APOE ε4, but not diabetes, is a risk factor for Alzheimer's Disease Open Access

Abstract

Alzheimer's Disease is an increasingly prevalent neurodegenerative disorder that systematically destroys cognitive skills and is the sixth leading cause of death in the United States. Apolipoprotein E ε4 allele (APOE ε4) and diabetes have previously been shown to increase the risk for Alzheimer's Disease (AD), mild cognitive impairment (MCI), and various other types of dementia. There is some evidence that having both APOE ε4 and diabetes increases the risk of AD, and that APOE ε4 modifies the relationship between diabetes and AD. We hypothesize that diabetes may modify the risk of AD in individuals with one or two APOE ε4 alleles. Thus, our primary aim was to examine the modifying effect of diabetes on the relationship between APOE ε4 and risk of AD. The National Alzheimer's Coordinating Center (NACC) data set used in this study is a publicly available sample designed to provide clinical evaluations, neuropathology data, and MRI data. Cognitive status was determined by clinical evaluation in Alzheimer's Disease Centers (ADCs). Presence of APOE ε4 alleles was determined by genotype sequencing. Diabetes was based on patient self-report. There were 33,456 subjects in the sample, with 24,336 individuals having APOE genotype data. Risk of cognitive impairment diagnosis was estimated using a multinomial logistic regression model adjusted for various demographic and clinical factors. Compared with those who had no APOE ε4 alleles, those with two copies of APOE ε4 had significantly higher odds of AD diagnosis (odds ratio, 8.75; 95% CI, 7.38-10.38). Diabetic individuals, on the other hand, did not have significantly higher odds of AD diagnosis (odds ratio, 1.09; 95% CI, 0.93-1.27) when compared to non-diabetic individuals. Compared with non-diabetic individuals with two APOE ε4 alleles, those with diabetes and two copies of APOE ε4 did not have significantly higher odds of AD diagnosis (odds ratio, 0.99; 95% CI, 0.55-1.75). Our results suggest that APOE ε4, but not diabetes is a risk factor for AD. Furthermore, there is no interaction between APOE ε4 and diabetes in relation to AD since diabetes does not modify the risk of AD in individuals with one or two APOE ε4 alleles.

Table of Contents

I. Introduction ...................................................................................................................................... 8

II. Methods ......................................................................................................................................... 11

III. Results ......................................................................................................................................... 15

IV. Discussion ..................................................................................................................................... 21

V. Tables and Figures .......................................................................................................................... 26

Table 1: Demographic information and neuropsychological test scores

Table 2: Performance on the Mini Mental State Exam

Table 3: Risk of cognitive impairment associated with APOE ε4 and diabetes

Figure 1: Odds ratios for adjusted model. Individuals effects of APOE ε4 and diabetes

Figure 2A: Predicted Probabilities for APOE ε4

Figure 2B: Predicted Probabilities for diabetes

Figure 3: Odds ratios for adjusted model calculated with zero APOE ε4 alleles and no diabetes as the baseline

Figure 4A: Odds ratios for adjusted model. Modifying Effect of APOE ε4 on diabetes

Figure 4B: Odds ratios for adjusted model. Modifying effect of diabetes on APOE ε4

VI. References .................................................................................................................................... 35

About this Honors Thesis

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School	Emory College
Department	Neuroscience and Behavioral Biology
Degree	BS
Submission	Honors Thesis
Language	English
Research Field	Psychology, Clinical Biology, Neuroscience Health Sciences, Epidemiology
Keyword	APOE ε4 Diabetes Alzheimer's Disease
Committee Chair / Thesis Advisor	Manns, Joseph, Emory University
Committee Members	Chen, Yunxiao, Emory University Roesch, Leah Anderson, Emory University

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