scores and both continuous serologies and categorical seropositivity of each pathogen, as well as a combined infectious burden index (IBI).

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Background: The progression of FLAIR white matter hyperintensities (WMHs) on MRI heralds vascular-mediated cognitive decline. Even before FLAIR WMH progression, adjacent normal appearing white matter (NAWM) already demonstrates microstructural deterioration on diffusion tensor imaging (DTI). We hypothesized that elevated DTI free water (FW) would precede FLAIR WMH progression, implicating interstitial fluid accumulation as a key pathological step in the progression of cerebral small vessel disease.

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Background: Brain perivascular spaces (PVS) are part of the glymphatic system and facilitate clearance of metabolic byproducts. Since enlarged PVS are associated with vascular health, we tested whether intensive systolic blood pressure (SBP) treatment affects PVS structure.

Methods: This is a secondary analysis of the Systolic PRessure INtervention Trial (SPRINT) MRI Substudy: a randomized trial of intensive SBP treatment to goal < 120 mm Hg vs < 140 mm Hg.

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Background: Osteopontin (OPN) is a proinflammatory cytokine that has been recently implicated in neuroinflammation and neurodegeneration. We hypothesized that an increase in plasma OPN is a deleterious neuroinflammatory marker in people with dementia and cerebral small vessel disease (CSVD).

Methods: A pilot study was conducted on participants in the Northern Manhattan Study (NOMAS).

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Objectives: Given Mediterranean-style diet (MeDi) reduces risk of cardiovascular events, we hypothesized MeDi may also be protective against intracranial large artery stenosis (ICAS), a common cause of stroke worldwide.

Methods: This cross-sectional study included stroke-free participants of the Northern Manhattan Study, a diverse population-based study of stroke risk factors. We represented MeDi continuously (range 0-8) based on enrollment food frequency questionnaires, excluding alcohol consumption.

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Article Synopsis
  • - The study addresses the issue of limited ancestral diversity in genome-wide association studies (GWAS), which makes it hard to find genetic risk variants in non-European ancestry groups, focusing on Alzheimer's Disease (AD).
  • - Researchers analyzed a multi-ancestry GWAS dataset within the Alzheimer's Disease Genetics Consortium (ADGC) involving individuals from various ancestries, identifying 13 shared risk loci and 3 ancestry-specific loci, highlighting the benefits of diverse samples.
  • - The findings underscore the importance of including underrepresented populations in genetic research, suggesting that even smaller sample sizes can lead to the discovery of novel genetic variants related to AD and implicating specific biological pathways like amyloid regulation and neuronal development.
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Background: Brain perivascular spaces (PVS) are part of the glymphatic system and facilitate clearance of metabolic byproducts. Since enlarged PVS are associated with vascular health, we tested whether intensive systolic blood pressure (SBP) treatment affects PVS structure.

Methods: This is a secondary analysis of the Systolic PRessure INTervention (SPRINT) Trial MRI Substudy: a randomized trial of intensive SBP treatment to goal < 120 mm Hg vs.

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Article Synopsis
  • The study examines the potential link between left atrial strain (LAε) and left atrial strain rate (LASR) with the risk of ischemic stroke in older adults, particularly those without a history of stroke or atrial fibrillation.
  • Conducted as part of the Cardiovascular Abnormalities and Brain Lesions study from 2005 to 2010, it involved 806 participants aged 55 or older, with follow-up interviews continuing until 2022.
  • Findings aimed to evaluate the associations of LAε and LASR using advanced imaging techniques and statistical models while adjusting for common stroke risk factors.
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Background: Brain arterial dilation and elongation characterize dolichoectasia, an arteriopathy associated with risk of stroke and death. We aim to determine whether brain arterial elongation increases the risk of stroke and death independent of brain arterial diameters.

Methods: We analyzed 1210 stroke-free participants (mean age 71±9 years, 41% men, 65% Hispanic) with available time-of-flight magnetic resonance angiogram from the Northern Manhattan Study, a population-based cohort study across a multiethnic urban community.

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Executive function is a cognitive domain with sizable heritability representing higher-order cognitive abilities. Genome-wide association studies (GWAS) of executive function are sparse, particularly in populations underrepresented in medical research. We performed a GWAS on a composite measure of executive function that included measures of mental flexibility and reasoning using data from the Northern Manhattan Study, a racially and ethnically diverse cohort (N = 1077, 69% Hispanic, 17% non-Hispanic Black and 14% non-Hispanic White).

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Background: We examined the association between asymptomatic intracranial artery stenosis (aICAS) and cortical thickness using brain magnetic resonance morphometry in two cohorts.

Methods: This cross-sectional study included stroke-free participants from the Northern Manhattan Study (NOMAS) and the National Alzheimer's Coordinating Center (NACC). We represented the predictor aICAS in NOMAS as a continuous global stenosis score reflecting an overall burden of stenosis (possible range 0-44) assessed by magnetic resonance angiography and in NACC as a dichotomous autopsy-determined Circle of Willis (CoW) atherosclerosis (none-mild vs moderate-severe).

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Background: Although protective in secondary stroke prevention of intracranial arterial stenosis (ICAS), it is uncertain if the benefits of leisure time physical activity (LTPA) extend to asymptomatic ICAS or extracranial carotid stenosis (ECAS). Therefore, we sought to determine LTPA's relationship with ECAS and ICAS in a stroke-free, race-ethnically diverse cohort.

Methods: This cross-sectional study included participants from the magnetic resonance imaging substudy of the Northern Manhattan Study, of whom 1274 had LTPA assessments at enrollment.

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