Affiliations: [a] University of Kansas Alzheimer’s Disease Center, Kansas City, KS, USA
| [b] Department of Psychology, University of Kansas, Lawrence, KS, USA
| [c] Department of Pharmacology and Toxicology, University of Kansas, Lawrence, KS, USA
| [d] Department of Neurology, University of Kansas Medical Center, Kansas City, KS, USA
| [e] Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS, USA
| [f] Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, KS, USA
Correspondence to: Amber Watts, PhD, University of Kansas Alzheimer’s Disease Center, 4350 Shawnee Mission Parkway, Fairway, KS 66205 USA. Tel.: +1 913 588 0555; Fax: +1 913 588 0681; E-mail: [email protected].
Abstract: TOMM40 ‘523 is associated with Alzheimer’s disease (AD), but APOE linkage disequilibrium confounds this association. In 170 APOE ɛ3 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 ɛ3 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 ɛ3 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.