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Alexander Drzezga

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15 papers
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15

YNIMG Journal 2025 Journal Article

Pragmatic algorithm for visual assessment of 4-Repeat tauopathies in [18F]PI-2620 PET Scans

  • Theresa Bauer
  • Matthias Brendel
  • Mirlind Zaganjori
  • Alexander M. Bernhardt
  • Alexander Jäck
  • Sophia Stöcklein
  • Maximilian Scheifele
  • Johannes Levin

AIM: F]PI-2620 images for diagnosing 4R-tauopathies and to develop a straight-forward reading algorithm to improve objectivity and data reproducibility. METHODS: F]PI-2620 PET scans were included. Participants were classified as probable 4R-tauopathies (n = 29), Alzheimer's disease (AD) (n = 20), α-synucleinopathies (n = 15), and healthy controls (n = 19) based on clinical criteria. Visual assessment of tau-PET scans (choice: 4R-tauopathy, AD-tauopathy, no-tauopathy) was conducted using either 20-40-minute or 40-60-minute intervals, with raw (common) and cerebellar grey matter scaled standardized reading settings (intensity-scaled). Two readers evaluated scans independently and blinded, with a third reader providing consensus in case of discrepant primary evaluation. A regional analysis was performed using the cortex, basal ganglia, midbrain, and dentate nucleus. Sensitivity, specificity, and interrater agreement were calculated for all settings and compared against the visual reads of parametric images (0-60-minutes, distribution volume ratios, DVR). RESULTS: Patients with 4R-tauopathies in contrast to non-4R-tauopathies were detected at higher sensitivity in the 20-40-minute frame (common: 79%, scaled: 76%) compared to the 40-60-minute frame (common: 55%, scaled: 62%), albeit with reduced specificity in the common setting (20-40-min: 78%, 40-60-min: 95%), which was ameliorated in the intensity-scaled setting (20-40-min: 91%, 40-60-min: 96%). Combined assessment of multiple brain regions did not significantly improve diagnostic sensitivity, compared to assessing the basal ganglia alone (76% each). Evaluation of intensity-scaled parametric images resulted in higher sensitivity compared to intensity-scaled static scans (86% vs. 76%) at similar specificity (89% vs. 91%). CONCLUSION: F]PI-2620 tau-PET scans demonstrated reliable detection of 4R-tauopathies, particularly when standardized processing methods and early imaging windows were employed. Parametric images should be preferred for visual assessment of 4R-tauopathies.

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YNICL Journal 2021 Journal Article

Dopaminergic pathways and resting-state functional connectivity in Parkinson’s disease with freezing of gait

  • Kenan Steidel
  • Marina C. Ruppert
  • Irina Palaghia
  • Andrea Greuel
  • Masoud Tahmasian
  • Franziska Maier
  • Jochen Hammes
  • Thilo van Eimeren

Freezing of gait is a common phenomenon of advanced Parkinson's disease. Besides locomotor function per se, a role of cognitive deficits has been suggested. Limited evidence of associated dopaminergic deficits points to caudatal denervation. Further, altered functional connectivity within resting-state networks with importance for cognitive functions has been described in freezers. A potential pathophysiological link between both imaging findings has not yet been addressed. The current study sought to investigate the association between dopaminergic pathway dysintegrity and functional dysconnectivity in relation to FOG severity and cognitive performance in a well-characterized PD cohort undergoing high-resolution 6-[18F]fluoro-L-Dopa PET and functional MRI. The freezing of gait questionnaire was applied to categorize patients (n = 59) into freezers and non-freezers. A voxel-wise group comparison of 6-[18F]fluoro-L-Dopa PET scans with focus on striatum was performed between both well-matched and neuropsychologically characterized patient groups. Seed-to-voxel resting-state functional connectivity maps of the resulting dopamine depleted structures and dopaminergic midbrain regions were created and compared between both groups. For a direct between-group comparison of dopaminergic pathway integrity, a molecular connectivity approach was conducted on 6-[18F]fluoro-L-Dopa scans. With respect to striatal regions, freezers showed significant dopaminergic deficits in the left caudate nucleus, which exhibited altered functional connectivity with regions of the visual network. Regarding midbrain structures, the bilateral ventral tegmental area showed altered functional coupling to regions of the default mode network. An explorative examination of the integrity of dopaminergic pathways by molecular connectivity analysis revealed freezing-associated impairments in mesolimbic and mesocortical pathways. This study represents the first characterization of a link between dopaminergic pathway dysintegrity and altered functional connectivity in Parkinson's disease with freezing of gait and hints at a specific involvement of striatocortical and mesocorticolimbic pathways in freezers.

