Steven E. Arnold
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View article: Metabolomic Relationships Between Lung Cancer and Alzheimer's Disease Using Serum Nuclear Magnetic Resonance Spectroscopy
Metabolomic Relationships Between Lung Cancer and Alzheimer's Disease Using Serum Nuclear Magnetic Resonance Spectroscopy Open
Lung cancer (LC) and Alzheimer's disease (AD) are both age‐associated diseases with high rates of mortality. Studies have reported a possible inverse relationship between LC and AD incidences; however, possible shared molecular mechanisms …
View article: Speech Acoustic Markers Detect APOE-ε4 Carrier Status in Cognitively Healthy Individuals
Speech Acoustic Markers Detect APOE-ε4 Carrier Status in Cognitively Healthy Individuals Open
Background: APOE-E4, the strongest genetic risk factor for Alzheimer's disease (AD), is linked to early motor vulnerability, including subtle speech control changes. Because speech integrates fine neuromotor processes, acoustic analysis co…
View article: Seeking optimal repeated fluid biomarker assessments to enhance precision and statistical power in clinical trials: SLIM method
Seeking optimal repeated fluid biomarker assessments to enhance precision and statistical power in clinical trials: SLIM method Open
INTRODUCTION Plasma biomarkers are increasingly used as surrogate outcomes in clinical trials for Alzheimer's disease and related dementias (ADRD) due to their non‐invasive nature. In early‐phase trials designed to evaluate mechanisms of a…
View article: Plasma NfL and cognitive functioning in older adults: The moderating role of HDL cholesterol
Plasma NfL and cognitive functioning in older adults: The moderating role of HDL cholesterol Open
BACKGROUND AND OBJECTIVES Plasma neurofilament light chain (NfL) is a marker of neuroaxonal injury associated with cognitive decline. High‐density lipoprotein (HDL) cholesterol has neuroprotective properties, but its interaction with neuro…
View article: 540. INFLAMMATION AND AGING IN PSYCHOSIS – A TRANSDIAGNOSTIC PROTEOMICS STUDY USING THE HUMAN CONNECTOME PROJECT FOR EARLY PSYCHOSIS (HCP-EP)
540. INFLAMMATION AND AGING IN PSYCHOSIS – A TRANSDIAGNOSTIC PROTEOMICS STUDY USING THE HUMAN CONNECTOME PROJECT FOR EARLY PSYCHOSIS (HCP-EP) Open
Background Since protein expression plays a key role in mediating genetic risk, the field of proteomics—the in-depth analysis of proteins—has gained renewed importance in neuropsychiatric research. Recent technical advancements now allow f…
View article: Multi-ancestry genome-wide meta-analysis of 56,241 individuals identifies known and novel cross-population and ancestry-specific associations as novel risk loci for Alzheimer’s disease
Multi-ancestry genome-wide meta-analysis of 56,241 individuals identifies known and novel cross-population and ancestry-specific associations as novel risk loci for Alzheimer’s disease Open
Using cross-population GWAS meta-analyses, we identify novel LOAD susceptibility loci in/near LRRC4C and LHX5-AS1, both with known roles in neuronal development, as well as several novel population-unique loci. Reflecting the power of dive…
View article: Design and Analysis of N‐Of‐1 Trials That Incorporate Sequential Monitoring
Design and Analysis of N‐Of‐1 Trials That Incorporate Sequential Monitoring Open
For many diseases and disorders, such as Alzheimer's disease, patients demonstrate considerable heterogeneity in their responses to treatment interventions. One treatment may be most effective for some patients, while another may be most e…
View article: Synthetic control methods for n‐of‐1 and parallel‐group trials in Alzheimer's disease: A proof‐of‐concept study using the I‐CONECT
Synthetic control methods for n‐of‐1 and parallel‐group trials in Alzheimer's disease: A proof‐of‐concept study using the I‐CONECT Open
INTRODUCTION With the advent of Alzheimer's disease (AD)‐modifying and symptomatic treatments of demonstrated efficacy, enrolling participants as concurrent placebo controls in trials can become increasingly difficult. Synthetic controls h…
View article: Distinct inflammatory profiles in young‐onset versus late‐onset Alzheimer's disease
Distinct inflammatory profiles in young‐onset versus late‐onset Alzheimer's disease Open
INTRODUCTION Neuroinflammation, a key player in Alzheimer's disease (AD) pathogenesis, may be differentially involved in young‐onset (YOAD) compared to late‐onset (LOAD) AD. METHODS Using proximity extension assay technology, we examined 7…
View article: Plasma tau and phosphorylated tau at T181 are altered in amyotrophic lateral sclerosis
Plasma tau and phosphorylated tau at T181 are altered in amyotrophic lateral sclerosis Open
There is an unmet need for reliable biomarkers for amyotrophic lateral sclerosis (ALS). Recent studies have demonstrated that the levels of the microtubule-associated protein tau, are altered in plasma and cerebrospinal fluid (CSF) from pe…
