title: The TOMM40 poly-T rs10524523 variant is associated with cognitive performance among non-demented elderly with type 2 diabetes.
abstract: 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.
authors.affiliation: Department of Neurology, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel; The Joseph Sagol Neuroscience Center, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel. Electronic address: liorgreenbaum@yahoo.com.
authors.forename: Lior
authors.initials: L
authors.lastname: Greenbaum
authors.affiliation: The Joseph Sagol Neuroscience Center, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel; Memory Clinic, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel.
authors.forename: Ramit Ravona
authors.initials: RR
authors.lastname: Springer
authors.affiliation: Duke University School of Medicine, Department of Neurology, Durham, NC, USA.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Lutz
authors.affiliation: Department of Family Medicine, University of Tel Aviv, Israel; Maccabi Health Services, Israel.
authors.forename: Anthony
authors.initials: A
authors.lastname: Heymann
authors.affiliation: The Joseph Sagol Neuroscience Center, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel.
authors.forename: Irit
authors.initials: I
authors.lastname: Lubitz
authors.affiliation: The Joseph Sagol Neuroscience Center, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel.
authors.forename: Itzik
authors.initials: I
authors.lastname: Cooper
authors.affiliation: The Joseph Sagol Neuroscience Center, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel.
authors.forename: Efrat
authors.initials: E
authors.lastname: Kravitz
authors.affiliation: Department of Psychiatry, Mount Sinai School of Medicine, NY, USA.
authors.forename: Mary
authors.initials: M
authors.lastname: Sano
authors.affiliation: Duke University School of Medicine, Department of Neurology, Durham, NC, USA; Zinfandel Pharmaceuticals Inc., Durham, NC, USA.
authors.forename: Allen D
authors.initials: AD
authors.lastname: Roses
authors.affiliation: Department of Psychiatry, Mount Sinai School of Medicine, NY, USA.
authors.forename: Jeremy M
authors.initials: JM
authors.lastname: Silverman
authors.affiliation: Duke University School of Medicine, Department of Neurology, Durham, NC, USA.
authors.forename: Ann M
authors.initials: AM
authors.lastname: Saunders
authors.affiliation: The Joseph Sagol Neuroscience Center, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel; Department of Psychiatry, Mount Sinai School of Medicine, NY, USA.
authors.forename: Michal Schnaider
authors.initials: MS
authors.lastname: Beeri
mesh_terms: D001057:Apolipoproteins E / Q000235:genetics; D003072:Cognition Disorders / Q000209:etiology* / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D009483:Neuropsychological Tests; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
chemical_list: D001057:Apolipoproteins E; D026901:Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; C400783:TOMM40 protein, human
keywords: APOE; Alzheimer׳s disease; Cognition; TOMM40; Type 2 diabetes