1,721,002 research outputs found
Biomarkers validation in Alzheimer’s Disease and related pathologies
No full textThe aim of this research project was to investigate biomarkers of Alzheimer’s disease (AD) and related pathologies. The future of these biomarkers relies in their proper validation in all settings (analytical and clinical). In the first two papers, I cooperated with a task force of expert in AD and oncology field, who adapted a framework for biomarkers development used in oncology to AD. We assessed existing evidence based on this framework for amyloid-PET; CSF Abeta42, tau/phospho-tau; FDG-PET; hippocampal atrophy, 123I-Ioflupane, 123I-MIBG, and neuropsychology.
Then, I focused my PhD projects on one of the most reliable biomarkers of AD: brain metabolism by means of FDG PET and its clinical and validity among the phases of the roadmap framework. As FDG-PET rely its utility in AD not only as a diagnostic but also as a progression biomarker, we tried to use this powerful tool to clarify functional pattern able to predict future conversion to AD. One of the limitations of the latter studies was to have excluded from the sample patients with other disease than AD. This was done essentially for research purpose, but hampered the possibility to explore different metabolic patterns underpinning a mild cognitive impairment not due to AD. So, we explore the utility of FDGPET in the context of a relatively frequent syndrome who could mimic early symptoms of AD, DPD.
Our results were: by means of strategic five-phase roadmap, sufficient evidence of analytical validity (phase 1) is available for all biomarkers, but their clinical validity (phases 2 and 3) and clinical utility (phases 4 and 5) are incomplete.
In order to assess the accuracy of FDG PET in discriminating MCI patients who converted to AD from those who did not, we found that MCI patients not converting to AD within a minimum follow-up time of 5 years and MCI patients converting within 5 years, baseline FDG PET and volume based analysis identified those who converted with an accuracy of 89%.
With the aim to identify the cortical regions where hypometabolism can predict the speed of conversion to dementia in MCIAD we found a diagnostic-pattern. This is a further, independent source of heterogeneity in MCI-AD and affects a primary-endpoint on interventional clinical trials (time of conversion to dementia).
Finally, with the aim to explore the role of FDG PET in the diagnosis of DPD, we compared brain FDG-PET among DPD patients, patients with early AD and normal subjects. We found that DPD patients had a specific relative hypometabolism both on caudate nuclei and right anterior cingulate (BA 25). This study confirms the role of FDG PET in the diagnosis of DPD and pave the way of a better understanding of its underpinning biological alterations.
In conclusion, during my PhD I explored the necessity to define the validity of biomarkers of AD and related pathologies in patients with MCI: from operative and analytic point of view, to clinical settings. Then I focused on the real clinical implication of one of the most useful and reliable biomarkers, FDG PET. Our findings support its role of a robust progression biomarker even in a naturalistic population, and underline its importance in the early diagnosis of AD
Amyloid positron emission tomography and cognitive reserve
No full textAlzheimer's disease (AD) is characterized by a non-linear progressive course and several aspects influence the relationship between cerebral amount of AD pathology and the clinical expression of the disease. Brain cognitive reserve (CR) refers to the hypothesized capacity of an adult brain to cope with brain damage in order to minimize symptomatology. CR phenomenon contributed to explain the disjunction between the degree of neurodegeneration and the clinical phenotype of AD. The possibility to track brain amyloidosis (Aβ) in vivo has huge relevance for AD diagnosis and new therapeutic approaches. The clinical repercussions of positron emission tomography (PET)-assessed Aβ load are certainly mediated by CR thus potentially hampering the prognostic meaning of amyloid PET in selected groups of patients. Similarly, amyloid PET and cerebrospinal fluid amyloidosis biomarkers have recently provided new evidence for CR. The present review discusses the concept of CR in the framework of available neuroimaging studies and specifically deals with the reciprocal influences between amyloid PET and CR in AD patients and with the potential consequent interventional strategies for AD
Screening of Early and Late Onset Alzheimer's Disease Genetic Risk Factors in a Cohort of Dementia Patients from Liguria, Italy.
No full textFunctional imaging in pre-motor Parkinson's disease
No full textSeveral non motor symptoms (NMS) can precede the onset of the classical motor Parkinson's disease (PD) syndrome. The existence of pre-motor and even pre-clinical PD stages has been proposed but the best target population to be screened to disclose PD patients in a pre-clinical, thus asymptomatic, stage is still matter of debate. The REM sleep behavior disorder (RBD) often affects PD patients at different stages of the disease and could precede the onset of motor symptoms by several years. However, RBD could also precede other synucleinopathies (namely, dementia with Lewy bodies and multisystem atrophy), and less frequently could be related to other neurological conditions or remain idiopathic. Moreover, not all PD patients exhibit RBD. Despite these caveats, RBD probably represents the best feature to disclose pre-motor PD patients given its high-risk of developing a full motor syndrome. Other clinical clues in the premotor stages of PD undergoing active investigation include hyposmia, depression, and autonomic dysfunction. Effective biomarkers are needed in order to improve the diagnostic accuracy in the pre-motor stage of PD, to monitor disease progression and to plan both pharmacological and non-pharmacological intervention. Functional imaging, in particular radionuclide methodologies, has been often used to investigate dopaminergic and non-dopaminergic features as well as cortical functioning in patients with RBD in its idiopathic form (iRBD) and/or associated with PD. Recently, new tracers to image α-synuclein pathologies are under development. Functional imaging in pre-motor PD, and in particular in iRBD, could improve our knowledge about the underlying mechanisms and the neurodegenerative progress of PD
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
- …
