Gérard Nisal Bischof

Gérard Nisal Bischof
University of Cologne | UOC · University Hospital, Department of Nuclear Medicine

Diploma Psych, MS, PhD

About

138
Publications
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2,659
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Additional affiliations
July 2014 - January 2015
The University of Texas at Dallas
Position
  • PostDoc Position
August 2009 - June 2014
The University of Texas at Dallas
Position
  • PhD

Publications

Publications (138)
Article
Cognitive reserve (CR) is defined as the ability to maintain functionality despite accumulating pathology and education has been used as a proxy for CR. For example, by using PET imaging higher educated Alzheimer’s disease (AD) patients presented increased beta amyloid pathology than lower educated patients despite equal symptomatology. Whether sim...
Article
Full-text available
In a multimodal PET imaging approach, we determined the differential contribution of neurofibrillary tangles (measured with [18F]AV-1451) and beta-amyloid burden (measured with [11C]PiB) on degree of neurodegeneration (i.e., glucose metabolism measured with [18F]FDG-PET) in patients with Alzheimer's disease. Across brain regions, we observed an int...
Chapter
This chapter addresses the evidence that indicates that cognitive interventions change neural function or structure of the brain. It also highlights that other excellent and recent comprehensive reviews of training effects in older adults are available. It also provides a brief overview of neural changes that occur in the brain with age, a theoreti...
Article
A stereotypical anatomical propagation of tau pathology has been described in Alzheimer's disease. According to recent concepts (network degeneration hypothesis), this propagation is thought to be indicative of misfolded tau proteins possibly spreading along functional networks. If true, tau pathology accumulation should correlate in functionally c...
Preprint
Full-text available
Patients with Alzheimer’s disease (AD) and clinically overlapping neurodegenerative diseases are classified molecularly using the A/T/N classification system. Apart from fluid biomarkers and structural MRI, the three-dimensional A/T/N system incorporates characteristic features from β-amyloid-PET (A), tau-PET (T), and FDG-PET (N). We evaluated if d...
Article
Full-text available
Background Tau‐PET imaging allows in‐vivo detection of neurofibrillary tangles. One tau‐PET tracer (i.e., [18F]flortaucipir) has received FDA‐approval for clinical use, and multiple other tau‐PET tracers have been implemented into clinical trials for participant selection and/or as a primary or secondary outcome measure. To optimize future use of t...
Article
Full-text available
Background Experience‐dependent cognitive plasticity can be induced by cognitive training well into the later decades of life. Although some prerequisites (education, intelligence) and constraints (age, genetic predisposition) on the extent of cognitive plasticity have been discussed, the impact of molecular age‐related changes in the form of fibri...
Article
Full-text available
Background There is a strong link between tau and progression of Alzheimer’s disease (AD), necessitating an understanding of tau spreading mechanisms. Prior research, predominantly in typical AD, suggested that tau propagates from epicenters (regions with earliest tau) to functionally connected regions. However, given the constrained spatial hetero...
Article
Full-text available
Background Late‐life depression (LLD) is a risk factor for Alzheimer's disease (AD) dementia. Previous morphological studies have often associated LLD with atrophy within the medial temporal lobe (MTL), including the hippocampus. A number of previous studies have demonstrated the changes in several MTL subfields in LLD, such as the perirhinal corte...
Article
Full-text available
Background Experience‐dependent cognitive plasticity can be induced by cognitive training well into the later decades of life. Although some prerequisites (education, intelligence) and constraints (age, genetic predisposition) on the extent of cognitive plasticity have been discussed, the impact of molecular age‐related changes in the form of fibri...
Article
Full-text available
Background There is a strong link between tau and progression of Alzheimer’s disease (AD), necessitating an understanding of tau spreading mechanisms. Prior research, predominantly in typical AD, suggested that tau propagates from epicenters (regions with earliest tau) to functionally connected regions. However, given the constrained spatial hetero...
Article
Full-text available
Background Tau‐PET imaging allows in‐vivo detection of neurofibrillary tangles. One tau‐PET tracer (i.e., [¹⁸F]flortaucipir) has received FDA‐approval for clinical use, and multiple other tau‐PET tracers have been implemented into clinical trials for participant selection and/or as a primary or secondary outcome measure. To optimize future use of t...
