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Die in dem letzten Jahrhundert in den Industrienationen zu beobachtende Alterung der Gesellschaft fuhrt neben der erfreulichen Alterszunahme der Menschen auch zu einer Zunahme der Haufigkeit altersbedingter Erkrankungen und von Multimorbiditat. Neben der Schluckstorung und dem Schwindel sind sensorische Defizite, wie Riech- und Horstorungen, beim alten Menschen haufig und tragen wesentlich zur Lebensqualitat bei. Die Alzheimer-Demenz ist die haufigste Demenzform. Kurzlich wurde in epidemiologischen Studien gezeigt, dass Riech- und Horstorungen nicht nur eine Assoziation mit demenziellen Erkrankungen zeigen, sondern auch spezifische Risikofaktoren fur das Auftreten und die Progression der Erkrankung darstellen. Somit kommt der Erkennung und der adaquaten Behandlung z. B. von Horstorungen durch den HNO-Arzt eine immer wichtiger werdende Rolle zu, nicht nur um die Lebensqualitat der Patienten zu erhalten, sondern in Zukunft auch, um das Risiko fur Demenzerkrankungen zu reduzieren.

Zielsetzung: Die Studie ermittelte den Ressourceneinsatz und die Gesamtkosten der Alzheimer-Demenz (AD), stratifiziert nach Schweregrad. Dazu wurden die Daten aus deutschen Privathaushalten von 552 Patienten mit leichter (n = 228), mittlerer (n = 157) oder mittelschwerer/schwerer (n = 167) AD ausgewertet, die an einer 18-monatigen Beobachtungsstudie (GERAS) teilgenommen hatten. Methodik: Demografische Daten und Charakteristika von Patienten und Pflegenden zu Studienbeginn wurden dokumentiert. Informationen zum Ressourceneinsatz und die aufgewendete Zeit fur die informelle Pflege durch pflegende Angehorige wurden mithilfe des „Resource Utilization in Dementia“-Fragebogens (RUD) ermittelt. Die gesellschaftlichen Gesamtkosten (direkte Gesundheits- und Pflege- /Unterstutzungskosten der Patienten, Gesundheitskosten der pflegenden Angehorigen und informelle Pflegekosten) wurden basierend auf den erhobenen Daten errechnet. Ergebnisse: Die durchschnittlichen gesellschaftlichen Gesamtkosten pro Jahr (Kostendaten fur 2010) unterschieden sich signifikant (p Schlussfolgerung: Die gesellschaftlichen Gesamtkosten fur im eigenen Haushalt lebende Alzheimer-Patienten erhohen sich mit zunehmender Verschlechterung der Krankheit. Die informellen Kosten der Pflegenden sind dabei der bestimmende Kostenfaktor.

Background Apathy is a frequent symptom in Parkinson's disease (PD), substantially aggravating the course of PD. Regarding the accumulating evidence of the key role of apathy in PD, time-efficient assessments are useful for fostering progress in research and treatment. The Apathy Evaluation Scale (AES) is widely used for the assessment of apathy across different nosologies. Objective To facilitate the application of the AES in PD, we reduced the AES to two-thirds its length and validated this abbreviated version. Design Data sets of 339 PD patients of the DEMPARK/LANDSCAPE study without dementia and depression were randomly split into two samples. Data of sample 1 were used to develop a brief version of the AES (AES-12PD). A cross-validation was conducted in sample 2 and in a subsample of 42 PD patients with comorbid dementia and depressive symptomatology. Receiver operating characteristic analysis was applied to determine the optimal cutoff of the AES-12PD as an indicator of apathy. Results The AES-12PD featured high internal consistency that was better compared to the AES. The abbreviated scale was well differentiated from motor impairment and cognitive deficits. The AES-12PD cutoff of 27/28 was the optimal cutoff for apathy in PD patients without dementia and depression. The cutoff of 25/26 indicated apathy in PD patients with comorbid dementia and depression. Conclusion Results confirm a high internal consistency and good discriminant validity of the AES-12PD. The AES-12PD represents a reliable tool for the efficient assessment of apathy that can be applied in PD patients with and without dementia and depression.

