Gene-Environment Interaction of Body Mass Index and Apolipoprotein E ε4 Allele on Cognitive Decline

Authors

Kumar B. Rajan, Rush University Medical CenterFollow
Kimberly A. Skarupski, Johns Hopkins University
Heather E. Rasmussen, Rush University Medical CenterFollow
Denis A. Evans, Rush University Medical Center

Document Type

Article

Date of this Version

2014

Citation

Alzheimer Dis Assoc Disord. 2014 ; 28(2): 134–140.

Comments

Copyright Rajan et al.

doi:10.1097/WAD.0000000000000013

Abstract

Genetic variation alone may not account for common chronic disease susceptibility. Rather, an interaction between genetic and environmental factors may clarify the underlying disease mechanism. Hence, we tested whether BMI modified the genetic association of the Apolipoprotein E (APOE) ε4 allele with cognitive decline. The data came from a longitudinal population-based sample of 4,055 participants interviewed at 3-year intervals from 1993 to 2012. Cognitive function was assessed using a standardized global cognitive score and BMI was assessed at baseline and classified as normal, overweight, and obese. There were 1,374 (34%) participants with the ε4 allele. In normal BMI participants, cognitive decline was 0.048-unit per without the ε4 allele, and increased by an additional 0.031-unit per year with the ε4 allele. In overweight participants, cognitive decline was 0.038-unit per year without the ε4 allele, and increased by an additional 0.026-unit per year with the ε4 allele. Finally, in obese participants, cognitive decline was 0.038- unit per year without the ε4 allele, and increased by an additional 0.014-unit per year with the ε4 allele. The association of ε4 allele with cognitive decline was significantly lower in obese participants compared to normal BMI participants (p=0.003), thereby suggesting significant gene-environment interaction on cognitive decline.