Publications by authors named "Clifford R Jack"

Background: Mild behavioral impairment (MBI) has been associated with global brain atrophy, but the regional neural correlates of MBI symptoms are less clear, particularly among community-dwelling older individuals without dementia.

Objective: Our objective was to examine the associations of MBI domains with gray matter (GM) volumes in a large population-based sample of older adults without dementia.

Methods: We performed a cross-sectional study of 1445 community-dwelling older adults in the Atherosclerosis Risk in Communities Study who underwent detailed neurocognitive assessment and brain magnetic resonance imaging in 2011-2013.

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Background And Purpose: Lower left atrial (LA) function is associated with higher dementia risk and may be mechanistically linked through vascular brain injury, an established correlate for higher dementia risk. Using data from the Atherosclerosis Risk in Communities study, we assessed the cross-sectional association between LA function and brain magnetic resonance imaging (MRI) markers of vascular brain injury.

Methods: We included 1488 participants who were free of prevalent dementia, stroke, or atrial fibrillation and who underwent a two-dimensional echocardiogram and brain MRI in 2011-2013 (mean [± standard deviation] age 76 [± 5] years, 60% female, 27% Black).

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Introduction: A key goal of the Alzheimer's Disease NeuroImaging Initiative (ADNI) positron emission tomography (PET) Core is to harmonize quantification of β-amyloid (Aβ) and tau PET image data across multiple scanners and tracers.

Methods: We developed an analysis pipeline (Berkeley PET Imaging Pipeline, B-PIP) for ADNI Aβ and tau PET images and applied it to PET data from other multisite studies. Steps include image pre-processing, refacing, magnetic resonance imaging (MRI)/PET co-registration, visual quality control (QC), quantification of tracer uptake, and standardization of Aβ and tau standardized uptake value ratios (SUVrs) across tracers.

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  • Recent advancements in Alzheimer's treatment now require verification of amyloid-β pathology using PET scans or cerebrospinal fluid, but blood tests could simplify this process.* -
  • A study involving nearly 7,000 individuals identified that the plasma biomarker p-tau217 can reliably indicate amyloid-β pathology, especially in patients with probable Alzheimer’s dementia.* -
  • The findings suggest that combining p-tau217 results with clinical assessments may allow for accurate diagnoses without the need for more invasive PET or CSF tests.*
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  • Subcortical brain structures play a crucial role in various developmental and psychiatric disorders, and a study analyzed brain volumes in 74,898 individuals, identifying 254 genetic loci linked to these volumes, which accounted for up to 35% of variation.
  • The research included exploring gene expression in specific neural cell types, focusing on genes involved in intracellular signaling and processes related to brain aging.
  • The findings suggest that certain genetic variants not only influence brain volume but also have potential causal links to conditions like Parkinson’s disease and ADHD, highlighting the genetic basis for risks associated with neuropsychiatric disorders.
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  • Obstructive sleep apnoea (OSA) is linked to a higher risk of cognitive impairment and dementia, potentially involving Alzheimer's disease pathology.
  • This study focused on the relationship between sleep patterns (specifically non-rapid eye movement slow-wave activity or SWA) and the accumulation of amyloid, a protein associated with Alzheimer's, in older adults with OSA.
  • The results showed that increased slow oscillation (SO) activity in sleep was correlated with greater amyloid accumulation, while certain sleep patterns also indicated a potential reduction in amyloid buildup.
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Introduction: Primary age-related tauopathy (PART) is characterized by neurofibrillary tangles and minimal β-amyloid deposition, diagnosed postmortem. This study investigates F-flortaucipir (FTP) PET imaging for antemortem PART diagnosis.

Methods: We analyzed FTP PET scans from 50 autopsy-confirmed PART and 13 control subjects.

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Cerebral small vessel disease (SVD), as defined by neuroimaging characteristics such as white matter hyperintensities (WMHs), cerebral microhemorrhages (CMHs), and lacunar infarcts, is highly prevalent and has been associated with dementia risk and other clinical sequelae. Although conditions such as hypertension are known to contribute to SVD, little is known about the diverse set of subclinical biological processes and molecular mediators that may also influence the development and progression of SVD. To better understand the mechanisms underlying SVD and to identify novel SVD biomarkers, we used a large-scale proteomic platform to relate 4,877 plasma proteins to MRI-defined SVD characteristics within 1,508 participants of the Atherosclerosis Risk in Communities (ARIC) Study cohort.

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Introduction: Recent technological advances have increased the risk that de-identified brain images could be re-identified from face imagery. The Alzheimer's Disease Neuroimaging Initiative (ADNI) is a leading source of publicly available de-identified brain imaging, who quickly acted to protect participants' privacy.

Methods: An independent expert committee evaluated 11 face-deidentification ("de-facing") methods and selected four for formal testing.

