Echoing the American Transcendentalist Henry David Thoreau, I wish to live deliberately, to discover what truly matters to me, to listen to the world around me and further my enlightenment, and when I come face to face with death, feel content with how and why I lived. This thesis aims to dissect the internal disconnect we have with our purpose and fulfillment, analyze the pieces, ask questions, and then relate it back to the societal disconnect seen in the world. To live deliberately, what we say, think, and do, all reflect our good intentions and morals; we live how we desire, and not merely how others wish us to. In order to discover what truly matters, to separate our contentment and satisfaction in life from our material possessions, our money, and our power, we need to focus on what truly fulfills us. In order to listen to the world around us, come with an open mind and listen to those different from us, we need to make room for diversity and respect that we all have a right to be treated with dignity and respect. To further our enlightenment, it is important to seek to educate ourselves, find the truth, and expand our minds; enlightenment is an individual journey that the further we go on it the more connected and content we become. Finally, wishing to face death accepting of it rather than regretting and fearing our end; we want to die knowing that how we lived and why we did the things we did were for a content life.

The burden of dementia and its primary cause, Alzheimer’s disease, continue to devastate many with no available cure although present research has delivered methods for risk calculation and models of disease development that promote preventative strategies. Presently Alzheimer’s disease affects 1 in 9 people aged 65 and older amounting to a total annual healthcare cost in 2023 in the United States of $345 billion between Alzheimer’s disease and other dementias making dementia one of the costliest conditions to society (“2023 Alzheimer’s Disease Facts and Figures,” 2023). This substantial cost can be dramatically lowered in addition to a reduction in the overall burden of dementia through the help of risk prediction models, but there is still a need for models to deliver an individual’s predicted time of onset that supplements risk prediction in hopes of improving preventative care. The aim of this study is to develop a model used to predict the age of onset for all-cause dementias and Alzheimer’s disease using demographic, comorbidity, and genetic data from a cohort sample. This study creates multiple regression models with methods of ordinary least squares (OLS) and least absolute shrinkage and selection operator (LASSO) regression methods to understand the capacity of predictor variables that estimate age of onset for all-cause dementia and Alzheimer’s disease. This study is unique in its use of a diverse cohort containing 346 participants to create a predictive model that originates from the All of Us Research Program database and seeks to represent an accurate sampling of the United States population. The regression models generated had no predictive capacity for the age of onset but outline a simplified approach for integrating public health data into a predictive model. The results from the generated models suggest a need for continued research linking risk factors that estimate time of onset.

This project is an investigation of the gene by environment (GxE) interactions’ effect on substance use outcomes among refugee communities. Substance use disorders (SUDs) are a major public health concern, affecting individuals and communities worldwide. The etiology of SUDs is complex, involving a combination of genetic, environmental, and social factors. In recent years, there has been growing interest in the role of gene by environment interactions in the development of SUDs, particularly in vulnerable populations such as refugees. Refugee populations are exposed to a range of environmental stressors that may interact with genetic factors to increase their risk of SUDs. However, a number of studies describe a “refugee paradox,” where despite having been exposed to risk factors that can lead to SUDs, they are less likely to develop SUDs. Understanding these gene by environment interactions in refugee communities is crucial for not only understanding this phenomenon, but developing effective prevention and treatment strategies for this population. This thesis aims to investigate the gene by environment interactions underlying substance use in refugee communities and to analyze different methods for gene by environment analyses, ultimately determining which method is best suited for this population.