Alzheimer Disease: Dal-Bianco P

Ransmayr G, Katzenschlager R, Dal-Bianco P, Wenning G, Bancher C, Jellinger K, Schmidt R, Poewe W. · Neurologische Universitätsklinik Graz, Medizinische Universität Graz. · Neuropsychiatr. · Pubmed #17640492 No free full text.

Abstract: Dementia with Lewy Bodies (DLB) accounts for approximately 20 % of all autopsy-confirmed dementias in the elderly. Presumably, DLB is underdiagnosed in patients without or with only mild Parkinsonian symptoms in the daily routine of memory clinics. This motivated the Austrian Alzheimer Society and the Austrian Parkinson Society to inform about core features, suggestive features and supportive clinical findings of DLB and to provide information on diagnostic possibilities leading to better differential diagnosis. We also guide in the management of DLB as pharmacological treatment can pose difficult dilemmas for the treating clinician.

Schmidt R, Neff F, Lampl C, Benke T, Anditsch M, Bancher C, Dal-Bianco P, Reisecker F, Marksteiner J, Rainer M, Kapeller P, Dodel R. · Universitätsklinik für Neurologie, Medizinische Universität Graz. · Neuropsychiatr. · Pubmed #18826870 No free full text.

Abstract: Cholinesterase inhibitors and memantine can slow the course of Alzheimer's disease. In Austria the frequency of treatment is in the upper third among countries of the EU. Yet, the majority of Alzheimer patients does not receive adequate medication. Compliance to treatment is low. Studies on cholinesterase inhibitors show that only one third and one fifth of patients adhere to medication after 3 months and 12 months, respectively. Causes for low compliance are only partly patient-related, many factors are system-inherent. Knowledge of these factors is a pre-requisite for the treating physician to improve current unfavourable situation. Present treatment strategies are symptomatic, causal disease-modifying therapies are urgently needed. Research activity in the field is high and dominated by the amyloid hypothesis. We here review the basis and recent studies on secretase-inhibitors, immunization, aggregation of Abeta, statins and PPARgamma-agonists. Research towards strategies against tau-pathology is less dominant and focuses on inhibition of kinases and increase of activity of phosphatases. Causal therapies would have great effects on a population basis even if efficacy is only moderate. A disease-modifying therapy which delays the onset of Alzheimer disease by 5 years, will probably reduce the number of patients by nearly 50% during the next 50 years.

Schmidt R, Kienbacher E, Benke T, Dal-Bianco P, Delazer M, Ladurner G, Jellinger K, Marksteiner J, Ransmayr G, Schmidt H, Stögmann E, Friedrich J, Wehringer C. · Univ.-Klinik für Neurologie, Medizinische Universität Graz. · Neuropsychiatr. · Pubmed #18381051 No free full text.

Abstract: The prevalence of Alzheimer disease is higher in women than in men. In the age group 65-69 years 0.7% of women and 0.6% of men suffer from the disease with increasing frequencies of 14.2% and 8.8% in individuals aged 85-89 years. The incidence is also higher in demented women. In Austria 74.1% of Alzheimer patients older than 60 years are women. Several studies report more pronounced language, mnestic, semantic and orientation deficits in women, but methodological shortcomings might be responsible for this finding. The validity of results reporting a more rapid cognitive decline in women can also be questioned. Women have a broader spectrum of dementiarelated behavioural symptoms with a predominance of depression, while aggression is more frequent in men than in women. Biological explanations for gender-specific differences in the phenotype of Alzheimer s disease include different brain morphology and function with higher susceptibility for pathological lesions in women and greater cognitive reserve in men. Sex differences were also reported for expression of antioxidative enzymes and post-menopausal hormonal changes. Interactions between gender nd response to treatment, if any, are subtle and have large intra-individual variability. In Austria, two thirds of patients receiving attendance allowance are women. Care takes place in 80% by the families and is provided by women in 78%. The rate of female care-givers in partly institutionalized care units in 91% in nursing homes it is 84%.

Schmidt R, Alf C, Bancher C, Benke T, Berek K, Dal-Bianco P, Führwürth G, Imarhiagbe D, Jagsch C, Lechner A, Rainer M, Reisecker F, Rotaru J, Uranüs M, Walter A, Winkler A, Wuschitz A. · Universitätsklinik für Neurologie, Medizinische Universität Graz. · Neuropsychiatr. · Pubmed #19272293 No free full text.

