Validation of amyloid-beta peptides in CSF diagnosis of neurodegenerative dementias.

Biomarkers for differential diagnosis of the three most frequent degenerative forms of dementia, Alzheimer's disease (AD), dementia with Lewy bodies (DLB) and frontotemporal dementias (FTD), are currently under intensive investigation, but disease-specific biomarkers for FTD and DLB are still lacking. We analyzed 303 cerebrospinal fluid (CSF) samples of 71 AD, 32 DLB and 36 FTD patients in comparison to 93 various other dementias (OD), 20 peripheral neurologic disease (PND) controls, 25 neurodegenerative disorders without dementia (ND) and 26 depressive cognitive complainers (DCC) for distinct CSF amyloid-beta (Abeta) peptide patterns, using the quantitative Abeta-SDS-PAGE/immunoblot. Additionally, the novel electrochemiluminescence technique (MSD) was used to validate the measures on Abeta1-38. The main outcome measures were a striking decrease of Abeta1-42 in AD (P=7.4 x 10(-19)), and most interestingly a pronounced decrease of Abeta1-38 in FTD (P=9.6 x 10(-7)). Moreover, a novel peptide that most probably represents an oxidized alpha-helical form of Abeta1-40 (Abeta1-40(ox)) displayed a highly significant increase in DLB (P=3.7 x 10(-3)) as compared to non-demented disease controls. The overall diagnostic accuracy of percentage Abeta peptide abundances (Abeta1-X%) was clearly superior to absolute CSF Abeta levels. Abeta1-42% and Abeta1-38% enabled contrasts of 85% or beyond to distinguish AD and FTD, respectively, from all other investigated subjects. Abeta1-40(ox)% yielded a diagnostic sensitivity and specificity of 88 and 73% for the detection of DLB among all other investigated patients. We found a strong correlation between Abeta1-38 levels as measured by the Abeta-SDS-PAGE/immunoblot and MSD, respectively. CSF Abeta peptides may reflect disease-specific impact of distinct neurodegenerative processes on Abeta peptide metabolism and represent a potential diagnostic biomarker for AD, FTD and DLB.

Filial maturity as a predictor for the burden of demented parents' caregivers.

In this study, we administered the Louvain Filial Maturity Scale [Marcoen 1993] to 61 adult children of demented elderly. The scores of the seven factors of this scale were compared to the scores of an unselected group of adult children examined by Marcoen. The results were taken into the context with caregiver's burden, and the effect of filial maturity on parents' institutionalisation was investigated. Marcoen's results were confirmed. Only the means of "filial help" and "parental consideration" differed slightly from the means of the unselected group. Overall, filial maturity had no influence on the caregiver's feeling of burden, but higher "parental consideration" resulted in lower caregiver burden. In addition, adult children with more "filial obligation" continued to care for their parents in the community more often, even when experiencing great burden and stress. However, institutionalisation was caused mainly by parents' growing needs and increasing behavioural problems. We conclude that "filial maturity" seems to be a very stable concept. Further investigations should focus on the relevance of the Louvain Filial Maturity Scale for caregiving relationship and also on the arrangement of the scale in order to exclude a "pseudo"-stability with regard to burdensome life events and situations.

Follow-up investigations in cerebrospinal fluid of patients with dementia with Lewy bodies and Alzheimer's disease.

Measuring proteins in cerebrospinal fluid (CSF) has gained wide acceptance for the differential diagnosis of dementia. Some groups have already extended these investigations in Alzheimer's disease (AD) by asking how stable these markers are in follow-up analysis, if they depend on the stage of disease and whether they can be used to monitor the progression and biological effects of treatment. We evaluated 21 patients with dementia with Lewy bodies (DLB) and 19 patients with AD, on two occasions, with regard to levels of tau protein, tau protein phosphorylated at threonine 181 (p-tau), Abeta42, Abeta40 and S-100B protein, using a set of commercially available assays. Tau protein levels were lower in DLB in first and second LP compared to AD and decreased during course of both groups. P-tau levels were increased in AD and DLB and decreased during follow-up. Abeta42 and Abeta40 remained relatively stable during follow-up but we found a slight increase of the median Abeta42 level in DLB, whereas in AD, Abeta42 tends to decrease during follow-up. S-100B protein increased during follow-up in both diseases. The protein dynamics in DLB and AD are relatively similar. S-100B protein may be a useful marker for follow-up in neurodegenerative diseases but has to be analysed in longer follow-up periods. Tau protein may be used to differentiate between DLB and AD. Follow-up CSF analyses are of limited value for the differentiation of AD and DLB. We conclude that more specific markers have to be established for the differentiation and follow-up of these diseases.

Clozapine-associated elevation of plasma cholinesterase.

OBJECTIVE: The goal of this study was to identify adverse effects of the atypical neuroleptic clozapine on liver function and lipid metabolism. METHODS: Data which included serum levels of clozapine and its hepatic metabolite N-desmethyl clozapine were collected from medical records of patients treated with clozapine and controls. RESULTS: We identified a clozapine-associated marked elevation of plasma cholinesterase (ChE) with unchanged levels of AST, ALT or g-GT. ChE was correlated to the serum level of clozapine and even closer to N-desmethyl clozapine. For the total patient group we observed significant correlations of ChE with the body-mass index and body weight. However, clozapine-treated patients and controls did not differ with regard to body-mass index, triglycerides, and cholesterol. CONCLUSION: We report for the first time a clozapine-associated and dose-dependent elevation of plasma ChE, which may be related to clozapine-associated effects on hepatic lipid metabolism or ChE enzyme induction.

[Future impact of population aging on local social budgets. A regionally differentiated impact study]. / Kunftige Auswirkungen der "Bevolkerungsalterung" auf die kommunalen Sozialbudgets. Eine raumlich differenzierende Wirkungsabschatzung.

PIP: The projected impact of population aging on local social budgets in West Germany is analyzed for the period 1990-2020. Comparisons are made between different types of settlement structure categories, and the effects of increased immigration are also assessed. (SUMMARY IN ENG)^ieng

["Urban flight" in densely populated regions--danger or necessity? Results of the new housing survey]. / "Stadtflucht" in hochverdichteten Regionen--Gefahr oder Erfordernis? Ergebnisse der neuen Wohnungsstichprobe

PIP: Data from a one percent sample housing survey conducted in 1978 are used to analyze the extent and nature of urban flight in densely populated regions of the Federal Republic of Germany. The dominant factors contributing to migration from central cities are examined, with particular attention to the role of the housing market.^ieng