Oral Tetrahydroaminoacridine in Long-Term Treatment of Senile Dementia, Alzheimer Type

We treated 17 patients who had moderate to severe Alzheimer's disease with oral tetrahydroaminoacridine (THA), a centrally active anticholinesterase, in a three-phase study. In the nonblinded first phase of the study, significant improvement occurred in subjects who received the drug, as compared with their pretreatment status, on the global assessment (P = 0.001), the Orientation Test (P = 0.001), and the more sophisticated Names Learning Test (P = 0.001). During the second phase, the subjects served as their own controls in a double-blind, placebo-controlled, cross-over study in which the order of administration of the drug and placebo was randomly assigned. Among the 14 subjects completing Phase II, THA treatment produced significantly better results than placebo on the global assessment (P = 0.003), the Orientation Test (P = 0.004), the Alzheimer's Deficit Scale (P = 0.003), and the Names Learning Test (P = 0.001). Twelve subjects have entered Phase III, which involves long-term administration of oral THA. The average duration of treatment in these subjects at present is 12.6 months; symptomatic improvements have occurred, and no serious side effects attributable to THA have been observed. These encouraging initial results suggest that THA may be at least temporarily useful in the long-term palliative treatment of patients with Alzheimer's disease. We stress that further observations will be required before a clear assessment of the role of this agent can be made. (N Engl J Med 1986; 315:1241–5.) DEMENTIA of the Alzheimer type is a slowly progressive neuropsychiatric condition that is principally manifested by memory deficits and that results in death from debilitating disease in 6 to 12 years. 1 Although its cause is unknown, some specific neurochemical and anatomical lesions have been observed. In 1976 Davies and Maloney demonstrated a specific deficit in choline acetyltransferase in autopsy material from patients with Alzheimer's disease. 2 This enzyme is responsible for the formation of acetylcholine from choline and acetyl-coenzyme A. The findings of Davies and Maloney have been confirmed by several other investigators. 3 4 5 6 Coyle et al. demonstrated a selective loss of . . .