UUttaahh SSttaattee UUnniivveerrssiittyy DDiiggiittaallCCoommmmoonnss@@UUSSUU All Graduate Theses and Dissertations Graduate Studies 5-2008 GGllyycceemmiicc LLooaadd aanndd RRiisskk ooff AAllzzhheeiimmeerr''ss DDiisseeaassee:: TThhee CCaacchhee CCoouunnttyy SSttuuddyy oonn MMeemmoorryy,, HHeeaalltthh,, aanndd AAggiinngg Eun Young Choi Utah State University Follow this and additional works at: https://digitalcommons.usu.edu/etd Part of the Dietetics and Clinical Nutrition Commons, Nutrition Commons, and the Public Health Commons RReeccoommmmeennddeedd CCiittaattiioonn Choi, Eun Young, "Glycemic Load and Risk of Alzheimer's Disease: The Cache County Study on Memory, Health, and Aging" (2008). All Graduate Theses and Dissertations. 127. https://digitalcommons.usu.edu/etd/127 This Thesis is brought to you for free and open access by the Graduate Studies at DigitalCommons@USU. It has been accepted for inclusion in All Graduate Theses and Dissertations by an authorized administrator of DigitalCommons@USU. For more information, please contact [email protected]. GLYCEMIC LOAD AND RISK OF ALZHEIMER’S DISEASE: THE CACHE COUNTY STUDY ON MEMORY, HEALTH, AND AGING by Eun Young Choi A thesis submitted in partial fulfillment of the requirements for the degree of MASTER OF SCIENCE in Nutrition and Food Sciences Approved: __________________________ ___________________________ Ronald G. Munger, Ph.D. Christopher Corcoran, Ph.D. Major Professor Committee Member __________________________ ___________________________ Heidi J. Wengreen, Ph.D. Byron R. Burnham, Ed.D. Committee Member Dean of Graduate Studies UTAH STATE UNIVERSITY Logan, Utah 2008 ii Copyright © Eun Young Choi 2008 All Rights Reserved iii ABSTRACT Glycemic Load and Risk of Alzheimer’s Disease: The Cache County Study on Memory, Health, and Aging by Eun Young Choi, Master of Science Utah State University, 2008 Major Professor: Dr. Ronald G. Munger Department: Nutrition and Food Science Carbohydrates are a major energy source for the human body and particularly glucose is the only energy source for the brain. Thus glucose metabolism is important to maintain normal brain function. Evidence showed insulin resistance and diabetes are associated with cognitive decline and a large amount of highly processed carbohydrate intake; in other words, a high glycemic load diet, which increases blood glucose faster and insulin demand, is associated with increased risk of insulin resistance and diabetes. Based on this premise, the hypothesis that a high glycemic load (GL) diet increases the risk of incident Alzheimer’s disease (AD) was examined among Cache County elderly people in Northern Utah. At the baseline survey, 3,831 participants 65 years of age or older completed a food frequency questionnaire (FFQ) and cognitive screening. Observation time to collect the data for incident AD was approximately 10 years. Incident AD was determined by final consensus conference after multi-steps of iv screening. GL was calculated as the product of carbohydrate intake and glycemic index (GI) and adjusted for energy intake. FFQs from diabetics were considered to be invalid to assess dietary carbohydrates intake and excluded. The analysis was examined separately by gender. The Cox proportional hazard regression model in survival analysis was used to relate GL to incident AD using a time variable with age of AD onset. There was no association in men but a negative association in women in the unadjusted model. Evidence of confounding by total kcal was apparent in women, particularly in the lowest GL group, which had the highest total kcal mean intake. Finally no association between GL and AD was found after adjustment for education, myocardial infarction (MI), stroke, Body Mass Index (BMI), physical activity, smoking, alcohol use, APOE ε-4 alleles, multi-vitamins use, total kcal, and controlling interaction between GL and total kcal. The low GL group had unique characteristics in lifestyle factors, macro-nutrients intake, and pattern of food use. The inverse relationship between GL and total kcal may partly be explained by lifestyle factors, particularly alcohol intake. The characteristics of low GL group, current smokers, alcohol users, and their relationship and interaction between total kcal and risk of AD should be explored further. (99 pages) v ACKNOWLEDGMENTS I would like to express my deep and sincere gratitude to my major professor, Ronald G. Munger, Ph.D., M.P.H., director for Center of Epidemiologic Studies, principal investigator and program director for Cache County Study on Memory, Health, and Aging. His wide knowledge on nutritional epidemiology, stimulating suggestions, invaluable guidance, encouragement, and personal understanding have provided a good basis and insight for the nutritional epidemiologic research and have made possible the present