APOLIPOPROTEIN-E GENOTYPE INFLUENCES COGNITIVE PHENOTYPE IN PATIENTS WITH ALZHEIMERS-DISEASE BUT NOT IN HEALTHY CONTROL SUBJECTS

We examined the association of apolipoprotein E (apo E) genotype with cognitive performance in Alzheimer's disease (AD) and Mild Cognitive I mpairment (MCI) patients and in normal subjects. One hundred fifty-sev en AD patients, 35 MCI patients who developed AD during longitudinal f ollow-up, and 341 normal control subjects from the Mayo Clinic Alzheim er's Disease Patient Registry were studied. All participants were type d for apo E using polymerase chain reaction-based assay. epsilon 4+ an d epsilon 4- groups were compared on cognitive factor scores of Verbal Comprehension, Perceptual Organization, Attention/Concentration, Lear ning, and Retention. Raw delayed verbal recall and visual confrontatio n naming scores supplemented these scores. Multivariate ANOVA was comp leted for cognitive scores. As expected, a main effect for diagnostic group was present across all scores. Multivariate main effects for age group and apo E genotype were also statistically significant. Subsequ ent within-group comparisons revealed no genotype differences for cont rol subjects across all cognitive scores except raw delayed recall whe re an interaction indicated that older epsilon 4+ control subjects act ually scored better than younger epsilon 4+ patients. Genotype differe nces were present for the Retention factor in the MCI sample and for V erbal Comprehension and Learning in the AD sample. In a combined cogni tive impairment sample (AD + MCI), genotype differences were present f or Verbal Comprehension, Learning, and Retention. Possession of an apo E epsilon 4 allele did not appear to be associated with poorer cognit ive performance among normal control subjects. In the AD and MCI sampl es, epsilon 4+ status was associated with greater memory impairment in analyses including duration of illness as a covariate. In combined AD + MCI analyses, epsilon 4 homozygosity was associated with poorer ret ention, learning, and verbal comprehension at a given disease duration . Possession of the epsilon 4 genotype may influence cognition in a do se-response relationship.