NEUROLOGY 1998;50:355-362
© 1998 American Academy of Neurology
Apolipoprotein E genotype influences cognitive ‘phenotype’ in patients with Alzheimer's disease but not in healthy control subjects
G. E. Smith, PhD,
D. L. Bohac, PhD,
S. C. Waring, PhD,
E. Kokmen, MD,
E. G. Tangalos, MD,
R. J. Ivnik, PhD and
R. C. Petersen, PhD, MD
From the Departments of Psychiatry and Psychology (Drs. Smith, Bohac, and Ivnik), Health Sciences Research (Dr. Waring), Neurology (Drs. Kokmen and Petersen), and Internal Medicine (Dr. Tangalos), Mayo Clinic and Mayo Foundation, Rochester, MN.
Address correspondence and reprint requests to Dr. Glenn E. Smith, Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN 55905
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.  4+ and 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 4+ control subjects actually scored better than younger 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 4 allele did not appear to be associated with poorer cognitive performance among normal control subjects. In the AD and MCI samples, 4+ status was associated with greater memory impairment in analyses including duration of illness as a covariate. In combined AD + MCI analyses, 4 homozygosity was associated with poorer retention, learning, and verbal comprehension at a given disease duration. Possession of the 4 genotype may influence cognition in a dose-response relationship.
Received May 30. 1997. Accepted in final form September 9, 1997.
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