Die Patienten-Compliance ist ein wichtiger Faktor zur Einschätzung des klinischen Effekts eines sich in Erprobung befindenden Medikamentes. Dies gilt besonders, wenn die Patienten zuhause inhalieren. Gewöhnlich werden Patiententagebücher, Dosis-Zähler oder zurückgegebene Dosen ausgewertet, allerdings sind aber diese durch die Studienteilnehmer beeinflussbar.

Neuropsychiatrische Erkrankungen wie die Alzheimer-Demenz sind komplexe Erkrankungen, die durch ein Zusammenspiel verschiedener Suszeptibilitätsgene und Umweltfaktoren verursacht werden. Erste Suszeptibilitätsgene sind bereits identifiziert worden, mit der Identifikation weiterer Gene ist in naher Zukunft zu rechnen. Ziel der molekulargenetischen Forschung ist es, ein umfassenderes Verständnis der Erkrankungen zu erlangen und somit die Entwicklung neuer Therapien für Betroffene und Prophylaxemöglichkeiten für Personen mit erhöhten genetischen bzw. umweltbedingten Risiken zu ermöglichen. Da der Anteil einzelner Gene an der Entstehung der Erkrankung jeweils nur klein ist, können prädiktive Gentests zum jetzigen Zeitpunkt allerdings nur Modifikationen des a priori-Risikos feststellen. Auch die Vorhersage von Beginn, Verlauf oder Schweregrad der Erkrankung ist derzeit nicht möglich. Deshalb werden zum jetzigen Zeitpunkt prädiktive Gentests bei Alzheimer-Demenz durch Fachverbände der Ärzte abgelehnt. Gleichwohl ist diese Einstellung nicht unwidersprochen und es wird kontrovers diskutiert, ob der Bevölkerung nicht bereits heute der Zugang zu prädiktiven Gentests zu gewähren sei. Ziel unserer Studie war es, die Einstellung der Allgemeinbevölkerung hierzu zu erfragen und zu erfassen, ob diese Einstellung durch Wissen um die Erkrankung und das Verstehen von Risikoangaben beeinflusst wird.

The airways of cystic fibrosis (CF) patients are characterised by neutrophils that release high amounts of elastase overwhelming the local antiprotease shield. Inhalation of alpha(1)-antitrypsin (AAT) may restore the protease-antiprotease balance and attenuate airway inflammation in CF airways. The aims of the present study were: 1) to assess the best deposition region for inhaled AAT by two different inhalation strategies; and 2) to examine the effect of 4 weeks of AAT inhalation on lung function, protease-antiprotease balance and airway inflammation in CF patients. In a prospective, randomised study, 52 CF patients received a daily deposition by inhalation of 25 mg AAT for 4 weeks targeting their peripheral or bronchial compartment. The levels of elastase activity, AAT, pro-inflammatory cytokines, neutrophils, immunoglobulin G fragments and the numbers of Pseudomonas aeruginosa were assessed in induced sputum before and after the inhalation period. Inhalation of AAT increased AAT levels and decreased the levels of elastase activity, neutrophils, pro-inflammatory cytokines and the numbers of P. aeruginosa. However, it had no effect on lung function. No difference was found between the peripheral and bronchial inhalation mode. In conclusion, although no effect on lung function was observed, the clear reduction of airway inflammation after alpha(1)-antitrypsin treatment may precede pulmonary structural changes. The alpha(1)-antitrypsin deposition region may play a minor role for alpha(1)-antitrypsin inhalation in cystic fibrosis patients.

We assessed the effects of induced hyperinsulinemia on plasma and cerebrospinal fluid (CSF) levels of norepinephrine (NE) and on cognition for patients with Alzheimer's disease (AD) and normal older adults. For normal adults, insulin increased plasma and CSF NE levels; also, recall for paraphrased details of a story improved as CSF NE levels increased. Mental control was positively correlated with CSF levels of NE for patients. These findings demonstrate that raising peripheral insulin levels can modulate CNS NE levels and suggest that insulin-stimulated increases in NE may modulate cognitive functions.

The objective was to evaluate the course and severity of dementia-related symptoms and their relationship to caregivers' subjective burden and depression over time. Forty-five patients with dementia and their caregivers were followed over a period of 2 years. Patients' cognition, function, and behavioral/psychological symptoms were assessed by the Mini Mental State Examination, Syndrome Kurz Test, Geriatric Depression Screening scale, Instrumental Activities of Daily Living Scale, Physical Self Maintenance Scale, Behavioral Abnormalities in Alzheimer's Disease Rating Scale, and Nurses Observation Scale for Geriatric Patients. Caregivers' depression and subjective burden were evaluated by the Geriatric Depression Screening scale or Beck Depression Inventory and the Caregiver Burden Interview. Global dementia severity, functional impairment, and behavioral disturbances increased significantly over the 2-year observation period. Caregivers' burden remained stable, and severe depression decreased over time. There were significant associations between burden and dementia-related symptoms. For deficits in activities of daily living as well as behavioral disturbances, these associations became stronger over time. It was concluded that stage of dementia, functional deficits, and behavioral disturbances are important factors when evaluating the relationship between patients' symptoms and caregivers' well-being.

