Alzheimer Disease: Stähelin HB

Stähelin HB. · Geriatrische Universitätsklinik, Kantonsspital Basel. · Schweiz Med Wochenschr. · Pubmed #10635084 No free full text.

Abstract: Several factors lead to a higher number of female patients with Alzheimer's disease, and thus prevention and treatment are of particular concern to women. Given the slow development of histopathological alterations in Alzheimer's disease, prevention should start early in life. Several lines of evidence document in vitro and in vivo a protective effect of oestrogen on neurons. Women substitute oestrogen during the immediate postmenopausal years, and this offers a natural experiment for testing the preventive action of oestrogen against Alzheimer's disease. Case control studies and cohort studies support a general protective effect of hormone (i.e. oestrogen) replacement therapy (HRT). Short-term and small-scale intervention trials in patients with Alzheimer's disease show positive results. However, it is not clear to what extent cognition is improved by the known effects of oestrogen on mood and behavioural symptoms. More studies are needed to establish the value of oestrogen replacement therapy in primary and secondary prevention of Alzheimer's disease. At present, oestrogen can be recommended in women at risk for familial Alzheimer's disease and as adjuvant therapy in mild early Alzheimer's disease.

Stähelin HB. · Clinique universitaire de gériatrie, Hôpital cantonal, Bâle. · Rev Med Suisse Romande. · Pubmed #10361469 No free full text.

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Bertoli S, Stähelin HB. · Geriatrische Universitätsklinik, Kantonsspital Basel. · Ther Umsch. · Pubmed #10095376 No free full text.

Abstract: New drugs are available now for the specific treatment of Alzheimer's disease. The lack of acetylcholine plays an important role in the pathophysiology of this disease. Centrally acting cholinesterase-inhibitors may prolong the action of acetylcholine and thus induce a temporary improvement or stabilization of cognitive performance. The disease progression continues; however, to a lesser extent than without therapy. The need for a patient to enter a nursing home can be delayed by one year on average. Nootropica may also have some modest success in treating cognitive dysfunctions, but the effect size is relatively small. Several agents, such as estrogens, anti-inflammatory drugs and antioxidants, are being investigated for their potential use in Alzheimer's disease, and additional drugs might be available for the treatment of this disease in the near future.

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.

Berres M, Monsch AU, Bernasconi F, Thalmann B, Stähelin HB. · Novartis Pharma AG, WSJ-27.5.016, CH-4002 Basel, Switzerland. · Stud Health Technol Inform. · Pubmed #11187541 No free full text.

Abstract: The diagnosis of early stage dementia is a highly complex process involving not only a somatic examination but also a neuropsychological assessment of the patient's cognitive capability. The American 'Consortium to Establish a Registry for Alzheimer's Disease' (CERAD) has proposed a set of tests in English which has been translated into German. This paper presents the statistical methodology applied to determine normal ranges adjusted for demographic variables for the German CERAD neuropsychological assessment battery (CERAD-NAB). The study population consists of participants of the Basel Study on the Elderly (Project BASEL) which aims at identifying preclinical markers of Alzheimer's disease. The normative sample has been defined by carefully excluding potentially relevant medical history and concomitant diseases and consists of 617 participants which are between 53 and 92 years old. Test results should be adjusted for gender, age, and years of education. For this purpose, a set of linear models including these predictors and subsets of their interactions and squares was evaluated for all 11 test scores derived from the CERAD-NAB battery. Model selection was based on the PRESS (predicted residual sum of squares) statistic. Although a strict application of this criterion selected 6 different models, a slight compromise allowed to fit all test scores by two models. In several tests of the CERAD-NAB many participants achieve maximal scores. Residuals of such test scores are heavily skewed. An arcsine transformation has been tuned to the data, so that residuals are close to a normal distribution, at least for residuals in the lower quartile which is relevant in diagnosing cognitive impairment. Test results are finally presented as z-scores which can be easily compared to a standard normal distribution. The evaluation of the CERAD-NAB is implemented on the Internet and in an Excel application.