Multimorbiditat wird als das gleichzeitige Vorliegen mehrerer Erkrankungen oder Gesundheitsprobleme (mindestens 2 oder mehr) bei einer Person definiert. Abzugrenzen hiervon ist der Begriff der Komorbiditat, der das Auftreten zusatzlicher Erkrankungen zu einer Haupt- oder Indexerkrankung bezeichnet. Die Wahrscheinlichkeit fur das Auftreten von Mehrfacherkrankungen steigt mit dem Alter an und stellt ein zunehmendes Problem fur die betroffenen Patienten, deren Angehorigen, aber auch fur das Gesundheitssystem dar, da multimorbide Patienten eine verringerte Lebensqualitat angeben, oftmals einen erhohten Pflegebedarf benotigen und auf allen Ebenen mehr Gesundheitsleistungen in Anspruch nehmen. Die Pravalenz der Multimorbiditat ist aufgrund der unterschiedlichen Konzeptualisierung und der altersabhangigen Haufung schwierig abzuschatzen. Die Zahlen variieren in den unterschiedlichen Studien stark und liegen entsprechend dem untersuchten Kollektiv zwischen 3 und 50 %, z. T. auch hoher. Die Behandlung der Patienten ist oftmals schwierig und fuhrt in nicht seltenen Fallen zur Verabreichung einer Vielzahl von Medikamenten und Wirkstoffen, die nicht aufeinander abgestimmt sind und so die Gefahr fur unerwunschte Arzneimittelwirkungen bei einer fragilen Population zusatzlich erhohen konnen. Ziel dieses Artikels ist es, einen kurzen Uberblich uber die Konzeptualisierung des Begriffes der Multi- und Komorbiditat zu geben und die Epidemiologie und Versorgung von Patienten mit Mehrfacherkrankungen im nationalen Kontext darzustellen.

Parkinson's disease (PD) frequently entails non-motor symptoms, worsening the course of the disease. Apathy is one of the core neuropsychiatric symptoms that has been investigated in recent years; research is however hampered by the limited availability of well-evaluated apathy scales for these patients. We evaluated the psychometric properties of the Apathy Evaluation Scale (AES) in a sample of PD patients. Psychometric properties, convergent and discriminant validity and sensitivity/specificity were evaluated in patients with (n = 582) or without dementia/depression (n = 339). Internal consistency was high in the entire sample as well as in patients without dementia/depression. Correlations were moderate for convergent validity (UPDRS I item 4: motivation). While apathy could be differentiated from cognitive decline, it was related to depression (Geriatric Depression Scale, GDS-15). The overall classification accuracy based on the UPDRS I item 4 was comparable for AES and GDS scores. The AES exhibits good psychometric properties in PD patients with and without dementia and/or depression. Commonly used screenings on the presence of apathy had low detection rates compared to the AES and reflected both apathetic and depressive symptoms. Psychometric evaluation of available instruments will support further research on the clinical relevance of apathy for disease progression and treatment approaches in PD patients.

ZusammenfassungDie Demenz vom Alzheimer-Typ ist die häufigste neurodegenerative Erkrankung und mehr als 15 Millionen Menschen sind weltweit betroffen. Die Erkrankung ist klinisch charakterisiert durch eine progressive Gedächtnisstörung, kognitiven Abbau und Einbußen in den Aktivitäten des täglichen Lebens; histopathologisch ist die Erkrankung definiert durch den Nachweis von ²-Amyloidplaques (A²), die aus aggregiertem A²-Peptiden bestehen und neurofibrillären Bündeln, die aus hyperphophoryliertem Tau-Protein entstehen. Die zur Testung gelangenden Therapieansätze fußen überwiegend auf diesen beiden Mechanismen. Insbesondere Therapieansätze basierend auf der Amyloidkaskaden-Hypothese, wie ³-Sekretaseinhibitoren, Inhibitoren der ²-Sekretase und immuntherapeutische Ansätze standen in den letzten Jahren im Mittelpunkt der Entwicklung. Ziel dieses Artikels ist es, die in der klinischen Entwicklung befindlichen krankheitsmodifizierenden Therapieansätze, die auf der Amyloidkaskaden-Hypothese beruhen, kurz darzustellen.

