Publications by authors named "Toga A"

Introduction: The effects of sex and apolipoprotein E (APOE)-Alzheimer's disease (AD) risk factors-on white matter microstructure are not well characterized.

Methods: Diffusion magnetic resonance imaging data from nine well-established longitudinal cohorts of aging were free water (FW)-corrected and harmonized. This dataset included 4741 participants (age = 73.

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The overall goal of the Alzheimer's Disease Neuroimaging Initiative (ADNI) is to optimize and validate biomarkers for clinical trials while sharing all data and biofluid samples with the global scientific community. ADNI has been instrumental in standardizing and validating amyloid beta (Aβ) and tau positron emission tomography (PET) imaging. ADNI data were used for the US Food and Drug Administration (FDA) approval of the Fujirebio and Roche Elecsys cerebrospinal fluid diagnostic tests.

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The Alzheimer's Disease Sequencing Project (ADSP) is a national initiative to understand the genetic architecture of Alzheimer's Disease and Related Dementias (AD/ADRD) by sequencing whole genomes of affected participants and age-matched cognitive controls from diverse populations. The Genome Center for Alzheimer's Disease (GCAD) processed whole-genome sequencing data from 36,361 ADSP participants, including 35,014 genetically unique participants of which 45% are from non-European ancestry, across 17 cohorts in 14 countries in this fourth release (R4). This sequencing effort identified 387 million bi-allelic variants, 42 million short insertions/deletions, and 2.

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Auditory perception is established through experience-dependent stimuli exposure during sensitive developmental periods; however, little is known regarding the structural development of the central auditory pathway in humans. The present study characterized the regional developmental trajectories of the ascending auditory pathway from the brainstem to the auditory cortex from infancy through adolescence using a novel diffusion MRI-based tractography approach and along-tract analyses. We used diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) to quantify the magnitude and timing of auditory pathway microstructural maturation.

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This study was conducted to clarify patterns of cortico-limbic volume abnormalities in late life depression (LLD) relative to non-depressed (ND) adults matched for amyloid β (Aβ) deposition and to evaluate the relationship of volume abnormalities with cognitive performance. Participants included 116 LLD and 226 ND. Classification accuracy of LLD status was estimated using area under the receiver operator characteristic curve.

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Article Synopsis
  • 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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  • 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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  • Alzheimer's disease (AD) exhibits varied brain atrophy patterns, identified through a semi-supervised learning technique (Surreal-GAN) that distinguishes between "diffuse-AD" (widespread atrophy) and "MTL-AD" (focal atrophy in the medial temporal lobe) dimensions in patients with mild cognitive impairment (MCI) and AD.
  • Only the "MTL-AD" dimension was linked to known AD genetic risk factors like APOE ε4, and both dimensions were later detected in asymptomatic individuals, revealing their association with different genetic and pathological mechanisms.
  • Aside from brain-related genes, up to 77 additional genes were identified in various organs, pointing to broader
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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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Resting-state functional connectivity (FC) is suggested to be cross-sectionally associated with both vascular burden and Alzheimer's disease (AD) pathology. For instance, studies in pre-clinical AD subjects have shown increases of cerebral spinal fluid soluble platelet-derived growth factor receptor-β (CSF sPDGFRβ, a marker of BBB breakdown) but have not demonstrated if this vascular impairment affects neuronal dysfunction. It's possible that increased levels of sPDGFRβ in the CSF may correlate with impaired FC in metabolically demanding brain regions (i.

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  • Researchers aim to develop a method to fill in missing slices in brain diffusion MRI scans caused by incomplete field of view (FOV), improving whole-brain tractography without discarding valuable data.
  • This new technique employs a deep generative model to accurately estimate absent brain regions by learning diffusion characteristics and anatomical features from existing images.
  • Evaluation of the approach on Alzheimer’s datasets showed improved tractography accuracy, indicating that the method effectively enhances brain imaging analysis and reduces uncertainty related to Alzheimer's disease research.
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Article Synopsis
  • - The aging process of the brain is affected by lifestyle, environmental, genetic factors, and age-related diseases, with advanced imaging and AI techniques helping to reveal the complexities of neuroanatomical changes.
  • - A study involving nearly 50,000 participants identified five major patterns of brain atrophy, which are quantified using R-indices to analyze their connections to various biomedical, lifestyle, and genetic factors.
  • - These R-indices not only predict disease progression and mortality but also offer a new, nuanced framework for understanding brain aging, which may enhance personalized diagnostics and improve clinical trial strategies.
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The Alzheimer's Disease Neuroimaging Initiative (ADNI) has revolutionized the landscape of Alzheimer's research through its Informatics Core, which has facilitated unprecedented data standardization and sharing. Over 20 years, ADNI established a robust informatics framework, enabling the validation of biomarkers and supporting global research efforts. The Informatics Core, centered at the Laboratory of Neuro Imaging (LONI), provides a comprehensive data hub that ensures data quality, accessibility, and security, fostering over 5600 publications and significant scientific advancements.

