Publications by authors named "Oscar L Lopez"
The relationship between key energy metabolites and brain health is not well understood. We investigated the association between circulating ketone bodies, pyruvate, and citrate with cognitive decline, structural brain characteristics, and risk of dementia. We measured ketone bodies (acetoacetate, β-hydroxybutyrate, and acetone), pyruvate, and citrate species using NMR in plasma samples from 1,850 older adults in the Cardiovascular Health Study collected in 1989-90 or 1992-93.
View Article and Find Full Text PDFIntroduction: Neighborhood environments may promote neurocognitive health in part by providing amenities that encourage physical activity. We examined associations between quantity of walkable facilities, including specifically physical activity facilities (e.g.
View Article and Find Full Text PDFBackground: We aimed to develop risk tools for dementia, stroke, myocardial infarction (MI), and diabetes, for adults aged ≥ 65 years using shared risk factors.
Methods: Data were obtained from 10 population-based cohorts (N = 41,755) with median follow-up time (years) for dementia, stroke, MI, and diabetes of 6.2, 7.
Objective: There is extensive literature indicating that inflammatory pathways are affected in Alzheimer's disease (AD). We examined whether plasma exchange with albumin replacement (PE-Alb) can impact the inflammatory status of AD patients and alter the relationship between inflammatory mediators and cognitive measures.
Methods: Serum and cerebrospinal fluid (CSF) samples from 142 AD patients participating in the AMBAR trial (14-month schedule of PE-Alb treatment vs.
Article Synopsis
- Subcortical brain structures play a crucial role in various developmental and psychiatric disorders, and a study analyzed brain volumes in 74,898 individuals, identifying 254 genetic loci linked to these volumes, which accounted for up to 35% of variation.
- The research included exploring gene expression in specific neural cell types, focusing on genes involved in intracellular signaling and processes related to brain aging.
- The findings suggest that certain genetic variants not only influence brain volume but also have potential causal links to conditions like Parkinson’s disease and ADHD, highlighting the genetic basis for risks associated with neuropsychiatric disorders.
Background: Blood-based biomarkers are gaining grounds for the detection of Alzheimer's disease (AD) and related disorders (ADRDs). However, two key obstacles remain: the lack of methods for multi-analyte assessments and the need for biomarkers for related pathophysiological processes like neuroinflammation, vascular, and synaptic dysfunction. A novel proteomic method for pre-selected analytes, based on proximity extension technology, was recently introduced.
View Article and Find Full Text PDFArticle Synopsis
- Subcortical brain structures play a crucial role in various disorders, and a study analyzed the genetic basis of brain volumes in nearly 75,000 individuals of European ancestry, revealing 254 loci linked to these volumes.
- The research identified significant gene expression in neural cells, relating to brain aging and signaling, and found that polygenic scores could predict brain volumes across different ancestries.
- The study highlights genetic connections between brain volumes and conditions like Parkinson's disease and ADHD, suggesting specific gene expression patterns could be involved in neuropsychiatric disorders.
Article Synopsis
- The study investigates the genetic factors contributing to Alzheimer's disease by analyzing tau deposition through a genome-wide association study involving 3,046 participants.
- It identifies the CYP1B1-RMDN2 locus as significantly linked to tau levels, with the variant rs2113389 explaining 4.3% of tau variation, while also correlating with cognitive decline.
- Findings suggest a connection between CYP1B1 expression and tau deposition, offering potential new avenues for Alzheimer's treatment and understanding its genetic basis.
Introduction: Whether circulating levels of sphingolipids are prospectively associated with cognitive decline and dementia risk is uncertain.
Methods: We measured 14 sphingolipid species in plasma samples from 4488 participants (mean age 76.2 years; 40% male; and 25% apolipoprotein E ( ε4 allele carriers).
Background: Tau accumulation in Alzheimer's disease is associated with short term clinical progression and faster rates of cognitive decline in individuals with high amyloid-β deposition. Defining an optimal threshold of tau accumulation predictive of cognitive decline remains a challenge.
Objective: We tested the ability of regional tau PET sensitivity and specificity thresholds to predict longitudinal cognitive decline.
