1,721,005 research outputs found
CSF biomarkers are differentially linked to brain areas high and low in noradrenaline, dopamine and serotonin across the Alzheimer’s disease spectrum
No full textAbstract Neurotransmitter systems of noradrenaline, dopamine, serotonin and acetylcholine are implicated in cognitive functions such as memory, learning and attention and are known to be altered in neurodegenerative diseases like Alzheimer’s disease. Specific brain structures involved in these systems, e.g. the locus coeruleus, the main source of noradrenaline in the cortex, are in fact affected earliest by Alzheimer’s disease tau pathology. Preserved volumetric neurotransmitter specific brain areas could therefore be an important neural resource for cognitive reserve in aging. The aim of this study was to determine whether volumes of brain areas known to be high in neurotransmitter receptors are relatively preserved in individuals with lower levels of Alzheimer’s disease pathology. Based on the Human Protein Atlas for neurotransmitter receptor distribution, we distinguished between ‘areas high and low’ in noradrenaline, dopamine, serotonin and acetylcholine and assessed associations of atrophy in those areas with CSF amyloid-ß 42/40, CSF phosphorylated tau protein and cognitive function across healthy controls (n = 122), individuals with subjective cognitive decline (n = 156), mild cognitive impairment or mild Alzheimer’s disease dementia (n = 126) using structural equation modelling. CSF pathology markers were inversely correlated and showed a stronger association with disease severity, suggesting distinguishable interrelatedness of these biomarkers depending on the stage of Alzheimer’s disease dementia. Across groups, amyloid pathology was linked to atrophy in areas high as well as low in neurotransmitter receptor densities, while tau pathology did not show any significant link to brain area volumes for any of the neurotransmitters. Within disease severity groups, individuals with more amyloid pathology showed more atrophy only in ‘areas high in noradrenaline’, whereas for dopamine tau pathology was linked to higher volumes in areas low in receptor density possibly indicating compensatory mechanisms. Furthermore, individuals with more tau pathology showed a selective decrease in memory function while amyloid pathology was related to a decline in executive function and language capacity as well as memory function. In summary, our analyses highlight the benefits of investigating disease-relevant factors in Alzheimer’s disease using a multivariate multigroup approach. Assessing multivariate dependencies in different disease stages and across individuals revealed selective links of pathologies, cognitive decline and atrophy in particular for areas modulated by noradrenaline, dopamine and serotonin
Altered limbic functional connectivity in individuals with subjective cognitive decline: Converging and diverging findings across Chinese and German cohorts
No full textApplication of IVDr NMR spectroscopy to stratify Parkinson’s disease with absolute quantitation of blood serum metabolites and lipoproteins
No full textAbstract The challenge of early detection and stratification in Parkinson’s disease (PD) is urgent due to the current emergence of mechanism-based disease-modifying treatments. In here, metabolomic and lipidomic parameters obtained by a standardized and targeted in vitro diagnostic research (IVDr) platform have a significant potential to address therapy-related questions and generate improved biomarker panels. Our study aimed to use IVDr nuclear magnetic resonance (NMR) spectroscopy to quantify metabolites and lipoproteins in PD blood serum from different cohorts to stratify metabolically driven subtypes of idiopathic and genetic PD. Serum aliquots from three neurodegeneration biobank cohorts (287 samples in total, including 62 PD patient samples with GBA mutation, 98/43 PD patient samples of early/late stages of disease duration, 20 PD samples from patients with mutations in recessive PD genes and some smaller subgroups of mitochondrial and double mutation cases) were prepared and analyzed with IVDr NMR spectroscopy, covering 39 blood serum metabolites and 112 lipoprotein parameters. Uni- and multivariate