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

Aim: Standardized evaluation of [F]PI-2620 tau-PET scans in 4R-tauopathies represents an unmet need in clinical practice. This study aims to investigate the effectiveness of visual evaluation of [F]PI-2620 images for diagnosing 4R-tauopathies and to develop a straight-forward reading algorithm to improve objectivity and data reproducibility.

Methods: A total of 83 individuals with [F]PI-2620 PET scans were included.

Neuronal and oligodendroglial, but not astroglial, tau translates to in vivo tau PET signals in individuals with primary tauopathies.

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 of [F]PI-2620 tau PET signals in individuals with 4R-tauopathies, including a pilot PET autopsy study in patients.

Houston, We Have AI Problem! Quality Issues with Neuroimaging-Based Artificial Intelligence in Parkinson's Disease: A Systematic Review.

In recent years, many neuroimaging studies have applied artificial intelligence (AI) to facilitate existing challenges in Parkinson's disease (PD) diagnosis, prognosis, and intervention. The aim of this systematic review was to provide an overview of neuroimaging-based AI studies and to assess their methodological quality. A PubMed search yielded 810 studies, of which 244 that investigated the utility of neuroimaging-based AI for PD diagnosis, prognosis, or intervention were included.

Neurophysiological markers of motor compensatory mechanisms in early Parkinson's disease.

Compensatory mechanisms in Parkinson's disease are defined as the changes that the brain uses to adapt to neurodegeneration and progressive dopamine reduction. Motor compensation in early Parkinson's disease could, in part, be responsible for a unilateral onset of clinical motor signs despite the presence of bilateral nigrostriatal degeneration. Although several mechanisms have been proposed for compensatory adaptations in Parkinson's disease, the underlying pathophysiology is unclear.

Pharmacological Enhancement of Dopamine Neurotransmission Does Not Affect Illusory Pattern Perception.

Psychotic symptoms and delusional beliefs have been linked to dopamine transmission in both healthy and clinical samples and are assumed to result at least in part from perceiving illusory patterns in noise. However, the existing literature on the role of dopamine in detecting patterns in noise is inconclusive. To address this issue, we assessed the effect of manipulating dopaminergic neurotransmission on illusory pattern perception in healthy individuals (= 48, = 19 female) in a double-blind placebo-controlled within-subjects design (see preregistration at https://osf.

Progressive Supranuclear Palsy: Subcortical Tau Depositions Are Associated with Cortical Perfusion in Frontal and Limbic Regions.

In progressive supranuclear palsy (PSP), subcortical tau and cortical perfusion can be assessed using the tracer [18F]PI-2620. We investigated if subcortical tau (globus pallidus internus, dentate nucleus) and frontal/limbic perfusion correlate in a cohort of 32 PSP patients. Tau in subcortical regions showed significant negative correlation with perfusion in limbic cortex.

Dynamic properties in functional connectivity changes and striatal dopamine deficiency in Parkinson's disease.

Recent studies in Parkinson's disease (PD) patients reported disruptions in dynamic functional connectivity (dFC, i.e., a characterization of spontaneous fluctuations in functional connectivity over time).

Putaminal dopamine modulates movement motivation in Parkinson's disease.

The relative inability to produce effortful movements is the most specific motor sign of Parkinson's disease, which is primarily characterized by loss of dopaminergic terminals in the putamen. The motor motivation hypothesis suggests that this motor deficit may not reflect a deficiency in motor control per se, but a deficiency in cost-benefit considerations for motor effort. For the first time, we investigated the quantitative effect of dopamine depletion on the motivation of motor effort in Parkinson's disease.

Sharing brain imaging data in the Open Science era: how and why?

The sharing of human neuroimaging data has great potential to accelerate the development of imaging biomarkers in neurological and psychiatric disorders; however, major obstacles remain in terms of how and why to share data in the Open Science context. In this Health Policy by the European Cluster for Imaging Biomarkers, we outline the current main opportunities and challenges based on the results of an online survey disseminated among senior scientists in the field. Although the scientific community fully recognises the importance of data sharing, technical, legal, and motivational aspects often prevent active adoption.

Structural underpinnings and long-term effects of resilience in Parkinson's disease.

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 is limited. Our study involved 151 Parkinson's patients from the Parkinson's Progression Marker Initiative Database with available Magnetic Resonance Imaging, Dopamine Transporter Single-Photon Emission Computed Tomography scans, and clinical information.

Improved Tau PET SUVR Quantification in 4-Repeat Tau Phenotypes with [F]PI-2620.

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-([F]fluoro)pyridin-4-yl)-9H-pyrrolo[2,3-b:4,5-c']dipyridine ([F]PI-2620) in a group of patients clinically diagnosed with 4-repeat tauopathy, specifically progressive supranuclear palsy or cortical basal syndrome. The study found that SUV ratios calculated using the identified reference regions (i.e.

Genetic forms of tauopathies: inherited causes and implications of Alzheimer's disease-like TAU pathology in primary and secondary tauopathies.

Tauopathies are a heterogeneous group of neurologic diseases characterized by pathological axodendritic distribution, ectopic expression, and/or phosphorylation and aggregation of the microtubule-associated protein TAU, encoded by the gene MAPT. Neuronal dysfunction, dementia, and neurodegeneration are common features of these often detrimental diseases. A neurodegenerative disease is considered a primary tauopathy when MAPT mutations/haplotypes are its primary cause and/or TAU is the main pathological feature.

