Albert Gjedde

Albert Gjedde
University of Copenhagen · Department of Neuroscience

MD DSc

About

769
Publications
65,426
Reads
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30,254
Citations
Introduction
Albert Gjedde currently works at the Translational Neuropsychiatry Unit at Aarhus University and University Hospital. Albert does research in Psychiatry, Neurology and Physiology. Two main projects focus on effects of insulin resistance in brain tissue and Alzheimer's disease. The projects are parts of the overall theme of investigation into the links between type 2 diabetes and Alzheimer's disease during neurodegeneration.
Additional affiliations
May 2009 - present
Johns Hopkins Medicine
Position
  • Adjunct Professor of Radiology and Radiological Science
December 2008 - present
University of Copenhagen
Position
  • Professor
December 2008 - November 2014
Aarhus University
Position
  • Adjunct Professor of Neuroscience

Publications

Publications (769)
Article
Full-text available
Decryption of brain images is the basis for the necessary translation of the findings from imaging to information required to meet the demands of clinical intervention. Tools of brain imaging, therefore, must satisfy the conditions dictated by the needs for interpretation in terms of diagnosis and prognosis. In addition, the applications must serve...
Preprint
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Background: Values of binding potentials (BPND) of dopamine D2/3 receptors differ in different regions of the brain, but we do not know with certainty how much of this difference is due either to different receptor numbers, or to different affinities of tracers to the receptors, or to both. Method: We tested the claim that both striatal and extrast...
Preprint
The corticofugal tracts (CFT) are key agents of upper limb motor function. Although the tracts form high-intensity regions relative to surrounding tissue in T2-weighted magnetic resonance images (T2WI), the precise relations of signal intensities of the left and right CFT regions to hand function are unknown. Here, we tested the hypothesis that the...
Article
Hypothesis and predictions: Here, we claim that amyloid beta (Aβ) accumulation is a protective mechanism that ultimately fails. We predict that more Aβ accumulates in regions with higher rates of glucose metabolism, reaching a maximum followed by progression of pathology. Background: Aβ accumulation is characteristic of Alzheimer's disease (AD)...
Preprint
The corticofugal tracts (CFT) are key agents of upper limb motor function. Although the tracts form high-intensity regions relative to surrounding tissue in T2-weighted magnetic resonance images (T2WI), the precise relations of signal intensities of the left and right CFT regions to hand function are unknown. Here, we tested the hypothesis that the...
Article
Background Disturbances in presynaptic dopamine activity and levels of gamma-aminobutyric acid (GABA) and glutamate plus glutamine (Glx) collectively may have a role in the pathophysiology of psychosis, although separately they are poor diagnostic markers. We tested whether these neurotransmitters in combination improve the distinction of antipsych...
Article
Full-text available
In recent years, the field of neuroimaging dramatically moved forward by means of the expeditious development of specific radioligands of novel targets. Among these targets, the synaptic vesicle glycoprotein 2A (SV2A) is a transmembrane protein of synaptic vesicles, present in all synaptic terminals, irrespective of neurotransmitter content. It is...
Article
Full-text available
We asked if sensation-seeking is linked to premorbid personality characteristics in patients with addictive disorders, or the characteristics follow the sensation-seeking activity. We interpreted the former as a state associated with normal rates of dopamine synthesis, and the latter as a trait of individuals with abnormally high rates of synthesis...
Article
Background Dopamine activity has been associated with the response to antipsychotic treatment. Our study used a four-parameter model to test the association between the striatal decarboxylation rate of ¹⁸F-DOPA to ¹⁸F-dopamine (k3) and the effect of treatment on psychotic symptoms in antipsychotic-naïve first-episode psychotic patients. We further...
Article
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Exposure to moderate hypoxia in humans leads to cerebral lactate production, which occurs even when the cerebral metabolic rate of oxygen (CMRO2) is unaffected. We searched for the mechanism of this lactate production by testing the hypothesis of upregulation of cerebral glycolysis mediated by hypoxic sensing. Describing the pathways counteracting...
Article
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We derived three widely used linearizations from the definition of receptor availability in molecular imaging with Positron Emission Tomography. The purpose of the present research was to determine the convergence of the results of the three methods in terms of three parameters, occupancy (s), distribution volume of the non-displaceable binding com...