Item does not contain fulltext BACKGROUND: The spectrum of disorders of the brain is large, covering hundreds of disorders that are listed in either the mental or neurological disorder chapters of the established international diagnostic classification systems. These disorders have a high prevalence as well as short- and long-term impairments and disabilities. Therefore they are an emotional, financial and social burden to the patients, their families and their social network. In a 2005 landmark study, we estimated for the first time the annual cost of 12 major groups of disorders of the brain in Europe and gave a conservative estimate of euro386 billion for the year 2004. This estimate was limited in scope and conservative due to the lack of sufficiently comprehensive epidemiological and/or economic data on several important diagnostic groups. We are now in a position to substantially improve and revise the 2004 estimates. In the present report we cover 19 major groups of disorders, 7 more than previously, of an increased range of age groups and more cost items. We therefore present much improved cost estimates. Our revised estimates also now include the new EU member states, and hence a population of 514 million people. AIMS: To estimate the number of persons with defined disorders of the brain in Europe in 2010, the total cost per person related to each disease in terms of direct and indirect costs, and an estimate of the total cost per disorder and country. METHODS: The best available estimates of the prevalence and cost per person for 19 groups of disorders of the brain (covering well over 100 specific disorders) were identified via a systematic review of the published literature. Together with the twelve disorders included in 2004, the following range of mental and neurologic groups of disorders is covered: addictive disorders, affective disorders, anxiety disorders, brain tumor, childhood and adolescent disorders (developmental disorders), dementia, eating disorders, epilepsy, mental retardation, migraine, multiple sclerosis, neuromuscular disorders, Parkinson's disease, personality disorders, psychotic disorders, sleep disorders, somatoform disorders, stroke, and traumatic brain injury. Epidemiologic panels were charged to complete the literature review for each disorder in order to estimate the 12-month prevalence, and health economic panels were charged to estimate best cost-estimates. A cost model was developed to combine the epidemiologic and economic data and estimate the total cost of each disorder in each of 30 European countries (EU27+Iceland, Norway and Switzerland). The cost model was populated with national statistics from Eurostat to adjust all costs to 2010 values, converting all local currencies to Euro, imputing costs for countries where no data were available, and aggregating country estimates to purchasing power parity adjusted estimates for the total cost of disorders of the brain in Europe 2010. RESULTS: The total cost of disorders of the brain was estimated at euro798 billion in 2010. Direct costs constitute the majority of costs (37% direct healthcare costs and 23% direct non-medical costs) whereas the remaining 40% were indirect costs associated with patients' production losses. On average, the estimated cost per person with a disorder of the brain in Europe ranged between euro285 for headache and euro30,000 for neuromuscular disorders. The European per capita cost of disorders of the brain was euro1550 on average but varied by country. The cost (in billion euroPPP 2010) of the disorders of the brain included in this study was as follows: addiction: euro65.7; anxiety disorders: euro74.4; brain tumor: euro5.2; child/adolescent disorders: euro21.3; dementia: euro105.2; eating disorders: euro0.8; epilepsy: euro13.8; headache: euro43.5; mental retardation: euro43.3; mood disorders: euro113.4; multiple sclerosis: euro14.6; neuromuscular disorders: euro7.7; Parkinson's disease: euro13.9; personality disorders: euro27.3; psychotic disorders: euro93.9; sleep disorders: euro35.4; somatoform disorder: euro21.2; stroke: euro64.1; traumatic brain injury: euro33.0. It should be noted that the revised estimate of those disorders included in the previous 2004 report constituted euro477 billion, by and large confirming our previous study results after considering the inflation and population increase since 2004. Further, our results were consistent with administrative data on the health care expenditure in Europe, and comparable to previous studies on the cost of specific disorders in Europe. Our estimates were lower than comparable estimates from the US. DISCUSSION: This study was based on the best currently available data in Europe and our model enabled extrapolation to countries where no data could be found. Still, the scarcity of data is an important source of uncertainty in our estimates and may imply over- or underestimations in some disorders and countries. Even though this review included many disorders, diagnoses, age groups and cost items that were omitted in 2004, there are still remaining disorders that could not be included due to limitations in the available data. We therefore consider our estimate of the total cost of the disorders of the brain in Europe to be conservative. In terms of the health economic burden outlined in this report, disorders of the brain likely constitute the number one economic challenge for European health care, now and in the future. Data presented in this report should be considered by all stakeholder groups, including policy makers, industry and patient advocacy groups, to reconsider the current science, research and public health agenda and define a coordinated plan of action of various levels to address the associated challenges. RECOMMENDATIONS: Political action is required in light of the present high cost of disorders of the brain. Funding of brain research must be increased; care for patients with brain disorders as well as teaching at medical schools and other health related educations must be quantitatively and qualitatively improved, including psychological treatments. The current move of the pharmaceutical industry away from brain related indications must be halted and reversed. Continued research into the cost of the many disorders not included in the present study is warranted. It is essential that not only the EU but also the national governments forcefully support these initiatives. 01 oktober 2011

ZusammenfassungKognitive Störungen bei neurologischen Erkrankungen sind häufig und führen zu einer deutlichen Einschränkung der Lebensqualität der betroffenen Patienten. Nur wenige randomisierte und doppelblinde Studien liegen vor, die eine Behandlung der kognitiven Defizite bei neurologischen Erkrankungen als primäres Zielkriterium hatten. Für die Parkinsonkrankheit mit Demenz liegt eine Zulassung für den Cholinesterasehemmer Rivastigmin vor. Für die Behandlung kognitiver Defizite beim Schlaganfall oder der Multiplen Sklerose stehen keine zugelassenen Medikamente zur Verfügung. Für die Wirksamkeit von Programmen zur Rehabilitation der Kognition sind nur wenige kontrollierte Studien durchgeführt worden. In diesem Übersichtsartikel soll der gegenwärtige Stand der Behandlung von kognitiven Störungen beim M. Parkinson, dem Schlaganfall und der Multiplen Sklerose dargestellt werden.

