Publications by authors named "Paul Cumming"

Article Synopsis
  • There is a recognized link between depression in the elderly and an increased risk of developing Alzheimer's disease, with both conditions potentially influencing each other through shared cognitive and social symptoms.
  • The study reviews existing literature on language disturbances and cognitive impairments in both depression and Alzheimer's disease, utilizing PET imaging to identify underlying neurobiological patterns.
  • Findings suggest that both disorders exhibit similar language issues, such as simplified speech patterns, and share common brain metabolic deficits, indicating that targeted language therapy could help improve cognitive function in patients experiencing both conditions.
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Article Synopsis
  • Alzheimer's disease (AD) is a major global health concern with limited treatment options, leading researchers to investigate non-invasive therapies like repetitive transcranial magnetic stimulation (rTMS) to improve cognitive function in patients.
  • A systematic review and meta-analysis of 22 studies found that high-frequency rTMS, especially targeting the dorsolateral prefrontal cortex, significantly enhanced cognitive abilities in AD patients with a moderate effect size.
  • While the findings are promising, they also revealed substantial variability among studies and potential publication bias, indicating the need for further investigation to optimize rTMS treatment parameters.
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Background: We examined the prevalence and spread of conspiracy beliefs about the origins of the COVID-19 pandemic among representatives of the Russian population. Our study aimed to identify belief clusters and develop predictive models to understand the factors that influence conspiracy beliefs, particularly in the context of how they might evolve in response to socio-political events and cause mental disturbances, thus in relation to specific pathways of the infodemic and psychodemic waves that spread among vulnerable population groups.

Methods: Data respondents to the international COMET-G study living in Russia during pandemic period (n=7,777) were analyzed using descriptive statistics, K-means clustering, and various machine learning models, including gradient boosting.

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The potent hallucinogen N,N-dimethyltryptamine (DMT) has garnered significant interest in recent years due to its profound effects on consciousness and its therapeutic psychopotential. DMT is an integral (but not exclusive) psychoactive alkaloid in the Amazonian plant-based brew ayahuasca, in which admixture of several β-carboline monoamine oxidase A (MAO-A) inhibitors potentiate the activity of oral DMT, while possibly contributing in other respects to the complex psychopharmacology of ayahuasca. Irrespective of the route of administration, DMT alters perception, mood, and cognition, presumably through agonism at serotonin (5-HT) 1A/2A/2C receptors in brain, with additional actions at other receptor types possibly contributing to its overall psychoactive effects.

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Background: Diagnosis and recovery tracking of mild traumatic brain injury (mTBI) is often challenging due to the lack of clear findings on routine imaging techniques. This also complicates defining safe points for returning to activities.

Hypothesis/purpose: Quantitative susceptibility mapping (QSM) can provide information about cerebral venous oxygen saturation (CSvO) in the context of brain injury.

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Introduction: Neuroinflammatory reactions play a significant role in the pathology and long-term consequences of traumatic brain injury (TBI) and may mediate salutogenic processes that white matter integrity. This study aimed to investigate the relationship between inflammatory markers and white matter integrity following TBI in both a rat TBI model and clinical TBI cases.

Methods: In the rat model, blood samples were collected following a controlled cortical impact (CCI) to assess a panel of inflammatory markers; MR-based diffusion tensor imaging (DTI) was employed to evaluate white matter integrity 60 days post-injury.

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The σ-1 receptor is a non-opioid transmembrane protein involved in various human pathologies including neurodegenerative diseases, inflammation, and cancer. The previously published ligand [ F]FTC-146 is among the most promising tools for σ-1 molecular imaging by positron emission tomography (PET), with a potential for application in clinical diagnostics and research. However, the published six- or four-step synthesis of the tosyl ester precursor for its radiosynthesis is complicated and time-consuming.

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Background: Until recently, quantitation of the net influx of 2-[F]fluorodeoxyglucose (FDG) to brain (K) and the cerebrometabolic rate for glucose (CMR) required serial arterial blood sampling in conjunction with dynamic positron emission tomography (PET) recordings. Recent technical innovations enable the identification of an image-derived input function (IDIF) from vascular structures, but are frequently still encumbered by the need for interrupted sequences or prolonged recordings that are seldom available outside of a research setting. In this study, we tested simplified methods for quantitation of FDG-K by linear graphic analysis relative to the descending aorta IDIF in oncology patients examined using a Biograph Vision 600 PET/CT with continuous bed motion (Aarhus) or using a recently installed Biograph Vision Quadra long-axial field-of-view (FOV) scanner (Bern).