Objectives To evaluate the impact of a combination of caregiver support group and memory training/music therapy in dementia patients on behavioural and psychological symptoms (BPSD) and caregiver burden compared to a control group.Method Eighteen patient-carer-dyads in the treatment group and 18 patient-carer-dyads as controls were studied in the setting of a memory clinic of a psychiatric university hospital over a period of 2 years. Controls were matched for age, gender. diagnosis, dementia severity, living arrangement and medication. The interventions were conducted once per week for 1 hour run by a clinical psychogeriatric team. Outcome measures were patients' cognitive and functional status as well as BPSD and caregivers subjective burden and depression measured by validated scales. Data were obtained 6, 12 and 24 months after baseline.Results There were no significant differences between the intervention and control group neither after 6, 12 nor after 24 months treatment.Conclusions The lack of a positive impact in alleviating caregiver burden or BPSD after intensive psychological interventions may result from extensive care in the routine clinical management including individual counselling for patients and families. The effect of 'treatment as usual' needs to be taken into account when comparing an intervention and control group, as well as the dosage of the intervention. Copyright (C) 2004 John Wiley Sons, Ltd.

Aims: To evaluate the association between psychosocial workplace factors and dementia in a case-control study. Methods: Patients with dementia (aged 55–99 years) were recruited from 23 general practices in the city of Frankfurt-on-Main and surrounding area in 1998–2000. Of these, 108 were suffering from possible Alzheimer’s disease, 59 from possible vascular dementia, and 28 from secondary or unclassified dementia. A total of 229 control subjects (aged 60–94 years) was recruited from the same study region: 122 population controls and 107 dementia-free ambulatory patients. A detailed job history was elicited in a structured personal interview (next-of-kin interviews of cases). Psychosocial work exposure was assigned to cases and control subjects by linking lifetime job histories with a Finnish job-exposure matrix. Data were analysed using logistic regression, to control for age, region, sex, dementia in parents, education, smoking, and the psychosocial network at age 30. Results: There were decreased odds ratios for high challenge at work, high control possibilities at work, and high social demands at work. High risks for error at work revealed a significant positive association with the diagnosis of dementia. Restriction of the analysis to cases with possible Alzheimer’s disease or to cases with possible vascular dementia led to similar results. Conclusions: These results support a role for psychosocial work factors in the aetiology of dementia. As an alternative explanation, people might have chosen jobs with poor work factors due to preclinical dementia, which becomes clinically manifest decades later.

Background: The modulation of attention by emotionally arousing stimuli is highly important for each individual's social function. Disturbances of emotional processing are a supportive feature for the diagnosis of subcortical vascular dementia (SVD). We address here whether these disturbances might be useful as an early disease marker.Methods: In order to examine the modulation of visual attention by emotionally arousing stimuli of different valence, 12 elderly patients with early SVD, 12 age-comparable healthy adults and 12 young healthy subjects were studied while looking at pairs of pictures from the International Affective Picture Battery that were either neutral-neutral, neutral-positive or neutral-negative in terms of emotional content. Eye movements were recorded with an infrared eye-tracking system. The direction of the first saccade and the dwell time during the 10 s of presentation were measured and compared among groups with parametric tests.Results: All subjects showed a modulation of initial attentional orienting as well as a higher percentage of dwell time towards the pictures containing emotional material. Patients with SVD and old controls did not differ in either experimental measure. Young patients showed a stronger bias towards emotionally negative material than both groups of older individuals.Conclusions: Modulation of visuospatial attention is preserved in early SVD. This might have implications for therapeutic interventional approaches. A weakened sustained attention towards negative but not positive emotional pictures in the elderly is in accordance with the socioemotional selectivity theory, describing a relative selection of positive stimuli with aging. (c) 2004 Elsevier B.V. All rights reserved.

