Publications by authors named "Justin B Miller"

Introduction: Understanding how contextual socioeconomic factors are associated with psychosocial distress among different ethnoracial groups is important for addressing health disparities in individuals at risk for Alzheimer's disease.

Methods: Using Health and Aging Brain Study-Health Disparities (HABS-HD) data collected between 2017 and 2023, we examined the association of neighborhood disadvantage with psychosocial distress using demographically adjusted linear regression models, stratified by ethnoracial group and cognitive status.

Results: We included 630 non-Hispanic Black, 1109 Hispanic, and 1068 non-Hispanic White older adults deemed cognitively normal (CN) or diagnosed with mild cognitive impairment (MCI).

View Article and Find Full Text PDF

Introduction: Identifying the associations between rural-living or neighborhood disadvantage and neurobiology may clarify rural-urban disparities in older adults with cognitive impairment related to Alzheimer's disease.

Methods: We examined rural-urban differences and neighborhood disadvantages in brain cortical thickness (CT) measures among 71 rural and 87 urban-dwelling older adults. Analysis of covariance was used to test each FreeSurfer-derived CT measures' associations with rural-urban living, clinical impairment status, and their interactions.

View Article and Find Full Text PDF
Article Synopsis
  • - Medical exome sequencing involves multiple steps to identify and prioritize genetic variants before interpretation by professionals, ultimately aiming to provide meaningful reports to patients.
  • - A study examined over 13,000 curated variants from 289 patients, identifying 278 clinically significant SNPs and a large number of technical artifacts, with variant allele frequencies (VAFs) playing a crucial role in filtering.
  • - The research suggests that excluding SNPs with a VAF below 0.30 could streamline the curation process by about 20% without missing important medical variants.
View Article and Find Full Text PDF

Importance: Determining the influence of race and ethnicity on change in cognitive test performance has significant implications for clinical practice and research in populations at risk for Alzheimer disease.

Objective: To evaluate the significance of race and ethnicity in predicting longitudinal cognitive test performance and to develop models to support evidence-based practice.

Design, Setting, And Participants: This prognostic study included baseline and 24-month follow-up data that were obtained from the Health and Aging Brain Study-Health Disparities (HABS-HD) study, an ongoing longitudinal observational study of aging and dementia in a multiracial, multiethnic cohort.

View Article and Find Full Text PDF

Introduction: Rural-dwelling older adults face unique health challenges that may increase risk for Alzheimer's disease and dementia but are underrepresented in aging research. Here, we present an initial characterization of a rural community cohort compared to an urban cohort from the same region.

Methods: Adults over age 50 living in a non-metropolitan area are clinically characterized using the Uniform Data Set, enriched with additional measures of verbal and non-verbal memory measures.

View Article and Find Full Text PDF

Background And Objectives: Up to 65% of people with multiple sclerosis (MS) experience disease-related cognitive impairment, but even after decades of research, still very little is known about the cognitive issues among older adults with MS (EwMS; individuals aged 60+). To date, few studies have attempted to characterize cognitive impairment in this group or compare EwMS with those with other neurodegenerative diseases. Our goal was to address this knowledge gap by comparing EwMS with individuals experiencing cognitive impairment due to probable Alzheimer disease (AD) with biomarker confirmation.

View Article and Find Full Text PDF

Determining whether the RNA isoforms from medically relevant genes have distinct functions could facilitate direct targeting of RNA isoforms for disease treatment. Here, as a step toward this goal for neurological diseases, we sequenced 12 postmortem, aged human frontal cortices (6 Alzheimer disease cases and 6 controls; 50% female) using one Oxford Nanopore PromethION flow cell per sample. We identified 1,917 medically relevant genes expressing multiple isoforms in the frontal cortex where 1,018 had multiple isoforms with different protein-coding sequences.

View Article and Find Full Text PDF

Objective: This article provides the test-retest reliability and Reliable Change Indices (RCIs) of the Philips IntelliSpace Cognition (ISC) platform, which contains digitized versions of well-established neuropsychological tests.

Method: 147 participants (ages 19 to 88) completed a digital cognitive test battery on the ISC platform or paper-pencil versions of the same test battery during two separate visits. Intraclass correlation coefficients (ICC) were calculated separately for the ISC and analog test versions to compare reliabilities between administration modalities.

View Article and Find Full Text PDF

Background: Emerging evidence suggests a potential causal role of neuroinflammation in Alzheimer's disease (AD). Using positron emission tomography (PET) to image overexpressed 18 kDA translocator protein (TSPO) by activated microglia has gained increasing interest. The uptake of 18F-GE180 TSPO PET was observed to co-localize with inflammatory markers and have a two-stage association with amyloid PET in mice.

View Article and Find Full Text PDF

Introduction: There is a tremendous need for identifying reliable blood-based biomarkers for Alzheimer's disease (AD) that are tied to the biological ATN (amyloid, tau and neurodegeneration) framework as well as clinical assessment and progression.

Methods: One hundred forty-four elderly participants underwent 18F-AV45 positron emission tomography (PET) scan, structural magnetic resonance imaging (MRI) scan, and blood sample collection. The composite standardized uptake value ratio (SUVR) was derived from 18F-AV45 PET to assess brain amyloid burden, and the hippocampal volume was determined from structural MRI scans.

View Article and Find Full Text PDF

Importance: Understanding how socioeconomic factors are associated with cognitive aging is important for addressing health disparities in Alzheimer disease.

Objective: To examine the association of neighborhood disadvantage with cognition among a multiethnic cohort of older adults.

Design, Setting, And Participants: In this cross-sectional study, data were collected between September 1, 2017, and May 31, 2022.