statistics were used to identify metabolism-driven changes under consideration of typical confounders such as age, sex and disease duration and set into context with clinical biomarkers such as CSF concentrations of alpha-synuclein, neurofilament light chain, and tau protein. Based on the different PD subgroups we performed a total of eight different comparisons. Highlights from these comparisons include increased citrate and dimethylglycine with a decrease of creatinine and methionine in healthy controls and early PD group compared to GBA, PD late and recessive PD. We furthermore identified decreased HDL-3 free cholesterol in genetic PD cases compared to sporadic subject samples (sum of the PD early and PD late groups). Considering medication, we found that the levodopa equivalent daily dose (LEDD) is mostly positively correlated with tyrosine and citrate in sporadic PD compared to pyruvate and phenylalanine in genetic PD. Cerebrospinal fluid levels of alpha-synuclein were negatively correlated with alanine. Further metabolites and lipoproteins with discriminatory power for double mutation PD cases involved ornithine, 2-aminobutyrate and 2-hydroxybutyrate as well as for mitochondrial phenotypes via LDL phospholipid, apolipoprotein and cholesterol subfractions. Quantitative IVDr NMR serum spectroscopy is able to stratify PD patient samples of different etiology and can contribute to a wider understanding of the underlying metabolism-driven alterations e.g. in energy, amino acid, and lipoprotein metabolism. Though our overall cohort was large, major confounders such as age, sex and medication have a strong impact. That is why absolute quantification and detailed patient knowledge about metabolic confounders, is a premise for future translation of NMR serum spectroscopy to routine PD diagnostics
Phänotypisierung neurodegenerativer Erkrankungen am Beispiel der Alzheimer-Erkrankung
Full text linkHintergrund: In einer alternden Bevölkerung stellt die Alzheimer-Erkrankung als häufigste Demenzform eine zunehmende Herausforderung für unsere Gesellschaft dar. Die Erkenntnisse aus der Forschung der letzten Jahrzehnte haben zu einem zunehmend besseren Verständnis der Pathomechanismen und zu zuverlässigeren Diagnosestellungen geführt. Dennoch werden atypische Verläufe und prodromale Stadien oft nicht erkannt. Um diese sicherer identifizieren zu können, ist neben der Entwicklung von paraklinischen Biomarkern die Kenntnis der typischen Präsentation des Krankheitsbildes, seiner selteneren Manifestationsformen und das Wissen um prodromale Symptome von Bedeutung. Ziel dieser Arbeit war es, unterschiedliche Ansätze der Phänotypisierung der Alzheimer-Krankheit und ihrer Vorstufen zu untersuchen.
Methodik: 1. Phänotypisierung über Data Mining: Es wurde mittels eines halbautomatisierten Data Mining-Verfahrens eine Liste mit Symptom-beschreibenden Begriffen erstellt, die in mit dem MeSH-Schlagwort „Alzheimer Disease“ annotierten Abstracts häufiger vorkamen als im Rest der PubMed-Datenbank. 2. Klinische Phänotypisierung über neuropsychologische Testverfahren: Es wurden neuropsychologische Daten von 168 Teilnehmern der longitudinalen Beobachtungsstudie DELCODE des Deutschen Zentrums für neurodegenerative Erkrankungen (DZNE) ausgewertet.
Ergebnisse: 1. Nach der oben beschriebenen Methode konnte eine Liste mit 90 klinischen Beschreibungen der Alzheimer-Erkrankung erstellt werden, die neben typischen Symptomen der Alzheimer-Erkrankung auch seltene, z.T. nur kasuistisch beschriebene Symptome, beinhaltete. 2. Mittels neuropsychologischer Testverfahren ließen sich Patienten in einem leichtgradigen Stadium einer Alzheimer-Demenz von Gesunden sowie von Probanden in einem möglichen Prodromalstadium unterscheiden. Eine besonders gute Aussagekraft für die diagnostische Abgrenzung fand sich dabei für Verfahren, die das verbale und das figurale episodische Gedächtnis, die kognitive Flexibilität, die verbale Flüssigkeit und die psychomotorische Geschwindigkeit testen. Bei möglichen Vorstufen einer Alzheimer-Demenz erwiesen sich v.a. Tests des verzögerten Abrufs und des Wiedererkennens gelernter verbaler Informationen als zeitsensible Messinstrumente. Außerdem prädizierten sie am besten eine Konversion zur Alzheimer-Demenz im Folgejahr.
