Medical Student Research Fellowship for Summer 2009
Mentor: Gloria Lena Vega, Ph.D.
Department: Center for Human Nutrition
Room number: Y3.206B
Mail Code: 9052
Phone number: 214 -648-2869
Project title: IS THERE A RELATIONSHIP BETWEEN POSSIBLE LONGEVITY FACTORS AND ALZHEIMER'S DISEASE?
Human subjects IRB approved project number (where applicable): UT-IRB 012006-012
Animal subjects IRB approved project number (where applicable):
Project Type (patient-based research, animal-based research, or basic research; this characterization is only to permit a general classification for grouping similar types of projects)
Brief Description of Project:
PURPOSE: The aims of this pilot study are: (1) to determine if Alzheimer's disease (AD) subjects and subjects at risk for AD have a lower prevalence of a "longevity" phenotype than control subjects; (2) to determine the prevalence of percent body fat > 25 for men and >33% for women in AD subjects and (3) to determine if there is a relation between body composition and prevalence of the "longevity" lipoprotein phenotype. The long-term goal of this study is to identify lipid factors that increase predisposition to AD.
BACKGROUND: This study aims to explore links between aging (the major risk factor for AD) and the development of AD. Recently, Barzilai et al1. proposed that nonagenarians have a familial phenotype including having large low-density lipoproteins (LDLs) and high-density lipoproteins (HDLs), a low risk of metabolic syndrome and other risk factors for cardiovascular disease, and a high prevalence of homozygosity for a variant of cholesteryl ester transferase protein (CETP) I4O5V. In the current study, we propose to examine the prevalence of this phenotype in persons who are at high risk for AD, persons with AD and control subjects matched for age, gender and body mass index (BMI). We hypothesize that subjects with AD will have a lower prevalence of the "longevity" phenotype than age-matched controls, and that persons at risk for AD will have a longevity phenotype prevalence intermediate between AD subjects and controls.
CONCISE SUMMARY OF PROJECT: This cross-sectional study will involve an equal number of AD, at-risk, and cognitively normal subjects matched for age and gender and BMI to the extent possible. Subjects for this study will be recruited from the patient population attending the AD clinic at the Aston Center directed by Dr. Myron Weiner. This patient population consists of English-speaking subjects. There are no non-English speaking subjects attending the clinic. We expect to have sufficient enrollment for the study from the patient population currently attending the clinic and we do not anticipate to have to recruit subjects from non-English speaking clinics. Subjects will be seen in the Aston Center once after recruitment, where they will have a blood sample (30 cc EDTA blood) collection by venipuncture after a 12 hour fast and assessment of body composition (relative percentage of muscle, body fat, and bone mineral mass) by dual energy X-ray absorptiometry (DXA). The recruitment study visit will likely last 20 to 30 minutes and the research clinic visit will likely last ½ a day. The research data will include measuring height, weight and waist circumference, body composition from DXA2, plasma lipids and lipoprotein cholesterol3, LDL and HDL size3, CETP levels4 and genotype5, and 24 S-hydroxy-cholesterol concentration6.
SOURCES OF RESEARCH MATERIAL: Research material will include measurements of height and body weight, waist circumference and blood specimens, and data from X-ray absorptiometry. Body composition will be determined with a Delphi W unit and the QDR software for Windows XP version 12.3.
RECRUITMENT OF SUBJECTS: Study subjects will be drawn largely from existing cohorts of normal controls, persons with MCI, and persons with early AD followed yearly at the UT Southwestern Alzheimer's Disease Center. These men and women have already given consent for DNA collection. Individuals will be contacted by telephone or at the time of their regular yearly visits by the study coordinator with Dr. Weiner's approval. Subjects will be interviewed and recruited at the AD clinic by Dr. Weiner and study coordinator. Informed consent will be obtained by Dr. Weiner and study coordinator. Each individual will be asked to sign an IRB-approved consent form by Dr. Weiner (cases) and Drs. Weiner or Vega (controls) or the study nurse.
The subjects are patients of Dr. Myron F. Weiner and they will be recruited during a clinic visit or they may be informed by phone about the study being conducted by a clinical staff and invited to attend clinic for recruitment if they are interested.
METHODS OF PROCEDURE TO BE CARRIED OUT BY THE MEDICAL STUDENT:
We have recruited 70 subjects into the study. The medical student will measure CETP, do LDL sizing in current patients, analyze DXA scans for abdominal fat and work on DNA extractions in preparation for analyses of CETP polymorphism. In addition, the student will tabulate data and do preliminary analyses.
Previous Research Activities or Publications with Medical Students:
1: Chang C, Garcia-Garcia AB, Hamilton E, Shah B, Meguro S, Grundy SM, Provost D, Vega GL. Metabolic syndrome phenotype in very obese women. Metab Syndr Relat Disord. 2007 Spring;5(1):3-12. PubMed PMID: 18370809.
2: Vega GL, Adams-Huet B, Peshock R, Willett D, Shah B, Grundy SM. Influence of body fat content and distribution on variation in metabolic risk. J Clin Endocrinol Metab. 2006 Nov;91(11):4459-66. Epub 2006 Aug 22. PubMed PMID: 16926254
3. Vega GL, Cater NB, Hadizadeh DR 3rd, Meguro S, Grundy SM. Free fatty acid metabolism during fenofibrate treatment of the metabolic syndrome. Clin Pharmacol Ther. 2003 Sep;74(3):236-44. PubMed PMID: 12966367