Publications by authors named "Nathaniel A. Chin"

Introduction: This study examined the association of longitudinal atrophy with baseline cerebrospinal fluid (CSF) amyloid beta (Aβ, A) and phosphorylated tau (p-tau, T) biomarkers (Aβ42/40, p-tau181) in 406 cognitively unimpaired (CU) individuals (6.670 years of follow-up on average, up to 13 imaging visits) to assess whether A+ is associated with Alzheimer's disease-like atrophy and whether this depends on p-tau181 levels.

Methods: An A-T- CU group free from abnormal neurodegeneration (N) was identified using a robust normative approach and used to model normal age-related atrophy via -scoring.

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Introduction: Understanding how a research sample compares to the population from which it is drawn can help inform future recruitment planning. We compared the Wisconsin Alzheimer's Disease Research Center (WADRC) participant sample to the Wisconsin state population (WI-pop) on key demographic, social exposome, and vascular risk measures.

Methods: The WADRC sample included 930 participants.

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Background: Alzheimer's disease (AD) can be diagnosed by in vivo abnormalities of amyloid-β plaques (A) and tau accumulation (T) biomarkers. Previous studies have shown that analyses of serial position performance in episodic memory tests, and especially, delayed primacy, are associated with AD pathology even in individuals who are cognitively unimpaired. The earliest signs of cortical tau pathology are observed in medial temporal lobe (MTL) regions, yet it is unknown if serial position markers are also associated with early tau load in these regions.

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Introduction: Targeted proteomic assays may be useful for diagnosing and staging Alzheimer's disease and related dementias (ADRD). We evaluated the performance of a 120-marker central nervous system (CNS) NUcleic acid-Linked Immuno-Sandwich Assay (NULISA) panel in samples spanning the AD spectrum.

Methods: Cross-sectional plasma samples (n=252) were analyzed using Alamar's NULISAseq CNS panel.

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Introduction: Patterns of signal from tau positron emission tomography (tau-PET) confined to the medial temporal lobe (MTL) or extended into the neocortex may be relevant for Alzheimer's disease (AD) research if they are linked to differential biomarker levels and cognitive decline.

Methods: Visual assessment of Tau-PET [F-18]florquinitau (FQT) exams from 728 initially non-demented older adults yielded four uptake groups: tau-negative (T-), MTL-only (T+), neocortex-only (T+), or both (T+). Mixed effects models assessed group differences in retrospective cognitive and plasma pTau217 trajectories.

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Introduction: Multi-etiology dementia necessitates in-vivo markers of copathologies including misfolded -synuclein (syn). We measured misfolded syn aggregates (syn-seeds) via qualitative seed amplifcation assays (synSAA) and examined relationships with markers of Alzheimer's disease (AD).

Methods: Cerebrospinal fluid (CSF) was obtained from 420 participants in two Wisconsin AD risk cohorts (35% male; 91% cognitively unimpaired; mean (SD) age, 65.

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Article Synopsis
  • The gut microbiome may play a significant role in Alzheimer's disease (AD), but more research is needed to fully understand its impact on AD pathology.
  • A study analyzed fecal microbiome data from participants in the Wisconsin Microbiome in Alzheimer's Risk Study, finding differences in gut microbiome composition between AD patients and cognitively healthy individuals, confirmed in another cohort.
  • The variations in gut microbiome features were linked to cerebrospinal fluid (CSF) biomarkers associated with AD, suggesting a connection between gut microbes and AD progression.
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  • * Results show that those with elevated amyloid levels had initial intrusive thoughts and avoidance behavior, which lessened over time, but concerns and distress about AD persisted.
  • * Participants with non-elevated amyloid levels reported feelings of happiness and relief, highlighting the differing emotional responses based on test outcomes.
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Background: Early detection of Alzheimer's disease (AD) is one of the critical components of the global response to the growing dementia crisis. Analysis of serial position performance in story recall tests has yielded sensitive metrics for the prediction of AD at low cost. In this study, we examined whether serial position markers in two story recall tests (the logical memory test, LMT, and the Craft Story 21 test, CST) were sensitive to cross-sectional biomarker-based assessment of in vivo neuropathology.

