Perfusion Imaging with SPECT in the Era of Pathophysiology-Based Biomarkers for Alzheimer's Disease

SPECT allows registration of regional cerebral blood flow (rCBF) which is altered in a characteristic temporoparietal pattern in Alzheimer's Dementia. Numerous studies have shown the diagnostic value of reduced cerebral blood flow and metabolic changes using perfusion SPECT and FDG-PEPT in AD diagnosis as well as in differential diagnosis against frontotemporal dementia, dementia with Lewy bodies and vascular disease. Recently more pathophysiology-based biomarkers in CSF and Amyloid-PET tracers have been developed that probably have a higher diagnostic accuracy than the more indirect rCBF changes seen in perfusion SPECT. In the paper review, we describe recent advances in AD biomarkers as well as improvements in the SPECT technique

Early and Differential Diagnosis of Dementia and Mild Cognitive Impairment Design and Cohort Baseline Characteristics of the German Dementia Competence Network

Background: The German Dementia Competence Network (DCN) has established procedures for standardized multicenter acquisition of clinical, biological and imaging data, for centralized data management, and for the evaluation of new treatments. Methods: A longitudinal cohort study was set up for patients with mild cognitive impairment (MCI), patients with mild dementia and control subjects. The aims were to establish the diagnostic, differential diagnostic and prognostic power of a range of clinical, laboratory and imaging methods. Furthermore, 2 clinical trials were conducted with patients suffering from MCI and mild to moderate Alzheimer's Disease (AD). These trials aimed at evaluating the efficacy and safety of the combination of galantamine and memantine versus galantamine alone. Results: Here, we report on the scope and projects of the DCN, the methods that were employed, the composition and flow within the diverse groups of patients and control persons and on the clinical and neuropsychological baseline characteristics of the group of 2,113 subjects who participated in the observational and clinical trials. Conclusion: These data have an impact on the procedures for the early and differential clinical diagnosis of dementias, the current standard treatment of AD as well as on future clinical trials in AD. Copyright (C) 2009 S. Karger AG, Base

Lymphotoxin β receptor signaling promotes tertiary lymphoid organogenesis in the aorta adventitia of aged ApoE−/− mice

Atherosclerosis involves a macrophage-rich inflammation in the aortic intima. It is increasingly recognized that this intimal inflammation is paralleled over time by a distinct inflammatory reaction in adjacent adventitia. Though cross talk between the coordinated inflammatory foci in the intima and the adventitia seems implicit, the mechanism(s) underlying their communication is unclear. Here, using detailed imaging analysis, microarray analyses, laser-capture microdissection, adoptive lymphocyte transfers, and functional blocking studies, we undertook to identify this mechanism. We show that in aged apoE−/− mice, medial smooth muscle cells (SMCs) beneath intimal plaques in abdominal aortae become activated through lymphotoxin β receptor (LTβR) to express the lymphorganogenic chemokines CXCL13 and CCL21. These signals in turn trigger the development of elaborate bona fide adventitial aortic tertiary lymphoid organs (ATLOs) containing functional conduit meshworks, germinal centers within B cell follicles, clusters of plasma cells, high endothelial venules (HEVs) in T cell areas, and a high proportion of T regulatory cells. Treatment of apoE−/− mice with LTβR-Ig to interrupt LTβR signaling in SMCs strongly reduced HEV abundance, CXCL13, and CCL21 expression, and disrupted the structure and maintenance of ATLOs. Thus, the LTβR pathway has a major role in shaping the immunological characteristics and overall integrity of the arterial wall

Einfluß vontransitorisch-ischämischen Attacken auf darauf folgenden ischämische Hirninfarkte

