title: Apolipoprotein E genotype influences cognitive 'phenotype' in patients with Alzheimer's disease but not in healthy control subjects.
abstract: We examined the association of apolipoprotein E (apo E) genotype with cognitive performance in Alzheimer's disease (AD) and Mild Cognitive Impairment (MCI) patients and in normal subjects. One hundred fifty-seven AD patients, 35 MCI patients who developed AD during longitudinal follow-up, and 341 normal control subjects from the Mayo Clinic Alzheimer's Disease Patient Registry were studied. All participants were typed for apo E using polymerase chain reaction-based assay, epsilon 4+ and epsilon 4- groups were compared on cognitive factor scores of Verbal Comprehension, Perceptual Organization, Attention/Concentration, Learning, and Retention. Raw delayed verbal recall and visual confrontation naming scores supplemented these scores. Multivariate ANOVA was completed 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. Subsequent within-group comparisons revealed no genotype differences for control subjects across all cognitive scores except raw delayed recall where an interaction indicated that older epsilon 4+ control subjects actually scored better than younger epsilon 4+ patients. Genotype differences were present for the Retention factor in the MCI sample and for Verbal Comprehension and Learning in the AD sample. In a combined cognitive impairment sample (AD + MCI), genotype differences were present for Verbal Comprehension, Learning, and Retention. Possession of an apo E epsilon 4 allele did not appear to be associated with poorer cognitive performance among normal control subjects. In the AD and MCI samples, 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 retention, learning, and verbal comprehension at a given disease duration. Possession of the epsilon 4 genotype may influence cognition in a dose-response relationship.
authors.affiliation: Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: G E
authors.initials: GE
authors.lastname: Smith
authors.forename: D L
authors.initials: DL
authors.lastname: Bohac
authors.forename: S C
authors.initials: SC
authors.lastname: Waring
authors.forename: E
authors.initials: E
authors.lastname: Kokmen
authors.forename: E G
authors.initials: EG
authors.lastname: Tangalos
authors.forename: R J
authors.initials: RJ
authors.lastname: Ivnik
authors.forename: R C
authors.initials: RC
authors.lastname: Petersen
mesh_terms: D000368:Aged; D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics* / Q000523:psychology*; D001057:Apolipoproteins E / Q000235:genetics*; D001288:Attention; D003071:Cognition; D003072:Cognition Disorders / Q000235:genetics* / Q000523:psychology; D016001:Confidence Intervals; D005260:Female; D005838:Genotype; D006801:Humans; D007858:Learning; D008297:Male; D008568:Memory; D010465:Perception; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012016:Reference Values; D013060:Speech
chemical_list: D001057:Apolipoproteins E