View article: Kinematic Correlates of Early Speech Motor Changes in Cognitively Intact APOE-ε4 Carriers: A Preliminary Study Using a Color-Word Interference Task
Kinematic Correlates of Early Speech Motor Changes in Cognitively Intact APOE-ε4 Carriers: A Preliminary Study Using a Color-Word Interference Task Open
Alzheimer’s disease (AD) is the most prevalent form of dementia and a major public health challenge. In the absence of a cure, accurate and innovative early diagnostic methods are essential for proactive life and healthcare planning. Speec…
View article: The NIH Toolbox Emotion Battery and Cerebrospinal Fluid Biomarkers in Alzheimer’s Disease: Findings from the Multisite ARMADA Study
The NIH Toolbox Emotion Battery and Cerebrospinal Fluid Biomarkers in Alzheimer’s Disease: Findings from the Multisite ARMADA Study Open
Objectives Investigating the relationships between socioemotional functioning and Alzheimer’s Disease (AD) pathology can contribute to screening and early detection of AD. This study explored the associations between socioemotional functio…
View article: Single-cell elderly blood–CSF atlas implicates peripherally influenced immune dysregulation in normal pressure hydrocephalus
Single-cell elderly blood–CSF atlas implicates peripherally influenced immune dysregulation in normal pressure hydrocephalus Open
We have generated a single-cell RNA sequencing atlas of peripheral blood and ventricular CSF in idiopathic normal pressure hydrocephalus (iNPH) patients totaling 140,207 single-cell transcriptomes. We found proinflammatory alterations in p…
View article: Precision Estimates of Longitudinal Brain Aging Capture Unexpected Individual Differences in One Year
Precision Estimates of Longitudinal Brain Aging Capture Unexpected Individual Differences in One Year Open
Longitudinal studies are required to measure individual differences in human brain aging, but they are dif>icult to estimate over short intervals because of measurement error. Using cluster scanning, an approach that reduces error by dense…
View article: Unbiased CSF Proteomics in Patients With Idiopathic Normal Pressure Hydrocephalus to Identify Molecular Signatures and Candidate Biomarkers
Unbiased CSF Proteomics in Patients With Idiopathic Normal Pressure Hydrocephalus to Identify Molecular Signatures and Candidate Biomarkers Open
Leveraging the etiologic insights from a typical neurologic clinical cohort, our results indicate that processes of immune response, coagulation, and neuronal signaling are affected in iNPH. We highlight specific markers of potential diagn…
View article: Sleep quality and efficiency in adults with post-acute sequelae of COVID-19
Sleep quality and efficiency in adults with post-acute sequelae of COVID-19 Open
Study Objectives Sleep disruptions are associated with adverse mental and physical health outcomes. Individuals with post-acute sequelae of COVID-19 (PASC) commonly report worsened sleep. This study examined sleep quality and efficiency an…
View article: Cognitive and Alzheimer's disease biomarker effects of oral nicotinamide riboside (NR) supplementation in older adults with subjective cognitive decline and mild cognitive impairment
Cognitive and Alzheimer's disease biomarker effects of oral nicotinamide riboside (NR) supplementation in older adults with subjective cognitive decline and mild cognitive impairment Open
INTRODUCTION Age‐associated depletion in nicotinamide adenine dinucleotide (NAD+) concentrations has been implicated in metabolic, cardiovascular, and neurodegenerative disorders. Supplementation with NAD+ precursors, such as nicotinamide …
View article: Brain MRI signatures across sex and CSF Alzheimer’s disease biomarkers
Brain MRI signatures across sex and CSF Alzheimer’s disease biomarkers Open
The relationship between cerebrospinal fluid (CSF) biomarkers of Alzheimer’s disease and neurodegenerative effects is not fully understood. This study investigates neurodegeneration patterns across CSF Alzheimer’s disease biomarker groups,…
View article: A compilation of reported alterations in the cerebrospinal fluid proteome in Alzheimer's disease
A compilation of reported alterations in the cerebrospinal fluid proteome in Alzheimer's disease Open
Alzheimer's disease is a multifaceted neurodegenerative disorder, with diverse underlying pathophysiological processes extending beyond amyloid-β and tau accumulation. The heterogeneity of Alzheimer's disease necessitates the identificatio…
View article: Immunoassay for pyruvate kinase M1/2 as an Alzheimer’s biomarker in CSF
Immunoassay for pyruvate kinase M1/2 as an Alzheimer’s biomarker in CSF Open
Alzheimer’s disease (AD) is characterized by amyloid-beta plaques and tau tangles in the brain, but these markers alone do not predict disease progression. The intersection of these pathologies with other processes including metabolic chan…
View article: Key considerations for combination therapy in Alzheimer's clinical trials: Perspectives from an expert advisory board convened by the Alzheimer's drug discovery foundation
