TOMM40 '523 Associations with Baseline and Longitudinal Cognition in APOE ε3 Homozygotes

TOMM40 '523 is associated with Alzheimer's disease (AD), but APOE linkage disequilibrium confounds this association. In 170 APOE epsilon 3 homozygotes, we evaluated relationships between short and very long TOMM40 alleles and longitudinal declines in three cognitive domains (attention, verbal memory, and executive function). We used factor analysis to create composite scores from 10 individual cognitive tests, and latent growth curve modeling adjusting for clinical status (normal, amnestic mild cognitive impairment, or AD) to summarize initial performance and change over three years. Relative to individuals with two very long TOMM40 alleles, APOE epsilon 3 homozygotes with one or two short alleles showed lower baseline cognitive performance regardless of clinical status. The number of short or very long TOMM40 alleles was not associated with longitudinal cognitive changes. In APOE epsilon 3 homozygotes from the University of Kansas Alzheimer's Disease Center cohort, an association between TOMM40 '523 and cognition is consistent with the possibility that TOMM40 influences cognition independent of APOE.