Abstract: We performed a 6-month open-label study on the use of the transdermal rivastigmine patch in clinical routine in 103 patients with Alzheimer's disease from 25 outpatient services in Austria. After baseline, safety and tolerability of the 10 cm2--rivastigmine patch was assessed at week 4, 12 and 24 in all patients. A Mini Mental State Examination was done at baseline and at week 12 and 24. Skin adherence of the patch was very good or good in 85% of study participants. Only 2.9% of patients had gastrointestinal adverse events. Local skin reactions occurred in 23% of individuals. Skin alteration were mostly mild in severity. In only 6.8% of subjects did they result in termination of treatment. At the earliest skin reactions were observed after 3 months of treatment. Cognitive functioning of patients improved comparable to the controlled trial which led to approval of the rivastigmine patch. In daily routine the safety profile of the rivastigmine patch is favourable, as is the response to treatment. Local, mostly mild skin reactions affect approximately every fifth patient, and they occur relatively late in the course of therapy. Patients and their caregivers should receive detailed information about skin reactions to omit unnecessary drop outs to treatment.

Bauer M, Langer O, Dal-Bianco P, Karch R, Brunner M, Abrahim A, Lanzenberger R, Hofmann A, Joukhadar C, Carminati P, Ghirardi O, Piovesan P, Forloni G, Corrado ME, Lods N, Dudczak R, Auff E, Kletter K, Müller M. · Department of Clinical Pharmacology, Division of Clinical Pharmacokinetics, University of Vienna, Vienna, Austria. · Clin Pharmacol Ther. · Pubmed #16952488 No free full text.

Abstract: This work describes a microdosing study with an investigational, carbon 11-labeled antiamyloid drug, 1,1'-methylene-di-(2-naphthol) (ST1859), and positron emission tomography (PET) in healthy volunteers (n = 3) and patients with Alzheimer's disease (n = 6). The study aimed to assess the distribution and local tissue pharmacokinetics of the study drug in its target organ, the human brain. Before PET studies were performed in humans, the toxicologic characteristics of ST1859 were investigated by an extended single-dose toxicity study according to guidelines of the Food and Drug Administration and European Medicines Agency, which are relevant for clinical trials with a single microdose. After intravenous bolus injection of 341 +/- 21 MBq [(11)C]ST1859 (containing <11.4 nmol of unlabeled ST1859), peripheral metabolism was rapid, with less than 20% of total plasma radioactivity being in the form of unchanged parent drug at 10 minutes after administration. In both the control and patient groups, uptake of radioactivity into the brain was relatively fast (time to reach maximum concentration, 9-17 minutes) and pronounced (maximum concentration [standardized uptake value], 1.3-2.2). In both healthy volunteers and patients, there was a rather uniform distribution of radioactivity in the brain, including both amyloid-beta-rich and -poor regions, with slow washout of radioactivity (half-life, 82-185 minutes). In conclusion, these data provide important information on the blood-brain barrier penetration and metabolism of an investigational antiamyloid drug and suggest that the PET microdosing approach is a useful method to describe the target-organ pharmacokinetics of radiolabeled drugs in humans.

Kropiunigg U, Sebek K, Leonhardsberger A, Schemper M, Dal-Bianco P. · Institut für Medizinische Psychologie, Universität Wien. · Psychother Psychosom Med Psychol. · Pubmed #10396132 No free full text.

Abstract: Psychosocial stress has been shown to contribute to neurodegenerative changes and has been discussed as a pathogenic element in Alzheimer's disease (AD). However, studies investigating this aspect are rare. We performed a case-control study on 50 clinically diagnosed probable AD patients and 90 controls consisting of surgical patients. Interviews were performed by trained personnel, using a questionnaire, a semi-structured interview, and a psychosocial risk list protocol. Findings are presented as marginal and partial odds ratio from linear logistic regressions. Adapting to an active but unproductive working style as well as living with a dominant spouse is associated with significant risk for AD. Protective factors are high self-esteem and working in one's desired job. Our results indicate psychosocial factors as a possible agent in the latent development of AD and may shift the focus from more traditional risk factors to hitherto almost neglected psychosocial factors in a disease of still unknown etiology.