ZusammenfassungZiel ist es, die Kosten und Versorgung von Patienten mit dem Parkinson-Syndrom und anderen neurologischen Erkrankungen in Deutschland zu untersuchen. Krankheitskostenstudien wurden für folgende Erkrankungen durchgeführt: Morbus Parkinson, Multisystematrophie, Progressive supranukleäre Blickparese, Restless-legs-Syndrom, Epilepsie, Narkolepsie, neuromuskuläre Erkrankungen und Schlaganfall. Es wurden für viele Erkrankungen erstmalig in Deutschland die direkten und indirekten Kosten der Erkrankung erhoben. Darüber hinaus wurden für die Behandlungsoptionen der Parkinson-Krankheit vergleichende Studien begonnen. Alle untersuchten Erkrankungen sind chronische Erkrankungen und führen zu einer schweren Beeinträchtigung und Belastung nicht nur für die Patienten, sondern auch für deren Angehörige und zu hohen Folgekosten für die Gesellschaft. Diese Belastungen werden sich durch die sich verändernde Altersstruktur verschärfen. Deshalb wird sich unsere zukünftige Forschung mit Versorgungsaspekten und deren Verbesserung auseinandersetzen.Diese Studien wurden alle erst ermöglicht durch die Forschungsförderung des Bundesministeriums für Bildung und Forschung (BMBF) im Rahmen des Kompetenznetzes Parkinson Syndrome.

Alteration of endoplasmic reticulum (ER) Ca(2+) homeostasis leads to excessive cytosolic Ca(2+) accumulation and delayed neuronal cell death in acute and chronic neurodegenerative disorders. While our recent studies established a protective role for SK channels against excessive intracellular Ca(2+) accumulation, their functional role in the ER has not been elucidated yet. We show here that SK2 channels are present in ER membranes of neuronal HT-22 cells, and that positive pharmacological modulation of SK2 channels with CyPPA protects against cell death induced by the ER stressors brefeldin A and tunicamycin. Calcium imaging of HT-22 neurons revealed that elevated cytosolic Ca(2+) levels and decreased ER Ca(2+) load during sustained ER stress could be largely prevented by SK2 channel activation. Interestingly, SK2 channel activation reduced the amount of the unfolded protein response transcription factor ATF4, but further enhanced the induction of CHOP. Using siRNA approaches we confirmed a detrimental role for ATF4 in ER stress, whereas CHOP regulation was dispensable for both, brefeldin A toxicity and CyPPA-mediated protection. Cell death induced by blocking Ca(2+) influx into the ER with the SERCA inhibitor thapsigargin was not prevented by CyPPA. Blocking the K(+) efflux via K(+)/H(+) exchangers with quinine inhibited CyPPA-mediated neuroprotection, suggesting an essential role of proton uptake and K(+) release in the SK channel-mediated neuroprotection. Our data demonstrate that ER SK2 channel activation preserves ER Ca(2+) uptake and retention which determines cell survival in conditions where sustained ER stress contributes to progressive neuronal death.

Increasingly, inflammatory responses in localized areas of brain parenchyma in response to the extracellular deposition of the Abeta peptides are thought to play a causative role in Alzheimer's disease (AD) progression. Anti-inflammatory agents, in particular non-steroid anti-inflammatory drugs (NSAIDs), such as aspirin and ibuprofen, have been shown to be associated with a delayed onset or slowed rate of disease progression in several epidemiological studies. Activation of glial cells and the subsequent expression of a number of proteins including alpha(2)-macroglobulin (alpha(2)M) are associated with the induction of brain tissue inflammation. Additionally cytokines, such as interleukin-1alpha (IL-1alpha), interleukin-1beta (IL-1beta), and interleukin-6 (IL-6) are co-localized to senile plaques, a neuropathological hallmark of AD. Alpha(2)M binds various cytokines, including IL-1beta, as well as Abeta. In this study, we demonstrate that IL-1beta induces alpha(2)M synthesis/release from a human astroglial cell line (U373) via the activation of the nuclear transcription factor NF-kappaB. Our data suggest that attenuation of IL-1beta-induced alpha(2)M synthesis/release by blocking NF-kappaB activation may potentially be 'protective' against the development of late-onset AD.

Multimorbidity is defined as the simultaneous presence of several diseases or health conditions (at least two or more) in one person. In contrast, comorbidity indicates the occurrence of additional diseases to a main or index disease. The probability for the occurrence of multimorbidity increases with advancing age and is a growing problem for affected patients, relatives, and also for the healthcare system, as multimorbid patients have a decreased quality of life, often requiring high levels of care and may increase the resource use at all levels of healthcare. The prevalence of multimorbidity is difficult to estimate due to the different conceptualizations and the age-related accumulation. Thus, the numbers vary greatly in the different studies and are estimated to be between 3 % and 50 %, in some studies numbers are even higher. The treatment of patients is often difficult and results in a variety of medications and drugs that are often not coordinated with each other and so may increase the risk for adverse drug effects, especially in a fragile population. The aim of this article is to give a brief overview on the concept of multimorbidity and comorbidity, to present epidemiological data and to describe the care of patients with multiple illnesses in the German context.

