We studied the efficacy and safety of oral tetrahydroaminoacridine (THA) combined with lecithin in 52 patients with Alzheimer's disease. The maximal tolerated dose of THA (up to 100 mg per day) was determined during an eight-week titration period, after which the tolerated dose of THA or placebo was given during two sequential randomized periods of treatment lasting eight weeks each. Highly purified lecithin (4.7 g per day) was administered during all phases of the study. Efficacy was expressed in terms of scores on the Mini-Mental State (MMS) test, the modified MMS test, the Hierarchic Dementia Scale, the Rapid Disability Rating Scale-II, and the behavioral scale of Reisberg et al. Safety was assessed by careful clinical monitoring as well as serial measurements of liver aminotransferases. Forty-six patients completed the titration period, and 39 completed the double-blind period, during which only the MMS score showed a small but significant increase (P less than 0.05) after four weeks of treatment with THA. Autonomic side effects of THA were common but mild. Reversible elevations of serum aspartate and alanine aminotransferase levels to three or more times the upper limit of normal occurred in 17 percent of patients; most of the patients affected were women. A liver biopsy performed in one patient showed resolving focal liver-cell necrosis. These studies fail to demonstrate a significant clinical benefit of THA given orally in a maximal dose of 100 mg per day over a period of eight weeks in combination with lecithin.

Background: With the aging of the population, dementia is increasing worldwide. The objective of this study was to identify risk factors for dementia in an elderly population utilizing a primary health care service in Dakar, Senegal. Methods: Through a cross-sectional study conducted from March 2004 to December 31, 2005, 507 elderly patients aged ≥65 years who came to the Social and Medical Center of IPRES, Dakar, Senegal, were first screened with the screening interview questionnaire ‘Aging in Senegal’. Those who were cognitively impaired underwent a clinical examination to detect dementia. Univariate, bivariate, and multivariate logistic regression analyses were done. Results: The whole population had a mean age of 72.4 years (±5.2) and was mostly male, married, and non-educated. Hypertension, arthritis, and gastrointestinal diseases were the main health conditions reported in the past medical history. Smoking was important while alcohol consumption was rare. Social network was high. Forty-five patients (8.87%) had dementia. In the multivariate model, only advanced age, education, epilepsy, and family history of dementia were independently associated with dementia. Conclusion: The risk factors identified are also found in developed countries confirming their role in dementia. It is important to take dementia into consideration in Senegal and to sensitize the community for prevention.

Since the discovery of a significant depletion of acetylcholine in discrete areas of the brain of patients affected by Alzheimer's disease, attempts at symptomatic therapy have concentrated on acetylcholine supplementation, an approach that is based upon the efficacy of dopaminergic supplementation therapy for Parkinson's disease. Choline, then lecithin, used orally, failed to improve symptoms but the hypothesis that long-term choline supplementation might stabilize the course of Alzheimer's disease remains to be tested. Nerve growth factor may also offer that possibility. Bethanechol administered intracerebroventricularly did not help when a fixed dose was used but individual titration of more selective muscarinic agonists may prove more effective. In this article we report that tetrahydroaminoacridine (THA), given together with highly concentrated lecithin, appears to bring improvement in cognition and in functional autonomy using the Mini Mental State and the Rapid Disability Rating Scale-2 respectively, without change in behavior as reflected by the Behave-AD. Double-blind cross-over studies are in progress to establish its efficacy. Improvement in study design and means of assessment of cognition, functional autonomy and behavior have been made possible by these drug trials. RESUME: Rapport d'etape sur 1'etude multicentrique Canadienne avec tetrahydroaminoacridine et lecithine pour la maladie d'Alzheimer. Depuis la d6couverte d'une perte substantcielle d'acetylcholine dans certaines regions du cerveau de patients souffrant de maladie d'Alzheimer, les essais pour traitment symptomatique ont vis6 a supplier l'ac6tylcholine, une approche fondee sur le succes de la supplementation en dopamine pour la maladie de Parkinson. La choline, puis la lecithine orale n'ont pas ameliore de symptomes mais l'hypothese qu'un supplement a long-terme de choline pourrait stabiliser devolution de la maladie d'Alzheimer reste a verifier. Le facteur de croissance neuronale pourrait 6galement agir en ce sens. Le bethanechol administre par voie intraventriculaire n'a pas aide lorsqu'administre' a une dose fixe mais une titration individuelle utilisant des agonistes muscariniques plus selectifs pourrait s'aveYer plus efficace. Dans cette publication nous rapportons que la tetrahydroaminoacridine avec lecithine hautement concentree semble ameliorer l'intellect et l'autonomie fonctionnelle tel que reflate par le Mini Mental State et la Rapid Disability Rating Scale-2 respectivement. Des etudes en double-insu avec chasse-croise sont en cours pour confirmer son efficacite. Des ameliorations dans le design des etudes et les mesures de fonctions intellectuelles, dautonomie fonctionnelle, de comportement et d'humeur ont ete rendues possibles par ces essais cliniques.

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