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YNIMG Journal 2016 Journal Article

A perspective on the future role of brain pet imaging in exercise science

  • Henning Boecker
  • Alexander Drzezga

Positron Emission Tomography (PET) bears a unique potential for examining the effects of physical exercise (acute or chronic) within the central nervous system in vivo, including cerebral metabolism, neuroreceptor occupancy, and neurotransmission. However, application of Neuro-PET in human exercise science is as yet surprisingly sparse. To date the field has been dominated by non-invasive neuroelectrical techniques (EEG, MEG) and structural/functional magnetic resonance imaging (sMRI/fMRI). Despite PET having certain inherent disadvantages, in particular radiation exposure and high costs limiting applicability at large scale, certain research questions in human exercise science can exclusively be addressed with PET: The “metabolic trapping” properties of 18F-FDG PET as the most commonly used PET-tracer allow examining the neuronal mechanisms underlying various forms of acute exercise in a rather unconstrained manner, i. e. under realistic training scenarios outside the scanner environment. Beyond acute effects, 18F-FDG PET measurements under resting conditions have a strong prospective for unraveling the influence of regular physical activity on neuronal integrity and potentially neuroprotective mechanisms in vivo, which is of special interest for aging and dementia research. Quantification of cerebral glucose metabolism may allow determining the metabolic effects of exercise interventions in the entire human brain and relating the regional cerebral rate of glucose metabolism (rCMRglc) with behavioral, neuropsychological, and physiological measures. Apart from FDG-PET, particularly interesting applications comprise PET ligand studies that focus on dopaminergic and opioidergic neurotransmission, both key transmitter systems for exercise-related psychophysiological effects, including mood changes, reward processing, antinociception, and in its most extreme form ‘exercise dependence’. PET ligand displacement approaches even allow quantifying specific endogenous neurotransmitter release under acute exercise interventions, to which modern PET/MR hybrid technology will be additionally fruitful. Experimental studies exploiting the unprecedented multimodal imaging capacities of PET/MR in human exercise sciences are as yet pending.

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YNICL Journal 2014 Journal Article

LRP-1 polymorphism is associated with global and regional amyloid load in Alzheimer's disease in humans in-vivo

  • Timo Grimmer
  • Oliver Goldhardt
  • Liang-Hao Guo
  • Behrooz H. Yousefi
  • Stefan Förster
  • Alexander Drzezga
  • Christian Sorg
  • Panagiotis Alexopoulos

OBJECTIVE: Impaired amyloid clearance has been proposed to contribute to β-amyloid deposition in sporadic late-onset Alzheimer's disease (AD). Low density lipoprotein receptor-related protein 1 (LRP-1) is involved in the active outward transport of β-amyloid across the blood-brain barrier (BBB). The C667T polymorphism (rs1799986) of the LRP-1 gene has been inconsistently associated with AD in genetic studies. We aimed to elucidate the association of this polymorphism with in-vivo brain amyloid load of AD patients using amyloid PET with [(11)C]PiB. MATERIALS AND METHODS: 72 patients with very mild to moderate AD were examined with amyloid PET and C667T polymorphism was obtained using TaqMan PCR assays. The association of C667T polymorphism with global and regional amyloid load was calculated using linear regression and voxel based analysis, respectively. The effect of the previously identified modulator of amyloid uptake, the apolipoprotein E genotype, on this association was also determined. RESULTS: The regression analysis between amyloid load and C667T polymorphism was statistically significant (p = 0.046, β = 0.236). In an additional analysis ApoE genotype and gender were identified to explain further variability of amyloid load. Voxel based analysis revealed a significant (p < 0.05) association between C667T polymorphism and amyloid uptake in the temporo-parietal cortex bilaterally. ApoE did not interact significantly with the LRP-1 polymorphism. DISCUSSION: In conclusion, C667T polymorphism of LRP-1 is moderately but significantly associated with global and regional amyloid deposition in AD. The relationship appears to be independent of the ApoE genotype. This finding is compatible with the hypothesis that impaired amyloid clearance contributes to amyloid deposition in late-onset sporadic AD.

