APOE, Smoking and Vigilance

Proposal details

Title: APOE and smoking: a gene x environment effect on vigilance
Research Area(s): Genetics
Background: Background: One of the most highly replicated findings in the neurobiology of Alzheimer's Disease (AD),the presence of an Apolipoprotein epsilon 4 (APOE E4) allele is the second most influential risk factor for sporadic AD behind age. However, APOE E4 is neither necessary nor sufficient to generate the disease (i.e., “the common disease, common variant hypothesis”) and the presence of an APOE E4 allele implies a potential moderating influence in the brain. APOE E4 has also contributed to neuronal alterations in non-demented individuals. In addition, there is support that the E4 allele and cigarette smoking synergistically reduce cognitive functioning. One specific cognitive area of interest is attention; attentional deficits have been noted in cognitively intact APOE E4 carriers, there are known nicotinic effects on attention, and reductions in attention result in real world implications.
Aims: Purpose: The purpose of the proposed manuscript is to investigate the effects of APOE and current smoking on reaction time using a continuous performance task. Hypotheses: We hypothesize that the APOE E4 allele and smoking status will demonstrate a significant interaction in that the E4 carriers will be slower than non-carriers in the smoking group.
Method: Methods: We propose to conduct general liner modeling to investigate the main effects and interaction of APOE and self-identified history of tobacco use in smokers who are part of the Brain Research International Database (BRID). Age will be a covariate. Only individuals of European decent will be used in the analysis (to avoid admixture) and only individuals over the age of 18 will be used (to ensure appropriate exposure of smoking initiation). If a significant gene x smoking interaction is observed, post-hoc simple effects analysis will be conducted using Independent Samples t-tests stratified by group.