Article
Quantitative measurements of resting cerebral blood flow (CBF) and metabolic rate of oxygen (CMRO 2 ) show large between-subject and regional variability, but the relationships between CBF and CMRO 2 measurements regionally and globally are not fully established. Here, we investigated the between-subject and regional associations between CBF and CM...
Article
Full-text available
Objective: By the association of nicotinic acetylcholine receptors in the brain, nicotine in the therapeutic window lowers neuronal damage and raises protective factors. These data, however, are contradicted by other findings. Here, we assessed the effects of transdermal nicotine administration on cognitive functions in healthy non-smoker adults b...
Article
Full-text available
Background Autonomic nervous system dysfunction (ANSD) is known to affect glucose metabolism in the mammalian body. Tradition holds that glucose homeostasis is regulated by the peripheral nervous system, and contemporary therapeutic intervention reflects this convention. Objectives The present study tested the role of cerebral regulation of ANSD a...
Article
Full-text available
RationaleAfter alcohol ingestion, the brain partly switches from consumption of glucose to consumption of the alcohol metabolite acetate. In heavy drinkers, the switch persists after abrupt abstinence, leading to the hypothesis that the resting brain may be “starved” when acetate levels suddenly drop during abstinence, despite normal blood glucose,...
Article
Background: Muscarinic acetylcholine receptor 4 (M4) modulates dopaminergic neurotransmission and is a target for novel treatments of schizophrenia, cognitive deficits, and addiction. Impulsive and compulsive behaviors are key traits of addiction, yet the importance of M4 receptor signaling to these traits is poorly understood. We investigated impu...
Article
Objective: We report the transcranial functional photoacoustic (fPA) neuroimaging of N-methyl-D-aspartate (NMDA) evoked neural activity in the rat hippocampus. Concurrent quantitative electroencephalography (qEEG) and microdialysis were used to record real-time circuit dynamics and excitatory neurotransmitter concentrations, respectively. Approac...
Article
Purpose Anaesthesia routinely is used in animal neuroimaging in order to reduce head motion artefacts and minimize the influence of stress. However, anaesthetics can modify radioligand binding profiles at receptor targets studied by positron emission tomography (PET). Here, we determined the effects of two routine anaesthetics on the binding of a t...
Article
Full-text available
Excessive sucrose consumption elicits addiction-like craving that may underpin the obesity epidemic. Opioids and dopamine mediate the rewarding effects of drugs of abuse, and of natural rewards from stimuli such as palatable food. We investigated the effects of sucrose using PET imaging with [11C]carfentanil (μ-opioid receptor agonist) and [11C]rac...
Preprint
Full-text available
Transcranial functional photoacoustic (fPA) voltage-sensitive dye (VSD) imaging promises to overcome current temporal and spatial limitations of current neuroimaging modalities. The technique previously distinguished global seizure activity from control neural activity in groups of rats. To validate the focal specificity of transcranial fPA neuroim...
Article
Full-text available
According to the World Health Organization (WHO), dementia is a disorder that occurs as result of a neurodegenerative process in brain, and usually is chronic or progressive by nature. Most descriptions of senile dementia date back to Alois Alzheimer. In 1906, Alzheimer described the first patient, Auguste Deter, who suffered from the disorder that...
Article
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The glymphatic system is a brainwide CSF transport system that uses the perivascular space for fast inflow of CSF. Arterial pulsations are a major driver of glymphatic CSF inflow, and hypertension that causes vascular pathologies, such as arterial stiffening and perivascular alterations, may impede the inflow. We used dynamic contrast-enhanced MRI...
Article
Full-text available
Minimally-invasive monitoring of electrophysiological neural activities in real-time—that enables quantification of neural functions without a need for invasive craniotomy and the longer time constants of fMRI and PET—presents a very challenging yet significant task for neuroimaging. In this paper, we present in vivo functional PA (fPA) imaging of...
Article
Full-text available
Purpose We tested the hypothesis that lateralized hemispheric glucose metabolism may have diagnostic implications in Alzheimer’s disease (AD) and mild cognitive impairment (MCI). Methods We performed FDG-PET/CT in 23 patients (mean age 63.7 years, range 50–78, 17 females) diagnosed with AD (n = 15) or MCI (n = 8) during a six-month period in 2014....
