A5045713654- Alzheimer's disease research and treatments
- Genetic Associations and Epidemiology
- Dementia and Cognitive Impairment Research
- Metabolomics and Mass Spectrometry Studies
- Bioinformatics and Genomic Networks
- Health, Environment, Cognitive Aging
- Vitamin D Research Studies
- Nutritional Studies and Diet
- Tryptophan and brain disorders
- Nutrition, Genetics, and Disease
- Diet and metabolism studies
- Folate and B Vitamins Research
- Health disparities and outcomes
- Telomeres, Telomerase, and Senescence
- Epigenetics and DNA Methylation
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Cognitive Abilities and Testing
- Gut microbiota and health
- Genetic Mapping and Diversity in Plants and Animals
- Noise Effects and Management
- Resilience and Mental Health
- Stress Responses and Cortisol
- Urban Transport and Accessibility
- Genetic and phenotypic traits in livestock
- Liver Disease Diagnosis and Treatment
University of Wisconsin–Madison
2016-2025
William S. Middleton Memorial Veterans Hospital
2017-2024
Geriatric Research Education and Clinical Center
2017-2024
Royal College of Physicians
2024
Columbia University
2024
Alzheimer's Association
2017-2022
University of Wisconsin Health
2014-2021
University of California, San Francisco
2017-2019
Alzheimer’s Disease Neuroimaging Initiative
2019
University College London
2017-2019
Random forest (RF) is a machine-learning method that generally works well with high-dimensional problems and allows for nonlinear relationships between predictors; however, the presence of correlated predictors has been shown to impact its ability identify strong predictors. The Forest-Recursive Feature Elimination algorithm (RF-RFE) mitigates this problem in smaller data sets, but approach not tested omics sets. We integrated 202,919 genotypes 153,422 methylation sites 680 individuals,...
Trimethylamine N-oxide (TMAO), a small molecule produced by the metaorganismal metabolism of dietary choline, has been implicated in human disease pathogenesis, including known risk factors for Alzheimer's (AD), such as metabolic, cardiovascular, and cerebrovascular disease. In this study, we tested whether TMAO is linked to AD examining levels cerebrospinal fluid (CSF) collected from large sample (n = 410) individuals with clinical syndrome 40), mild cognitive impairment (MCI) 35),...
Understanding how metabolites are longitudinally influenced by age and sex could facilitate the identification of metabolomic profiles trajectories that indicate disease risk. We investigated metabolomics using longitudinal plasma samples from Wisconsin Registry for Alzheimer's Prevention (WRAP), a cohort participants who were dementia free at enrollment. Metabolomic quantified 2,344 fasting among 1,212 participants, each with up to three study visits. Of 1,097 tested, 623 (56.8%) associated...
Vitamin D deficiency is associated with many adverse health outcomes, yet little known about the genetic epidemiology of vitamin or its metabolites.Our objective was to examine relationship among three D-related genes and levels 25-hydroxyvitamin [25(OH)D] 1,25-dihydroxyvitamin [1,25(OH)2D] in Hispanics (HAs) African Americans (AAs).The cross-sectional Insulin Resistance Atherosclerosis Family Study recruited examined subjects in: Los Angeles, California (AAs; 513 individuals from 42...
Context: Previous studies have suggested vitamin D insufficiency is associated with increased obesity; however, the relationship between 25-hydroxyvitamin (25[OH]D) and 1,25-dihydroxyvitamin (1,25[OH]2D) measures of adiposity has not been well characterized in minority populations. Objective: The objective study was to examine levels 25[OH]D 1,25[OH]2D Hispanic African-Americans at baseline on change these over time. Design Setting: Insulin Resistance Atherosclerosis (IRAS) Family Study...
We tested variants in genes related to lutein and zeaxanthin status for association with age-related macular degeneration (AMD) the Carotenoids Age-Related Eye Disease Study (CAREDS).Of 2005 CAREDS participants, 1663 were graded AMD from fundus photography genotyped 424 single nucleotide polymorphisms (SNPs) 24 candidate carotenoid status. Of 337 cases 91% had early or intermediate AMD. The SNPs individually using logistic regression. A carotenoid-related genetic risk model was built...
Polygenic risk scores (PRSs) have been used to combine the effects of variants with small identified by genome-wide association studies. We explore potential for using pathway-specific PRSs as predictors early changes in Alzheimer's disease (AD)-related biomarkers and cognitive funct ion. Participants were from Wisconsin Registry Prevention, a longitudinal study adults who cognitively asymptomatic at enrollment enriched parental history AD. Using genes associated AD International Genomics...