Key considerations for combination therapy in Alzheimer's clinical trials: Perspectives from an expert advisory board convened by the Alzheimer's drug discovery foundation Open
There is growing consensus in the Alzheimer's community that combination therapy will be needed to maximize therapeutic benefits through the course of the disease. However, combination therapy raises complex questions and decisions for stu…
View article: Evidence that minocycline treatment confounds the interpretation of neurofilament as a biomarker
Evidence that minocycline treatment confounds the interpretation of neurofilament as a biomarker Open
Neurofilament light (NfL) concentration in CSF and blood serves as an important biomarker in neurology drug development. Changes in NfL are generally assumed to reflect changes in neuronal damage, while little is known about the clearance …
View article: Multimodal Digital Phenotyping of Behavior in a Neurology Clinic: Development of the Neurobooth Platform and the First Two Years of Data Collection
Multimodal Digital Phenotyping of Behavior in a Neurology Clinic: Development of the Neurobooth Platform and the First Two Years of Data Collection Open
Quantitative analysis of human behavior is critical for objective characterization of neurological phenotypes, early detection of neurodegenerative diseases, and development of more sensitive measures of disease progression to support clin…
View article: Brain phosphoproteomic analysis identifies diabetes‐related substrates in Alzheimer's disease pathology in older adults
Brain phosphoproteomic analysis identifies diabetes‐related substrates in Alzheimer's disease pathology in older adults Open
INTRODUCTION Type 2 diabetes increases the risk of Alzheimer's disease (AD) dementia. Insulin signaling dysfunction exacerbates tau protein phosphorylation, a hallmark of AD pathology. However, the comprehensive impact of diabetes on patte…
View article: Plasma synapse proteins discriminate between AD, DLB, and FTD dementias and closely predict memory dysfunction
Plasma synapse proteins discriminate between AD, DLB, and FTD dementias and closely predict memory dysfunction Open
Background Robust biomarkers are urgently needed to detect, diagnose, and predict memory decline in the three most common neurodegenerative dementia syndromes, Alzheimer disease (AD), dementia with Lewy bodies (DLB), and frontotemporal dem…
View article: IGFBP‐5 Potentially Mediates the Association of Brain Insulin Signaling with Late‐Life Cognitive Decline
IGFBP‐5 Potentially Mediates the Association of Brain Insulin Signaling with Late‐Life Cognitive Decline Open
Background Abnormal brain insulin signaling has been associated with Alzheimer’s disease pathology and a faster rate of late‐life cognitive decline. However, the underlying mechanisms remain unclear. In this study, we examined whether AD‐r…
View article: Semi‐passive monitoring of game play detects learning curves distinctive to subjective cognitive decline (SCD) and mild cognitive impairment (MCI)/mild‐stage dementia
Semi‐passive monitoring of game play detects learning curves distinctive to subjective cognitive decline (SCD) and mild cognitive impairment (MCI)/mild‐stage dementia Open
Background The ability to monitor cognitive trajectories over the course of trials can provide valuable insights into treatment efficacy. However, existing trial methods are limited in monitoring cognition in real‐time and at high frequenc…
View article: Dried blood spots as a matrix for measuring AD biomarkers: optimizing parameters of analysis and evaluating technical stability
Dried blood spots as a matrix for measuring AD biomarkers: optimizing parameters of analysis and evaluating technical stability Open
Background An advantage of blood‐based biomarkers of Alzheimer’s disease (AD) is that collection is easily repeatable and minimally invasive. Repeated biomarker measurements provide greater sensitivity for detecting within‐person change, w…
View article: How Much Time Can be Saved in Cognitive Decline? the Internet‐based Conversational Engagement Clinical Trial (I‐CONECT)
How Much Time Can be Saved in Cognitive Decline? the Internet‐based Conversational Engagement Clinical Trial (I‐CONECT) Open
Background Clinical trials should strive to yield results that are clinically meaningful rather than solely relying on statistical significance. However, the determination of clinical meaningfulness of dementia clinical trials lacks standa…
View article: The relationship between amyloid‐β, plasma/brain GFAP, and neocortical tau: a Mendelian randomization study
The relationship between amyloid‐β, plasma/brain GFAP, and neocortical tau: a Mendelian randomization study Open
Background Plasma glial fibrillary acidic protein (GFAP) is associated with amyloid‐β (Aβ) and tau, but their causal relationships remain unclear. We used Mendelian randomization (MR; using genetic causal anchors to avoid reverse causation…