Article
Full-text available
Background: Electroconvulsive therapy is an effective therapy of depression. We hypothesized that the beneficial effects are mediated partly by decreased serotonin receptor availability in the cortex. Aims: We used positron emission tomography with the serotonin 5HT2A receptor radioligand [11C]MDL100,907 to determine serotonin receptor availabil...
Article
Full-text available
Disturbances in mitochondrial biogenesis and bioenergetics, combined with neuroinflammation, play cardinal roles in the cognitive impairment during aging that is further exacerbated by transient cerebral ischemia. Both near-infrared (NIR) photobiomodulation (PBM) and Coenzyme Q10 (CoQ10), administration are known to stimulate mitochondrial electron...
Article
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Background: The alleged procognitive effects of nicotine and its metabolites in brain are controversial. Objective: Here, we review the pharmacologically active metabolites of nicotine in brain and their effects on neuronal mechanisms involving two main cognitive domains, i.e., learning and memory. Methods: We searched Embase, Medline via PubMed, S...
Article
INTRODUCTION: Stress is one of the greatest burdens of our society and often implies impairments in cognitive and emotional functions. Here, we hypothesise that changes in the brain's dopamine (DA)-based mesocorticolimbic projec-tions in patients with work-related stress (adjustment disorder) will manifest themselves as altered glucose metabolism i...
Article
Full-text available
Brain growth across childhood is a dynamic process associated with specific energy requirements. A disproportionately higher rate of glucose utilization (CMRglucose) compared with oxygen consumption (CMRO2) was documented in children's brain and suggestive of non-oxidative metabolism of glucose. Several candidate metabolic pathways may explain the...
Article
Purpose: Malignant cells exhibit increased rates of aerobic glycolysis. Here, we tested whether the accumulation of fluoro-deoxyglucose-6-phosphate (FDG6P) in ovarian cancers of differential malignancy reflects inversely correlated elevations of hexokinase (HK) and glucose-6-phosphatase (G6Pase) activities. Procedures: Twenty-nine women with sus...
Article
Full-text available
Here, we tested the claim that nicotine attenuates the signs of brain dysfunction in the model of brain aging induced by D-galactose (DGal) in mice. We administered nicotine at doses of 0.1, 0.5 and 1 mg/kg by the subcutaneous (s.c.) or at 0.1 mg/kg by the intranasal (i.n.) routes in mice that had received DGal at the dose of 500 mg/kg subcutaneous...
Article
Full-text available
Because the human brain consumes a disproportionate fraction of the resting body’s energy, positron emission tomography (PET) measurements of absolute glucose metabolism (CMR glc ) can serve as disease biomarkers. Global mean normalization (GMN) of PET data reveals disease-based differences from healthy individuals as fractional changes across regi...
Data
Figure S1: voxel-to-voxel correlations of qCMRglc in gray matter of the human brain. Figure S2: voxel-to-voxel correlations of qCMRglc in white matter of the human brain. Figure S3: thresholded t-maps of metabolic variations in disorders of consciousness. Figure S4: thresholded t-maps of metabolic variations in anesthetic sedation. Figure S5: thres...
Preprint
Full-text available
Transcranial photoacoustic (PA) voltage-sensitive dye (VSD) imaging promises to overcome current temporal and spatial limitations of functional neuroimaging. The technique previously distinguished global seizure activity from control neural activity in groups of rats. To validate the focal specificity of transcranial PA with VSD (IR780) imaging in...
Preprint
Full-text available
Article
In the present study we tested the claim that the dopaminergic dysfunction of Rett Syndrome (RTT) also occurs in Mecp2-deficient mice that serve as a model of the syndrome. We used positron emission tomography (PET) to image dopamine D2 receptors (D2R) and transporters (DAT) in women with RTT and in Mecp2-deficient mice, and D1R and D2R density was...
Article
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A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
Article
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Background: The α7 nicotinic acetylcholine receptor (nAChR) increasingly has been implicated in normal brain physiology, as well as in neuropsychiatric disorders. The highly cortical distribution of α7-nAChR suggests a role in cognition. Methods: We expanded the first-in-human PET imaging of α7-nAChR with [18F]ASEM from five to 21 healthy non-sm...
Article
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Aims/hypothesis: The aim of this randomised, crossover trial was to compare cognitive functioning and associated brain activation patterns during hypoglycaemia (plasma glucose [PG] just below 3.1 mmol/l) and euglycaemia in individuals with type 1 diabetes mellitus. Methods: In this patient-blinded, crossover study, 26 participants with type 1 di...
