Alzheimer Disease: Boada-Rovira M

Boada-Rovira M, Hernández-Ruiz I, Badenas-Homiar S, Buendía-Torras M, Tárraga-Mestre L. · Fundació ACE, Institut Català de Neurociències Aplicades, Barcelona, Spain. · Rev Neurol. · Pubmed #16047294 links to  free full text

Abstract: INTRODUCTION: People with Down syndrome have an early aging process, especially form their 40s. There is a significant average of them who initiate, from that age on, a progressive decline of their cognitive and functional abilities, due to a primary degenerative process Alzheimer's disease type. When assessing response to treatment with, pilot clinical trials on this population have demonstrated real benefits therapeutically. AIMS: To assess the efficacy and safety of a pharmacological treatment with donepezil over cognitive and behavioral disturbances on patients with Down syndrome older than 40 years, areas where family and professional educators of reference have observed cognitive and behavioral changes in comparison with their previous level of disability. PATIENTS AND METHODS: Patients have been selected from different institutions affiliated at the Catalan Foundation for the Down syndrome and by the Catalan Federation Pro Persons with Psychic Disability. Several deterioration, behavioral and functional assessment scales have been used, all of them validated into this population. RESULTS: The results of study demonstrated that donepezil slowed the progression of the cognitive dysfunction, especially during the first three months of treatment. This occurred for both cognitive and social-behavioral outcomes. CONCLUSIONS: Donepezil appears to be effective in the treatment of cognitive and behavioural disturbances associated with the progressive dementia syndrome in Down's. However, the sample sizes used in this, and all published studies are small and this emphasizes the need for a larger, multi-center trial to fully evaluate the nature and extent of the response of Down's syndrome patients to anticolinesterase therapy.

Castañé M, Boada-Rovira M, Hernández-Ruíz I. · Department d'Optica i Optometria, Universitat Politècnica de Catalunya, Terrassa, Spain. · Rev Neurol. · Pubmed #15597262 links to  free full text

Abstract: AIMS: The purpose of this study was to determine the refractive status and ocular health of a group of patients with Down's syndrome, all over the age of 40, with possible involvement of Alzheimer's disease (AD). We also aimed to compare the results obtained from sufferers and non-sufferers of the disease. PATIENTS AND METHODS: We examined 49 patients, between 40 and 62 years of age. The visual examination consisted in visual acuity (VA) measurement, binocularity test, ocular motility, retinoscopy, ocular health and subjective examination. RESULTS: Of the 49 patients studied, 24.5% were diagnosed as suffering from AD and were treated accordingly; 4% of the patients diagnosed as suffering from the disease were unable to go on with the treatment for a number of different reasons and 8.2% were at the limit of being diagnosed. 68.7% of the patients presented VA in long distance sight below 0.5 and 48% had values below 0.4 in near sight. Results showed 61.4% myopias, 45.8% astigmatisms and 23% hyperopias. 31.2% of the patients showed signs of needing prescription regarding near sight. 66.7% presented strabismus and altered motility. The main pathologies found were: 59.4% of crystalline opacities, 25% nystagmus, 13.5% interventions due to cataracts, and 6.2% keratoconus, among others. CONCLUSIONS: Diagnosis of AD is a very complex task in this population due to the heterogeneity of the level of retardation, the presence of concomitant psychiatric diseases and associated sensory problems. Findings confirm the high incidence among this population of ametropias and pathologies, especially cataracts, and VA values outside the functional limits both in far and near sightedness. No significant differences were found among patients who had been diagnosed and those who had not been diagnosed as suffering from AD.

Boada-Rovira M, Brodaty H, Cras P, Baloyannis S, Emre M, Zhang R, Bahra R, Anonymous00040. · Fundació ACE, Barcelona, Spain. · Drugs Aging. · Pubmed #14715043 No free full text.

Abstract: BACKGROUND: Donepezil has consistently been shown to be effective and well tolerated in the symptomatic treatment of Alzheimer's disease in placebo-controlled clinical trials. It has been shown to provide significant benefits in cognition, global function and activities of daily living in patients with mild-to-moderate Alzheimer's disease. However, in order to control for confounding factors, some clinical trials of donepezil have excluded patients with comorbid illness and concomitant medication use. OBJECTIVE: The objective of this study was to evaluate the efficacy, tolerability and safety of donepezil in a wider and more diverse sample of patients and centres than previous trials, reflecting routine clinical practice. METHODS: In this 12-week, open-label, multicentre trial, patients with probable mild-to-moderate Alzheimer's disease received donepezil 5 mg/day for 28 days, after which the dosage was increased to 10 mg/day according to the investigating clinician's judgement. Patients were enrolled at 246 study centres in 18 countries worldwide. Cognition was assessed by a trained clinician using the Mini-Mental State Examination (MMSE) at baseline, week 4 and week 12 (or last visit). Changes in patient activity and social interaction were evaluated using a caregiver diary. Each week, caregivers recorded their impression of change compared with baseline on three aspects of patient behaviour using a 5-point scale. Efficacy analyses were performed on the intent-to-treat population. Significance was determined using the paired t-test (0.05 significance level). Tolerability and safety were assessed by monitoring adverse events, physical examinations, vital signs, clinical laboratory test abnormalities and ECG findings throughout the study. RESULTS: A total of 1113 patients received donepezil (mean baseline MMSE score [+/-SD] 18.74 +/- 5.21). 989 (88.9%) patients completed the study; 59 (5%) patients discontinued because of adverse events. Most patients were taking at least one concomitant medication (n = 802; 72%) and had at least one comorbid medical condition (n = 745; 67%) on study entry. Donepezil significantly improved cognition compared with baseline at weeks 4 and 12, and at week 12 using a last observation carried forward (LOCF) analysis (all p < 0.0001). Mean change from baseline MMSE score (+/-SE) at week 12-LOCF was +1.73 +/- 0.10. Donepezil was also associated with significant improvements in patient social interaction, engagement and interest, and initiation of pleasurable activities at all weekly assessments and week 12-LOCF (all p < 0.0001). Donepezil was generally well tolerated; adverse events were consistent with the known safety profile of donepezil. CONCLUSION: Donepezil treatment resulted in statistically significant improvements in cognition and patient activity and social behaviour, and was generally well tolerated despite high levels of comorbid illness and concomitant medication use. The results of this open-label study in a large patient population are consistent with those from controlled trials and support that donepezil is effective in the treatment of mild-to-moderate Alzheimer's disease in everyday practice.