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Purpose: Metabolic network analysis of FDG-PET utilizes an index of inter-regional correlation of resting state glucose metabolism and has been proven to provide complementary information regarding the disease process in parkinsonian syndromes. The goals of this study were (i) to evaluate pattern similarities of glucose metabolism and network connectivity in dementia with Lewy bodies (DLB) subjects with subthreshold dopaminergic loss compared to advanced disease stages and to (ii) investigate metabolic network alterations of FDG-PET for discrimination of patients with early DLB from other neurodegenerative disorders (Alzheimer's disease, Parkinson's disease, multiple system atrophy) at individual patient level via principal component analysis (PCA).

Methods: FDG-PETs of subjects with probable or possible DLB (n = 22) without significant dopamine deficiency (z-score < 2 in putamen binding loss on DaT-SPECT compared to healthy controls (HC)) were scaled by global-mean, prior to volume-of-interest-based analyses of relative glucose metabolism.

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The psychedelic effects of the traditional Amazonian botanical decoction known as ayahuasca are often attributed to agonism at brain serotonin 5-HT receptors by -dimethyltryptamine (DMT). To reduce first pass metabolism of oral DMT, ayahuasca preparations additionally contain reversible monoamine oxidase A (MAO-A) inhibitors, namely β-carboline alkaloids such as harmine. However, there is lacking biochemical evidence to substantiate this pharmacokinetic potentiation of DMT in brain via systemic MAO-A inhibition.

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Background: Spinal muscular atrophy (SMA) is a rare genetic disorder, in which, for the common childhood onset forms, loss of function of the SMA 5q gene leads to disability and death before adulthood. Symptomatic treatment focusses on respiratory and nutritional support, and physical therapy, but there is little consideration of psychiatric manifestations of SMA. The aim of this study was to explore blood biomarker levels, electromyography (EMG) data, and clinical manifestations, including psychiatric impairments, in patients with SMA 5q.

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Background: Post-traumatic stress disorder (PTSD) is a trauma- or stressor-related mental health condition with high socioeconomic burden. We aimed in this review to identify promising genetic markers predisposing for PTSD, which might serve in the design subsequent studies aiming to develop PTSD prevention and remediation measures.

Subjects And Methods: Our search queries in the PubMed database yielded 547 articles, of which 20 met our inclusion criteria for further analysis: published between 2018 and 2022, original research, containing molecular-genetic and statistical data, containing diagnosis verification methods, PTSD as a primary condition, and a sample of at least 60 patients.

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Background: Electroconvulsive therapy (ECT) is one of the most effective treatments for depressive disorders. However, ECT has a number of limitations, such as significant side effects in the neurocognitive domain and the requirement for general anesthesia. Transcranial magnetic stimulation (TMS) is an intervention that applies electric stimulation to the brain without causing convulsions, thus representing an attractive alternative to ECT.

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Psilocybin (a classic serotonergic psychedelic drug) has received appraisal for use in psychedelic-assisted therapy of several psychiatric disorders. A less explored topic concerns the use of repeated low doses of psychedelics, at a dose that is well below the psychedelic dose used in psychedelic-assisted therapy and often referred to as microdosing. Psilocybin microdose users frequently report increases in mental health, yet such reports are often highly biased and vulnerable to placebo effects.

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We have established a method for nucleophilic one-pot, two-step radiosynthesis of the popular opioid receptor radioligand 6--(2-[F]fluoroethyl)-6--desmethyl-diprenorphine ([F]FE-DPN) from the novel precursor 6--(2-tosyloxyethyl)-6--desmethyl- 3--trityl-diprenorphine (TE-TDDPN), which we designate as the Henriksen precursor. We undertook an optimization of the synthesis conditions, aiming to enhance the accessibility of [F]FE-DPN for positron emission tomography (PET) studies of μ-opioid receptors. Herein, we report an optimized direct nucleophilic F-fluorination and the deprotection conditions for a fully automated radiosynthesis of [F]FE-DPN on a modified GE Tracerlab FX FE synthesis panel.

