Publications by authors named "Phil H Lee"

Differences in the patterning of genetic sharing between groups of individuals may arise from biological pathways, social mechanisms, phenotyping and ascertainment. We expand genomic structural equation modeling to allow for testing genomic structural invariance (GSI), that is, the formal comparison of multivariate genetic architecture across groups. We apply GSI to compare the autosomal multivariate genetic architecture of eight psychiatric disorders spanning three factors (psychotic, neurodevelopmental and internalizing) between cisgender males and females.

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Purpose: While many studies have explored the link between biomarkers and cognitive decline in Parkinson's disease (PD), a more comprehensive approach is needed, combining striatal dopamine depletion, cerebral glucose metabolism, and cognitive assessments. In this study, we investigated the relationships between striatal dopamine transporter (DAT) uptake, cerebral glucose hypometabolism, and cognition, as well as the potential progression pattern of these changes in PD.

Methods: We enrolled 62 patients with PD and 33 healthy controls.

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Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder and is characterized by progressive dopaminergic and non-dopaminergic neuronal loss and the presence of Lewy bodies, which are primarily composed of aggregated α-synuclein. Despite advancements in symptomatic therapies, such as dopamine replacement and deep brain stimulation, no disease-modifying therapies (DMTs) have been identified to slow or arrest neurodegeneration in PD. Challenges in DMT development include disease heterogeneity, the absence of reliable biomarkers, and the multifaceted pathophysiology of PD, encompassing neuroinflammation, mitochondrial dysfunction, lysosomal impairment, and oxidative stress.

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The growing availability of pre-trained polygenic risk score (PRS) models has enabled their integration into real-world applications, reducing the need for extensive data labeling, training, and calibration. However, selecting the most suitable PRS model for a specific target population remains challenging, due to issues such as limited transferability, data het-erogeneity, and the scarcity of observed phenotype in real-world settings. Ensemble learning offers a promising avenue to enhance the predictive accuracy of genetic risk assessments, but most existing methods often rely on observed phenotype data or additional genome-wide association studies (GWAS) from the target population to optimize ensemble weights, limiting their utility in real-time implementation.

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Background And Objectives: Parkinson disease (PD) exhibits a characteristic pattern of brain perfusion or metabolism, thereby being considered network disorder. Using dual-phase -(3-fluoropropyl)-2β-carbomethoxy-3β-(4-iodophenyl) nortropane (F-FP-CIT) PET, we investigated the role of brain perfusion in motor symptoms and disease progression, independent of striatal dopamine depletion.

Methods: We recruited patients with de novo PD and healthy controls (HCs) who underwent dual-phase F-FP-CIT PET and brain MRI.

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Individual variability exists in parkinsonian motor symptoms despite a similar degree of nigrostriatal dopamine depletion in Parkinson's disease (PD), called motor reserve. We enrolled 397 patients newly diagnosed with PD who underwent dual-phase F-FP-CIT PET upon initial assessment. Individual motor reserve was estimated based on initial parkinsonian motor symptoms and striatal dopamine transporter availability using a residual model.

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This multicentre, prospective, single-arm study evaluated safinamide as add-on therapy to levodopa in Korean patients with Parkinson's disease (PD) with motor fluctuations with ≥ 1.5 h of "off" time daily, who took levodopa ≥ 3 times/day (n = 199). Baseline levodopa and dopamine agonist doses were maintained without escalation during the 18-week treatment period.

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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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Article Synopsis
  • 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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Rh(III)-catalyzed B(4)-azo coupling reactions of -carborane acids with aryl diazonium tetrafluoroborates have been developed, leading to the regioselective formation of B(4)-azo-coupled -carboranes. Moreover, B(4)-azo-coupled -carboranes can be further functionalized by introducing a second azo group, producing B(4)-C(1)-di(arylazo) -carborane. The B(4)-azo group as an efficient directing group enables catalytic C-H amidation reactions, providing a new synthetic route for complex -carborane derivatives.

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Iron and myelin are primary susceptibility sources in the human brain. These substances are essential for a healthy brain, and their abnormalities are often related to various neurological disorders. Recently, an advanced susceptibility mapping technique, which is referred to as χ-separation (pronounced as "chi"-separation), has been proposed, successfully disentangling paramagnetic iron from diamagnetic myelin.

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Background And Purpose: The co-occurrence of amyloid-β pathology in Parkinson's disease (PD) is common; however, the role of amyloid-β deposition in motor prognosis remains elusive. This study aimed to investigate the association between striatal amyloid deposition, motor complications and motor prognosis in patients with PD.

Methods: Ninety-six patients with PD who underwent F florbetaben (FBB) positron emission tomography were retrospectively assessed.

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Background And Objectives: Although the potential role of enlarged perivascular spaces (EPVSs) in Parkinson disease (PD) is increasingly recognized, whether EPVSs located in different anatomical regions exert differential effects on clinical manifestation remains uncertain. We investigated the regional EPVS burden and its association with cognition and neuropsychiatric symptoms (NPSs) in newly diagnosed PD population.

Methods: In this retrospective, cross-sectional study, EPVS in the temporal lobe (T-EPVS), centrum semiovale (CS-EPVS), and basal ganglia (BG-EPVS) were visually rated in drug-naive patients with PD who underwent magnetic resonance imaging, dopamine transporter (DAT) scans, neuropsychological assessments, and Neuropsychiatric Inventory Questionnaire at baseline.

