Longitudinal modeling of cognitive aging and the TOMM40 effect

详细信息    查看全文

• 作者：Richard J. Caselli^a ; ^b ; ^{Caselli.Richard@Mayo.edu} ; Amylou C. Dueck^c ; Matthew J. Huentelman^b ; ^d ; Michael W. Lutz^e ; ^f ; Ann M. Saunders^e ; ^f ; Eric M. Reiman^b ; ^d ; ^g ; Allen D. Roses^e ; ^f
• 关键词：TOMM40 ; APOE ; Preclinical Alzheimer&rsquo ; s disease ; Cognitive aging
• 刊名：Alzheimer's Dementia
• 出版年：2012
• 出版时间：November, 2012
• 年：2012
• 卷：8
• 期：6
• 页码：490-495
• 全文大小：452 K

文摘

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.