APOE genotype: No influence on galantamine treatment efficacy nor on rate of decline in Alzheimer's disease

Apolipoprotein E (APOE) has been extensively demonstrated to be a genetic r isk factor for Alzheimer's disease (AD). Associations of APOE genotype have been reported with age at AD onset, rate of decline, and responsiveness to therapy. This study aimed to test these hypotheses in a large study popula tion of AD patients. APOE genotype was determined from 1,528 Caucasian subj ects, diagnosed by NINCDS/ADRDA criteria as probable AD patients, enrolled in four international placebo-controlled clinical trials of 3-12 months dur ation, designed to evaluate efficacy of treatment with galantamine or sabel uzole. In addition to patient demographics and baseline scores for Mini Men tal State Examination, scores on the Disability Assessment for Dementia (DA D) and the cognitive subscale of the Alzheimer's Disease Assessment Scale ( ADAS-cog) were recorded at the start, during, and at the end of the study. APOE epsilon4 homozygotes had a significantly lower age at disease onset co mpared to patients with other APOE genotypes. The epsilon4 allele was signi ficantly over-represented in females compared to mates, and in the group of subjects with an AD family history. Based on longitudinal data of 504 plac ebo-treated AD patients, the linear annual rate of change in score was 5 po ints on the ADAS-cog scale and 11 on the DAD scale. The epsilon4 allele cop y number did not influence these rates of decline. Sabeluzole treatment was not effective in the overall group compared to the placebo-treated group, nor in any subgroup stratified by epsilon4 allele count. Galantamine produc ed cognitive and functional improvement that were not affected by epsilon4 allele count. In conclusion, our data confirm a strong association between epsilon4 homozygotes and age at onset of AD but do not support an effect of epsilon4 allele copy number on rate of cognitive and functional decline no r on the efficacy of galantamine in patients with AD. Copyright (C) 2001 S. Karger AG, Basel.