Article
Full-text available
Background and Objectives Apraxia is a frequently observed symptom in Alzheimer disease (AD), but the causal pathomechanism underlying this dysfunction is not well understood. Previous studies have demonstrated associations between various cognitive dysfunctions in AD and cortical tau deposition in specific brain areas, suggesting a causal relation...
Article
Full-text available
Tau PET has attracted increasing interest as an imaging biomarker for 4-repeat (4R)-tauopathy progressive supranuclear palsy (PSP). However, the translation of in vitro 4R-tau binding to in vivo tau PET signals is still unclear. Therefore, we performed a translational study using a broad spectrum of advanced methodologies to investigate the sources...
Article
Full-text available
Several studies have demonstrated strong agreement between routine clinical visual assessment and quantification, suggesting that quantification approaches could support assessment by less experienced readers or in challenging cases. However, all studies to date have implemented a retrospective case collection, and challenging cases were generally...
Preprint
Full-text available
Objective Recent evidence suggests that disturbances of sleep architecture are linked to Alzheimer’s disease (AD) pathology. Here, we assessed the association between sleep architecture and regional amyloid and tau pathology employing a portable sleep-monitoring device in addition to PET imaging. Methods 18 cognitively normal adults (CN; M(Age) =...
Preprint
Full-text available
Objective: To examine interactive effects of modifiable factors, genetic determinants and load-dependent pathology effects on tau pathology progression. Methods: Data of 162 amyloid-positive individuals were included, for whom longitudinal [18F]AV-1451-PET scans, baseline information on global amyloid load, ApoE4 status, body-mass-index (BMI), hype...
Article
Full-text available
Plain Language Summary In a study of 32 patients with progressive supranuclear palsy (PSP), we used a molecular imaging tracer called [¹⁸F]PI-2620 to measure two things: the presence of a protein called tau in deep brain areas (specifically, the globus pallidus internus and dentate nucleus) and the function of the brain’s cortex by assessing blood...
Preprint
Full-text available
Several studies have demonstrated the high agreement between routine clinical visual assessment and quantification, suggesting that quantification approaches could support the assessment of less experienced readers and/or in challenging cases. However, all studies to date have implemented a retrospective case collection and challenging cases were g...
Preprint
Full-text available
Tau-PET receives growing interest as an imaging biomarker for the 4-repeat tauopathy progressive supranuclear palsy (PSP). However, the translation of in vitro 4R-tau binding to in vivo tau-PET signals is still unclear. Therefore, we conducted a longitudinal [18F]PI-2620 PET/MRI study in a 4-repeat-tau mouse model (PS19) and found elevated [18F]PI-...
Article
Full-text available
Resilience in neuroscience generally refers to an individual’s capacity to counteract the adverse effects of a neuropathological condition. While resilience mechanisms in Alzheimer’s disease are well-investigated, knowledge regarding its quantification, neurobiological underpinnings, network adaptations, and long-term effects in Parkinson’s disease...
Preprint
Objectives: Apraxia is a core feature of Alzheimer's disease, but the pathomechanism of this characteristic symptom is not well understood. Here, we systematically investigated apraxia profiles in a well-defined group of patients with Alzheimer's disease (AD; N=32) who additionally underwent PET imaging with the second-generation tau PET tracer [18...
Preprint
Full-text available
Apraxia represents a core feature of Alzheimer's disease, a neurodegenerative disorder associated with increased β-amyloid plaques and tau deposition. However, descriptions of apraxic deficits in AD patients are still scarce. Here, we comprehensively investigate apraxia profiles and their impact on general cognitive deficits in patients with biomar...
Preprint
Full-text available
Apraxia is a common symptom in individuals with Alzheimer's disease (AD). However, the neural mechanisms underlying apraxic deficits in AD remain elusive. Therefore, the current study focuses on the association between altered functional connectivity and apraxia in individuals with AD examining the hypothesis that apraxic deficits in AD result from...