The prediction of Alzheimer's dementia is relevant for the development and design of prevention trials but also for individual counselling of patients. There are two key characteristics which determine the level of prediction that can be achieved. Firstly, the prevalence of Alzheimer's dementia in the respective setting is important. In low prevalence settings, such as primary care populations, it is probably impossible to achieve positive predictive values above 50%. In high prevalence settings, such as memory clinics, the positive predictive value of Alzheimer's dementia can be much higher. The second major characteristic is the level of cognitive impairment of an individual. The predictive power for Alzheimer's dementia increases from the cognitively healthy status to the status of progressive mild cognitive impairment. Prediction can further be increased by the use of cerebral spinal fluid and brain imaging biomarkers of Alzheimer's disease. The combination of different biomarkers may increase prediction even further. The present article reviews studies and outlines the principles of prediction of Alzheimer's dementia.

Insomnia is a prevalent condition with significant morbidity and mortality and substantial direct and indirect costs. In the Unites States, estimated costs of insomnia from the societal perspective in 1994 reached up to US $107.53 billion per year. Increased healthcare utilization including drugs, outpatient physicians’ services, and hospital admissions has been found to a greater degree among individuals with insomnia. In addition, insomnia is associated with a number of medical (e.g., lung diseases, diabetes) or psychiatric conditions, with depression as the most commonly reported psychiatric comorbidity. Insomnia also leads to decreased workplace productivity, increased work absenteeism, and impaired everyday functioning resulting in high indirect costs. The risk of traffic and nonmotor vehicle accidents is considerably increased in individuals suffering from insomnia compared to those with normal sleep patterns. Individuals with insomnia also have a notably reduced health-related quality of life. Altogether, the current available data confirm that direct and indirect consequences of insomnia result in a significant economic burden to both the patients and their families, as well as to the society.

Health-related quality of life (HrQoL) has become an important outcome for evaluating patients’ subjective perspective. In contrast to quality of life, which is a fairly broad term, HrQoL relates to those domains of life that are considered to be affected by a particular illness. Only a few articles that evaluate HrQoL in patients suffering from hypersomnias are available, and there are currently no clinical trials available that use HrQoL as a primary outcome in such patients. The available evidence clearly shows that hypersomnias such as narcolepsy considerably reduce HrQoL and affect various domains of HrQoL to varying extents. The effect of drugs on HrQoL has not yet been evaluated in patients with hypersomnias.

Under current guidelines surgical care of hip fractures has to be initiated within 48 h which is a challenge for the management of patients on medical anticoagulation. The aim of this study was to evaluate the in-house standard operation procedure (SOP) concerning these patients.All geriatric hip fracture patients were included in this prospective study. Data concerning medical anticoagulation and hemoglobin levels on admission and at discharge, the start and duration of surgery, transfusion rates and postoperative complications were collectedA total of 154 (62%) out of 247 patients were on anticoagulants. Patients on acetylsalicylic acid (ASA) demonstrated a significant increase in the rate of transfusion (62%, 95% CI, range 53%-72%, p0.05) but lost significantly less hemoglobin during hospitalization (1.25 g/dl, 95% CI 0.62-1.88g/dl, p0.05) in comparison to the control group (40% transfused, hemoglobin loss 3.00 g/dl). Patients on phenprocoumon were operated on later (26 h versus 20 h,95% CI 22-30, p0.001). There were no significant differences concerning complications.Under this SOP anticoagulation has no impact on complication rates after hip fracture. The increased transfusion rates under ASS can be attributed to early blood transfusions. Antagonization of coumarin with vitamin K delays surgery but seems adequate. An analysis of more patients over a longer period of time should be conducted.

Parkinson’s disease (PD) is frequently compounded by neruropsychiatric complications, increasing disability. The combined effect of motor and mental status on care-dependency in PD outpatients is not well characterized. We conducted a cross-sectional study of 1449 PD outpatients. The assessment comprised the Montgomery–Asberg Depression Rating Scale (MADRS) and the diagnostic criteria for dementia. PD severity and treatment complications were rated using Hoehn and Yahr staging and the Unified Parkinson’s Disease Rating Scale (UPDRS) IV. The acknowledged level of care-dependency was documented. Care-dependency was present in 18.3% of all patients. A total of 13.9% had dementia, 18.8% had depression, and 14.3% had both. Regression analyses revealed increasing effects of age, PD duration, and PD severity on care-dependency in all three mental-disorder subgroups with the strongest effects in patients with depression only. Depressed patients with antidepressive treatment still had significantly higher PD severity, higher MADRS and UPDRS-IV scores but were not more likely to be care-dependent than non-depressed patients. Older age, longer duration and increased severity of PD contribute to care-dependency in patients with untreated depression. Treatment of depression is associated with lower rates of care-dependency.

Review on MIF (macrophage migration inhibitory factor (glycosylation-inhibiting factor)), with data on DNA, on the protein encoded, and where the gene is implicated.

