No 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.

This study was designed to assess the effects of rivastigmine (Exelon^®) on the cognitive functioning of patients suffering from dementia with Lewy bodies. This was a prospective, multi-centre, randomised, double-blind, placebo-controlled exploratory study conducted at sites in the UK, Spain and Italy. The treatment period was 20 weeks with a 3-week posttreatment follow-up. The primary outcome measures were the Cognitive Drug Research (CDR) computerised assessment system and the Neuropsychiatric Inventory. Testing was conducted prior to dosing and then again at weeks 12, 20 and 23. Analysis of the data from the 92 patients who completed the study identified a significant pattern of benefits of rivastigmine over placebo on the CDR system. These benefits were seen on tests of attention, working memory and episodic secondary memory. Taking attention for example, patients given placebo showed a significant deterioration from predosing scores at 12 and 20 weeks, whereas patients on rivastigmine performed significantly above their predosing levels. These effects were also large in magnitude, the decline under placebo at week 12 being 19%, while the improvement under rivastigmine was 23%. The clinical relevance of this 23% improvement was that it took the patients 33% towards being normal for their age on this assessment of attention. These benefits to cognitive function were accompanied by a significant improvement of the other primary outcome measure, the Neuropsychiatric Inventory. Three weeks after discontinuation of rivastigmine, most parameters of cognitive performance returned to predrug levels.

To identify subunit variants of the GABAA-receptor antisera were developed against specific cDNA-derived peptide sequences of the alpha 1- and alpha 3-subunits of rat brain. The alpha 1-subunit antiserum selectively recognized a protein of 50 +/- 1 kDa in rat and bovine GABAA-receptor preparations, while the alpha 3-subunit antiserum interacted with a protein doublet of 59 +/- 2 kDa and 61 +/- 3 kDa. The alpha 1-subunit immunoreactivity resides in a large population of GABAA-receptors as shown by immunoprecipitation of 63 +/- 6% of [3H]flumazenil binding sites with the alpha 1-subunit antiserum. In contrast, only 24 +/- 3% of receptor binding sites were precipitated with the alpha 3-subunit antiserum. Co-precipitation studies suggest that the alpha 1- and alpha 3-subunit immunoreactivities do not share the same receptor population while the gamma 2-subunit immunoreactivity is associated with the alpha 1-subunit immunoreactivity.

Objectives. To describe the baseline demographic, neuropsychiatric and neurological data of a large selected clinical sample of patients with dementia with Lewy Bodies (DLB) from an international multicentre trial with rivastigmine. To examine the usefulness of the Consensus Criteria for the diagnosis of DLB in different countries. Methods. Seventeen centres from Spain, the UK and Italy recruited patients diagnosed clinically as probable DLB according to recent Consensus Criteria (McKeith et al., 1996). A standard clinical protocol including inclusion/exclusion criteria, collection of demographic and medical data, cognitive (Mini Mental State Examination: MMSE), motor (Unified Parkinson's Disease Rating Scale: UPDRS) and neuropsychiatric (Neuropsychiatric Inventory: NPI) examinations, was applied after obtaining informed consent. Data were summarised and compared across countries with uni‐ and multivariate analyses. Results. One hundred and twenty patients were recruited: 56.7% males, mean (SD) age 73.9 (6.4) years, range 57 – 87 years. Sixty percent fulfilled all three core diagnostic features of DLB, and 40% only two (‘parkinsonism’ 92.4%, ‘cognitive fluctuations’ 89.1%, ‘visual hallucinations’ 77.3%). ‘Systematised delusions’ (46%) and ‘repeated falls’ (42%) were the most frequent supportive diagnostic features. There were no differences across countries in demographic, diagnostic or clinical features. Patients showed a wide range of psychopathology which was weakly correlated with cognitive impairment. Some mild extrapyramidal signs (EPS) were observed in most patients. Conclusions. The Consensus Criteria for DLB can be consistently applied across many different sites for multicentre studies. ‘Parkinsonism’ and ‘cognitive fluctuations’ as core features and ‘systematised delusions’ and ‘repeated falls’ as supportive features are the most frequent diagnostic clues. Neuropsychiatric disturbances, in particular apathy, delusions, hallucinations and anxiety, and mild symmetric EPS are frequent in DLB and are only related weakly to cognitive impairment. Copyright © 2000 John Wiley & Sons, Ltd.