1,721,029 research outputs found

    Risk and Resilience: a Multimodal Neuroimaging Integration in Aging and Alzheimer’s Disease

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    Der Alterungsprozess ist mit einem breiten Spektrum von Veränderungen der Gehirnstruktur und -funktion, sowie altersbedingter kognitiver Verschlechterung und pathologischer Neurodegeneration verbunden. Jahrelange Forschungen haben gezeigt, dass Pathologien wie neurofibrilläre Bündel, Amyloid Ablagerungen (Aβ) und zerebrovaskuläre Störungen zur Abnahme der kognitiven Leistungsfähigkeit im Alter und bei der Alzheimer Demenz (AD) beitragen. Jüngste Forschungsergebnisse deuten darauf hin, dass bestimmte Lebensstilfaktoren die Fähigkeit, mit Pathologien umzugehen, fördern. Hierbei handelt es sich um die sogenannten Resilienzfaktoren. Im Gegensatz dazu stehen die Risikofaktoren, welche die Vulnerabilität für kognitive Verschlechterung und Neurodegeneration erhöhen und diese Prozesse beschleunigen können. Diese Arbeit exploriert Risiko- und Resilienzfaktoren in einem breiten Spektrum von Probanden, von kognitiv normalen älteren Menschen über Personen mit leichter kognitiver Beeinträchtigung bis hin zu Personen mit klinischer AD mittels einer holistischen Integration behavioraler Messungen und Markern multimodaler Neurobildgebung. Basierend auf vier Studien untersucht diese Dissertation die Assoziation von AD und zerebrovaskulärer Störungen, funktioneller Konnektivitätsnetzwerke und Kognition in einem gepoolten Datensatz bestehend aus 645 Individuen. Zusammenfassend erweitern die Ergebnisse der vorliegenden Dissertation die Literatur zu Resilienz- und Risikofaktoren im Kontext gesunden Alterns und AD, indem sie eine holistische Integration der komplexen Mechanismen während des Alterungsprozesses liefert.Aging alone is associated with a wide range of alterations in brain structure and function as well as age-associated cognitive decline and pathological neurodegeneration. Years of research have shown that brain pathology such as neurofibrillary tangles, amyloid deposition (Aβ), and cerebrovascular pathology contribute to decline of cognitive functions in aging and Alzheimer’s Disease (AD). Recent research has pointed out that certain lifestyle factors contribute to the ability to cope with pathology, known as resilience factors, while in contrast, risk factors can accelerate and increase the vulnerability towards cognitive decline and neurodegeneration. This work explores risk and resilience factors across a diverse spectrum of participants ranging from cognitively intact older adults, to mild cognitive impairment (MCI), and clinical AD with a holistic integration of behavioral measures and multimodal neuroimaging markers. Based on four studies this dissertation investigates the association of AD and cerebrovascular pathology, functional connectivity networks and cognition in a pooled data set of 645 individuals. In summary, our results shed light on the diverse mechanistic underpinning of functional brain networks, hinting at the complex interplay between the brain’s functionality at-rest and the multiple pathological processes. Overall, these findings extend the literature on the resilience and risk factors in the context of healthy aging and AD, while providing a holistic integration of the complex mechanisms at play during the aging process

    Long-term environmental enrichment is associated with better fornix microstructure in older adults

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    Background Sustained environmental enrichment (EE) through a variety of leisure activities may decrease the risk of developing Alzheimer’s disease. This cross-sectional cohort study investigated the association between long-term EE in young adulthood through middle life and microstructure of fiber tracts associated with the memory system in older adults. Methods N = 201 cognitively unimpaired participants (≥ 60 years of age) from the DZNE-Longitudinal Cognitive Impairment and Dementia Study (DELCODE) baseline cohort were included. Two groups of participants with higher ( n = 104) or lower ( n = 97) long-term EE were identified, using the self-reported frequency of diverse physical, intellectual, and social leisure activities between the ages 13 to 65. White matter (WM) microstructure was measured by fractional anisotropy (FA) and mean diffusivity (MD) in the fornix, uncinate fasciculus, and parahippocampal cingulum using diffusion tensor imaging. Long-term EE groups (lower/higher) were compared with adjustment for potential confounders, such as education, crystallized intelligence, and socio-economic status. Results Reported participation in higher long-term EE was associated with greater fornix microstructure, as indicated by higher FA (standardized β = 0.117, p = 0.033) and lower MD (β = −0.147, p = 0.015). Greater fornix microstructure was indirectly associated (FA: unstandardized B = 0.619, p = 0.038; MD: B = −0.035, p = 0.026) with better memory function through higher long-term EE. No significant effects were found for the other WM tracts. Conclusion Our findings suggest that sustained participation in a greater variety of leisure activities relates to preserved WM microstructure in the memory system in older adults. This could be facilitated by the multimodal stimulation associated with the engagement in a physically, intellectually, and socially enriched lifestyle. Longitudinal studies will be needed to support this assumption

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The 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

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    “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

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    We 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

    Structural and metabolic changes in language areas linked to formal thought disorder

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    BACKGROUND: The role of the language network in the pathophysiology of formal thought disorder has yet to be elucidated. AIMS: To investigate whether specific grey-matter deficits in schizophrenic formal thought disorder correlate with resting perfusion in the left-sided language network. METHOD: We investigated 13 right-handed patients with schizophrenia and formal thought disorder of varying severity and 13 matched healthy controls, using voxel-based morphometry and magnetic resonance imaging perfusion measurement (arterial spin labelling). RESULTS: We found positive correlations between perfusion and the severity of formal thought disorder in the left frontal and left temporoparietal language areas. We also observed bilateral deficits in grey-matter volume, positively correlated with the severity of thought disorder in temporoparietal areas and other brain regions. The results of the voxel-based morphometry and the arterial spin labelling measurements overlapped in the left posterior superior temporal gyrus and left angular gyrus. CONCLUSIONS: Specific grey-matter deficits may be a risk factor for state-related dysfunctions of the left-sided language system, leading to local hyperperfusion and formal thought disorder

    Theta burst TMS increases cerebral blood flow in the primary motor cortex during motor performance as assessed by arterial spin labeling (ASL)

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    Theta burst stimulation (TBS) is a novel variant of repetitive transcranial magnetic stimulation (rTMS), which induces changes in neuronal excitability persisting up to 1h. When elicited in the primary motor cortex, such physiological modulations might also have an impact on motor behavior. In the present study, we applied TBS in combination with pseudo continuous arterial spin labeling (pCASL) in order to address the question of whether TBS effects are measurable by means of changes in physiological parameters such as cerebral blood flow (CBF) and if TBS-induced plasticity can modify motor behavior. Twelve right-handed healthy subjects were stimulated using an inhibitory TBS protocol at subthreshold stimulation intensity targeted over the right motor cortex. The control condition consisted of within-subject Sham treatment in a crossover design. PCASL was performed before (pre TBS/pre Sham) and immediately after treatment (post TBS/post Sham). During the pCASL runs, the subjects performed a sequential fingertapping task with the left hand at individual maximum speed. There was a significant increase of CBF in the primary motor cortex after TBS, but not after Sham. It is assumed that inhibitory TBS induced a "local virtual lesion" which leads to the mobilization of more neuronal resources. There was no TBS-specific modulation in motor behavior, which might indicate that acute changes in brain plasticity caused by TBS are immediately compensated. This compensatory reaction seems to be observable at the metabolic, but not at the behavioral level
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