Parkinson's disease (PD) is frequently accompanied by dementia or depression which can aggravate the clinical picture of the disease and increase the risk of care dependency (CD). Little is known about the associations between PD, these neuropsychiatric comorbidities and CD in outpatients.A nationwide sample of outpatients (n=1,449) was examined by office-based neurologists (n=315) comprising the documentation of the general, neurological status and the degree of CD. The dementia status was clinically rated according to the established DSM-IV criteria. Depression was screened with the Montgomery-Asberg Depression Rating Scale (MADRS).Overall, 18.3% of all patients were care dependent. Even after adjustment for PD severity, patients with depression (OR=2.8; 95% CI 1.8-4.3), dementia (OR=2.7; 95% CI 1.8-4.1) or both (OR=3.9; 95% CI 2.5-60,0) were at higher risk for CD than patients without dementia or depression. Patients aged ≥76 years were fourfold more likely to be care dependent than patients aged ≤65 years (OR=3.5; 95% CI 2.3-5.5). Across all age groups, patients with depression featured the highest increments (from 11.9 to 42.0%).The risk for CD is substantially elevated in outpatients with PD when further neuropsychiatric symptoms are present. The data suggest that depression contributes equally to disability as does dementia.

Parkinson's disease (PD) is a common neurodegenerative disorder with a considerable socioeconomic burden. Health-economic evaluations of PD in the Southern European countries are limited.To evaluate the costs of PD in an outpatient cohort in Portugal.49 consecutive PD patients were recruited at the neurological outpatient clinic of the University of Lisbon between October 2004 and December 2005. Clinical status was evaluated using the Unified Parkinson's Disease Rating Scale and the Hoehn and Yahr stages. Costs were assessed from the societal perspective using health-economic questionnaires. Human capital approach was used to estimate indirect costs. Health-related quality of life was evaluated by means of the EQ-5D.Direct costs were 2,717 euros (95% CI = 1,147-3,351) per patient for a six-month period. Main contributors to the direct costs included drugs (544 euros; 95% CI = 426-6,940) and hospitalizations (690 euros; 95% CI = 229-1,944). Indirect costs amounted to 850 euros (95% CI = 397-1,529), whereas patient expenditures constituted 12% of direct costs. Assistance by family and other relatives played a major role. In general, costs were lower than in other Western countries.The economic burden of PD in Portugal is considerable. Important cost components include medications and hospitalizations. More research is needed in order to describe a comprehensive health service patterns in Portugal and to guide health policy decisions more effectively.

The aim of this study was to evaluate the direct and indirect costs in a cohort of German outpatients with Parkinson's disease (PD) and to identify major cost drivers in PD.91 PD patients were consecutively enrolled in the outpatient department of the neurological clinic at the University of Marburg, Germany. Patients had to fill out a standardised questionnaire at baseline and at a 3-month follow-up and report their health service resource utilisation for the past three months, retrospectively. In addition, information on clinical parameters of PD (UPDRS, Hoehn and Yahr stage) were assessed. For 86 patients, the direct and indirect cost data were analysed. Indirect costs were calculated by the human capital approach.Total costs per patient and 6-month period amounted to € 8,400 [95%CI 6,768-10,302]. Of these, 30% were indirect costs (€ 2,505 [95%CI 1,541-4,047]) and 70% were direct costs (€ 5,895 [95%CI 4,846-7,376]). The major parts of the direct costs were triggered by antiparkinsonian medication (€ 2,889 [95%CI 2,392-3,655]) and inpatient stays (hospital und rehabilitation, € 1,556 [95%CI 865-2,892]). A linear multivariate model with disease severity, disease duration, sleep disorders, psychosis and dystonia explained 24% of the variance of total costs and 33% of variance of direct costs, respectively.Parkinson's disease imposes a high financial burden on both patient and society. A reduced health-related quality of life reflects the individual patient's impairment by PD.

Five different antihistamines (astemizole, clemastine, dimethindene, pheniramine and terfenadine) were tested for their antagonistic actions on histamine-induced contractions in isolated strips of the aorta and the trachea of the guinea pig. All antagonists led to a shift of the concentration-response curves for histamine and a decrease in the maximal response. pA2-values were calculated from the competitive part of the antagonism, whereas pD′2-values were calculated for the non-competitive part of the antagonism. Marked differences were observed for the various compounds: clemastine and dimethindene with pA2-values for the aorta (trachea) of 9.31 (8.64) and 9.12 (8.39), respectively, showed the highest affinity, whereas pheniramine with a pA2-value for the aorta (trachea) of 7.42 (7.10) showed the lowest affinity. The compounds astemizole and terfenadine took an intermediate position. Similar results were obtained for the non-competitive part of the antagonism with a marked antagonistic effect produced by dimethindene and clemastine (pD′2 values for the aorta: 7.99 and 6.50; trachea: 7.71 and 7.10, respectively) and less suppression of the maximal response for astemizole, terfenadine and pheniramine.