Ischämietoleranz bezeichnet das Phänomen, dass ein kurzer ischämischer, metabolischer oder physikalischer Stimulus das Gehirn paradoxerweise "resistent" macht gegenüber einer darauffolgenden, längerdauernden Ischämie. In einer retrospektiven Studie versuchten wir die Hypothese zu untermauern, dass transiente ischämische Attacken (als kurzdauernde ischämische Stimuli) vor einem Infarkt (prodromale TIAs) protektiv sind gegen eine nachfolgende zerebrale Ischämie. Es zeigte sich dabei, dass Patienten mit prodromalen TIAs ein geringeres Defizit und einen günstigeren Verlauf zeigten und im CT seltener Infarktfrühzeichen hatten. Somit könnten transiente ischämische Attacken, vor einem Schlaganfall, analog zu der Situation am Herzen und wie in zahlreichen in vivo Modellen gezeigt, ein klinisches Korrelat zur hypoxischen Präkonditionierung darstellen. Im experimentellen Teil der vorliegenden Arbeit wird gezeigt, dass sich hypoxische Präkonditionierung in vitro in neuronalen Kulturen modellieren lässt. Eine kurzzeitige Sauerstoff-Glucose-Deprivation (OGD) 1-3 Tage vor einer längeren OGD führt zu einem signifikanten Schutz von Neuronen, bis zu 90%. Hypoxietoleranz kann auch durch andere metabolische Stimuli, wie Inhibition von Atmungskettenenzymen durch 3-NPA im gleichen Zeitrahmen simuliert werden. Eine genaue Kenntnis der endogenen Neuroprotektion durch Ischämietoleranz könnte in Zukunft helfen, den Schaden durch ischämische Infarkte und ischämische Enzephalopathien zu minimieren.Ischemic tolerance is a phenomenon where a brief episode of ischemia renders the brain resistant against a subsequent, longerlasting ischemic event. In a retrospective study we tested the hypothesis that transient ischemic attacks (as brief ischemic stimuli) before cerebral ischemia (prodromal TIA's) may have a protective effect. Here we show that patients with prodromal TIA's have less severe neurologic impairment, a better clinical course and have less early infarct signs. Therefore we siggest that TIA's, before stroke could represent a clinical correlate to hypoxic preconditioning, as shown in the heart. Experimentally we were able to model hypoxic preconditioning in vitro using neuronal cultures. Brief oxygen-glucose deprivation (OGD) 1-3 days before longer lasting OGD protects neurons, up to 90%. Hypoxic tolerance was also simulated by metabolic stimuli like inhibition of the respiratory chain by 3-NPA. Increasing knowledge of this endogenous neuroprotection by ischemic tolerance might help to minimize neuronal damage following ischemic strokes and hypoxic encephalopathy

Abrahamsons Erkrankungen des Curriculums und mögliche Therapien [Abrahamson´s Diseases of the Curriculum and possible cures]

[english] In 1978 Stephen Abrahamson described nine typical problems with medical curricula, which he summarized as "diseases of the curriculum". After the last reform of the national medical license law in Germany, many curricular changes of the German medical faculties were started. Many of the symptoms originally described by Abrahamson occurred in traditional German medical curricula. In the present debate we literally translated Abrahamson´s original article and, with the author, added possible therapeutic options and added later published, additional diseases. <br>[german] Stephen Abrahamson beschrieb 1978 neun typische Probleme der medizinischen Curricula, die er als "Erkrankungen des Curriculums" zusammenfasste. Nach der letzten Reform der Approbationsordnung kam deutliche Bewegung in die Curriculumsplanung der deutschen medizinischen Fakultäten. Viele der von Abrahamson beschriebenen Symptome sind auch in traditionellen deutschsprachigen Curricula zu beobachten. In der derzeitigen Debatte wurde der Originalartikel zunächst wörtlich übersetzt. Anschließend wurden in Zusammenarbeit mit Stephen Abrahamson Therapievorschläge erarbeitet und bisher nicht veröffentlichte weitere Erkrankungen des Curriculums hinzugefügt

Web-Based Application to Eliminate Five Contraindicated Multiple-Choice Question Practices

Multiple-choice questions (MCQs) evaluate factual knowledge in medical education and have a high reliability, if performed appropriately. However, many MCQs contain formal errors leading to reduced validity. The authors developed a Web application capable of recognizing and eliminating five frequent contraindicated practices in MCQs: negative stem, unfocused stem, cueing words, longest item = right item flaw, and stem/item similarities. The authors used simple string algorithms and dynamic comparisons with keywords. The system was successfully validated with a sample of approximately 800 continuous medical education (CME) questions, showing that our system automatically detects 60% of all formal didactic errors. Flaws not detected by the software can easily be avoided using quick manuals on item wording or clear instruction to the authors. The authors conclude that it is feasible to improve the quality of MCQs by designing a Web application that is capable of detecting common flaws by simple string operations

Multiple Discriminant Analysis of SPECT Data for Alzheimer’s Disease, Frontotemporal Dementia and Asymptomatic Controls