Schlussfolgerung: 1. Mit Hilfe von Methoden des Data Mining ist es möglich, eine unvoreingenommene und umfangreiche Phänotypbeschreibung der Alzheimer Erkrankung vorzunehmen. 2. Spezielle neuropsychologische Testverfahren helfen, die Prodromalstadien einer Alzheimer-Erkrankung besser zu charakterisieren. Sie können zudem eine Konversion zur Alzheimer-Demenz anzeigen.Background: In an aging population, Alzheimer's disease, the most common form of dementia, represents an increasing challenge for our society. Research findings in recent decades have led to a better understanding of the pathomechanisms and to more reliable diagnoses. Nevertheless, atypical courses and prodromal stages are often not recognized. In order to be able to identify them more reliably, knowledge of the typical presentation of the disease pattern, its rarer manifestations and knowledge of prodromal symptoms is important in addition to the development of biomarkers. The aim of this study was to investigate different approaches to phenotyping Alzheimer's disease and its prodromal stages.
Methods: 1. Phenotyping via data mining: A list of symptom-describing terms that occurred more frequently in abstracts annotated with the MeSH term "Alzheimer's disease" than in the rest of the PubMed database was compiled using a semi-automated data mining procedure. 2. clinical phenotyping using neuropsychological testing: Neuropsychological data of 168 participants of the longitudinal observational study DELCODE of the German Center for Neurodegenerative Diseases (DZNE) were analysed.
Results: 1. 90 clinical descriptions of Alzheimer's disease could be compiled using the method described above, which included typical symptoms of Alzheimer's disease as well as rare symptoms, some of which were only described casuistically. 2. By means of neuropsychological testing procedures, patients in a mild stage of Alzheimer's dementia could be distinguished from healthy participants and participants with a possible prodromal stage. A particularly good diagnostic differentiation was found for procedures testing verbal and figural episodic memory, cognitive flexibility, verbal fluency and psychomotor speed. In prodromal stages of Alzheimer's dementia, tests of delayed recall and recognition of learned verbal information proved to be time-sensitive instruments. In addition, they best predicted a conversion to Alzheimer's dementia in the following year.
Conclusion: 1. With the help of data mining methods it is possible to provide an unbiased and comprehensive phenotype description of Alzheimer's disease. 2. Neuropsychological test procedures can help to better characterize the prodromal stages of Alzheimer's disease. They can also indicate conversion to Alzheimer's dementia
Relevance of Subjective Cognitive Decline in Older Adults with a First-Degree Family History of Alzheimer’s Disease
No full textBackground: It is unclear whether subjective cognitive decline (SCD) is a relevant clinical marker of incipient Alzheimer’s disease (AD) and future cognitive deterioration in individuals with a family history of AD (FHAD). Objective: To investigate the association of SCD with cross-sectional cerebrospinal fluid (CSF) AD biomarker levels and cognitive decline in cognitively normal older adults with or without a first-degree FHAD. Methods: We analyzed data from cognitively normal individuals with first-degree FHAD (n = 82 “AD relatives”; mean age: 65.7 years (SD = 4.47); 59% female) and a similar group of n = 236 healthy controls without FHAD from the DELCODE study. We measured SCD with an in-depth structured interview from which we derived a SCD score, capturing features proposed to increase likelihood of underlying AD (“SCD-plus score”). We tested whether higher SCD-plus scores were associated with more pathological CSF AD biomarker levels and cognitive decline over time and whether this association varied by group. Results: AD relatives showed higher SCD-plus scores than healthy controls and more cognitive decline over time. Higher SCD-plus scores also related stronger to cognitive change and abnormal CSF AD biomarker levels in the AD relatives as compared to the healthy controls group. Conclusion: Quantification of specific SCD features can provide further information on the likelihood of early AD pathology and cognitive decline among AD relatives. FHAD and SCD appear as synergistically acting enrichment strategies in AD research, the first one as a permanent indicator of genetic risk, the latter one as a correlate of disease progression
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
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