Fragestellung: Longitudinale Erhebung der Lebensqualitat und der krankheitsassoziierten Kosten sowie ihre Veranderungen nach 6 Monaten bei Patienten mit schubformiger- und sekundar-progredienter Multipler Sklerose (MS). Methoden: 144 konsekutive MS-Patienten (n=97 RR-MS, n=39 SP-MS, n=8 PP-MS) wurden uber einen Zeitraum von 6 Monaten rekrutiert und zu Baseline (BL) und nach 6 Monaten (6 Mo-FU) neurologisch (Expanded Disability Status Scale, EDSS; Multiple Sclerosis Functional Composite, MSFC) und mittels validierter Fragebogen (Modified Fatigue Impact Scale, MFIS; Beck Depression Inventory II; BDI II) untersucht. Daruber hinaus wurden soziodemographische und okonomische Parameter erhoben. Die gesundheitsbezogene Lebensqualitat wurde mit dem EuroQol Instrument und der FAMS (Functional Assessment of Multiple Sclerosis) Skala gemessen. Ergebnisse: Die mittlere Krankheitsauspragung (EDSS) lag bei BL und 6Mo-FU bei 3,5±2,0 (102 Patienten konnten nach 6 Monaten nochmals untersucht werden, der durchschnittliche EDSS betrug unverandert 3,5±2,0). Der Mittelwert der gesundheitsbezogenen Lebensqualitat lag fur die BL bei 0,8±0,2 (EQ-Index), 62±20 (EQ VAS), 114±31 (FAMS). Im 6 Mo-FU lagen die Parameter der Lebensqualitat bei 0,8±0,2 (EQ-Index, n.s.), 64±19 (EQ VAS, n.s.) und 114±32 (FAMS, n.s.). Depressionen gemessen mit dem BDI II lagen unverandert bei BL und 6 Mo FU bei 13±11 Punkten. Die gesellschaftlichen Kosten pro Patient und Jahr betrugen bei BL €38.700, davon machten die Medikamente (€14.830) den grosten Anteil aus. Im 6Mo-FU lagen die Jahresgesamtkosten bei €37.500, die Medikamentenkosten stiegen auf €16.600. Auffallig war dabei ein Anstieg des Patientenanteils, der mit neuen, kostenintensiven spezifischen Immuntherapeutika behandelt wurden, von 17% (BL) auf 25% (6 Mo-FU). In univariaten Analysen konnten signifikante negative Korrelationen fur steigendes Alter, hoheren Behinderungsgrad (EDSS), Krankheitsdauer, Fatigue (MFIS;) und Schwere der Depression (BDI;) mit der gesundheitsbezogenen Lebensqualitat in EQ5D und FAMS gezeigt werden. Schlussfolgerung:Uber einen Zeitraum von 6 Monaten konnte keine signifikante Veranderung bei den klinischen Parametern und der Lebensqualitat beider untersuchten Gruppe von MS Patienten nachgewiesen werden. Wahrend die Jahresgesamtkosten pro MS Patient im 6Mo-FU durchschnittlich leicht zuruckgingen, nahm der Anteil der Medikamentenkosten zu. Dies konnte am verstarkten Einsatz neuer Immuntherapeutika liegen.

Hintergrund: Die Krankheitslast von Patienten mit leichter oder mittelschwerer Alzheimer Demenz (AD) und deren pflegenden Angehorigen kann durch medikamentose und nichtmedikamentose Masnahmen gesenkt werden. Im Hinblick auf eine verbesserte Gestaltung derartiger Masnahmen konnen differenzierte epidemiologische Erkenntnisse uber die Problemkonstellationen und Interaktionen von Patienten und Angehorigen wertvolle Hinweise liefern. Die IDEA-Studie hat folgende Ziele: (a) Beschreibung der aktuellen Versorgungs- und Therapiesituation von Patienten mit leichter oder mittelschwerer AD (b) Beschreibung der Situation der pflegenden Angehorigen und deren Belastungen in Bezug auf instrumentelle, funktionale und emotionale Aspekte (c) Identifikation von Faktoren bei Patienten, Arzten und pflegenden Angehorigen, die einen Einfluss auf die Belastung haben konnten. (d) Identifikation gedeckter und ungedeckter Versorgungsbedurfnisse. Methoden: IDEA (Improving Alzheimer Dementia Treatment: Epidemiological Assessment of Doctors', Patients' and Caregivers' Unmet Needs and Barriers) ist eine strikt naturalistische zweistufige Beobachtungsstudie an 2.500 AD-Patienten und deren Angehorigen. Im ersten Schritt wird bundesweit eine reprasentative Stichprobe von Neurologen, Psychiatern und Hausarzten im ambulanten Versorgungssektor eingeladen an der Studie teilzunehmen und gebeten, mindestens 5 zufallig ausgewahlte Patienten mit leichter oder mittelschwerer AD und deren pflegende Angehorige in die Studie aufzunehmen. Im zweiten Schritt wird jeder Patient durch seinen Arzt klinisch beurteilt (Dauer und Schwere der Demenz, Medikation und andere Therapien, Adharenz, Funktionsniveau des Patienten, neuropsychiatrische Komplikationen). Die pflegenden Angehorigen werden danach durch Mitarbeiter der Forschungsgruppe befragt (Interview/Fragebogen). Die Interviews werden bei einem personlichen Besuch durch die Mitarbeiter der Forschungsgruppe oder per Telefon durchgefuhrt. Dabei werden die aktuelle Pflegesituation (Beschreibung der Hilfen, Zeitaufwand), sowie die Belastung, psychische Erkrankungen, Lebensqualitat und die korperliche Situation (WHO-DAS, korperliche Erkrankungen) der pflegenden Angehorigen erfasst. Weiterhin wird der Einfluss der aktuellen Pflegetatigkeit auf das alltagliche Leben erfragt. Eine Teilstichprobe der Patienten und deren pflegenden Angehorigen (N=600) wird zusatzlich prospektiv-longitudinal uber einen 10-Wochen Zeitraum untersucht. Zusatzlich werden die teilnehmenden Arzte gebeten einen Fragebogen zu Problemen der Alzheimerversorgung auszufullen. Ergebnisse: (erste Ergebnisse fur Juli 2009 erwartet).

