Quantitative Imaging of Regional Cerebral Protein Synthesis in Clinical Alzheimer's Disease by [C]Leucine PET.

Purpose: Protein synthesis is essential to maintain integrity and function of the human brain, and protein synthesis is associated specifically with the formation of long-term memory. Experimental and clinical observations indicate that this process is disturbed in Alzheimer's dementia and other neurodegenerative diseases. In-vivo investigation with positron emission tomography (PET) using [C]leucine provides a unique possibility to measure regional cerebral protein synthesis (rCPS) rates in human brain and to determine whether it is altered in Alzheimer's disease (AD), and thus may provide a target for future therapeutic interventions.

Structural and metabolic correlates of neuropsychological profiles in multiple system atrophy and Parkinson's disease.

Background: Despite increased recognition of cognitive impairment in Multiple System Atrophy (MSA), its neuroanatomical correlates are not well defined. We aimed to explore cognitive profiles in MSA with predominant parkinsonism (MSA-P) and Parkinson's disease (PD) and their relationship to frontostriatal structural and metabolic changes.

Methods: Detailed clinical and neuropsychological evaluation was performed together with diffusion tensor imaging (DTI) and [F]-fluoro-deoxyglucose positron emission tomography ([F]-FDG-PET) in patients with MSA-P (n = 11) and PD (n = 11).

Amyloid-β and APOE genotype predict memory decline in cognitively unimpaired older individuals independently of Alzheimer's disease polygenic risk score.

Background: What combination of risk factors for Alzheimer's disease (AD) are most predictive of cognitive decline in cognitively unimpaired individuals remains largely unclear. We studied associations between APOE genotype, AD-Polygenic Risk Scores (AD-PRS), amyloid-β pathology and decline in cognitive functioning over time in a large sample of cognitively unimpaired older individuals.

Methods: We included 276 cognitively unimpaired older individuals (75 ± 10 years, 63% female) from the EMIF-AD PreclinAD cohort.

Evaluation of in vivo staging of amyloid deposition in cognitively unimpaired elderly aged 78-94.

Amyloid-beta (Aβ) deposition is common in cognitively unimpaired (CU) elderly >85 years. This study investigated amyloid distribution and evaluated three published in vivo amyloid-PET staging schemes from a cognitively unimpaired (CU) cohort aged 84.9 ± 4.

Imaging Clinical Subtypes and Associated Brain Networks in Alzheimer's Disease.

Alzheimer's disease (AD) does not present uniform symptoms or a uniform rate of progression in all cases. The classification of subtypes can be based on clinical symptoms or patterns of pathological brain alterations. Imaging techniques may allow for the identification of AD subtypes and their differentiation from other neurodegenerative diseases already at an early stage.

Amyloid-PET and F-FDG-PET in the diagnostic investigation of Alzheimer's disease and other dementias.

Various biomarkers are available to support the diagnosis of neurodegenerative diseases in clinical and research settings. Among the molecular imaging biomarkers, amyloid-PET, which assesses brain amyloid deposition, and F-fluorodeoxyglucose (F-FDG) PET, which assesses glucose metabolism, provide valuable and complementary information. However, uncertainty remains regarding the optimal timepoint, combination, and an order in which these PET biomarkers should be used in diagnostic evaluations because conclusive evidence is missing.

Competencies and training of radiographers and technologists for PET/MR imaging - a study from the UK MR-PET network.

Background: After the success of PET/CT as a clinical diagnostic tool, the introduction of PET/MRI is a natural development aimed at further improving combined diagnostic imaging and reduced ionising radiation dose for half-body imaging. As with PET and CT, the combination of PET and MRI presents a series of issues that need to be addressed regarding workforce training and education. At present, there is a lack of agreement over the competencies, training requirements and educational pathways needed for PET/MRI operation.

Harmonization of neuroimaging biomarkers for neurodegenerative diseases: A survey in the imaging community of perceived barriers and suggested actions.

Introduction: Molecular, functional, and structural neuroimaging biomarkers are largely used to study neurodegenerative diseases, but their benefits to patients/science might be greatly enhanced by improving standardization and cross-validation. In this EU Joint Programme-Neurodegenerative Diseases Research-funded project, we surveyed the neuroimaging community to assess perceived barriers in multicentric neuroimaging harmonization and actions to overcome them.

Methods: An anonymous survey addressed researchers, clinicians, pharma industry, and professional associations, inquiring about both general and modality-specific harmonization barriers.

[18F]Florbetapir positron emission tomography: identification of muscle amyloid in inclusion body myositis and differentiation from polymyositis.

Objectives: With the tools available currently, confirming the diagnosis of inclusion body myositis (IBM) can be difficult. Many patients are initially misdiagnosed with polymyositis (PM). In this observational study at a UK adult neuromuscular centre, we investigated whether amyloid positron emission tomography could differentiate between IBM and PM.

Astrocyte Biomarkers in Alzheimer's Disease.

Astrocytic contributions to Alzheimer's disease (AD) progression were, until recently, largely overlooked. Astrocytes are integral to normal brain function and astrocyte reactivity is an early feature of AD, potentially providing a promising target for preclinical diagnosis and treatment. Several in vivo AD biomarkers already exist, but presently there is a paucity of specific and sensitive in vivo astrocyte biomarkers that can accurately measure preclinical AD.

Dual-phase [18F]florbetapir in frontotemporal dementia.

Purpose: The PET tracer [18F]florbetapir is a specific fibrillar amyloid-beta (Aβ) biomarker. During the late scan phase (> 40 min), it provides pathological information about Aβ status. Early scan phase (0-10 min) can provide FDG-'like' information.

Resilience to cognitive impairment in the oldest-old: design of the EMIF-AD 90+ study.

