Gérard Nisal Bischof

University of Cologne | UOC · University Hospital, Department of Nuclear Medicine

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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....

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...

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...

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...

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...

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...

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.

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...

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...

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...

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...

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...

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...

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...

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...

Tau protein aggregations are a hallmark of pathology in the amyloid-associated Alzheimer's disease and some forms of non-amyloid-associated fronto-temporal lobar degeneration (FTLD). In recent years, several tracers for in-vivo tau imaging are under evaluation. This study investigates the ability of Flortaucipir PET to not only assess tau-positivit...

Introduction La paralysie supranucléaire progressive (PSP) est une maladie neurodégénérative rare, avec une accumulation d’isoforme de la protéine tau à quatre motifs répétés (4R). Cette tauopathie est caractérisée par un syndrome parkinsonien atypique associé à une atteinte oculomotrice supra-nucléaire, une instabilité posturale et à un déclin cog...

Our understanding on human neurodegenerative disease was previously limited to clinical data and inferences about the underlying pathology based on histopathological examination. Animal models and in vitro experiments have provided evidence for a cell-autonomous and a non-cell-autonomous mechanism for the accumulation of neuropathology. Combining m...

p>Almost 50 million people worldwide are affected by Alzheimer’s disease (AD), the most common neurodegenerative disorder. Development of disease-modifying therapies would benefit from reliable, non-invasive positron emission tomography (PET) biomarkers for early diagnosis, monitoring of disease progression, and assessment of therapeutic effects. T...

Purpose Using PET imaging in a group of patients with Alzheimer’s disease (AD), we investigated whether level of education, a proxy for resilience, mitigates the harmful impact of tau pathology on neuronal function. Methods We included 38 patients with mild-to-moderate AD (mean age 67 ± 7 years, mean MMSE score 24 ± 4, mean years of education 14 ±...

The development of in vivo imaging of the pathologic hallmark of Alzheimer disease (AD), β-amyloid (Aβ), altered the framing of its pathophysiology and formulation of inclusion criteria for clinical trials. Recent evidence suggests that in vivo measures of Aβ deposition below a threshold indicative of Aβ positivity carry critical information on fut...

PurposeCerebral glucose metabolism measured with [18F]-FDG PET is a well established marker of neuronal dysfunction in neurodegeneration. The tau-protein tracer [18F]-AV-1451 PET is currently under evaluation and shows promising results. Here, we assess the feasibility of early perfusion imaging with AV-1451 as a substite for FDG PET in assessing n...

Current disease models suggest that many neurodegenerative disorders are associated with pathological protein aggregations that start to develop in the brain long before the onset of clinical symptoms. Therefore, biomarkers allowing early and reliable characterization of neurodegenerative disease are required. Here we illustrate the potential value...

We tested how an intervention aimed to increase challenging leisure activities affected cognition and brain function. Thirty-nine participants engaged in 15 hours of activities per week over 14 weeks in either high-challenge activities (digital photography and quilting) or low-challenge activities (socializing or performing low-challenge cognitive...

Importance Presently, the clinical standard for reporting the results of an amyloid positron emission tomography scan is to assign a dichotomous rating of positive or negative for the presence of amyloid. In a 4-year longitudinal study, we investigated whether using a continuous measure of the magnitude of baseline amyloid burden would provide valu...

Objective: To examine the relationship of β-amyloid (Aβ) deposition to episodic memory in younger (30-49 years), middle-older (50-69 years), and older adults (70-89 years). We hypothesized that subclinical levels of amyloid would be linked to memory in adults across the lifespan in a dose-dependent fashion. Of great interest was whether, within th...

The clinical heterogeneity of Alzheimer's disease is not reflected in the rather diffuse cortical deposition of amyloid-β. We assessed the relationship between clinical symptoms, in vivo tau pathology, amyloid distribution, and hypometabolism in variants of Alzheimer's disease using novel multimodal PET imaging techniques. Tau pathology was primari...

Regional cortical SUVRs and white to gray matter SUVR quotients of [F-18]-AV-1451 may differentiate amyloid positive (Azheimer’s disease) and amyloid negative (FTLD) forms of dementia with comparable regional FDG hypometabolism of affected areas. This may represent higher in vivo binding affinity of the tracer to tau protein aggregations in AD as c...

Recently [18F]-AV-1451 (f.k.a. T807), a new ligand has become available, which reliably binds to pathological aggregates of the microtubule associated protein tau, (Marquié et al., 2015). Pathological subcortical tau accumulation occurs in many neurodegenerative disorders, including cortico-basal degeneration (CBD) and Huntington's disease (HD). Ho...

Objective: To explore the potential of [F-18]-AV-1451 PET as a diagnostic tool in Parkinson plus syndromes. Background: Clinically, atypical Parkinson syndromes are often difficult to separate from idiopathic Parkinson's disease (iPD). However, there are marked differences in terms of underlying pathology and treatment response. Corticobasal syndr...

Introduction Assessing quantity and distribution of pathological cerebral tau protein aggregation with PET in suspected tau associated neurodegeneration is currently in the scientific focus and may also become more common in clinical practice, particularly with regard to novel therapies directed against tau pathology (Dani, Brooks, and Edison 2015)...