Longitudinal modeling of cognitive aging and the TOMM40 effect.

Journal Article (Journal Article)

BACKGROUND: TOMM40 (translocase of the outer mitochondrial membrane pore subunit) is in linkage disequilibrium with apolipoprotein E (APOE). APOE e4 is linked to long (L; 21-29 T residues) poly-T variants within intron 6 of TOMM40, whereas APOE e3 can be associated with either a short (S; <21 T residues) or very long (VL; >29 T residues) variant. To assess the possible contribution of TOMM40 to Alzheimer's disease onset, we compared the effects of TOMM40 and APOE genotype on preclinical longitudinal memory decline. METHODS: An APOE e4-enriched cohort of 639 cognitively normal individuals aged 21 to 97 years with known TOMM40 genotype underwent longitudinal neuropsychological testing every 2 years. We estimated the longitudinal effect of age on memory using statistical models that simultaneously modeled cross-sectional and longitudinal effects of age on the Auditory Verbal Learning Test Long-Term Memory score by APOE, TOMM40, and the interaction between the two. RESULTS: There were significant effects overall for both TOMM40 (linear effect, P = .04; quadratic effect, P = .03) and APOE (linear effect, P = .06; quadratic effect, P = .008), with no significant interaction (P = .63). In a piecewise model, there was a significant TOMM40 effect before age 60 years (P = .009), characterized by flattened test-retest improvement (VL/VL subgroup only) but no significant APOE effect, and a significant APOE effect after age 60 years (P = .006), characterized by accelerated memory decline (e4 carriers) but no significant TOMM40 effect. CONCLUSION: Both TOMM40 and APOE significantly influence age-related memory performance, but they appear to do so independently of each other.

Full Text

Duke Authors

Cited Authors

  • Caselli, RJ; Dueck, AC; Huentelman, MJ; Lutz, MW; Saunders, AM; Reiman, EM; Roses, AD

Published Date

  • November 2012

Published In

Volume / Issue

  • 8 / 6

Start / End Page

  • 490 - 495

PubMed ID

  • 23102119

Pubmed Central ID

  • PMC3483561

Electronic International Standard Serial Number (EISSN)

  • 1552-5279

Digital Object Identifier (DOI)

  • 10.1016/j.jalz.2011.11.006


  • eng

Conference Location

  • United States