A multi-site study on sex differences in cortical thickness in non-demented Parkinson's disease.

Clinical, cognitive, and atrophy characteristics depending on sex have been previously reported in Parkinson's disease (PD). However, though sex differences in cortical gray matter measures in early drug naïve patients have been described, little is known about differences in cortical thickness (CTh) as the disease advances. Our multi-site sample comprised 211 non-demented PD patients (64.

Imaging Biomarkers in Prodromal and Earliest Phases of Parkinson's Disease.

Assessing imaging biomarker in the prodromal and early phases of Parkinson's disease (PD) is of great importance to ensure an early and safe diagnosis. In the last decades, imaging modalities advanced and are now able to assess many different aspects of neurodegeneration in PD. MRI sequences can measure iron content or neuromelanin.

Working Memory Training Responsiveness in Parkinson's Disease Is Not Determined by Cortical Thickness or White Matter Lesions.

Patients with Parkinson's disease are highly vulnerable for cognitive decline. Thus, early intervention by means of working memory training (WMT) may be effective for the preservation of cognition. However, the influence of structural brain properties, i.

MRI or F-FDG PET for Brain Age Gap Estimation: Links to Cognition, Pathology, and Alzheimer Disease Progression.

Deviations of brain age from chronologic age, known as the brain age gap (BAG), have been linked to neurodegenerative diseases such as Alzheimer disease (AD). Here, we compare the associations of MRI-derived (atrophy) or F-FDG PET-derived (brain metabolism) BAG with cognitive performance, neuropathologic burden, and disease progression in cognitively normal individuals (CNs) and individuals with subjective cognitive decline (SCD) or mild cognitive impairment (MCI). Machine learning pipelines were trained to estimate brain age from 185 matched T1-weighted MRI or F-FDG PET scans of CN from the Alzheimer's Disease Neuroimaging Initiative and validated in external test sets from the Open Access of Imaging and German Center for Neurodegenerative Diseases-Longitudinal Cognitive Impairment and Dementia studies.

Impulsive-compulsive behaviour in early Parkinson's disease is determined by apathy and dopamine receptor D3 polymorphism.

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 in Parkinson's disease raises questions about their relationship and underlying pathophysiological determinants.

In Vivo Measurement of Tau Depositions in Anti-IgLON5 Disease Using [18F]PI-2620 PET.

Objectives: Anti-IgLON5 disease is a recently discovered neurologic disorder combining autoimmunity and neurodegeneration. Core manifestations include sleep disorders, bulbar symptoms, gait abnormalities, and cognitive dysfunction, but other presentations have been reported. Hallmarks are autoantibodies targeting the neuronal surface protein IgLON5, a strong human leukocyte antigen system Class II association, and brainstem and hypothalamus-dominant tau deposits.

Educational level and its association with dopamine transporter loss in patients with Parkinson's disease.

Background: According to the cognitive-reserve concept, higher educated dementia patients tolerate more brain pathology than lower educated patients with similar impairment. Here, we examined whether higher education is associated with more severe dopamine terminal loss at the diagnosis of Parkinson's disease (PD).

Methods: Dopamine transporter (DaT) SPECT information of 352 de novo PD patients and 172 healthy controls (HC) were retrieved from PPMI.

Dopamine regulates decision thresholds in human reinforcement learning in males.

Dopamine fundamentally contributes to reinforcement learning, but recent accounts also suggest a contribution to specific action selection mechanisms and the regulation of response vigour. Here, we examine dopaminergic mechanisms underlying human reinforcement learning and action selection via a combined pharmacological neuroimaging approach in male human volunteers (n = 31, within-subjects; Placebo, 150 mg of the dopamine precursor L-dopa, 2 mg of the D2 receptor antagonist Haloperidol). We found little credible evidence for previously reported beneficial effects of L-dopa vs.

Neuroimaging biomarkers in Huntington's disease: Preparing for a new era of therapeutic development.

Background: A critical challenge for Huntington's disease (HD) clinical trials in disease modification is the definition of endpoints that can capture change when clinical signs are subtle/non-existent. Reliable biomarkers are therefore urgently needed to facilitate drug development by allowing the enrichment of clinical trial populations and providing measures of benefit that can support the establishment of efficacy.

Methods: By systematically examining the published literature on HD neuroimaging biomarker studies, we sought to advance knowledge to guide the validation of neuroimaging biomarkers.

Significance of clinical symptoms and red flags in early differential diagnosis of Parkinson's disease and atypical Parkinsonian syndromes.

The clinical presentation of Parkinson's disease and atypical Parkinsonian syndromes is often heterogeneous. Additional diagnostic procedures including brain imaging and biomarker analyses can help to appreciate the various syndromes, but a precise clinical evaluation and differentiation is always necessary. To better assess the relevance of distinct clinical symptoms that arose within 1 year of disease manifestation and evaluate their indicative potential for an atypical Parkinsonian syndrome, we conducted a modified Delphi panel with seven movement disorder specialists.

Brain abscess with Ureaplasma parvum in a patient with granulomatosis with polyangiitis.

Purpose: Ureaplasma species are associated with urogenital infections, infertility and adverse pregnancy outcomes as well as neonatal infections. Involvement of the central nervous system in adults is extremely rare. We report an unusual case of a brain abscess secondary to otitis media with Ureaplasma parvum in a patient with granulomatosis with polyangiitis (GPA).