In a case–control study, we investigated the possible etiological relevance to dementia of psychosocial network factors, such as marital status, confidants and close relatives, sports activities, cultural activities, club membership; and education. In 23 general practices we recruited 195 patients with dementia. Of these, 108 were suffering from possible Alzheimer's disease, 59 from possible vascular dementia and 28 from secondary or unclassified dementia. A total of 229 control subjects was recruited: 122 population controls and 107 dementia-free ambulatory patients. Data were gathered in a structured personal interview and analyzed using logistic regression, to control for age, region, sex, dementia in parents, education and smoking. There were significantly decreased odds ratios for the number of confidants, sports activities, and cultural activities at age 30, at age 50 and at 10 years before data collection. When all psychosocial network factors were included simultaneously in the logistic regression model, these factors remained statistically significant, indicating independent effects. Restriction of the analysis to cases with possible Alzheimer's disease or to cases with possible vascular dementia led to similar results. Adjustment for the psychosocial network neutralized the otherwise protective effect of education for dementia of any type and for possible vascular dementia. In keeping with the results from recently published studies, these results support a protective role for the psychosocial network—especially for the number of confidants and for sports and cultural activities—in the etiology of dementia.

In the etiology of dementia several genetic and various environmental factors are assumed to interact. Most epidemiological studies on risk factors have focused on "constitutional" factors like age, sex, birth order, dementia in the family and "life style" factors like smoking and alcohol consumption. Only few studies have investigated the role of psychosocial factors at work and during leisure time on the risk to develop dementia. Our paper gives a systematic review of all published results of controlled studies about psychosocial risk factors. A positive association has been observed between dementia and living alone, having no close social ties, not participating in social and leisure activities, and never having married. Recent studies have found that Alzheimer's disease in particular is negatively associated with diversity of activities and intensity of intellectual activities and positively associated with psychosocial inactivity, unproductive working style, living with a dominant spouse and with physical inactivity.

In der Literatur gibt es bisher wenige Ergebnisse aus kontrollierten Studien über den Nutzen psychologischer Trainingsmaßnahmen bei dementiellen Erkrankungen. In der Regel werden sehr spezielle Gedächtnisstrategien trainiert, die nicht auf die Alltagsprobleme der Patienten übertragbar sind. Aus diesem Grund haben wir ein Trainingsprogramm entwickelt, dass versucht, die unterschiedliche Leistungsfähigkeit der Teilnehmer zu berücksichtigen und einen hohen Alltagstransfer zu ermöglichen. Kurz- und Langzeitgedächtnis sowie das Verrichten alltäglicher Aktivitäten wurden über einen Zeitraum von 6Wochen in 12 Stunden gezielt trainiert. Unsere Ergebnisse zeigen eine signifikante Verbesserung der Experimentalgruppe in ihrer Aufmerksamkeits- und Gedächtnisleistung im Vergleich zur Kontrollgruppe.

There are few results of controlled studies about psychological interventions, i.e. training of cognitive functions in dementing illnesses. Most frequently very specific memory strategies are trained, (the effects of) which cannot be generalized to activities of daily living. Thus, a memory training program was developed considering the different cognitive abilities of the participants and which was meant to be generalized to daily tasks. Short-term and long-term memory were trained as well as activities of daily living in 12 lessons for a period of 6 weeks. We can show significant improvements of attention and memory performance in our experimental group in comparison to the control group.

There are few results of controlled studies about psychological interventions, i.e. training of cognititve functions in dementing illnesses. Most frequently very specific memory strategies are trained, (the effects of) which cannot be generalized to activities of daily living.Thus, a memory training program was developed considering the different cognitive abilities of the participants and which was meant to be generalized to daily tasks.Short-term and long-term memory were trained as well as activities of daily living in 12 lessons for a period of 6 weeks. We can show significant improvements of attention and memory performance in our experimental group in comparison to the control group.

We have developed a two-step method to purify fatty acid ethyl esters (FAEE) using solid-phase extraction (SPE), with a recovery of 70±3% (mean±S.E.M.) as assessed using ethyl oleate as a recovery marker from a standard lipid mixture in hexane. The first step of the SPE procedure involves application of a lipid mixture to an aminopropyl-silica column with simultaneous elution of FAEE and cholesteryl esters from the column with hexane. Gas chromatographic analysis of FAEE without interference from cholesteryl esters may be performed using the eluate from the aminopropyl-silica column, thus eliminating the need for an octadecylsily (ODS) column in this case. The FAEE can then be separated from the cholesteryl esters, if necessary, by chromatography on an ODS column and elution with isopropanol-water (5:1, v/v). Both the aminopropyl-silica and ODS columns were found to be effective for up to four uses. To permit isolation of specific FAEE species following isolation of total FAEE by the two-step SPE method, we have also developed a purification scheme for individaal FAEE by high-performance liquid chromatography (HPLC). Thus, this simple method allows for reproducible isolation of total FAEE by SPE and isolation of individual FAEE species by HPLC.

AbstractThe use of certain codes for the Vibroseis system of exploration has been investigated. The codes considered are well‐known in communication theory. The effect of coding the Vibroseis input signal is the suppression of correlation noise and therefore an improvement of the signal to noise ratio.It is believed that, during the course of research, a new property of one of the codes used has been discovered.