Abstract Approximately 30% of older adults exhibit the neuropathological features Alzheimer’s disease without signs cognitive impairment. Yet, little is known about genetic factors that allow these potentially resilient individuals to remain cognitively unimpaired in face substantial neuropathology. We performed a large, genome-wide association study (GWAS) two previously validated metrics resilience quantified using latent variable modelling approach and representing better-than-predicted...
Abstract The study of metabolomics and disease has enabled the discovery new risk factors, diagnostic markers, drug targets. For neurological psychiatric phenotypes, cerebrospinal fluid (CSF) is particular importance. However, CSF metabolome difficult to on a large scale due relative complexity procedure needed collect fluid. Here, we present metabolome-wide association (MWAS), which uses genetic metabolomic data impute metabolites into samples with genome-wide summary statistics. We conduct...
Alzheimer's disease biomarkers are becoming increasingly important for characterizing the longitudinal course of disease, predicting timing clinical and cognitive symptoms, recruitment treatment monitoring in trials. In this work, we develop evaluate three methods modelling amyloid accumulation cohorts using PET imaging. We then use these novel approaches to investigate factors that influence onset from impairment continuum. Data were acquired Disease Neuroimaging Initiative (ADNI),...
Abstract Approximately 30% of elderly adults are cognitively unimpaired at time death despite the presence Alzheimer’s disease neuropathology autopsy. Studying individuals who resilient to cognitive consequences may uncover novel therapeutic targets treat disease. It is well established that there sex differences in response pathology, and growing evidence suggests genetic factors contribute these differences. Taken together, we sought elucidate sex-specific drivers resilience. We extended...
Abstract INTRODUCTION A hallmark of Alzheimer's disease (AD) is the aggregation proteins (amyloid beta [A] and hyperphosphorylated tau [T]) in brain, making cerebrospinal fluid (CSF) particular interest. METHODS We conducted a CSF proteome‐wide analysis among participants varying AT pathology ( n = 137 participants; 915 proteins) with nine biomarkers neurodegeneration neuroinflammation. RESULTS identified 61 significantly associated category P < 5.46 × 10 −5 ) 636 significant...
The relationship between elevated blood pressure and cardiovascular cerebrovascular disease risk is well accepted. Both systolic diastolic hypertension are associated with this increase, but appears to be a more important determinant of than pressure. Subjects for study derived from the Framingham Heart Study data set. Each subject had five records clinical which pressure, age, height, gender, weight, treatment were selected characterize phenotype in analysis. We modeled as function age...
Evidence-based public health requires the existence of reliable information systems for priority setting and evaluation interventions. Existing data in United States are either too crude (e.g., vital statistics), rely on administrative Medicare) or, because their national scope NHANES), lack discriminatory power to assess specific needs evaluate community activities at state local level. This manuscript describes rationale methods Survey Health Wisconsin (SHOW), a novel infrastructure...
To investigate genetic determinants of macular pigment optical density in women from the Carotenoids Age-Related Eye Disease Study (CAREDS), an ancillary study Women's Health Initiative Observational Study.1585 2005 CAREDS participants had (MPOD) measured noninvasively using customized heterochromatic flicker photometry and blood samples genotyped for 440 single nucleotide polymorphisms (SNPs) 26 candidate genes related to absorption, transport, binding, cleavage carotenoids directly, or via...
Abstract Introduction The present study investigated the relationship between beta‐amyloid (Aβ) and cognition in a late middle‐aged cohort at risk for Alzheimer's disease (AD). Methods One eighty‐four participants (mean age = 60; 72% parental history of AD) completed [C‐11]Pittsburgh compound B positron emission tomography scan serial cognitive evaluations. A global measure Aβ burden was calculated, composite scores assessing learning, delayed memory, executive functioning were computed....
Introduction The Survey of the Health Wisconsin (SHOW) was established in 2008 by University (UW) School Medicine and Public (SMPH) with goals (1) providing a timely accurate picture health state residents; (2) serving as an agile resource infrastructure for ancillary studies. Today, SHOW program continues to serve unique vital population research advancing public health. Methods currently includes 5,846 adult 980 minor participants recruited between 2019 four primary waves. WAVE I...
Detecting cognitive decline in presymptomatic Alzheimer's disease (AD) and early mild impairment (MCI) is challenging, but important for treatments targeting AD-related neurodegeneration. The current study aimed to investigate the utility performance of internally developed robust norms standard identifying late middle-age (baseline age range = 36-68; M 54).Robust were neuropsychological measures based on longitudinally confirmed cognitively normal (CN) participants (n= 476). Seven hundred...