Multiple discriminant analysis (MDA) is a generalization of the Fisher discriminant analysis (FDA) and makes it possible to discriminate more than two classes by projecting the data onto a subspace. In this work, it was applied to technetium- 99methylcysteinatedimer (99mTc-ECD) SPECT datasets of 10 Alzheimer’s disease (AD) patients, 11 frontotemporal dementia (FTD) patients and 11 asymptomatic controls (CTR). Principal component analysis (PCA) was used for dimensionality reduction, followed by projection of the data onto a discrimination plane via MDA. In order to separate the different groups, linear boundaries were calculated by applying FDA to two classes at a time (linear machine). By executing the F-test for different numbers of principal components and examining the corresponding classification accuracy, an optimal discrimination plane based on the first three principal components was determined. In order to further assess the method, another dataset comprising patients with early-onset AD and FTD (beginning or suspected disease) was projected by the same method onto this discrimination plane, resulting in a correct classification for most cases. The successful iscrimination of another dataset on the same plane indicates that the model is well suited to account fordisease-specific characteristics within the classes, even for patients with early-onset AD and FTD

Der Einsatz von medizinischen Trainingszentren für die Ausbildung zum Arzt in Deutschland, Österreich und der deutschsprachigen Schweiz [Clinical Skills Labs in Medical Education in Germany, Austria and German Speaking Switzerland]

[english] Introduction: Following the reform of the medical licensure law in 2002 German medical faculties have started implementing clinical skills labs. This survey aims to present a review about the stage of development in this domain in Germany as well as in Austria and in German-speaking Switzerland. Method: In the period between August and December 2007 all the 43 medical faculties in Germany, Austria and in German-speaking Switzerland were interviewed with a questionnaire covering 7 topics. The further analysis included skills labs where more than one medical specialty was involved (“central” skills labs) Results: The response rate was 100 %. By the time of the survey 33 of the existing 43 faculties maintained a skills lab, 24 of them entered the overview. 22 skills labs were managed by physicians. The number of employees varied between 1 and 8, the number of student tutors between 0 and 40. The size of the existing skills labs varied between below 100 m² and 2500 m². Most of the skills labs (19) based their tuition upon instruction manuals, and 19 worked with simulated patients (mostly using both). In 15 skills labs simulated patients were also set in for assessment. 17 skills labs taught with problem based learning, 16 taught with computer based learning. Questions about personal costs, acquisition cost and current costs were answered scarcely and inhomogeneously. Discussion: The foundation of clinical skills labs in Germany was furthered by the medical licensure law reform and by the recent introduction of tuition fees. Marked similarities amongst the skills labs existed in teaching methods and content and in assessment. The increasing number of new skills labs since tuition fees have been introduced suggests that medical faculties use such resources for the improvement of practical competencies in medical education. Conclusion: In order to save resources we suggest an exchange and co-operation between existing medical skills labs. This would facilitate the development of common quality standards and guidelines for medical skills labs. It also seems to be necessary to define the term “central skills lab” accurately. The authors recommend the Committee on Practical Skills of the Gesellschaft für Medizinische Ausbildung (GMA) as a platform for such co-operation. <br>[german] Zielsetzung: Seit der Novellierung der ÄAppO im Jahr 2002 werden im deutschsprachigen Raum an den medizinischen Universitäten zunehmend Medizinische Trainings- und Prüfungszentren eingerichtet. Die vorliegende Erhebung soll einen Überblick über den Stand der Entwicklung in diesem Bereich in Deutschland, Österreich und der deutschsprachigen Schweiz bieten. Methodik: In der Zeit von August bis Dezember 2007 wurden alle 43 medizinischen Fakultäten in Deutschland, Österreich und der deutschsprachigen Schweiz schriftlich befragt. Der Fragebogen umfasste 7 Themenbereiche. Die weitere Auswertung bezieht sich auf Trainingszentren, in denen mehr als eine Disziplin unterrichtet wird („zentrale“ Trainingszentren). Ergebnisse: Der Rücklauf betrug 100%. Von 43 Fakultäten verfügten 33 zum Zeitpunkt der Befragung über ein Trainingszentrum, 24 davon gingen in die weitere Auswertung ein. 22 Trainingszentren waren ärztlich geleitet, die Zahl der Mitarbeiter lag zwischen 1 bis 8, die der studentischen Tutoren zwischen 0 und 40. Das Spektrum der zur Verfügung stehenden Grundfläche reichte von unter 100 Quadratmetern bis zu 2500 Quadratmetern. An den meisten Trainingszentren wurde mit strukturierten Arbeitsanleitungen gearbeitet (19 Einrichtungen), in 18 Einrichtungen unterrichteten Ärzte und studentische Tutoren. In der Mehrheit der Fälle (13) war der Unterricht curricular integriert. An 19 Zentren wurden OSKE durchgeführt. An 19 Zentren wurde mit Simulationspatienten gearbeitet, die in 15 Zentren auch für Prüfungen eingesetzt wurden. 17 Zentren arbeiteten mit problemorientiertem Lernen, 16 setzten computerbasiertes Lernen ein. Die Fragen zu Personalkosten, laufenden Kosten und Anschaffungskosten wurden nur von sehr wenigen Zentren und sehr inhomogen beantwortet. Diskussion: Die Einrichtung von Medizinischen Trainingszentren im deutschsprachigen Raum ist durch die neue ÄAppO und durch die Erhebung von Studiengebühren deutlich vorangetrieben worden. Große Ähnlichkeiten zwischen den Zentren zeigten sich in den Bereichen Lehrinhalte, -methoden und Prüfungen. Es fand sich keine Korrelation zwischen der Größe des Trainingszentrums und seinem Gründungszeitpunkt oder den Anschaffungs- bzw. Personalkosten. Der deutliche Anstieg von neu eröffneten TZ in zeitlichem Zusammenhang mit der Einführung der Studiengebühren legt nahe, dass hiermit eine konkrete Verbesserung der Ausbildungssituation durch die Studiengebühren beabsichtigt wird. Schlussfolgerung: Um Ressourcen zu sparen, wird eine enge Zusammenarbeit der bestehenden Trainingszentren und eventuell die Entwicklung gemeinsamer Qualitätsstandards oder einer Leitlinie für medizinische Trainingszentren empfohlen. Auch erscheint eine genaue Klärung des Begriffes “zentrales Trainingszentrum“ notwendig. Als Plattform für eine solche Zusammenarbeit empfehlen die Autoren den