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The redox regulation, maintaining a balance between oxidation and reduction in living cells, is vital for cellular homeostasis, intricate signaling networks, and appropriate responses to physiological and environmental cues. Here, a novel redox sensor, based on DNA-encapsulated silver nanoclusters (DNA/AgNCs) and well-defined chemical fluorophores, effectively illustrating cellular redox states in live cells is introduced. Among various i-motif DNAs, the photophysical property of poly-cytosines (C)-encapsulated AgNCs that sense reactive oxygen species (ROS) is adopted.

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Background And Purpose: Olfactory dysfunction or dysautonomia is one of the earliest prodromal nonmotor symptoms of Parkinson's disease (PD). We aimed to investigate whether PD patients with dysautonomia and hyposmia at the de novo stage present different prognoses regarding PD dementia (PDD) conversion, motor complication development, and change in levodopa-equivalent doses (LED).

Methods: In this retrograde cohort study, we included 105 patients with newly diagnosed PD patients who underwent cross-cultural smell identification test (CC-SIT), autonomic function tests (AFT), and dopamine transporter (DAT) scan at the de novo stage.

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Article Synopsis
  • Impulsivity develops from childhood to adulthood and is influenced by brain maturation, but there's limited research on its relationships with brain structure and genetics in children.
  • A study involving 9112 children found weak associations between impulsivity measures and smaller cortical area in certain brain regions, but no link between impulsivity and cortical volume or thickness.
  • Higher genetic risk for externalizing behaviors correlated with increased impulsivity and smaller brain structures, highlighting the complex relationship between genetics and brain structure in affecting impulsivity. Future research is needed to explore these links through adolescence and their implications for behaviors like substance use.
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Introduction: Cerebrospinal fluid (CSF) flow is involved in brain waste clearance and may be impaired in neurodegenerative diseases such as Parkinson's disease. This study aims to investigate the relationship between the CSF pulsation and the development of dementia in Parkinson's disease (PD) patients using EPI-based fMRI.

Methods: We measured CSF pulsation in the 4th ventricle of 17 healthy controls and 35 PD patients using a novel CSF pulsation index termed "CSFpulse" based on echo-planar imaging (EPI)-based fMRI.

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Article Synopsis
  • The study focused on evaluating the effectiveness of the COMT inhibitor opicapone compared to an extra dose of levodopa in managing early wearing-off symptoms in Parkinson's disease (PD) patients.
  • The research involved a randomized trial with 168 participants in Korea, where patients received either opicapone 50 mg or an additional 100 mg dose of levodopa for 4 weeks.
  • Results showed that opicapone significantly reduced off time and increased on time more effectively than the additional levodopa dose, demonstrating its superiority in treating early wearing-off symptoms in PD patients.
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Purpose Of The Report: Although early detection of individuals at risk of dementia conversion is important in patients with Parkinson's disease (PD), there is still no consensus on neuroimaging biomarkers for predicting future cognitive decline. We aimed to investigate whether cerebral perfusion patterns on early-phase 18 F-N-(3-fluoropropyl)-2β-carboxymethoxy-3β-(4-iodophenyl) nortropane ( 18 F-FP-CIT) PET have the potential to serve as a neuroimaging predictor for early dementia conversion in patients with PD.

Materials And Methods: In this retrospective analysis, we enrolled 187 patients with newly diagnosed PD who underwent dual-phase 18 F-FP-CIT PET at initial assessment and serial cognitive assessments during the follow-up period (>5 years).

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Article Synopsis
  • - The study aimed to evaluate the reliability and validity of the Korean version of the SCales for Outcomes in Parkinson's Disease-Cognition (K-SCOPA-Cog) for assessing cognition in Parkinson's disease patients in South Korea.
  • - A total of 129 patients participated, and various statistical methods, including Cronbach's alpha and Spearman’s rank correlation, were employed to test the reliability and concurrent validity against established cognitive assessments.
  • - Results showed that the K-SCOPA-Cog has strong reliability (Cronbach's alpha of 0.797, ICC of 0.887) and a significant correlation with other cognitive measures (MOCA-K and K-MMSE), indicating it is a valid tool for cognitive assessment in this
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Introduction: This study aimed to investigate whether regional cerebral perfusion patterns on early-phase F-FP-CIT PET scans, which is typically coupled to cerebral metabolism, predict the long-term prognosis of Parkinson's disease (PD).

Methods: We enrolled 397 drug-naïve patients with early-stage PD who underwent dual-phase F-FP-CIT PET scans. After quantifying the early-phase F-FP-CIT PET images, cluster analysis was performed to delineate the PD subtypes according to the patterns of regional cerebral perfusion.

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Objective: The Montreal Cognitive Assessment (MoCA) is recommended for general cognitive evaluation in Parkinson's disease (PD) patients. However, age- and education-adjusted cutoffs specifically for PD have not been developed or systematically validated across PD cohorts with diverse education levels.

Methods: In this retrospective analysis, we utilized data from 1,293 Korean patients with PD whose cognitive diagnoses were determined through comprehensive neuropsychological assessments.

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As a part of the glymphatic system, the choroid plexus (CP) is involved in the clearance of harmful metabolites from the brain. We investigated the association between CP volume (CPV), amyloid-β (Aβ) burden, and cognition in patients on the Alzheimer's disease (AD) continuum. We retrospectively reviewed the records of 203 patients on the AD continuum and 82 healthy controls who underwent brain magnetic resonance imaging and F-florbetaben positron emission tomography.

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