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Investigating the genetic underpinnings of human aging is essential for unraveling the etiology of and developing actionable therapies for chronic diseases. Here, we characterize the genetic architecture of the biological age gap (BAG; the difference between machine learning-predicted age and chronological age) across nine human organ systems in 377,028 participants of European ancestry from the UK Biobank. The BAGs were computed using cross-validated support vector machines, incorporating imaging, physical traits and physiological measures.

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Auditory perception is established through experience-dependent stimuli exposure during sensitive developmental periods; however, little is known regarding the structural development of the central auditory pathway in humans. The present study characterized the regional developmental trajectories of the ascending auditory pathway from the brainstem to the auditory cortex from infancy through adolescence using a novel diffusion MRI-based tractography approach and along-tract analyses. We used diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) to quantify the magnitude and timing of auditory pathway microstructural maturation.

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Introduction: The effects of sex, race, and Apolipoprotein E () - Alzheimer's disease (AD) risk factors - on white matter integrity are not well characterized.

Methods: Diffusion MRI data from nine well-established longitudinal cohorts of aging were free-water (FW)-corrected and harmonized. This dataset included 4,702 participants (age=73.

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This case series investigates the efficacy of the "sashimi technique," a novel surgical approach utilizing a curved chisel for the resection of heterotopic ossification (HO). The main focus is on reducing resection margins and preventing excessive bone removal while maintaining optimal functional outcomes and preventing recurrence. Two cases illustrate successful outcomes in patients with spinal cord injuries and severe HO of the hip, emphasizing the precision of using the curved chisel-based technique in improving patient mobility while still achieving a desired resection margin.

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The complex biological mechanisms underlying human brain aging remain incompletely understood. This study investigated the genetic architecture of three brain age gaps (BAG) derived from gray matter volume (GM-BAG), white matter microstructure (WM-BAG), and functional connectivity (FC-BAG). We identified sixteen genomic loci that reached genome-wide significance (P-value < 5×10).

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Background And Objectives: In Parkinson disease (PD), Alzheimer disease (AD) copathology is common and clinically relevant. However, the longitudinal progression of AD CSF biomarkers-β-amyloid 1-42 (Aβ), phosphorylated tau 181 (p-tau), and total tau (t-tau)-in PD is poorly understood and may be distinct from clinical AD. Moreover, it is unclear whether CSF p-tau and serum neurofilament light (NfL) have added prognostic utility in PD, when combined with CSF Aβ.

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Article Synopsis
  • Late-life depression (LLD) is common in older adults and often occurs alongside neurodegenerative diseases, with anxiety being a significant factor influencing LLD variation.
  • A study involving 121 participants (ages 65-91) assessed the connection between anxiety severity and various neurodegenerative factors such as brain volume, cognitive dysfunction, and functional ability.
  • Results indicated that higher anxiety was linked to reduced orbitofrontal cortex volume and greater cognitive dysfunction, highlighting cognitive issues as a crucial factor in understanding anxiety within LLD, which may inform treatment strategies.
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Brain aging is a complex process influenced by various lifestyle, environmental, and genetic factors, as well as by age-related and often co-existing pathologies. MRI and, more recently, AI methods have been instrumental in understanding the neuroanatomical changes that occur during aging in large and diverse populations. However, the multiplicity and mutual overlap of both pathologic processes and affected brain regions make it difficult to precisely characterize the underlying neurodegenerative profile of an individual from an MRI scan.

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Hoarding disorder (HD) is a debilitating neuropsychiatric condition that affects 2%-6% of the population and increases in incidence with age. Major depressive disorder (MDD) co-occurs with HD in approximately 50% of cases and leads to increased functional impairment and disability. However, only one study to date has examined the rate and trajectory of hoarding symptoms in older individuals with a lifetime history of MDD, including those with current active depression (late-life depression; LLD).

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Elevated β oscillations (13-35 Hz) are characteristic pathophysiology in Parkinson's Disease (PD). Cortical thinning has also been reported in the disease, however the relationship between these biomarkers of PD has not been established. By comparing electrophysiological measurements with cortical thickness, this study aims to reveal the pathoetiology of disease and symptoms in PD.

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Neocortical maturation is a dynamic process that proceeds in a hierarchical manner; however, the spatiotemporal organization of cortical microstructure with diffusion MRI has yet to be fully defined. This study characterized cortical microstructural maturation using diffusion MRI (fwe-diffusion tensor imaging [DTI] and neurite orientation dispersion and density imaging [NODDI] multicompartment modeling) in a cohort of 637 children and adolescents between 8 and 21 years of age. We found spatially heterogeneous developmental patterns broadly demarcated into functional domains where NODDI metrics increased, and fwe-DTI metrics decreased with age.

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  • This study examines how brain morphologic changes during the third trimester of pregnancy relate to neurodevelopment outcomes in preterm infants.
  • Researchers analyzed MRI scans of preterm neonates to derive a predicted brain age (PBA) and found that it correlates with postnatal health and developmental scores.
  • The findings suggest that using brain morphology for age prediction can aid in identifying potential developmental issues early, helping to improve interventions for at-risk infants.
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