thesis. I would also like to thank members of my supervisory committee, Dr. Christopher Corcoran and Dr. Heidi J. Wengreen, for willingness to help and their support throughout the master’s program. Dr. Christopher Corcoran has provided superior statistical knowledge and various approaches on an epidemiologic study including survival analysis through epidemiology seminar. I am deeply grateful to Dr. Heidi J. Wengreen for helping the entire graduate, work including dietary assessment, practical use of the SPSS software program, and always kindly answering my uncountable questions. I am thankful for collaborative work of the Nutrition Core meeting members, including Dr. Ronald G. Munger, Dr. Heidi J. Wengreen, and Chailyn Nelson, RD, since last summer. I warmly thank my colleague, Chailyn Nelson, RD, for helping with dietary glycemic load calculations and other work related to dietary assessment. I greatly thank Ms. Roxane Pfister for assisting in the statistical analysis, Ms. Georgiann Sanborn for helping my technical difficulties on the computer, and Ms. Cara vi Brewer for all administrative help. I also wish to thank to epidemiology seminar participants during my master’s program for sharing ideas and inter-departmental collaborations. Finally, I owe my loving thanks to my husband, Yong Sun Choi. Without my husband’s unconditional support, encouragement, and love, it would have been impossible to accomplish my study abroad. I thank my two sons, Won Jun Choi (Andy) and Ki Jun Choi (Eddie), for growing healthy and doing a great job in their schools with different language in the different environments. My special gratitude is due to my parents, my sister and her family, and my bothers and their family for their loving support. The financial support of Utah State University for the out-of-state tuition waiver during my master’s program is gratefully acknowledged. Eun Young Choi vii CONTENTS Page ABSTRACT……………………………………………………………………………...iii ACKNOWLEDGMENTS………………………………………………………………...v LIST OF TABLES……………………………………………………………………...viii LIST OF FIGURES………………………………………………………………….........x INTRODUCTION………………………………………………………………………...1 LITERATURE REVIEW…………………………………………………………………3 RESEARCH OBJECTIVE………………………………………………………………34 SUBJECTS AND METHODS………………………………….……………………….35 RESULTS………………………………………………………………………………..42 DISCUSSION…………………………………………………………………………....58 REFERENCES…………………………………………………………………………. 63 APPENDIX………………………………………………………………………………76 viii LIST OF TABLES Table Page 1 Criteria for the diagnosis of diabetes (cited from ADA)…………………………7 2 Abnormalities related to insulin resistance and hyperinsulinemia (cited from Reaven (80))……………………………..….15 3 Reports from prospective cohort & cross-sectional studies examining the relationship between dietary glycemic index & glycemic load and chronic diseases……………………………………………………………...30 4 Demographic and clinical characteristics of baseline in the Cache County Study on Memory, Health, and Aging by gender. 1……....44 5 Dietary and macro-nutrients characteristic of baseline in the Cache County Study on Memory, Health, and Aging by gender.1…….......45 6 Correlations of glycemic load (GL) with other dietary variables………………..46 7 Correlations of energy-adjusted glycemic load with other dietary variables………………..………………………......................46 8 Demographic and clinical characteristics among energy-adjusted glycemic load quintiles in men…………………………………………………..48 9 Demographic and clinical characteristics among energy-adjusted glycemic load quintiles in women………………..………….…49 10 Diabetes distribution among gycemic load quintiles1 stratified by gender………………………………………….……………..….…50 11 Dementia distribution among diabetes stratified by gender……………….….....50 12 Distribution of dementia among kcal adjusted glycemic load quintiles by gender and diabetes………….………………………………......….50 13 Dementia distribution comparison across gender stratified by diabetes among energy adjusted GL quintile 1 vs. quintile 2-5……...…...…..51 14 Dementia distribution comparison across gender by energy adjusted GL quintile 1 vs. quintile 2-5 after exclusion of diabetes (n=464)……………....52 ix 15 Cox proportional hazard models for AD by GL…………………………….…...52 16 Mean intake of kcal & macro-nutrients by GL quintiles in men………………...54 17 Mean intake of kcal & macro-nutrients by GL quintiles in women…………..…54 18 Smoking distribution by GL quintiles in men (n=1334)………………………....55 19 Alcohol use distribution by GL quintiles in men (n=1334)……………………...55 20 Smoking distribution by GL quintiles in women (n=1814)………………….......55 21 Alcohol use distribution by GL quintiles in women (n=1819)……………….….55 22 Mean servings of food groups by GL quintiles in men……………………….....56 23 Mean servings of food groups by GL quintiles in women…………………….…57 24 Cox proportional hazard models for AD by GL after controlling total kcal…….57