Progress report on the Canadian Multicentre Trial of tetrahydroaminoacridine with lecithin in Alzheimer's disease.

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.

Tetrahydroaminoacridine-lecithin combination treatment in patients with intermediate-stage Alzheimer's disease. Results of a Canadian double-blind, crossover, multicenter study.

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.

Le Test Du Sénégal: Un Instrument Valide Et Fiable Pour Le Dépistage De La Démence Dans Une Population De Personnes Âgées Sénégalaises

"Description. Face au vieillissement de la population et au developpement de la demence; il est necessaire de disposer d'outil de depistage valide et fiable qui soit adapte au contexte socio-culturel. Objectif.Valider le Test du Senegal; un instrument de depistage de la demence aupres de la population agee senegalaise. Methode .Le Test du Senegal est un instrument de depistage de la demence incluant des items en rapport avec l'orientation; la memoire; l'attention/calcul; la praxie et le langage avec un score de 0-39 points. Sa validation s'est deroulee en deux phases aupres de personnes agees de 55 ans et plus frequentant le Centre Medicosocial et Universitaire de l'IPRES (Institut de Prevoyance Retraite du Senegal) pour des soins : 1) etude transversale aupres de 872 patients interviewes avec le questionnaire ""Vieillir au Senegal"" pour identifier les cas selon les criteres DSM IV-R; 2) une etude cas-temoins avec 116 patients (58 sujets dements et 58 temoins apparies par le sexe) pour la validation proprement dite. Le Test du Senegal a ete administre lors de la premiere phase; re-administre une semaine puis deux semaines apres lors de la deuxieme phase. La validite de critere; la validite de construit et la fidelite du test ont ete estimees. L'effet de l'age et de l'instruction sur la performance du test pour depister la demence a ete etudie avec des analyses de regression logistique. Resultat. Le Test du Senegal identifiait les cas de demence avec les caracteristiques suivantes au point de coupure de 28/29 : sensibilite : 93;1; specificite : 89;6; valeur predictive positive : 93;1; valeur predictive negative : 92;8; surface sous la courbe caracteristique de performance: 0;967; kappa : 0;82; coefficient de correlation intraclasse variant entre 0;67 et 0;87. L'age et l'education n'avaient aucune influence sur la performance au Test du Senegal. Conclusion Le Test du Senegal est un instrument valide et fiable pour le depistage de la demence dans la population agee senegalaise. Il pourra etre utilise comme outil de depistage de la demence dans les services de sante."