University of Tennessee, Knoxville TRACE: Tennessee Research and Creative Exchange Doctoral Dissertations Graduate School 5-2002 Investigation of Cognitive Impairments using functional Magnetic Resonance Imaging (fMRI) and Positron Emission Tomography (PET) in patients with mild Alzheimer's disease Mateja de Leonni Stanonik University of Tennessee - Knoxville Follow this and additional works at: https://trace.tennessee.edu/utk_graddiss Part of the Medicine and Health Sciences Commons Recommended Citation Stanonik, Mateja de Leonni, "Investigation of Cognitive Impairments using functional Magnetic Resonance Imaging (fMRI) and Positron Emission Tomography (PET) in patients with mild Alzheimer's disease. " PhD diss., University of Tennessee, 2002. https://trace.tennessee.edu/utk_graddiss/2199 This Dissertation is brought to you for free and open access by the Graduate School at TRACE: Tennessee Research and Creative Exchange. It has been accepted for inclusion in Doctoral Dissertations by an authorized administrator of TRACE: Tennessee Research and Creative Exchange. For more information, please contact [email protected]. To the Graduate Council: I am submitting herewith a dissertation written by Mateja de Leonni Stanonik entitled "Investigation of Cognitive Impairments using functional Magnetic Resonance Imaging (fMRI) and Positron Emission Tomography (PET) in patients with mild Alzheimer's disease." I have examined the final electronic copy of this dissertation for form and content and recommend that it be accepted in partial fulfillment of the equirr ements for the degree of Doctor of Philosophy, with a major in Comparative and Experimental Medicine. Joseph H. Dougherty, Major Professor We have read this dissertation and recommend its acceptance: Karl F. Hubner, R. Kent Hutson, Joseph A. Thie, Joel Lubar, Gary T. Smith, Xuemin Xu Accepted for the Council: Carolyn R. Hodges Vice Provost and Dean of the Graduate School (Original signatures are on file with official studentecor r ds.) To the Graduate Council: I am submitting here with a dissertation written by Mateja de Leonni Stanonik entitled "Investigation of Cognitive Impairments using functional Magnetic Resonance Imaging (fMRI) and Positron Emission Tomography (PET) in patients with mild Alzheimer's disease". I have examined the final electronic copy of this dissertation for form and content and recommend that it be accepted in partial fulfillment of the requirements for the degree of Doctor of Philosophy, with a major in Comparative and Experimental Medicine. John H. Dougherty, Major Professor We have read this dissertation and recommend its acceptance: Karl F. Hübner R. Kent Hutson Joseph A. Thie Joel Lubar Gary T. Smith Xuemin Xu Accepted for the Council: Dr. Anne Mayhew Vice Provost and Dean of Graduate Studies (Original signatures are on file in the Graduate Student Services Office.) Investigation Of Cognitive Impairments Using functional Magnetic Resonance Imaging (fMRI) and Positron Emission Tomography (PET) In Patients With Mild Alzheimer’s Disease A Dissertation Presented for the Doctor of Philosophy Degree The University of Tennessee, Knoxville Mateja de Leonni Stanonik May, 2002 Copyright © Mateja de Leonni Stanonik, 2002 All rights reserved ii Dedication This dissertation is dedicated to Prof. Dr. John H. Dougherty Jr., M.D. Whose sound advice, affectionate mentorship, careful supervision, and uncompromizing support motivate my continuous fascination with the intricacies of the human mind. Eppur, si muove. Gallilleo Disertacija je posveèena mojemu professorju ter mentorju Prof. Dr. John H. Dougherty Jr., M.D. Uspeh, ki ga ta disertacija predstavlja, mi je bil omogoèen zaradi njegove neomejene podpore, ljubezni, vseh požrtvovanj ter skrbnega nadzora. iii Acknowledgements No matter how independent I like to think myself, I could not have completed this thesis without the help of many good people to whom I owe at great amount of debt and gratitude. At the top of the list is Charles A. Licata, whose patience, care, and support rarely wavered over the three years this project required. In addition to his personal support, I could have never completed the project without his help and guidance in statistics, psychometrics, and above all without his expertise in computer programming and computer technology. Obtaining my Ph.D. degree represents one of the milestones in my life and carries an even greater personal affective significance since I had to leave my homeland in pursuit of higher education in the area of my interest – affective neuroscience. Luck, persistence, and hard work have finally resulted in the completion of a truly interdisciplinary as well as multidisciplinary approach to the study of cognitive changes in early Alzheimer’s disease. Many people who have noticed my fascination with the human brain have helped me along the way, however there are a few persons who directly influenced my educational career. I would like to single out and express my tremendous gratitude to Dr. Karl F. Hübner, M.D., a professor who served as a