A5021852555- Dementia and Cognitive Impairment Research
- Genetic Associations and Epidemiology
- Genetics and Neurodevelopmental Disorders
- Resilience and Mental Health
- Retinal Imaging and Analysis
- Health, Environment, Cognitive Aging
- Ergonomics and Musculoskeletal Disorders
- Diet and metabolism studies
- Circadian rhythm and melatonin
- Sleep and Work-Related Fatigue
- Sleep and Wakefulness Research
- Glaucoma and retinal disorders
- Alzheimer's disease research and treatments
- Retinal and Optic Conditions
- Cognitive Abilities and Testing
- Traffic and Road Safety
- Functional Brain Connectivity Studies
- Receptor Mechanisms and Signaling
- Birth, Development, and Health
- Advanced Neuroimaging Techniques and Applications
- Sleep and related disorders
- Connexins and lens biology
- Renin-Angiotensin System Studies
- Traumatic Brain Injury Research
- Folate and B Vitamins Research
University of Washington
2007-2025
Harvard University
2013-2023
Brigham and Women's Hospital
2014-2023
Circadian (United States)
2014-2023
Seattle University
2020
Sleep and Human Health Institute
2017
Bristol-Myers Squibb (Germany)
1997
Orthopaedic Research Laboratories
1997
Orthopaedic Research
1997
University of Michigan
1997
Significance Drowsy driving is a major public health issue, particularly impacting the 9.5 million shift workers in America. Previous reports have assessed impact of night work on simulators. This real-vehicle study demonstrated increased objective and subjective drowsiness degraded daytime performance 16 night-shift while after work, deteriorating with drive duration. No near-crashes occurred during sleep; 11 night-work; all at least 45 min driving. Policy makers night-workers should...
Visual function is important for older adults. Interventions to preserve vision, such as cataract extraction, may modify dementia risk.To determine whether extraction associated with reduced risk of among adults.This prospective, longitudinal cohort study analyzed data from the Adult Changes in Thought study, an ongoing, population-based randomly selected, cognitively normal members Kaiser Permanente Washington. Study participants were 65 years age or and free at enrollment followed up...
Objective: To compare the mechanical effectiveness of three different techniques for stabilization transverse fractures patella. Design: Cadaveric knees were used to model acute test treatment in pairs knees, specimen assigned randomly a set predetermined so as provide equal numbers paired and unpaired data sets. Results then analyzed using two-way analysis variance. Setting: The are widely applicable clinical setting No specialized equipment or training is required general subspecialized...
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 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...
Studies use different instruments to measure cognitirating cognitive tests permit direct comparisons of individuals across studies and pooling data for joint analyses.
Proper functioning of the human circadian timing system is crucial to physical and mental health. Much what we know about this based on experimental protocols that induce desynchronization behavioral physiological rhythms within individual subjects, but neural (or extraneural) substrates for such are unknown. We have developed an animal model internal desynchrony in which rats exposed artificially short (22-h) light-dark cycles. Under these conditions, locomotor activity, sleep-wake,...
Importance Sex differences are established in associations between apolipoprotein E ( APOE ) ε4 and cognitive impairment Alzheimer disease (AD). However, it is unclear whether sex-specific consequences of consistent across races extend to the ε2 allele. Objective To investigate sex race modify with cognition. Design, Setting, Participants This genetic association study included longitudinal data from 4 AD aging cohorts. were older than 60 years self-identified as non-Hispanic White or Black...
Accurately assessing temporal order of cognitive decline across multiple domains is critical in Alzheimer's disease (AD). Existing literature presented controversial conclusions likely due to the use a single cohort and different analytical strategies. Harmonized composite measures memory, language executive functions from 13 cohorts ADSP-PHC data are used. A novel double anchoring events-based sigmoidal mixed model was developed using time incident AD diagnosis as scale. Decline memory...
"SuperAgers" are oldest-old adults (ages 80+) whose memory performance resembles that of in their 50s to mid-60s. Factors underlying exemplary underexplored large, racially diverse cohorts. To determine the frequency APOE genotypes non-Hispanic Black and White SuperAgers compared middle-aged 50-64), old 65-79), controls Alzheimer's disease (AD) dementia cases. This multicohort study selected data from eight longitudinal cohort studies normal aging AD. Variable recruitment criteria follow-up...
Background Some studies have suggested that glaucoma may be associated with neurodegeneration and a higher risk of dementia. Objective To evaluate whether exposure to different categories topical medications is differential dementia risks in people glaucoma. Methods We used data from Adult Changes Thought, population-based, prospective cohort study follows cognitively normal older adults Kaiser Permanente Washington (KPWA) until Alzheimer's disease (AD) related development. included...