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  • COVID-19 has significantly affected global health, but most studies on dementia's impact during the pandemic have focused on Europe and Asia without differentiating dementia subtypes.
  • A study analyzing health records from 21 U.S. healthcare systems found that all-cause dementia was linked to higher mortality rates, while Alzheimer's and vascular dementia did not independently show this association.
  • Patients with any form of dementia had longer hospital stays and were less likely to be admitted to the ICU, indicating a unique set of health care challenges for these individuals during the pandemic.
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Introduction: Understanding longitudinal change in key plasma biomarkers will aid in detecting presymptomatic Alzheimer's disease (AD).

Methods: Serial plasma samples from 424 Wisconsin Registry for Alzheimer's Prevention participants were analyzed for phosphorylated-tau217 (p-tau217; ALZpath) and other AD biomarkers, to study longitudinal trajectories in relation to disease, health factors, and cognitive decline. Of the participants, 18.

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  • The study investigates the relationship between motor function and Alzheimer's disease (AD) pathology, particularly looking at brain regions involved in motor control.
  • In a sample of 206 participants, findings revealed that increased neurodegeneration and AD biomarkers (like amyloid and tau) were linked to worse motor skills, specifically dexterity and walking speed.
  • The results suggest that declines in dexterity associated with AD could indicate potential areas for non-drug therapies to improve motor function in affected individuals.
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Introduction: Recruitment and retention pose a significant challenge to Alzheimer's disease (AD) research. Returning AD biomarker results to participants has been proposed as a means to improve recruitment and retention. We present findings related to participant satisfaction, utility, and impact on research attitudes from the amyloid positron emission tomography (PET) disclosure sub-study within the Wisconsin Registry for Alzheimer's Prevention (WRAP).

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  • Published norms typically miss early cognitive changes linked to dementia, prompting the development of new standards using data from two Alzheimer's risk cohorts.
  • The research utilized quantitative regression to create both cross-sectional and longitudinal normative standards based on data from nearly 1,400 cognitively healthy participants over an average of 9 years.
  • Findings indicate that lower percentile scores correlate with cognitive impairment and higher Alzheimer’s biomarker levels, while a ShinyApp was created to help visualize scores and identify low performance.
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Background: The sensitivity of amyloid to pre-analytic factors complicates cerebrospinal fluid (CSF) diagnostics for Alzheimer disease. We report reliability and validity evidence for automated immunoassays from frozen and fresh CSF samples in an ongoing, single-site research program.

Methods: CSF samples were obtained from 2 Wisconsin cohorts (1256 measurements; 727 participants).

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Neuropsychological measures sensitive to decline in the preclinical phase of Alzheimer's disease are needed. We previously demonstrated that higher amyloid-beta (Aβ) assessed by positron emission tomography in adults without cognitive impairment was associated with recall of fewer proper names in Logical Memory story recall. The current study investigated the association between proper names and cerebrospinal fluid biomarkers (Aβ, phosphorylated tau [pTau], neurofilament light) in 223 participants from the Wisconsin Registry for Alzheimer's Prevention.

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Background: Alzheimer's disease involves accumulating amyloid (A) and tau (T) pathology, and progressive neurodegeneration (N), leading to the development of the AD clinical syndrome. While several markers of N have been proposed, efforts to define normal vs. abnormal neurodegeneration based on neuroimaging have been limited.

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Background: As Alzheimer disease (AD) biomarker testing becomes more widely available, adults may opt to learn results. Considering potential reactions to learning biomarker results can guide prebiomarker and postbiomarker testing education and counseling programs.

Methods: Cognitively healthy adults enrolled in observational Alzheimer research responded to a telephone survey about learning AD risk information (n=334; 44% Black or African American; mean age=64.

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Recommendations for communicating Alzheimer's disease (AD) biomarkers include pre-disclosure participant education and counseling, to allow individuals to make an informed decision. In a cohort of largely non-Hispanic White, cognitively unimpaired older adults from the Wisconsin Registry for Alzheimer's Prevention, we conducted a structured amyloid PET disclosure process that included knowledge assessment and education. Baseline participant knowledge about AD biomarkers and research was high, but information needs existed around dementia causes, early AD symptoms, genetic information, and psychosocial consequences of disclosure.

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