Objective: To address the differences in disease progression between familial and sporadic multiple scleroris (MS) and the association within sib-pairs. Methods: 48 sibling pairs and 98 controls from a databank of 445 sporadic MS-patients, randomly pair-matched for age, gender, clinical course and disease duration were included. In 33 available sibling-pairs follow-up data were collected prospectively Outcome parameters included baseline expanded disability status scale (EDSS), age at onset, mono- or multifocal onset and disease progression. For analyses within-group distributions were described and compared, using Wilcoxon's signed-rank statistics for categorical differences, and t-statistics for continous variables. Relative frequencies of categories were tested by McNemar's test, and within sibling-pair associations using an intraclass correlation coefficient. Statistical tests were performed 2-sided at the 5% level using UNIVARIATE and FREQ SAS software 9.1. Results: Disease onset was slightly earlier (29.01 vs. 29.44 years, p=0.492) and multifocal onset significantly more often (p=0.0052) in familial than sporadic MS. Notably, a substantial within-pair correlation for disease progression could be observed (rho=0.40; r2=0.16, p=0.0062). However, there was neither a difference in baseline EDSS, nor in EDSS progression between the groups. Conclusions: Familial MS differs from sporadic cases with respect to age at onset and multifocal involvement as first clinical event. The progression rate of one out of two affected siblings may provide as a predictor for the other sib. However, prognosis over a six-year follow-up concerning the EDSS was similar in both groups. Larger longitudinal studies are required to find clinical, genetic, immunological or therapeutic implications.

Aim of this study was to assess the direct costs of Parkinson's disease (PD) within a 3-month period (i.e. the accounting period for the German statutory health insurance) in 12 neurological outpatient practices in Berlin during 2006.A total of 425 patients (age 69.1+/-9.3 years, 185 females) were recruited, and sociodemographic and clinical data were obtained by a specific questionnaire. The distribution of costs was analyzed based on several clinical and patient parameters. The costs were calculated with different approaches: (1) prospectively, with the practices' accounting according to German uniform scales (GoA, EbM) and (2) retrospectively, with questionnaires for the Parkinson's patients. Costs were calculated according to current German guidelines of the statutory health insurance. Clinical parameters were assessed with a questionnaire for physicians.The direct medical costs totaled 1,667 EUR (range 1,436-1,995 EUR, CI 95%) per patient per 3 months. Charges by physicians were 42 EUR (39-45 EUR, CI 95%) for patients with statutory health insurance and 135 EUR (106-177 EUR, CI 95%) for those with private insurance. Disease severity and disease duration correlated with higher direct medical costs. Motor fluctuations and depression also were major factors influencing cost.Our study emphasizes the large economic burden caused mainly by PD medication and hospitalization. For the first time a direct comparison between costs and actual physicians' reimbursement was possible. In combination with further economic studies, this comparison will help to define shortcomings and excesses in PD health care services.

Immunotherapeutic approaches for treating Alzheimer's disease were first described in 1999. A clinical trial using an active immunization with Abeta1-42 was initiated shortly thereafter, but it was halted early because of serious safety issues (acute meningoencephalitis in 6% of the treated patients). Despite this drawback, encouraging data from preclinical and clinical data were available, prompting researchers to seek alternative approaches for safer active and passive immunization. Currently, several passive and active immunotherapeutic approaches are being tested in clinical trials. However, our understanding of the mechanisms behind immunization in neurodegenerative disorders is still incomplete. In this review we present the current status of the different approaches in relation to Alzheimer's disease as well as to other neurodegenerative disorders.