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Background: We present a cross-sectional, case-matched, and pair-wise comparison of structural magnetic resonance imaging (MRI), diffusion tensor imaging (DTI), and neurite orientation dispersion and density imaging (NODDI) measures in vivo and ex vivo in a mouse model of concussion, thus aiming to establish the concordance of structural and diffusion imaging findings in living brain and after fixation.

Methods: We allocated 28 male mice aged 3-4 months to sham injury and concussion (CON) groups. CON mice had received a single concussive impact on day 0 and underwent MRI at day 2 (n = 9) or 7 (n = 10) post-impact, and sham control mice likewise underwent imaging at day 2 (n = 5) or 7 (n = 4).

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We report the dosimetric evaluation of prostate-specific membrane antigen-based radioligand therapy (RLT) for metastatic prostate cancer in a patient with autosomal-dominant polycystic kidney disease. The patient received hemodialysis during each of 6 RLT cycles while staying as an inpatient. We used voxel dosimetry and blood sampling for the dose calculation.

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Purpose: Blood-brain barrier (BBB) dysregulation and pro-inflammatory signalling molecules are secondary factors that have been associated with injury severity and long-term clinical outcome following traumatic brain injury (TBI). However, the association between BBB permeability and inflammation is unknown in human TBI patients. In this study, we investigated whether BBI integrity as measured by Dynamic Contrast-Enhanced (DCE) Magnetic Resonance Imaging (MRI) correlates with plasma levels of immunological markers following TBI.

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Carboxypeptidase II (CBPII) in brain metabolizes the neuroactive substance N-acetyl-L-aspartyl-L-glutamate (NAGG) to yield the elements of glutamate and N-acetyl-aspartate (NAA). In peripheral organs, CBPII is known as prostrate specific membrane antigen (PSMA), which presents an important target for nuclear medicine imaging in prostate cancer. Available PSMA ligands for PET imaging do not cross the blood-brain barrier, and there is scant knowledge of the neurobiology of CBPII, despite its implication in the regulation of glutamatergic neurotransmission.

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Structural and functional deficits in the hippocampus are a prominent feature of moderate-severe traumatic brain injury (TBI). In this work, we investigated the potential of Quantitative Susceptibility Imaging (QSM) to reveal the temporal changes in myelin integrity in a mouse model of concussion (mild TBI). We employed a cross-sectional design wherein we assigned 43 mice to cohorts undergoing either a concussive impact or a sham procedure, with QSM imaging at day 2, 7, or 14 post-injury, followed by Luxol Fast Blue (LFB) myelin staining to assess the structural integrity of hippocampal white matter (WM).

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Hyperphosphorylated tau aggregates, also known as neurofibrillary tangles, are a hallmark neuropathological feature of Alzheimer's disease (AD). Molecular imaging of tau by positron emission tomography (PET) began with the development of [F]FDDNP, an amyloid β tracer with off-target binding to tau, which obtained regional specificity through the differing distributions of amyloid β and tau in AD brains. A concerted search for more selective and affine tau PET tracers yielded compounds belonging to at least eight structural categories; F-flortaucipir, known variously as [F]-T807, AV-1451, and Tauvid, emerged as the first tau tracer approved by the American Food and Drug Administration.

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Introduction: Traumatic brain injury (TBI) induces a cascade of cellular alterations that are responsible for evolving secondary brain injuries. Changes in brain structure and function after TBI may occur in concert with dysbiosis and altered amino acid fermentation in the gut. Therefore, we hypothesized that subacute plasma amino acid levels could predict long-term microstructural outcomes as quantified using neurite orientation dispersion and density imaging (NODDI).

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Alcohol use disorder (AUD) is a serious public health problem in many countries, bringing a gamut of health risks and impairments to individuals and a great burden to society. Despite the prevalence of a disease model of AUD, the current pharmacopeia does not present reliable treatments for AUD; approved treatments are confined to a narrow spectrum of medications engaging inhibitory γ-aminobutyric acid (GABA) neurotransmission and possibly excitatory N-methyl-D-aspartate (NMDA) receptors, and opioid receptor antagonists. Molecular imaging with positron emission tomography (PET) and single-photon emission computed tomography (SPECT) can open a window into the living brain and has provided diverse insights into the pathology of AUD.

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