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YNIMG Journal 2013 Journal Article

Metabolic and structural connectivity within the default mode network relates to working memory performance in young healthy adults

  • Igor Yakushev
  • Gael Chételat
  • Florian U. Fischer
  • Brigitte Landeau
  • Christine Bastin
  • Armin Scheurich
  • Audrey Perrotin
  • Mohamed Ali Bahri

Studies of functional connectivity suggest that the default mode network (DMN) might be relevant for cognitive functions. Here, we examined metabolic and structural connectivity between major DMN nodes, the posterior cingulate (PCC) and medial prefrontal cortex (MPFC), in relation to normal working memory (WM). DMN was captured using independent component analysis of [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) data from 35 young healthy adults (27. 1±5. 1years). Metabolic connectivity, a correlation between FDG uptake in PCC and MPFC, was examined in groups of subjects with (relative to median) low (n=18) and high (n=17) performance on digit span backward test as an index of verbal WM. In addition, fiber tractography based on PCC and MPFC nodes as way points was performed in a subset of subjects. FDG uptake in the DMN nodes did not differ between high and low performers. However, significantly (p=0. 01) lower metabolic connectivity was found in the group of low performers. Furthermore, as compared to high performers, low performers showed lower density of the left superior cingulate bundle. Verbal WM performance is related to metabolic and structural connectivity within the DMN in young healthy adults. Metabolic connectivity as quantified with FDG-PET might be a sensitive marker of the normal variability in some cognitive functions.

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YNIMG Journal 2008 Journal Article

Imaging of amyloid plaques and cerebral glucose metabolism in semantic dementia and Alzheimer’s disease

  • Alexander Drzezga
  • Timo Grimmer
  • Gjermund Henriksen
  • Isabelle Stangier
  • Robert Perneczky
  • Janine Diehl-Schmid
  • Chester A. Mathis
  • William E. Klunk

Semantic dementia (SD) is a rare clinical syndrome, assigned to the group of frontotemporal lobar degenerations (FTLD). Histopathological analysis has not revealed the deposition of amyloid plaques in the majority of SD cases, in contrast to dementia of the Alzheimer type (AD). However, based on clinical examination alone a reliable differentiation of the underlying pathology cannot be guaranteed, i. e. AD and SD may be confused in some cases. Our aim was to determine, whether AD and SD can be differentiated in vivo by means of amyloid plaque PET imaging. In groups of AD and SD patients, matched for gender, age and overall degree of cognitive impairment, cerebral glucose metabolism was examined with [18F]Fluorodeoxyglucose (FDG)-PET and cerebral amyloid plaque density was assessed using [11C]6-OH-BTA-1 (PIB)-PET. A volume-of-interest analysis (VOI), using the cerebellum as a reference region, and voxel-based statistical group comparisons (SPM2) were carried out between the patient groups and matched groups of healthy controls. To control for a potential influence of atrophy on the PET findings, a correction of partial volume effects was performed. Characteristic patterns of hypometabolism could be demonstrated in both clinically defined AD and SD with some regional overlap and subtle differences (AD: bilateral posterior cingulate, temporoparietal and frontal cortex; SD: left>right polar temporal, frontal mesial cortex). Compared with healthy controls, significant [11C]PIB amyloid plaque tracer binding was observed only in patients with AD (in bilateral temporoparietal, frontal and posterior cingulate cortex and the precuneus) but not in SD. This difference in amyloid plaque deposition could be reproduced in direct statistical comparison of AD and SD and clearly extended the metabolic differences between the patient groups. These findings support the notion that SD can be diagnosed in vivo as a separate entity from AD using amyloid plaque imaging. In general, amyloid plaque PET may complement neuropsychological assessment regarding reliable differential diagnosis of AD and FTLD dementias based on characterization of underlying pathology and may improve the definition of individual prognosis and the selection of patients for scientific trials.

