RT Journal Article
SR Electronic
T1 Fat mass and obesity gene and cognitive decline
JF Neurology
JO Neurology
FD Lippincott Williams & Wilkins
SP 92
OP 99
DO 10.1212/WNL.0b013e3182768910
VO 80
IS 1
A1 Jan Bressler
A1 Myriam Fornage
A1 Ellen W. Demerath
A1 David S. Knopman
A1 Keri L. Monda
A1 Kari E. North
A1 Alan Penman
A1 Thomas H. Mosley
A1 Eric Boerwinkle
YR 2013
UL http://n.neurology.org/content/80/1/92.abstract
AB Objective: To determine whether 4 genetic variants in the fat mass and obesity associated gene (FTO) identified in genome-wide association studies of diabetes and obesity are associated with cognitive change in midlife in the Atherosclerosis Risk in Communities (ARIC) Study.Methods: ARIC is a prospective cohort study of the development of atherosclerosis in 15,792 individuals aged 45 to 64 years at baseline from 1986 to 1989. FTO is highly expressed in human fetal and adult brain, and a single nucleotide polymorphism in FTO has previously been associated with reduced brain volume in cognitively normal subjects. Since a relationship between brain atrophy and diminished cognitive function has been demonstrated in ARIC participants, general linear models were used to evaluate the association between 6-year change in scores on 3 neuropsychological tests and FTO genotype.Results: In a sample of 8,364 white and 2,083 African American men and women with no clinical history of stroke, significantly greater mean change in performance on the Delayed Word Recall Test was associated with 2 of 4 FTO single nucleotide polymorphisms examined (rs9939609, rs805136, rs17817449, and rs1421085) in whites but not in African Americans (p ≤ 0.002). The association of the FTO polymorphisms with cognitive change was independent of potential confounding clinical and demographic variables including age, gender, education, diabetes, hypertension, and body mass index.Conclusions: Further studies will be needed to clarify the biological mechanisms and genetic pathways through which variants in FTO can increase susceptibility to decline in verbal memory detectable in middle-aged, community-dwelling adults.ARIC=Atherosclerosis Risk in Communities; BMI=body mass index; CI=confidence interval; DSST=Digit Symbol Substitution Test; DWRT=Delayed Word Recall Test; SNP=single nucleotide polymorphism; WFT=Word Fluency Test; WHR=waist-to-hip ratio