title: Oral tetrahydroaminoacridine treatment of Alzheimer's disease evaluated clinically and by regional cerebral blood flow and EEG.
abstract: Neurochemical evidence indicates that cognitive impairment in dementia of Alzheimer type (DAT) is related to degeneration of cholinergic neurons in the brain. A pharmacological approach is treatment with a cholinesterase inhibitor such as tetrahydroaminoacridine (THA). THA treatment of 17 patients with DAT was studied with a double-blind crossover design with three types of treatment, THA + lecithin, THA + placebo and placebo + placebo. Each treatment period was 6 weeks with wash out periods of 2 weeks. The treatment was evaluated with clinical ratings, psychometric testing, EEG and regional cerebral blood flow (rCBF) measurements. No significant clinical differences between treatment periods were found in the total sample, but marked individual differences were observed. The patients were subdivided into three outcome groups based on four clinical measures: 6 patients improved (responders), 5 patients were mainly unchanged, and 6 patients showed further deterioration during the trial period of 26 weeks. Pretreatment rCBF in responders differed significantly from that of the deteriorated patients. EEG showed more high frequency activity among responders. Hepatotoxic side effects were observed in several cases. Three subjects showed marked increases of liver enzymes, with normalization following dose reduction. The majority of patients who improved or remained unchanged during the study chose to continue THA treatment in an open trial.
authors.affiliation: Department of Psychogeriatrics, Hospital Pharmacy, University of Lund, Sweden.
authors.forename: L
authors.initials: L
authors.lastname: Minthon
authors.forename: L
authors.initials: L
authors.lastname: Gustafson
authors.forename: G
authors.initials: G
authors.lastname: Dalfelt
authors.forename: B
authors.initials: B
authors.lastname: Hagberg
authors.forename: K
authors.initials: K
authors.lastname: Nilsson
authors.forename: J
authors.initials: J
authors.lastname: Risberg
authors.forename: I
authors.initials: I
authors.lastname: Rosén
authors.forename: B
authors.initials: B
authors.lastname: Seiving
authors.forename: P E
authors.initials: PE
authors.lastname: Wendt
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D056486:Chemical and Drug Induced Liver Injury / Q000201:enzymology; D004311:Double-Blind Method; D004569:Electroencephalography / Q000187:drug effects*; D005260:Female; D006801:Humans; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010713:Phosphatidylcholines / Q000627:therapeutic use; D013619:Tacrine / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D010713:Phosphatidylcholines; D013619:Tacrine