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YNIMG Journal 2008 Journal Article

Multivariate and univariate neuroimaging biomarkers of Alzheimer's disease

  • Christian Habeck
  • Norman L. Foster
  • Robert Perneczky
  • Alexander Kurz
  • Panagiotis Alexopoulos
  • Robert A. Koeppe
  • Alexander Drzezga
  • Yaakov Stern

We performed univariate and multivariate discriminant analysis of FDG–PET scans to evaluate their ability to identify Alzheimer's disease (AD). FDG–PET scans came from two sources: 17 AD patients and 33 healthy elderly controls were scanned at the University of Michigan; 102 early AD patients and 20 healthy elderly controls were scanned at the Technical University of Munich, Germany. We selected a derivation sample of 20 AD patients and 20 healthy controls matched on age with the remainder divided into 5 replication samples. The sensitivity and specificity of diagnostic AD-markers and threshold criteria from the derivation sample were determined in the replication samples. Although both univariate and multivariate analyses produced markers with high classification accuracy in the derivation sample, the multivariate marker's diagnostic performance in the replication samples was superior. Further, supplementary analysis showed its performance to be unaffected by the loss of key regions. Multivariate measures of AD utilize the covariance structure of imaging data and provide complementary, clinically relevant information that may be superior to univariate measures.

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YNIMG Journal 2007 Journal Article

A fronto-parietal network is mediating improvement of motor function related to repetitive peripheral magnetic stimulation: A PET-H2O15 study

  • Albrecht Struppler
  • Ferdinand Binkofski
  • Bernhard Angerer
  • Michael Bernhardt
  • Sabine Spiegel
  • Alexander Drzezga
  • Peter Bartenstein

Repetitive peripheral magnetic stimulation (RPMS) is a focused and painless stimulation method, in which muscle contractions are elicited by depolarization of the terminal motor branches. Clinical–experimental investigations on different disorders of sensorimotor integration in the last decade have shown that RPMS can be used for the rehabilitation of motor functions after stroke. It is supposed that this therapeutic effect is based on the RPMS-induced proprioceptive inflow to the CNS. To analyze the conditioning effects of RPMS on reorganization of the motor system on cortical level positron emission tomography (PET) is used. Regional cerebral blood flow (rCBF) has been measured using H2O15-PET in eight patients with arm paresis following focal cerebral ischemic infarction before and after treatment using RPMS on upper arm flexor muscles. Behavioral measures showed a significant improvement of kinematics of finger movements and a reduction of spasticity in the affected arm following RPMS treatment. The recovery was associated with significant increase of neural activation within the superior posterior parietal lobe and the premotor cortex (PM) areas. The increase of activation of the parieto-premotor network following RPMS treatment indicates a significant conditioning effect of RPMS on the cortical level. These results emphasize the positive therapeutic effect of RPMS and describe the physiological bases of its function on the central level.

