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Thesis (M. Med. Sc.)--University of Hong Kong, 2006. / Also available in print.

Thesis (M. Med. Sc.)--University of Hong Kong, 2006.

OBJECTIVES: In older age, body composition changes as fat mass increases and redistributes. Due to this, the current body mass index (BMI) classification proposed by the World Health Organization (WHO) may not accurately classify older adults (65+) by health risk. The objectives of thesis were to: 1) conduct a scoping review of the literature to investigate the association between BMI and mortality in older adults, 2) define age-specific BMI cut-offs for older adults with regards to health outcomes using data from the Canadian Longitudinal Study on Aging (CLSA), and 3) test the performance of the age-specific BMI thresholds in comparison to WHO thresholds. METHODS: The Ovid MEDLINE and EMBASE databases were searched for English language observational studies examining the association between BMI and all-cause mortality in older adults (objective 1). CART decision tree analysis was then used to define age-appropriate BMI cut-points in relation to health outcomes (i.e. cardiovascular (CV) conditions and frailty) (objective 2). Logistic regression models were utilized to determine the association between BMI and health outcomes, and area under the receiver operating characteristic curve (AUC) and sensitivity/specificity were used to test the performance of new BMI cut-offs (objective 3). RESULTS: The scoping review found that older adults classified as overweight had reduced mortality compared to normal BMI, thereby necessitating a need for revised cut-offs. In our analyses, age-specific cardiovascular- and frailty-BMI groups were created. Compared to the BMIFrailty- Risk groups, the BMI-CV-Risk groups demonstrated the most improvement in classification from the WHO groups. When evaluating the association between cut-points and outcomes, the model performance and specificity both improved for the new age-specific cut-points compared to the original WHO thresholds, suggesting improved classification with use of these revised groups. The results propose increased overweight thresholds (25.9-27.1) and lowered obese thresholds (28.7-30.9) for older adults. CONCLUSIONS: This novel analysis is the first attempt at revising the WHO-BMI thresholds for older Canadian adults. The age-specific BMI-CV-Risk groups offered improvements in classification of older adults from the WHO-BMI groups, and these findings suggest that a higher overweight but lowered obese thresholds may be best suited to older adults. Further work must be done to validate these thresholds in other populations and ethnicities, as well as in the context of other health outcomes. / Thesis / Master of Science (MSc)

Source: Dissertation Abstracts International, Volume: 70-03, Section: B, page: 1621. Adviser: Deanna M. Hoelscher. Includes bibliographical references.

Introduction: Body Mass Index (BMI) is a relative measure of whether an individual’s weight is at a healthy level for their height. A higher BMI is associated with an increased risk of cancer and cardiovascular disease (CVD). However, the biologic mechanisms are not well understood. One proposed mechanism is through changes in global DNA methylation levels, particularly global DNA hypomethylation. Global DNA hypomethylation refers to lower levels of DNA methylation across the entire genome and hypermethylation refers to higher levels of DNA methylation across the entire genome. Changes in methylation levels can affect gene expression, genomic stability, and chromosomal structure. The methylation status of repetitive sequences in the DNA, such as LINE-1, is commonly used to represent a surrogate measure of global DNA methylation levels. Objectives: 1. Quantify and describe LINE-1 DNA methylation in leukocytes in a large sample of healthy volunteers. 2. Examine the relationship between BMI and LINE-1 DNA methylation levels. 3. Assess if sex is an effect modifier of the relationship between BMI and LINE-1 DNA methylation levels. Methods: A nested cross-sectional study was composed of 502 healthy volunteers between the ages of 20 and 50. Subjects completed a study questionnaire and provided blood samples for laboratory analyses. For each subject, DNA was isolated, underwent bisulfite conversion, and LINE-1 DNA methylation levels were measured by Polymerase Chain Reaction (PCR) High-Resolution Melting Curve analysis. For the main analysis, a multivariate linear regression model was used to examine the relationship between BMI and LINE-1 DNA methylation levels, while controlling for confounders. Results: LINE-1 DNA methylation was normally distributed with a mean of 84.52% and a standard deviation of 3.19%. BMI (normal, overweight, and obese categories) was not significantly associated with LINE-1 DNA methylation levels in the adjusted linear regression model (p=0.41) and the interaction term between BMI and sex was not significant (p=0.50). Conclusions: LINE-1 DNA methylation was measured with a high degree of reliability in a sample of healthy volunteers. This research provided a description of LINE-1 DNA methylation levels in a large healthy population and showed that BMI was not associated with global DNA methylation. / Thesis (Master, Community Health & Epidemiology) -- Queen's University, 2012-04-03 17:23:59.843

Univ., Diss., 2009--Marburg.

Thesis PlanB (M.S.)--University of Wisconsin--Stout, 2009. / Includes bibliographical references.

Dopamine has an important role in normal cognition and reward processing, both of which are impaired in disorders involving dopamine dysfunction such as addiction, schizophrenia, and Parkinson's disease. However, our understanding of the interplay between different aspects of the dopamine system and reward-guided behavior in humans is limited. Food is an important type of reward that is critical for survival and impacts the decisions we make every day. Here, we characterize the relationship between two food-reward related phenotypes and dopamine synthesis capacity (related to tonic dopamine) as well as dopamine D1 and D2 receptor availability in healthy humans. First, we examined the link between dopamine synthesis and receptor availability and body mass regulation in 117 individuals with body mass index (BMI) values ranging from normal to obese. We found that current BMI was related to a pattern of increased dopamine synthesis in the hypothalamus, a region important for homeostatic control of appetite, but decreased dopamine D₂ receptor availability in the midbrain, where D₂ autoreceptors regulate dopamine release throughout the brain. This suggests that increased BMI is related to a dopamine imbalance between homeostatic drivers of appetite and reward system regulatory control mechanisms that could result in an overactive, unregulated intake of food. Building on this finding, we studied the link between dopamine synthesis capacity and receptor availability and an important food-reward related behavior, foraging. Fifty-seven healthy volunteers completed a computer-based foraging task where we measured their threshold for leaving one group of rewards to search for another in four different reward environments varying from a low to high rate of reward receipt. We found that two particular patterns of dopamine synthesis and receptor availability in the anterior cingulate cortex and basal ganglia were linked to the amount that individuals changed their threshold based on the reward rate of the environment. Finally, since the prefrontal cortex is known to be important for reward-guided behavior, we implemented two methodological advancements aimed to address limitations that make it difficult to measure cortical dopamine in humans with PET imaging. The first method involves partial volume correction and surface-based smoothing in order to increase the signal to noise in the cortex. The second method is a data-driven PET data parcellation and automated reference region selection algorithm to optimize the voxels included in the reference region. In conclusion, we have characterized the dopaminergic contribution of two different foodreward guided phenotypes and have developed two techniques that will aid future research on the role of cortical dopamine. Understanding the neural mechanisms underlying these rewardguided behaviors helps us to not only understand normal behavior, but also serves as a reference for comparison when studying related pathological states.

published_or_final_version / abstract / Medical Sciences / Master / Master of Medical Sciences