Article
Zusammenfassung Das Wort „Altern“ nutzen wir in unserem alltäglichen Leben als einfachen Begriff zur Beschreibung von Veränderungen, die mit der Zeit auftreten. Das Wort stammt von den germanischen Ableitungen „ala“ - „wachsen, nähren“ und *aldra - „Lebensalter“. Somit umfasst der Begriff des Alterns einen multifaktoriellen Prozess, der im frühen u...
Article
Full-text available
We used a new data-driven methodology to identify a set of reference regions that enhanced the quantification of the SUV ratio of the second-generation tau tracer 2-(2-([18F]fluoro)pyridin-4-yl)-9H-pyrrolo[2,3-b:4,5-c']dipyridine ([18F]PI-2620) in a group of patients clinically diagnosed with 4-repeat tauopathy, specifically progressive supranuclea...
Article
Objectives Higher-educated patients with Alzheimer disease (AD) can harbor greater neuropathologic burden than those with less education despite similar symptom severity. In this study, we assessed whether this observation is also present in potential preclinical AD stages, namely in individuals with subjective cognitive decline and clinical featur...
Preprint
Full-text available
Aquaporin-4 (AQP4) is an integral component of the glymphatic system, today considered a crucial pathway for removing brain interstitial solutes like amyloid-β (Aβ). Evidence exists that genetic variation of AQP4 impacts Aβ clearance, clinical outcome in Alzheimer’s disease as well as sleep measures. We examined whether a risk score calculated from...
Conference Paper
Alzheimer's disease (AD) is a progressive neurodegenerative disorder leading to cognitive decline. [18F]-Fluoro-deoxyglucose positron emission tomography ([18F]-FDG PET) is used to monitor brain metabolism, aiding in the diagnosis and assessment of AD over time. However, the feasibility of multi-time point [18F]-FDG PET scans for diagnosis is limit...
Preprint
Full-text available
Introduction: Consistent with the amyloid-cascade-hypothesis, we tested whether regional amyloid burden is associated with tau pathology increases in spatially independent brain regions and whether functional connectivity serves as a mediator bridging the observed spatial gap between these pathologies. Methods: Data of 98 amyloid-positive and 35 am...
Article
Background Alzheimer’s disease (AD) is characterized by the cerebral accumulation of amyloid‐beta (A), tau (T), and progressive neurodegeneration (N). The widely used ATN system, with regard to positron emission tomography (PET) biomarkers, categorizes AD based on the mean signal in specific regions of interest (ROI). However, this procedure disreg...
Conference Paper
Background Depression and anxiety are two frequent neuropsychiatric symptoms in Alzheimer’s disease (AD). Moreover, depressive symptoms and anxiety are frequently associated with greater amyloid deposition and risk of Alzheimer’s dementia. The aim of the present study is to assess the association between anxiety and depression and amyloid burden....
Conference Paper
Full-text available
Background In clinical practice, amyloid‐PET images are visually assessed to determine the presence or absence of amyloid pathology. The expected arrival of disease‐modifying treatments warrants the need for objective quantification of amyloid burden to further support treatment decisions. Here, we investigated whether quantification increases read...
Article
Full-text available
Stereotypical isocortical tau protein pathology along the Braak stages has been described as an instigator of neurodegeneration in Alzheimer's disease (AD). Less is known about tau pathology in motor regions, although higher-order motor deficits such as praxis dysfunction are part of the clinical description. Here, we examined how tau pathology in...
Article
Impulsive-compulsive behaviour (ICB) is a frequently observed non-motor symptom in early Parkinson's disease after initiating dopamine replacement therapy. At the opposite end of the motivated behaviour spectrum, apathy occurs in early Parkinson's disease even before dopamine replacement is started. The co-occurrence of these behavioural conditions...
Article
Full-text available
Impulsive-compulsive behaviour (ICB) is a frequently observed non-motor symptom in early Parkinson’s disease after initiating dopamine replacement therapy. At the opposite end of the motivated behaviour spectrum, apathy occurs in early Parkinson’s disease even before dopamine replacement is started. The co-occurrence of these behavioural conditions...