View Article and Find Full Text PDF

Due to alternative splicing, human protein-coding genes average over eight RNA isoforms, resulting in nearly four distinct protein coding sequences per gene. Long-read RNAseq (IsoSeq) enables more accurate quantification of isoforms, shedding light on their specific roles. To assess the medical relevance of measuring RNA isoform expression, we sequenced 12 aged human frontal cortices (6 Alzheimer's disease cases and 6 controls; 50% female) using one Oxford Nanopore PromethION flow cell per sample.

View Article and Find Full Text PDF

Background And Objectives: Limbic-predominant age-related TDP-43 encephalopathy (LATE) affects similar neuroanatomical networks as Alzheimer disease (AD) and is often comorbid with AD, though frequently missed in clinical diagnosis. The primary aim of this study was to elucidate the clinical and cognitive differences at baseline between patients with autopsy-confirmed LATE and patients with AD and comorbid LATE + AD.

Methods: Clinical and neuropathologic datasets were requested from the National Alzheimer Coordination Center.

View Article and Find Full Text PDF

Background: Patterns of cognitive impairment in former American football players are uncertain because objective neuropsychological data are lacking. This study characterized the neuropsychological test performance of former college and professional football players.

Methods: One hundred seventy male former football players (n=111 professional, n=59 college; 45-74 years) completed a neuropsychological test battery.

View Article and Find Full Text PDF

The process of identifying suitable genome-wide association (GWA) studies and formatting the data to calculate multiple polygenic risk scores on a single genome can be laborious. Here, we present a centralized polygenic risk score calculator currently containing over 250,000 genetic variant associations from the NHGRI-EBI GWAS Catalog for users to easily calculate sample-specific polygenic risk scores with comparable results to other available tools. Polygenic risk scores are calculated either online through the Polygenic Risk Score Knowledge Base (PRSKB; https://prs.

View Article and Find Full Text PDF

Protein-protein functional interactions arise from either transitory or permanent biomolecular associations and often lead to the coevolution of the interacting residues. Although mutual information has traditionally been used to identify coevolving residues within the same protein, its application between coevolving proteins remains largely uncharacterized. Therefore, we developed the Protein Interactions Calculator (PIC) to efficiently identify coevolving residues between two protein sequences using mutual information.

View Article and Find Full Text PDF

Ramp sequences occur when the average translational efficiency of codons near the 5' end of highly expressed genes is significantly lower than the rest of the gene sequence, which counterintuitively increases translational efficiency by decreasing downstream ribosomal collisions. Here, we show that the relative codon adaptiveness within different tissues changes the existence of a ramp sequence without altering the underlying genetic code. We present the first comprehensive analysis of tissue and cell type-specific ramp sequences and report 3108 genes with ramp sequences that change between tissues and cell types, which corresponds with increased gene expression within those tissues and cells.

View Article and Find Full Text PDF

Background: The Multiple Sclerosis Performance Test (MSPT) is a self-administered, iPad®-based, computerized system for quantifying neuroperformance (cognition, upper and lower extremity motor function, and vision) in patients with multiple sclerosis (MS).

Objective: The goal of the study is to provide regression-based norms for the four MSPT test modules to adjust for the influence of demographic variables (age, education, and sex).

Methods: The MSPT was administered to 428 cognitively intact, healthy adults (ages 18 to 89 years).

View Article and Find Full Text PDF
Article Synopsis
  • Researchers are focusing on collecting repeated data in studies to track changes in measurements over time, which may help identify new drug targets related to disease progression.
  • To accurately determine the relationship between measurements, they recommend using partial correlation after adjusting for a third variable that influences one of the measurements.
  • The study suggests using linear regression models to calculate residuals and then applying these in a linear mixed model for better partial correlation estimates, supported by real-world examples and numerical comparisons.
View Article and Find Full Text PDF

Alzheimer's disease is a complex and multifactorial condition regulated by both genetics and lifestyle, which ultimately results in the accumulation of β-amyloid (Aβ) and tau proteins in the brain, loss of gray matter, and neuronal death [...

View Article and Find Full Text PDF

The Alzheimer's Disease Neuroimaging Initiative (ADNI) contains extensive patient measurements (e.g., magnetic resonance imaging [MRI], biometrics, RNA expression, etc.

View Article and Find Full Text PDF

To collect evidence of validity for a selection of digital tests on the Philips IntelliSpace Cognition (ISC) platform. A total of 200 healthy participants (age 50-80) completed both the ISC battery and an analog version of the battery during separate visits. The battery included the following screeners and cognitive tests: Mini-Mental State Examination (2 edition), Clock Drawing Test, Trail-Making Test (TMT), Rey Auditory Verbal Learning Test (RAVLT), Rey-Osterrieth Complex Figure Test (ROCFT), Letter Fluency, Star Cancellation Test, and Digit Span Test.

View Article and Find Full Text PDF

Background: Cognitive impairment is common sequelae of multiple sclerosis (MS); however, relatively little is known about cognitive impairment in late-onset multiple sclerosis (LOMS).

Objective: To investigate differences in disease characteristics and cognition in LOMS and adult-onset multiple sclerosis (AOMS) patients.

Methods: Archival medical records and neuropsychological evaluations from an MS specialty center were reviewed.

View Article and Find Full Text PDF

Objective: Story memory tasks are among the most commonly used memory tests; however, research suggests they may be less sensitive to memory decline and have a weaker association with hippocampal volumes than list learning tasks. To examine its utility, we compared story memory to other memory tests on impairment rates and association with hippocampal volumes.

Method: Archival records from 1617 older adults (M = 74.

View Article and Find Full Text PDF