mentor on my doctoral committee. Dr. Hübner’s excitement, knowledge, patience and generosity ignited my interest in functional neuroimaging while I was still an undergraduate. Subsequent completion iv of my senior honors thesis on a project evaluating tumor recurrence with 11C-ACBC also provided me with the basics of PET methodology. In addition, Dr. Hübner became my first true mentor, a person I trusted and whom I will always look up to. It is difficult for me to believe that there are no coincidences in life for it was Dr. Hübner who yet again changed my life several years later by introducing me to the person who became my major professor during my doctoral studies and enabled me to explore cognitive impairments in early Alzheimer’s patients. Dr. Hübner has been the calming and powerful presence during the course of my studies who helped weather even the most trying of circumstances. If the completion of this degree presents any measure of success in pursuit of multidisciplinary research, it is a prominent reflection of Dr. Hübner’s care, guidance, care, and respect for my interests in neuroimaging in addition to my fascination with the human mind. For this, I extend Dr. Karl F. Hübner my deepest appreciation and gratitude. Similarly, I also owe Dr. Hübner many thanks for suggesting excellent professors who agreed to serve on my doctoral committee. I would like to thank Dr. Gary T. Smith, M.D., for sharing with me his expertise in Nuclear Medicine in teaching me about PET. Furthermore, I have been most honored that Dr. R. Kent Hutson, M.D., agreed to join my doctoral committee. He taught me almost everything I know about neuroanatomy, MRI, functional MRI, computers, and image processing. In addition, his invaluable expertise in Neuroradiology has contributed to a broader education than most students in neuroscience normally receive. I am very much looking forward to working on other research projects in the future with Drs. Smith and Hutson. v Furthermore, I would like to thank Dr. Joseph A. Thie, Ph.D., for providing me with his tremendous knowledge of statistics. His suggestions and expedient review of my written pursuits have guided me through the tricky portions and interpretations of statistical results in this study. Finally, I would like to thank Dr. Joel Lubar, Ph.D. and Xuemin Xu, Ph.D., for sharing with me their expertise in neuropsychology, neuroanatomy, and pathology of AD. Of course, this study would not have been possible without the AD patients and control participants. I thank all of them for their contributions as well. A bird sings not because it has an answer, but because it has a song. (Herman de Zwaan, 1899) Whatever accomplishment is presented by the completion of my doctorate would have been impossible without my friends whom I have come to consider my family in the United States. I would like to thank all of those who helped me pursue my higher education when I first came to this country. Without the encouragement and financial support of Drs. Bruce and Shirley Avery, without the guidance, care, and financial support of Mr. James Domina and his family, without the support of a most excellent teacher and my dear friend, Mrs. Tommye Sue McGinnis and her husband Gary McGinnis, without the love and encouragement of Ms. Deanna Burnett, her daughter Stephanie and her son Joshua, without the encouragement of such friends as Mary Lou Horner, Sandra Clark, Dave and Katherine Long, Jerry Galyean, and Bob Griffits, I would have never achieved my goal of becoming a doctor. To all of you, I owe my deepest appreciation and gratitude. It is a humbling but equally joyous experience to consciously realize how many good vi people have touched my life in so many different ways. It has been a privilege to know you for you have all become a part of my family. Only through experiences of the last decade have I realized that I carry a great responsibility to give something back to the amerian community from which I have so generously received. After everything is done and said, the main reason for the success exhibited by the completion of my doctorate was made possible because of my mother, Mrs. Vita Stanonik. Her unconditional love, great courage, enormous strength, unrestricted support, and above all her trust and courage to “alow me to spread my wings and experience life on my own terms at such a young age” is truly a reflection of her trust and love for her me. Moja mami me je nauèila, da v življenju obstajajo razliène ljubezni, ki zmešajo glavo, èute, duha in srce; med vsemi pa je ena sama, ki ne zmede, ampak prodre v globino in ta umrje edino le z bitjem, v katerem se je zakoreninila. Zaradi njene neomejene ljubezni do vseh mojih slabosti in prednosti, mi je bil omogoèen uspeh, ki ga predstavlja moj doktorat. “Mami, ustvarila si prvega Dr. Stanonik v naši družini – bodi ponosna nase!” vii Abstract Awareness and interest in diseases, which pertain to cognitive and affective functions in the elderly, has been increasing, as the proportion of elderly people in the population grows larger.