Article
Full-text available
Background and Objective Anti-IgLON5 disease is a recently discovered neurological disorder combining autoimmunity and neurodegeneration. Core manifestations include sleep disorders, bulbar symptoms and gait abnormalities followed by cognitive dysfunction, but other presentations have been reported. Hallmarks are autoantibodies targeting the neuron...
Chapter
The brain is the most complex and intriguing part of the human body. Acceleration of neuroscience research and development over the last few decades has given us exciting new technologies to better understand brain function. Imaging modalities have become fundamental tools for the diagnosis and evaluation of brain pathologies, with molecular imagin...
Article
Background Utilization of a data‐driven approach to find a more sensitive reference region (RR) for [18F]‐AV45 PET imaging that differentiates the spectrum of Alzheimer’s disease (AD) and improves especially longitudinal study designs. Method Data of 283 participants (135 amyloid‐negative cognitively normal (CN), and 148 amyloid‐positive AD) from...
Article
Full-text available
Objective: Elevated cortisol levels have been frequently reported in Alzheimer's disease (AD) and linked to brain atrophy, especially of the hippocampus. Besides, high cortisol levels have been shown to impair memory performance and increase the risk of developing AD in healthy individuals. We investigated the associations between serum cortisol l...
Poster
Full-text available
Explainable artificial intelligence identifies an AQP4 polymorphism-based risk score associated with brain amyloid burden The influence of the glymphatic system on ß-amyloid plaques in Alzheimer's disease (AD) through Aquaporin-4 (AQP4) is increasingly discussed. Studies showed that AQP4 Single Nucleotide Polymorphisms (SNPs) are associated with co...
Article
Full-text available
Importance Individuals who are amyloid-positive with subjective cognitive decline and clinical features increasing the likelihood of preclinical Alzheimer disease (SCD+) are at higher risk of developing dementia. Some individuals with SCD+ undergo amyloid-positron emission tomography (PET) as part of research studies and frequently wish to know the...
Article
Imaging of mild traumatic brain injury (TBI) using conventional techniques such as CT or MRI often results in no specific imaging correlation that would explain cognitive and clinical symptoms. Molecular imaging of mild TBI suggests that secondary events after injury can be detected using PET. However, no single specific pattern emerges that can ai...
Article
Full-text available
4‐repeat (4R) tauopathies are neurodegenerative diseases characterized by cerebral accumulation of 4R tau pathology. The most prominent 4R‐tauopathies are progressive‐supranuclear‐palsy (PSP) and corticobasal‐syndrome (CBS) characterized by tau accumulation in subcortical nuclei as well as cortical neuronal dysfunction, as shown by PET‐assessed hyp...
Article
Zusammenfassung Die Ablagerung von Tau-Proteinen ist ein grundlegendes pathophysiologisches Merkmal vieler neurodegenerativer Demenzerkrankungen. Die Entwicklung sensitiver Tau-PET Tracer in den letzten Jahren hat die Lokalisation von Tau-Ablagerungen in unterschiedlichen klinischen neurodegenerativen Phänotypen in vivo ermöglicht. Bei der Alzheime...
Article
4‐repeat (4R) tauopathies are neurodegenerative diseases characterized by cerebral accumulation of 4R tau pathology. The most prominent 4R‐tauopathies are progressive‐supranuclear‐palsy (PSP) and corticobasal‐syndrome (CBS) characterized by tau accumulation in subcortical nuclei as well as cortical neuronal dysfunction, as shown by PET‐assessed hyp...
Article
Full-text available
Purpose Early after [ ¹⁸ F]PI-2620 PET tracer administration, perfusion imaging has potential for regional assessment of neuronal injury in neurodegenerative diseases. This is while standard late-phase [ ¹⁸ F]PI-2620 tau-PET is able to discriminate the 4-repeat tauopathies progressive supranuclear palsy and corticobasal syndrome (4RTs) from disease...
Article
Full-text available
Background In patients with mild cognitive impairment (MCI), enhanced cerebral amyloid-β plaque burden is a high-risk factor to develop dementia with Alzheimer’s disease (AD). Not all patients have immediate access to the assessment of amyloid status (A-status) via gold standard methods. It may therefore be of interest to find suitable biomarkers t...