Abstract Up to 30% of older adults meet pathological criteria for a diagnosis Alzheimer’s disease at autopsy yet never show signs cognitive impairment. Recent work has highlighted genetic drivers this resilience, or better-than-expected performance given level neuropathology, that allow the aged brain protect itself from downstream consequences amyloid and tau deposition. However, models resilience have been constrained by reliance on measures substantially limiting number participants...
Abstract Study Objectives To examine whether drivers are aware of sleepiness and associated symptoms, how subjective reports predict driving impairment physiological drowsiness. Methods Sixteen shift workers (19–65 years; 9 women) drove an instrumented vehicle for 2 hours on a closed-loop track after night sleep work. Subjective sleepiness/symptoms were rated every 15 minutes. Severe moderate was defined by emergency brake maneuvers lane deviations, respectively. Physiological drowsiness eye...
To calibrate cognitive assessment data across multiple waves of the Framingham Heart Study (FHS), addressing study design considerations, ceiling effects, and measurement precision.
To define the roles of calmodulin-stimulated adenylyl cyclases (AC1 and AC8) in morphine-induced analgesia, tolerance, physical dependence, conditioned place preference, we used mice having targeted disruptions either AC1 or AC8 genes both [double knockout (DKO)]. Mice lacking DKO did not differ from wild-type short-term antinociceptive responses to morphine measured tail-flick analgesia assay. Morphine tolerance that developed immediately within 3 h administration (10 mg/kg s.c.) was...
The effects of phosphorylation the tyrosine residue in highly conserved DRY motif expressed putative second cytoplasmic loop μ-opioid receptor were assessed after expression human embryonic kidney (HEK) 293 cells. Tyrosine kinase activation by epidermal growth factor (EGF) or hydrogen peroxide treatment effectively increased tyrosine-166 (MOR-Tyr166p) as measured a novel phosphoselective antibody. We surprised to find that increase MOR-Tyr166p immunoreactivity (ir) required coactivation...
Abstract BACKGROUND Women demonstrate a memory advantage when cognitively healthy yet lose this to men in Alzheimer's disease. However, the genetic underpinnings of sex difference performance remain unclear. METHODS We conducted largest sex‐aware study on late‐life date ( N males = 11,942; females 15,641). Leveraging harmonized composite scores from four cohorts cognitive aging and AD, we performed sex‐stratified sex‐interaction genome‐wide association studies 24,216 non‐Hispanic White 3367...
Vascular disease is a risk factor for Alzheimer's (AD) and related dementia in older adults. Retinal artery/vein occlusion (RAVO) an ophthalmic complication of systemic vascular pathology. Whether there are associations between RAVO unknown.To determine whether RAVOs associated with increased developing or AD.Data from Adult Changes Thought (ACT) study participants were analyzed. This prospective, population-based cohort followed adults (age ≥65 years) who dementia-free at enrollment...
Sleep is important for consolidation of hippocampus-dependent memories. It hypothesized that the temporal sequence nonrapid eye movement (NREM) sleep and rapid (REM) critical weakening nonadaptive memories subsequent transfer temporarily stored in hippocampus to more permanent neocortex. A great body evidence supporting this hypothesis relies on behavioral, pharmacological, neural, and/or genetic manipulations induce deprivation or stage-specific deprivation.We exploit an experimental model...
Although large-scale genome-wide association studies (GWAS) have been conducted on AD, few continuous measures of memory performance and decline.
Abstract Background/Objectives To determine the predictors of narrow angle detection in a United States population-based cohort. Materials and methods This was retrospective cohort study using Massachusetts All-Payer Claims Database. Demographic information all patients eye care provider during years 2011–2015 were extracted from All Payers Data. payers who received 1/1/2012–12/31/2015 without any previous visit 2011 included analyses. Laser peripheral iridotomy identified by Current...
Abstract Background The Alzheimer’s Disease Neuroimaging Initiative includes cognitive assessments at every study visit. We have had the opportunity to use modern psychometric approaches including confirmatory factor analysis (CFA) and item response theory (IRT) with these rich data. Here we discuss lessons learned from analyses of memory, executive functioning, language, visuospatial functioning in ADNI. Method analyzed data all ADNI waves. considered granular for each test. Our panel...
Abstract Background KBASE is a prospective cohort study launched at Seoul National University (SNU), South Korea, in 2014 using similar design and methods as the North American Alzheimer’s Disease Neuroimaging Initiative (ADNI). The consists of well‐characterized participants (420 cognitively normal, 140 mild cognitive impairment, 90 AD dementia) ( Figure 1 ). It includes systematic longitudinal collection comprehensive clinical, lifestyle data, multimodal neuroimaging, bio‐specimens for...