| Popis: |
Although the use of apolipoprotein E (APOE) genotyping in the diagnosis of Alzheimer’s disease (AD) is controversial,’ the consensus statement on APOE genotyping in ADZ suggests that this test may be of some value in predicting response to drug treatments for AD. We carried out APOE genotyping in a multicentre, multinational, double-blind, randomised, placebo-controlled trial in AD. The drug S12024 tested in this phase IIb clinical trial facilitates brain noradrenergic and vasopressinergic activity. Experimental evidence of cognitive enhancement in animals suggested that this substance might lead to symptomatic improvement in some cases of AD. In people, the drug had a good clinical and biological safety profile, and increased speed and accuracy of response on computerised tests of memory and attention were ob~erved.~ In six countries, 404 patients with probable AD (NINCDS-ADRDA classification) were randomised to three groups: placebo, 100 mg daily of S12024, or 300 mg daily of S12024. The treatment period lasted 12 weeks. In 339 patients, the APOE genotype was done with the promise that no genetic data would be transferred back to the patient, carer, or physician whatever the circumstances. The mean (SD) age of the patients was 69-9 (7.9) years, with an age at onset of the disease of 66.6 (8.1) years. The mean (SD) Mini Mental State Examination score (MMSE) was 19.5 (3.5). No significant differences existed between the genotyped and non-genotyped patients; 60% of them carried at least one APOE ~4 allele, 14% were homozygous. The ~ 4 , ~ 3 , and ~ 2 , allele frequencies were 0.37, 0.60, and 0.03, respectively. The 300 mg daily dose produced frequent adverse effects and early withdrawals, and was not considered any further in the analyses. With an intention-to-treat analysis of the whole sample, the 100 mg daily dose did not produce results that differed from placebo. The sample was stratified for the presence or absence of the APOE ~4 allele. In those with the &4 allele |