Preprint
Full-text available
Purpose Early after [¹⁸F]PI-2620 PET tracer administration, perfusion imaging has potential for regional assessment of neuronal injury in neurodegenerative diseases. This is while standard late-phase [¹⁸F]PI-2620 tau-PET is able to discriminate 4-repeat tauopathies (4RTs) from disease controls and healthy controls. Here, we investigated whether ear...
Article
Background Dynamic 60‐minute positron‐emission‐tomography (PET) imaging with the novel tau radiotracer [ ¹⁸ F]PI‐2620 facilitated accurate discrimination between patients with progressive supranuclear palsy (PSP) and healthy controls (HCs). We now aimed to investigate if shorter acquisition and static time windows of [ ¹⁸ F]PI‐2620 tau‐PET can be u...
Article
Background Here, we investigated the contribution of education and regional amyloid as potential de‐ and accelerators in the spread of tau pathology. Method 85 amyloid‐positive subjects (age=76.80±1.08, education=16.70 ±.50 years, M/F=42/43) were included, for whom [18F]AV‐1451 PET at two timepoints, baseline [18F]AV‐45 PET, ApoE‐status and clinic...
Poster
Background Regional differences in amyloid‐beta burden were examined between healthy controls (HC), mild cognitive impairment (MCI) and Alzheimer’s disease (AD) and its prognostic value was compared to other biomarkers. Method ADNI data (http://adni.loni.usc.edu/) of four age‐matched amyloid‐beta‐positive groups were included: cognitively stables...
Poster
Background Amyloid‐β (Aβ) accumulation is a characteristic hallmark for Alzheimer’s disease (AD), which is known to be modified by the APOE genotype. Current diagnostic recommendations for AD include the assessment of amyloid status (A‐status: Aβ+ or Aβ‐) through positron‐emission‐tomography (PET) or invasive lumbar puncture. Amyloid‐PET imaging is...
Article
Full-text available
Purpose Dynamic 60-min positron emission tomography (PET) imaging with the novel tau radiotracer [¹⁸F]PI-2620 facilitated accurate discrimination between patients with progressive supranuclear palsy (PSP) and healthy controls (HCs). This study investigated if truncated acquisition and static time windows can be used for [¹⁸F]PI-2620 tau-PET imaging...
Article
Full-text available
Background The 2017 Alzheimer’s disease (AD) Strategic Biomarker Roadmap (SBR) structured the validation of AD diagnostic biomarkers into 5 phases, systematically assessing analytical validity (Phases 1–2), clinical validity (Phases 3–4), and clinical utility (Phase 5) through primary and secondary Aims. This framework allows to map knowledge gaps...
Article
Although beta-amyloid (Aβ) positivity has shown to be associated with higher risk of progression to Alzheimer's disease (AD) in mild cognitive impairment (MCI), information on the time to conversion to manifest dementia cannot be readily deduced from this binary classification. Here, we assessed if regional patterns of Aβ deposition measured with ¹...
Article
Full-text available
The novel tau-PET tracer [18F]PI-2620 detects the 3/4-repeat-(R)-tauopathy Alzheimer's disease (AD) and the 4R-tauopathies corticobasal syndrome (CBS) and progressive supranuclear palsy (PSP). We determined whether [18F]PI-2620 binding characteristics deriving from non-invasive reference tissue modelling differentiate 3/4R- and 4R-tauopathies. Ten...
Article
To date, three fluorine-18 labelled tracers have been approved for assessing cerebral amyloid plaques pathology to assist in the diagnosis of Alzheimer's Disease (AD). Although scanning protocols are relatively similar across tracers, FDA/EMA approved visual rating guidelines to render scans as positive or negative differ between the three tracers....
Article
Full-text available
Purpose In 2017, the Geneva Alzheimer’s disease (AD) strategic biomarker roadmap initiative proposed a framework of the systematic validation AD biomarkers to harmonize and accelerate their development and implementation in clinical practice. Here, we use this framework to examine the translatability of the second-generation tau PET tracers into th...