Background And Objectives: The clinical diagnosis of dementia with Lewy bodies (DLB) depends on identifying significant cognitive decline accompanied by core features of parkinsonism, visual hallucinations, cognitive fluctuations, and REM sleep behavior disorder (RBD). Hyposmia is one of the several supportive features. α-Synuclein seeding amplification assays (αSyn-SAAs) may enhance diagnostic accuracy by detecting pathologic αSyn seeds in CSF.
View Article and Find Full Text PDFBackground: Blood-based biomarkers are gaining grounds for Alzheimer's disease (AD) detection. However, two key obstacles need to be addressed: the lack of methods for multi-analyte assessments and the need for markers of neuroinflammation, vascular, and synaptic dysfunction. Here, we evaluated a novel multi-analyte biomarker platform, NULISAseq CNS disease panel, a multiplex NUcleic acid-linked Immuno-Sandwich Assay (NULISA) targeting ~120 analytes, including classical AD biomarkers and key proteins defining various disease hallmarks.
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- - The study investigates the genetic factors behind neuropsychiatric symptoms common in Alzheimer's disease, specifically psychosis (AD+P) and affective disturbances like depression and anxiety (AD+A).
- - Using a large sample of nearly 10,000 Alzheimer's participants, researchers found genetic correlations between AD+P and AD+A, but these two conditions also showed distinct genetic profiles when compared to psychiatric disorders in non-AD individuals.
- - The findings highlight the need for integrating genetic data to develop better treatments, as both psychosis and affective symptoms in Alzheimer's have shared and differing genetic associations.
Article Synopsis
- Vascular disease is linked to dementia risk, and the study aims to clarify how specific markers like white matter hyperintensity (WMH), clinical stroke, and blood pressure (BP) contribute to this risk.
- The research utilized a two-sample mendelian randomization approach and population-based studies, examining genetic influences on WMH, stroke, and BP in relation to Alzheimer's disease (AD) and all-cause dementia.
- Findings suggest that a higher WMH burden is causally associated with an increased risk of AD, while certain blood pressure traits might offer a protective effect against dementia.
Background: Sphingolipids are implicated in neurodegeneration and neuroinflammation. We assessed the potential role of circulating ceramides and sphingomyelins in subclinical brain pathology by investigating their association with brain magnetic resonance imaging (MRI) measures and circulating biomarkers of brain injury, neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) in the Cardiovascular Health Study (CHS), a large and intensively phenotyped cohort of older adults.
Methods: Brain MRI was offered twice to CHS participants with a mean of 5 years between scans, and results were available from both time points in 2,116 participants (mean age 76 years; 40% male; and 25% ε4 allele carriers).
This paper describes pharmacokinetic analyses of the monoamine-oxidase-B (MAO-B) radiotracer [F]()-(2-methylpyrid-5-yl)-6-[(3-fluoro-2-hydroxy)propoxy]quinoline ([F]SMBT-1) for positron emission tomography (PET) brain imaging. Brain MAO-B expression is widespread, predominantly within astrocytes. Reactive astrogliosis in response to neurodegenerative disease pathology is associated with MAO-B overexpression.
View Article and Find Full Text PDFBackground: The size/magnitude of cognitive changes after incident heart failure (HF) are unclear. We assessed whether incident HF is associated with changes in cognitive function after accounting for pre-HF cognitive trajectories and known determinants of cognition.
Methods: This pooled cohort study included adults without HF, stroke, or dementia from six US population-based cohort studies from 1971-2019: Atherosclerosis Risk in Communities Study, Coronary Artery Risk Development in Young Adults Study, Cardiovascular Health Study, Framingham Offspring Study, Multi-Ethnic Study of Atherosclerosis, and Northern Manhattan Study.
Background And Objectives: Higher YKL-40 levels in the CSF are a known biomarker of brain inflammation. We explored the utility of plasma YKL-40 as a biomarker for accelerated brain aging and dementia risk.
Methods: We performed cross-sectional and prospective analyses of 4 community-based cohorts in the United States or Europe: the Age, Gene/Environment Susceptibility-Reykjavik Study, Atherosclerosis Risk in the Communities study, Coronary Artery Risk Development in Young Adults study, and Framingham Heart Study (FHS).
Importance: Neuropsychiatric symptoms are commonly encountered and are highly debilitating in patients with Alzheimer disease. Understanding their underpinnings has implications for identifying biomarkers and treatment for these symptoms.
Objective: To evaluate whether glial markers are associated with neuropsychiatric symptoms in individuals across the Alzheimer disease continuum.