Rösler M, Anand R, Cicin-Sain A, Gauthier S, Agid Y, Dal-Bianco P, Stähelin HB, Hartman R, Gharabawi M. · Sektion Gerontopsychiatric, Psychiatrische Universitätsklinik, Fuchsleinstrasse 15, D 97080 Würzburg, Germany. · BMJ. · Pubmed #10066203 links to  free full text

Abstract: OBJECTIVES: To assess the effects of rivastigmine on the core domains of Alzheimer's disease. DESIGN: Prospective, randomised, multicentre, double blind, placebo controlled, parallel group trial. Patients received either placebo, 1-4 mg/day (lower dose) rivastigmine, or 6-12 mg/day (higher dose) rivastigmine. Doses were increased in one of two fixed dose ranges (1-4 mg/day or 6-12 mg/day) over the first 12 weeks with a subsequent assessment period of 14 weeks. SETTING: 45 centres in Europe and North America. PARTICIPANTS: 725 patients with mild to moderately severe probable Alzheimer's disease diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, and the criteria of the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association. OUTCOME MEASURES: Cognitive subscale of the Alzheimer's disease assessment scale, rating on the clinician interview based impression of change incorporating caregiver information scale, and the progressive deterioration scale. RESULTS: At the end of the study cognitive function had deteriorated among those in the placebo group. Scores on the Alzheimer's disease assessment scale improved in patients in the higher dose group when compared with patients taking placebo (P<0.05). Significantly more patients in the higher dose group had improved by 4 points or more than had improved in the placebo group (24% (57/242) v 16% (39/238)). Global function as rated by the clinician interview scale had significantly improved among those in the higher dose group compared with those taking placebo (P<0.001), and significantly more patients in the higher dose group showed improvement than did in the placebo group (37% (80/219) v 20% (46/230)). Mean scores on the progressive deterioration scale improved from baseline in patients in the higher dose group but fell in the placebo group. Adverse events were predominantly gastrointestinal, of mild to moderate severity, transient, and occurred mainly during escalation of the dose. 23% (55/242) of those in the higher dose group, 7% (18/242) of those in the lower dose group, and 7% (16/239) of those in the placebo group discontinued treatment because of adverse events. CONCLUSIONS: Rivastigmine is well tolerated and effective. It improves cognition, participation in activities of daily living, and global evaluation ratings in patients with mild to moderately severe Alzheimer's disease. This is the first treatment to show compelling evidence of efficacy in a predominantly European population.

Lehrner J, Gufler R, Guttmann G, Maly J, Gleiss A, Auff E, Dal-Bianco P. · University Clinic of Neurology, Medical University of Vienna, Vienna, Austria. · Wien Klin Wochenschr. · Pubmed #16416345 No free full text.

Abstract: OBJECTIVE: The goals of this study were to determine the annual conversion rate to Alzheimer disease (AD) among patients reporting memory problems, including a subgroup with amnestic mild cognitive impairment (aMCI), and to investigate the predictive value of neurocognitive testing for future dementia. METHODS: A prospective study was carried out in an outpatient memory clinic. One hundred and seven patients underwent a clinical examination and completed a battery of standard cognitive tests at study entry and two years later. The conversion rate to clinically manifested AD two years later was investigated and sensitivity, specificity, receiver operating characteristics (AUC), positive predictive value and negative predictive value for each neuropsychological test were determined. RESULTS: We found an annual rate of conversion to AD of 6.5% among patients reporting memory decline in the setting of our clinic. Specifically, patients with aMCI had an annual conversion rate of approximately 20%. The annual conversion rate for patients reporting memory problems but showing no memory deficit at memory testing was approximately 3%. Receiver operating characteristics (AUC) of the neuropsychological tests ranged from 0.60 to 0.94. CONCLUSIONS: Patients with aMCI have 8.6-fold higher odds of developing AD compared with patients without evident memory impairment on neuropsychological testing. Although the risk of developing AD among patients without objective memory decline is small, some patients in this group still convert to AD and therefore close clinical monitoring of patients is necessary.

Dal-Bianco P. · Universitätsklinik für Neurologie, Währinger Gürtel 18-20, A-1090 Wien. · Wien Med Wochenschr. · Pubmed #11925772 No free full text.

Abstract: Owing to the progress of individual life expectancy, the number of demented people will clearly increase in the next decades. Cognitive impairment refers not only to dementia, but also to mild cognitive impairment (MCI), associated with reduced complex daily activity and decreased quality of live. It may, in many cases (10-15% per year) progress to permanent dementia. The most frequent aetiologies of dementia syndromes are the Alzheimer's Disease (AD), vascular Dementia (VD), the combination of both and Lewy-Body-Disease. Primarily neuro-psychiatric and internal medical reasons for cognitive decline have also to be taken into account for rational treatment.