Preprint
Full-text available
PurposeDynamic 60-minute positron-emission-tomography (PET) imaging with the novel tau radiotracer [ ¹⁸ F]PI-2620 facilitated accurate discrimination between patients with progressive supranuclear palsy (PSP) and healthy controls (HCs). This study investigated if truncated acquisition and static time windows can be used for [ ¹⁸ F]PI-2620 tau-PET i...
Article
Full-text available
PurposeTau pathology progression in Alzheimer’s disease (AD) is explained through the network degeneration hypothesis and the neuropathological Braak stages; however, the compatibility of these models remains unclear.Methods We utilized [18F]AV-1451 tau-PET scans of 39 subjects with AD and 39 sex-matched amyloid-negative healthy controls (HC) in th...
Chapter
Today, a number of complementary molecular imaging methods are at our disposal, which can make a relevant contribution to early diagnosis, differential diagnosis, disease monitoring, and follow-up of neurodegenerative diseases. This includes long-established FDG-PET which provides valuable information on location and extent of pathology and has dem...
Article
Full-text available
Background: Graph-theoretical analyses have been previously used to investigate changes in the functional connectome in patients with Alzheimer's disease (AD). However, these analyses generally assume static organizational principles, thereby neglecting a fundamental reconfiguration of functional connections in the face of neurodegeneration. Metho...
Article
Full-text available
This cross-sectional study examines positron emission tomography (PET) imaging to investigate the burden of tau tangles and amyloid β plaques in super agers, normal agers, and patients with mild cognitive impairment vs younger amyloid-negative controls.
Article
Background To date, it remains unclear how the hallmark pathological changes of Alzheimer’s disease (AD), amyloid plaques, and neurofibrillary tangles, affect neuronal activity and, consequently, cognition. In cognitively normal aging, it appears that tau accumulation may drive hippocampal hyperactivity, however, studies investigating this associat...
Article
Background Impaired insight in cognitive deficits (anosognosia) in Alzheimer’s disease (AD) is frequent and problematic, but pathophysiological mechanisms are not fully understood. So far, several regions such as the cingulate cortex or frontotemporal regions have been identified as crucial. The aim of the present study was to explore the neural su...
Article
Background Not much is known about the aging‐associated in vivo accumulation of proteinopathies such as amyloid‐β and tau‐pathology in super‐agers (i.e. individuals performing cognitively above the norm even at high age). Here, we examined the intracerebral amyloid and tau burden in a group of super‐agers (SA), normal‐agers (NA) and patients with m...
Article
Background In the last decade, the research community focused on defining reliable biomarkers for the early detection of the pathological hallmarks of Alzheimer’s Disease (AD). In 2017, the Geneva AD Biomarker Roadmap Initiative adapted the framework for the systematic validation of oncological diagnostic biomarkers to AD, with the aim to accelerat...
Article
Background In the last decade, the research community has focused on defining reliable biomarkers for the early detection of the pathological hallmarks of Alzheimer’s Disease (AD). In 2017, the Geneva AD Biomarker Roadmap Initiative adapted the framework for the systematic validation of oncological diagnostic biomarkers (Pepe et al., 2001) to AD, w...
Article
Background Selective positron emission tomography (PET) tracers to target neurofibrillary tangles of the second generation have indicated to overcome some of the methodological issues observed with the tau‐tracers of the first generation. How these second‐generation tau tracers may be better suitable for clinical practice was assessed in the contex...
Article
Background Though cerebrospinal fluid (CSF) Aβ42, p‐tau181 and t‐tau have been shown to increase diagnostic accuracy for early Alzheimer’s disease (i.e. AD at the MCI stage), several challenges remain with respect to their routine clinical use. In order to address these and related issues, a multidisciplinary task force was formed (Geneva Biomarker...
Article
Background: To date, it remains unclear how amyloid plaques and neurofibrillary tangles are related to neural activation and, consequently, cognition in Alzheimer's disease (AD). Recent findings indicate that tau accumulation may drive hippocampal hyperactivity in cognitively normal aging, but it remains to be elucidated how tau accumulation is re...