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YNIMG Journal 2004 Journal Article

Short-term modulation of regional excitability and blood flow in human motor cortex following rapid-rate transcranial magnetic stimulation

  • Beatrice Takano
  • Alexander Drzezga
  • Martin Peller
  • Iris Sax
  • Markus Schwaiger
  • Lucy Lee
  • Hartwig Roman Siebner

Repetitive transcranial magnetic stimulation (rTMS) of the human primary motor cortex (M1) provides a means of inducing lasting changes in cortical excitability and synaptic activity. Here we combined rTMS with positron emission tomography of regional cerebral blood flow (rCBF) to examine how an rTMS-induced change in intracortical excitability of inhibitory circuits affects regional synaptic activity. In a first set of experiments, we gave 150 biphasic pulses of 5 Hz rTMS at 90% of active motor threshold to left M1 and used single- and paired-pulse TMS to assess the conditioning effects of rTMS on motor cortical excitability at rest. rTMS conditioning led to a selective decrease in short-latency intracortical inhibition (SICI) without affecting short-latency intracortical facilitation or corticospinal excitability. The decrease in SICI lasted for approximately 8 min. In a second experiment, we used the same rTMS protocol and measured changes in regional synaptic activity (as indexed by rCBF) during and for up to 14 min after the end of rTMS. Subthreshold 5 Hz rTMS induced a region-specific increase in resting rCBF in the stimulated M1 lasting approximately 8 min. These \ suggest that in the stimulated M1, temporary attenuation of SICI is paralleled by an increase in synaptic activity, consistent with reduced efficacy of intracortical GABAA-ergic synapses. The present findings demonstrate that short trains of low-intensity 5 Hz rTMS can be used to induce a transient change in function within a distinct cortical area. This opens up new possibilities for studying acute reorganization at the systems level in the intact human brain.

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YNIMG Journal 2002 Journal Article

Linking Actions and Their Perceivable Consequences in the Human Brain

  • Birgit Elsner
  • Bernhard Hommel
  • Claudia Mentschel
  • Alexander Drzezga
  • Wolfgang Prinz
  • Bastian Conrad
  • Hartwig Siebner

Voluntaryaction is goal-directed and therefore depends on the ability to learn associations between movements and their perceivable consequences. The neural substrate of this ability was investigated with H2 15O positron emission tomography (PET). Healthy adults first learned that self-initiated keypresses were consistently followed by certain tones (i. e. , action effects). During PET imaging, participants listened to varied ratios of action–effect tones and neutral tones without performing any movement. The caudal supplementary motor area and the right hippocampus increased their activity with the frequency of action–effect tones, suggesting that both cortical areas play a role in linking the consequences of an action and the action itself. This integration process represents a highly flexible mechanism that helps to promote the learning, automatization, and control of voluntary actions.

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YNIMG Journal 2001 Journal Article

Continuous Transcranial Magnetic Stimulation during Positron Emission Tomography: A Suitable Tool for Imaging Regional Excitability of the Human Cortex

  • Hartwig Roman Siebner
  • Beatrice Takano
  • Alexander Peinemann
  • Markus Schwaiger
  • Bastian Conrad
  • Alexander Drzezga

In six healthy volunteers, H2 15O positron emission tomography (PET) was employed to evaluate rate-dependent functional activation of the left primary sensorimotor hand area (SM1HAND) during subthreshold repetitive transcranial magnetic stimulation (rTMS). Using an eight-shaped coil, continuous trains of rTMS were delivered during nine 50-s H2 15O PET scans. Nine different stimulation frequencies were used, ranging from 1 to 5 Hz. Stimulus intensity was set at 10% below active motor threshold. During three additional PET scans, an ineffective rTMS was applied via another eight-shaped coil, which was held 10 cm above the vertex. Statistical parametric mapping was employed to assess relative differences in normalized regional cerebral blood flow (rCBF) across conditions. Compared with ineffective rTMS, subthreshold rTMS increased normalized rCBF in the stimulated SM1HAND. Moreover, the increase in rCBF in the left SM1HAND showed a linear positive relationship with the rate of rTMS, indicating a rate-dependent functional activation of the stimulated SM1HAND. These data demonstrate that, by varying the variables of rTMS across scans, continuous rTMS during H2 15O PET provides a noninvasive tool to study the regional excitability profile of a distinct cortical area.

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v2026.09.13