Article
Referring to a recent international article stating that amyloid PET has a high additive value in making a diagnosis of Alzheimer's disease (AD) when previous investigations are inconclusive, the authors of this editorial argue that this statement is based on circular reasoning and, hence, misleading. Since autopsy findings and other potential indi...
Preprint
Full-text available
The α7 nicotinic acetylcholine receptor (nAChR) increasingly has been implicated in normal brain physiology, as well as in neuropsychiatric disorders. The a7-nAChR primarily is located in cerebral cortex and sub-cortical regions, compared to the α4β2 nAChR subtype that has a more subcortical distribution. The highly cortical distribution suggests a...
Chapter
Noradrenergic neurons in both the peripheral nervous system and in the central nervous system (CNS) undergo severe degeneration in patients with Parkinson's disease (PD). This loss of noradrenaline may play essential roles in the occurrence of a wide range of prevalent non-motor symptoms and can further complicate the lives of PD patients. In vivo...
Article
Full-text available
There are fewer than normal glucose transporters at the blood-brain barrier (BBB) in Alzheimer's disease (AD). When reduced expression of transporters aggravates the symptoms of AD, the transporters become a potential target of therapy. The incretin hormone GLP-1 prevents the decline of cerebral metabolic rate for glucose (CMRglc) in AD, and GLP-1...
Article
Incretin hormones, notably glucagon-like peptide-1 (GLP-1), are gluco-regulatory hormones with pleiotropic effects also in the central nervous system. Apart from a local production of GLP-1, systemic administration of the hormone has been shown to influence a number of cerebral pathologies, including neuroinflammation. Given the brains massive depe...
Article
Full-text available
We describe a novel method of kinetic analysis of radioligand binding to neuroreceptors in brain in vivo, here applied to noradrenaline receptors in rat brain. The method uses positron emission tomography (PET) of [¹¹C]yohimbine binding in brain to quantify the density and affinity of α2 adrenoceptors under condition of changing radioligand binding...
Chapter
Full-text available
In this chapter, we review how light affects humans: first by describing the ways in which light impacts physiology and behavior, and then by discussing how different char- acteristics of light (timing, pattern, intensity, duration, and past light exposure) can influence alertness, cognitive performance, mood, sleep, and well-being, in addition to...
Chapter
Full-text available
In this chapter, we review how light affects humans: first by describing the ways in which light impacts physiology and behavior, and then by discussing how different char- acteristics of light (timing, pattern, intensity, duration, and past light exposure) can influence alertness, cognitive performance, mood, sleep, and well-being, in addition to...
Article
Full-text available
Minimally-invasive monitoring of electrophysiological neural activities in real-time—that enables quantification of neural functions without a need for invasive craniotomy and the longer time constants of fMRI and PET—presents a very challenging yet significant task for neuroimaging. In this paper, we present in vivo functional PA (fPA) imaging of...
Article
Rationale: Degeneration of noradrenergic neurons may underlie the disabling non-motor symptoms in patients with Parkinson's disease. Quantification of the loss of noradrenergic neurons by means of neuroimaging has been limited by the lack of radioligands that are selective for noradrenergic neurotransmission. The radioligand (11)C-MeNER is a highly...
Article
Full-text available
Leber's Hereditary Optic Neuropathy (LHON) shares features with Multiple Sclerosis (MS). Both diseases develop optic lesions. Frequent secondary LHON mutations in MS patients may explain the optic damage. Here, we tested the hypothesis that secondary LHON mutations are associated with optic neuritis (ON) in MS patients. We recruited 56 MS subjects...
Article
Full-text available
Evidence suggests that synapses are affected first in Parkinson’s disease (PD). Here, we tested the claim that pathological accumulation of α-synuclein, and subsequent synaptic disruption, occur in absence of dopaminergic neuron loss in PD. We determined early synaptic changes in rats that overexpress human α-synuclein by local injection of viral-v...
Article
Full-text available
Electroconvulsive therapy (ECT), a direct form of brain stimulation, is an effective antidepressant. We hypothesized that the beneficial effects of ECT are mediated by increased dopaminergic neurotransmission, in which the baseline activity of D1 receptors may predict the response to ECT. We established a novel model of brain stimulation in Götting...