Background: The oldest-old (subjects aged 90 years and older) population represents the fastest growing segment of society and shows a high dementia prevalence rate of up to 40%. Only a few studies have investigated protective factors for cognitive impairment in the oldest-old. The EMIF-AD 90+ Study aims to identify factors associated with resilience to cognitive impairment in the oldest-old.

The EMIF-AD PreclinAD study: study design and baseline cohort overview.

Background: Amyloid pathology is the pathological hallmark in Alzheimer's disease (AD) and can precede clinical dementia by decades. So far it remains unclear how amyloid pathology leads to cognitive impairment and dementia. To design AD prevention trials it is key to include cognitively normal subjects at high risk for amyloid pathology and to find predictors of cognitive decline in these subjects.

Diagnostic utility of 18F-Fluorodeoxyglucose positron emission tomography (FDG-PET) in asymptomatic subjects at increased risk for Alzheimer's disease.

Purpose: To assess the clinical utility of 18F-Fluorodeoxyglucose positron emission tomography (FDG-PET) for detection of early signs of neurodegeneration in conditions of increased risk for Alzheimer's disease (AD) as defined by: subjective cognitive decline (SCD), evidence of cerebral amyloid-pathology, apolipoprotein E (APOE) ε4-positive genotype, or autosomal dominant forms of AD (ADAD) in asymptomatic stages.

Methods: A comprehensive literature search was conducted using the PICO model to extract evidence from relevant studies. An expert panel then voted using the Delphi method on three different diagnostic scenarios.

Revolution of Alzheimer Precision Neurology. Passageway of Systems Biology and Neurophysiology.

The Precision Neurology development process implements systems theory with system biology and neurophysiology in a parallel, bidirectional research path: a combined hypothesis-driven investigation of systems dysfunction within distinct molecular, cellular, and large-scale neural network systems in both animal models as well as through tests for the usefulness of these candidate dynamic systems biomarkers in different diseases and subgroups at different stages of pathophysiological progression. This translational research path is paralleled by an "omics"-based, hypothesis-free, exploratory research pathway, which will collect multimodal data from progressing asymptomatic, preclinical, and clinical neurodegenerative disease (ND) populations, within the wide continuous biological and clinical spectrum of ND, applying high-throughput and high-content technologies combined with powerful computational and statistical modeling tools, aimed at identifying novel dysfunctional systems and predictive marker signatures associated with ND. The goals are to identify common biological denominators or differentiating classifiers across the continuum of ND during detectable stages of pathophysiological progression, characterize systems-based intermediate endophenotypes, validate multi-modal novel diagnostic systems biomarkers, and advance clinical intervention trial designs by utilizing systems-based intermediate endophenotypes and candidate surrogate markers.

Strategic roadmap for an early diagnosis of Alzheimer's disease based on biomarkers.

The diagnosis of Alzheimer's disease can be improved by the use of biological measures. Biomarkers of functional impairment, neuronal loss, and protein deposition that can be assessed by neuroimaging (ie, MRI and PET) or CSF analysis are increasingly being used to diagnose Alzheimer's disease in research studies and specialist clinical settings. However, the validation of the clinical usefulness of these biomarkers is incomplete, and that is hampering reimbursement for these tests by health insurance providers, their widespread clinical implementation, and improvements in quality of health care.

Metabolic regional and network changes in Alzheimer's disease subtypes.

Clinical variants of Alzheimer's disease (AD) include the common amnestic subtype as well as subtypes characterised by leading visual processing impairments or by multimodal neurocognitive deficits. We investigated regional metabolic patterns and networks between AD subtypes. The study comprised 9 age-matched controls and 25 patients with mild to moderate AD.

Clinical validity of presynaptic dopaminergic imaging with I-ioflupane and noradrenergic imaging with I-MIBG in the differential diagnosis between Alzheimer's disease and dementia with Lewy bodies in the context of a structured 5-phase development framework.

The use of biomarkers (BMs) for accurate diagnosis of Alzheimer's disease (AD) has been proposed by recent diagnostic criteria; however, their maturity is not sufficient to grant implementation in the clinical routine. A proper diagnostic process requires not only confirmation of the disease but also the exclusion of similar disorders entering differential diagnosis, like dementia with Lewy bodies (DLB). This review is aimed at evaluating the clinical validity of I-ioflupane brain single photon emission tomography and I-MIBG cardiac scintigraphy as imaging BMs for DLB.

Clinical validity of increased cortical uptake of amyloid ligands on PET as a biomarker for Alzheimer's disease in the context of a structured 5-phase development framework.

The use of biomarkers has been proposed for diagnosing Alzheimer's disease in recent criteria, but some biomarkers have not been sufficiently investigated to justify their routine clinical use. Here, we evaluate in a literature review the clinical validity of amyloid positron emission tomography (PET) imaging using a structured framework developed for the assessment of oncological biomarkers. Homogenous criteria have been addressed in reviews of other Alzheimer's disease biomarkers.

Clinical validity of brain fluorodeoxyglucose positron emission tomography as a biomarker for Alzheimer's disease in the context of a structured 5-phase development framework.

The use of Alzheimer's disease (AD) biomarkers is supported in diagnostic criteria, but their maturity for clinical routine is still debated. Here, we evaluate brain fluorodeoxyglucose positron emission tomography (FDG PET), a measure of cerebral glucose metabolism, as a biomarker to identify clinical and prodromal AD according to the framework suggested for biomarkers in oncology, using homogenous criteria with other biomarkers addressed in parallel reviews. FDG PET has fully achieved phase 1 (rational for use) and most of phase 2 (ability to discriminate AD subjects from healthy controls or other forms of dementia) aims.