Publications by authors named "David Keator"

Background And Objectives: Cerebral small vessel disease (CSVD) is a leading cause of cognitive decline and functional loss in older adults. Obstructive sleep apnea (OSA) is common in older adults, can increase cerebrovascular disease risk, and is linked to medial temporal lobe (MTL) degeneration and cognitive impairment. However, the interaction between OSA features and CSVD burden and their combined effect on MTL structure and function are not well understood.

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Introduction: Adults with Down syndrome demonstrate striatum-first amyloid accumulation with [C]Pittsburgh Compound-B (PiB) positron emission tomography (PET) imaging, which has not been replicated with [F]florbetapir (FBP). Early striatal accumulation has not been temporally quantified with respect to global cortical measures.

Methods: Longitudinal PiB (n = 175 participants) and FBP (n = 92 participants) data from the Alzheimer Biomarkers Consortium-Down Syndrome (ABC-DS) were used to measure cortical and striatal binding.

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Importance: Major depressive disorder (MDD) is a severe mental illness characterized more by functional rather than structural brain abnormalities. The pattern of regional homogeneity (ReHo) deficits in MDD may relate to underlying regional hypoperfusion. Capturing this functional deficit pattern provides a brain pattern-based biomarker for MDD that is linked to the underlying pathophysiology.

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Introduction: Aging adults with Down syndrome (DS) accumulate Alzheimer's disease (AD) neuropathology, including amyloid beta plaques and neurofibrillary tangles, by age 40.

Methods: We present findings from an individual with DS who remained cognitively stable despite AD neuropathology. Clinical assessments, fluid biomarkers, neuroimaging, and neuropathological examinations were conducted to characterize her condition.

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Introduction: Adults with Down syndrome demonstrate striatum-first amyloid accumulation with [C]PiB PET imaging, which has not been replicated with [F]florbetapir (FBP). Early striatal accumulation has not been temporally quantified with respect to global cortical measures.

Methods: Longitudinal PiB (n=175 participants) and FBP (n=92 participants) data from the Alzheimer Biomarkers Consortium-Down Syndrome were used to measure cortical and striatal binding.

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Introduction: Adverse childhood experiences (ACEs) are linked to higher rates of psychiatric disorders in adults. Previous neuroimaging studies with small samples have shown associations between ACEs and alterations in brain volume, connectivity, and blood flow. However, no study has explored these associations in a large clinical population to identify brain regions that may mediate the relationship between ACEs and psychiatric diagnoses.

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Background: Unpredictable childhood experiences are an understudied form of early life adversity that impacts neurodevelopment in a sex-specific manner. The neurobiological processes by which exposure to early-life unpredictability impacts development and vulnerability to psychopathology remain poorly understood. The present study investigates the sex-specific consequences of early-life unpredictability on the limbic network, focusing on the hippocampus and the amygdala.

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Article Synopsis
  • The Brain Imaging Data Structure (BIDS) is a community-created standard for organizing neuroscience data and metadata, helping researchers manage various modalities efficiently.
  • The paper discusses the evolution of BIDS, including the guiding principles, extension mechanisms, and challenges faced during its development.
  • It also highlights key lessons learned from the BIDS project, aiming to inspire and inform researchers in other fields about effective data organization practices.
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Article Synopsis
  • * Key findings include her ApoE genotype (E2/3) linked to a lower dementia risk, neuroimaging showing stable amyloid and moderate tau levels, and intermediate Alzheimer’s pathology with added Lewy body and cerebrovascular issues.
  • * The study highlights the complex relationship between Alzheimer's symptoms and brain changes in Down syndrome, suggesting the need for more research on factors that contribute to cognitive resilience in this population.
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Adults with Down syndrome are less likely to have hypertension than neurotypical adults. However, whether blood pressure measures are associated with brain health and clinical outcomes in this population has not been studied in detail. Here, we assessed whether pulse pressure is associated with markers of cerebrovascular disease and is linked to a diagnosis of dementia in adults with Down syndrome via structural imaging markers of cerebrovascular disease and atrophy.

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Introduction: Virtually all people with Down syndrome (DS) develop neuropathology associated with Alzheimer's disease (AD). Atrophy of the hippocampus and entorhinal cortex (EC), as well as elevated plasma concentrations of neurofilament light chain (NfL) protein, are markers of neurodegeneration associated with late-onset AD. We hypothesized that hippocampus and EC gray matter loss and increased plasma NfL concentrations are associated with memory in adults with DS.

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Obstructive sleep apnea (OSA) is common in older adults and is associated with medial temporal lobe (MTL) degeneration and memory decline in aging and Alzheimer's disease (AD). However, the underlying mechanisms linking OSA to MTL degeneration and impaired memory remains unclear. By combining magnetic resonance imaging (MRI) assessments of cerebrovascular pathology and MTL structure with clinical polysomnography and assessment of overnight emotional memory retention in older adults at risk for AD, cerebrovascular pathology in fronto-parietal brain regions was shown to statistically mediate the relationship between OSA-related hypoxemia, particularly during rapid eye movement (REM) sleep, and entorhinal cortical thickness.

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Individuals with Down syndrome (DS) are less likely to have hypertension than neurotypical adults. However, whether blood pressure measures are associated with brain health and clinical outcomes in this population has not been studied in detail. Here, we assessed whether pulse pressure is associated with markers of cerebrovascular disease, entorhinal cortical atrophy, and diagnosis of dementia in adults with DS.