Unsuitable readability levels of patient information pertaining to dementia and related diseases: a comparative analysis

Background: Our study investigated the readability of printed material about dementia that is offered to patients and caregivers. Methods: Comparisons of various brochures (at least three standard pages in length) on dementia and related disorders were made using automated measuring by the SMOG readability index grade. Results: 118 brochures were assessed (25 in English, 93 in German), for which the mean readability was found to be high school/college level as measured by the SMOG readability index (grade 13.6 ± 1.8). No differences in readability were observed between materials produced by pharmaceutical companies and other sources. Furthermore, recently published brochures were not more readable than older ones. Shorter brochures, English brochures and those containing medical facts were easier to read than longer ones, those written in German or brochures primarily addressing psychosocial care/social issues. The sentence length was above the 20 word recommendation in 25% of the brochures. The average font size of the brochure texts was small (mean font size 11.1 ± 1.6 point) with only 25% of brochures having a font size of 12 or more, as recommended. Conclusions: Written patient information and educational material of more than three standard pages is often published at unsuitably high readability levels using small fonts. Information material about dementia should be designed and tested prior to distribution among patients and caregivers. Future studies should address material shorter than three pages and material for younger caregivers

Strengthening the occupational and social participation of multiple sclerosis patients - design of a multicenter, parallel-group randomized controlled trial (MSnetWork-study)

Background Multiple Sclerosis is an autoimmune inflammatory disease of the central nervous system that often leads to premature incapacity for work. Therefore, the MSnetWork project implements a new form of care and pursues the goal of maintaining or even improving the state of health of MS patients and having a positive influence on their ability to work as well as their participation in social life. A network of neurologists, occupational health and rehabilitation physicians, psychologists, and social insurance suppliers provide patients with targeted services that have not previously been part of standard care. According to the patient’s needs treatment options will be identified and initiated. Methods The MSnetWork study is designed as a multicenter randomized controlled trial, with two parallel groups (randomization at the patient level with 1:1 allocation ratio, planned N = 950, duration of study participation 24 months). After 12 months, the patients in the control group will also receive the interventions. The primary outcome is the number of sick leave days. Secondary outcomes are health-related quality of life, physical, affective and cognitive status, fatigue, costs of incapacity to work, treatment costs, out-of-pocket costs, self-efficacy, and patient satisfaction with therapy. Intervention effects are analyzed by a parallel-group comparison between the intervention and the control group. Furthermore, the long-term effects within the intervention group will be observed and a pre-post comparison of the control group, before and after receiving the intervention in MSnetWork, will be performed. Discussion Due to the multiple approaches to patient-centered, multidisciplinary MS care, MSnetWork can be considered a complex intervention. The study design and linkage of comprehensive, patient-specific primary and secondary data in an outpatient setting enable the evaluation of this complex intervention, both on a qualitative and quantitative level. The basic assumption is a positive effect on the prevention or reduction of incapacity for work as well as on the patients’ quality of life. If the project proves to be a success, MSnetWork could be adapted for the treatment of other chronic diseases with an impact on the ability to work and quality of life. Trial registration The trial MSnetWork has been retrospectively registered in the German Clinical Trials Register (DRKS) since 08.07.2022 with the ID DRKS00025451