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  • - The study examines the relationship between amyloid beta (Aβ) PET scans and Aβ biomarkers in cerebrospinal fluid (CSF) to assess their effectiveness in treating Aβ-related conditions.
  • - A total of 505 participants aged 50 and older were analyzed, with a focus on their Aβ levels as measured by both PET and CSF, and a subgroup of 47 who underwent autopsy for further validation.
  • - Results indicated that Aβ PET scans detected earlier Aβ accumulation in the brain compared to CSF biomarkers, showing a higher sensitivity for identifying early stages of Aβ deposition.
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  • Subcortical brain structures play a crucial role in various disorders, and a study analyzed the genetic basis of brain volumes in nearly 75,000 individuals of European ancestry, revealing 254 loci linked to these volumes.
  • The research identified significant gene expression in neural cells, relating to brain aging and signaling, and found that polygenic scores could predict brain volumes across different ancestries.
  • The study highlights genetic connections between brain volumes and conditions like Parkinson's disease and ADHD, suggesting specific gene expression patterns could be involved in neuropsychiatric disorders.
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  • The study investigates the genetic factors contributing to Alzheimer's disease by analyzing tau deposition through a genome-wide association study involving 3,046 participants.
  • It identifies the CYP1B1-RMDN2 locus as significantly linked to tau levels, with the variant rs2113389 explaining 4.3% of tau variation, while also correlating with cognitive decline.
  • Findings suggest a connection between CYP1B1 expression and tau deposition, offering potential new avenues for Alzheimer's treatment and understanding its genetic basis.
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Objective: Anxiety is a common comorbid feature of late-life depression (LLD) and is associated with poorer global cognitive functioning independent of depression severity. However, little is known about whether comorbid anxiety is associated with a domain-specific pattern of cognitive dysfunction. We therefore examined group differences (LLD with and without comorbid anxiety) in cognitive functioning performance across multiple domains.

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There is increasing interest in Alzheimer's disease related plasma biomarkers due to their accessibility and scalability. We hypothesized that integrating plasma biomarkers with other commonly used and available participant data (MRI, cardiovascular factors, lifestyle, genetics) using machine learning (ML) models can improve individual prediction of cognitive outcomes. Further, our goal was to evaluate the heterogeneity of these predictors across different age strata.

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The magnetic resonance imaging (MRI) Core has been operating since Alzheimer's Disease Neuroimaging Initiative's (ADNI) inception, providing 20 years of data including reliable, multi-platform standardized protocols, carefully curated image data, and quantitative measures provided by expert investigators. The overarching purposes of the MRI Core include: (1) optimizing and standardizing MRI acquisition methods, which have been adopted by many multicenter studies and trials worldwide and (2) providing curated images and numeric summary values from relevant MRI sequences/contrasts to the scientific community. Over time, ADNI MRI has become increasingly complex.

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  • * The paper aims to help radiologists by discussing MRI protocols, workflows, and reporting practices for monitoring amyloid-related imaging abnormalities (ARIA).
  • * Key topics include FDA guidelines for ARIA evaluation, standard MRI sequences, patient imaging scenarios, the radiologist's role in treatment, and results from a 2023 survey on dementia imaging practices.
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Introduction: Well-chosen biomarkers have the potential to increase the efficiency of clinical trials and drug discovery and should show good precision as well as clinical validity.

Methods: We suggest measures that operationalize these criteria and describe a general approach that can be used for inference-based comparisons of biomarker performance. The methods are applied to measures obtained from structural magnetic resonance imaging (MRI) from individuals with mild dementia (n = 70) or mild cognitive impairment (MCI; n = 303) enrolled in the Alzheimer's Disease Neuroimaging Initiative.

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Phase four of the Alzheimer's Disease Neuroimaging Initiative (ADNI4) magnetic resonance imaging (MRI) protocols aim to maintain longitudinal consistency across two decades of data acquisition, while adopting new technologies. Here we describe and justify the study's design and targeted biomarkers. The ADNI4 MRI protocol includes nine MRI sequences.

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  • The study investigates how changes in the density of retinal capillaries, observable through optical coherence tomography angiography (OCTA), can be used as noninvasive biomarkers for Alzheimer’s disease and related small vessel diseases.* -
  • Researchers analyzed data from 41 participants without dementia, connecting OCTA measurements with neuroimaging findings like white matter hyperintensity and amyloid positivity obtained from PET scans.* -
  • Results revealed that reduced capillary density in the fovea was linked to higher levels of white matter hyperintensity and amyloid positivity, suggesting that OCTA could help identify potential Alzheimer's indicators before clinical symptoms develop.*
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Introduction: Age-related and Alzheimer's disease (AD) dementia-related neurodegeneration impact brain health. While morphometric measures from T1-weighted scans are established biomarkers, they may be less sensitive to earlier changes. Neurite orientation dispersion and density imaging (NODDI), offering biologically meaningful interpretation of tissue microstructure, may be an advanced brain health biomarker.

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