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Alzheimer's disease (AD) is the most common type of dementia, characterized by early memory impairments and gradual worsening of daily functions. AD-related pathology, such as amyloid-beta (Aβ) plaques, begins to accumulate many years before the onset of clinical symptoms. Predicting risk for AD via related pathology is critical as the preclinical stage could serve as a therapeutic time window, allowing for early management of the disease and reducing health and economic costs.

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Article Synopsis
  • The Brain Imaging Data Structure (BIDS) is a collaborative standard designed to organize various neuroscience data and metadata.
  • The paper details the history, principles, and mechanisms behind the development and expansion of BIDS, alongside the challenges it faces as it evolves.
  • It also shares lessons learned from the project to help researchers in other fields apply similar successful strategies.
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Older adults may harbor large amounts of amyloid-β (Aβ) pathology, yet still perform at age-normal levels on memory assessments. We tested whether functional brain networks confer resilience or compensatory mechanisms to support memory in the face of Aβ pathology. Sixty-five cognitively normal older adults received high-resolution resting state fMRI to assess functional networks, 18F-florbetapir-PET to measure Aβ, and a memory assessment.

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The biomedical research community is motivated to share and reuse data from studies and projects by funding agencies and publishers. Effectively combining and reusing neuroimaging data from publicly available datasets, requires the capability to query across datasets in order to identify cohorts that match both neuroimaging and clinical/behavioral data criteria. Critical barriers to operationalizing such queries include, in part, the broad use of undefined study variables with limited or no annotations that make it difficult to understand the data available without significant interaction with the original authors.

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Introduction: We tested whether Alzheimer's disease (AD) pathology predicts memory deficits in non-demented older adults through its effects on medial temporal lobe (MTL) subregional volume.

Methods: Thirty-two, non-demented older adults with cerebrospinal fluid (CSF) (amyloid-beta [Aβ]/Aβ, phosphorylated tau [p-tau], total tau [t-tau]), positron emission tomography (PET; 18F-florbetapir), high-resolution structural magnetic resonance imaging (MRI), and neuropsychological assessment were analyzed. We examined relationships between biomarkers and a highly granular measure of memory consolidation, retroactive interference (RI).

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The perforant path, the white matter bundle connecting the entorhinal cortex (ERC) with the hippocampal formation deteriorates with age-related cognitive decline. Previous investigations using diffusion-weighted MRI to quantify perforant path integrity in-vivo have been limited due to image resolution or have quantified the perforant path using methods susceptible to partial volume effects such as the tensor model and without consideration of its 3-dimensional morphology. In this investigation, we use quantitative-anisotropy informed tractography derived from ultra-high resolution diffusion imaging (ZOOMit) to investigate structural connectivity of the perforant path and other medial temporal lobe (MTL) pathways in older adults (63 to 98 years old, n = 51).

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Mnemonic discrimination, a cognitive process that relies on hippocampal pattern separation, is one of the first memory domains to decline in aging and preclinical Alzheimer's disease. We tested whether functional connectivity (FC) within the entorhinal-hippocampal circuit, measured with high-resolution resting state fMRI, is associated with mnemonic discrimination and amyloid-β (Aβ) pathology in a sample of 64 cognitively normal human older adults (mean age, 71.3 ± 6.

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Empirical observations of how labs conduct research indicate that the adoption rate of open practices for transparent, reproducible, and collaborative science remains in its infancy. This is at odds with the overwhelming evidence for the necessity of these practices and their benefits for individual researchers, scientific progress, and society in general. To date, information required for implementing open science practices throughout the different steps of a research project is scattered among many different sources.

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The Neuroimaging Data Model (NIDM) is a series of specifications for describing all aspects of the neuroimaging data lifecycle from raw data to analyses and provenance. NIDM uses community-driven terminologies along with unambiguous data dictionaries within a Resource Description Framework (RDF) document to describe data and metadata for integration and query. Data from different studies, using locally defined variable names, can be retrieved by linking them to higher-order concepts from established ontologies and terminologies.

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Medial temporal lobe (MTL) atrophy is a core feature of age-related cognitive decline and Alzheimer's disease (AD). While regional volumes and thickness are often used as a proxy for neurodegeneration, they lack the sensitivity to serve as an accurate diagnostic test and indicate advanced neurodegeneration. Here, we used a submillimeter resolution diffusion weighted MRI sequence (ZOOMit) to quantify microstructural properties of hippocampal subfields in older adults (63-98 years old) using tensor derived measures: fractional anisotropy (FA) and mean diffusivity (MD).

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We determined the extent to which obstructive sleep apnea (OSA) is associated with increased cerebrovascular disease and amyloid burden, and the relation of the two processes across clinical Alzheimer's disease (AD) diagnostic groups in adults with Down syndrome (DS). Adults with DS from the Biomarkers of Alzheimer's Disease in Down Syndrome (ADDS) study were included given available research MRI ( = 116; 50 ± 8 years; 42% women) and amyloid PET scans ( = 71; 50 ± 7 years; 39% women) at the time of analysis. Participants were characterized as cognitively stable (CS; 64%), with mild cognitive impairment-DS (MCI-DS; 23%), with possible AD dementia (5%), or with definite AD dementia (8%).

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