The TOMM40 poly-T rs10524523 variant is associated with cognitive performance among non-demented elderly with type 2 diabetes

The variable length poly-T, rs10524523 ('523') located within the TOMM40 gene, was recently associated with several phenotypes of cognitive function. The short (S) allele is associated with later AD onset age and better cognitive performance, compared to the longer alleles (long and very-long (VL)). There is strong linkage disequilibrium between variants in the TOMM40 and APOE genes. In this study, we investigated the effect of '523' on cognitive performance in a sample of cognitively normal Jewish elderly with type 2 diabetes, a group at particularly high risk for cognitive impairment. Using a MANCOVA procedure, we compared homozygous carriers of the S/S allele (N=179) to carriers of the VL/VL allele (N=152), controlling for demographic and cardiovascular covariates. The S/S group performed better than the VL/VL group (p=0.048), specifically in the executive function (p=0.04) and episodic memory (p=0.050) domains. These results suggest that previous findings of an association of the TOMM40 short allele with better cognitive performance, independently from the APOE variant status, are pertinent to elderly with diabetes.