EVALUATING THE EFFECTS OF MODIFIABLE LIFESTYLE AND CARDIOVASCULAR HEALTH FACTORS ON DIABETES LIFE EXPECTANCY IN NHANES AND BRAIN AGING IN UK BIOBANK

Abstract

This dissertation explored the impact of lifestyle and cardiovascular health factors on aging, particularly focusing on individuals with diabetes, the effects of blood pressure on brain aging, and the influence of cardiovascular health and genetic predispositions on brain white matter aging.The first study examined the trends in lifestyle quality among US adults with type 2 diabetes from 1999 to 2018 using NHANES data, involving 7,410 participants. A healthy lifestyle score encompassing smoking, drinking, physical activity, and diet showed a slight increased over the years. Notably, disparities remained significant by socioeconomic groups. The study found that adherence to low-risk lifestyle factors was associated with a 55%-57% lower risk of all-cause mortality, emphasizing the importance of lifestyle modification in diabetes management, and it was independent of cardiovascular risk control. The second study investigated the causal effect of elevated blood pressure on white matter brain aging in a cohort of 228,473 European ancestries aged 40-69 from the UK Biobank by using two-sample Mendelian randomization. Our result revealed that high blood pressure, particularly diastolic, accelerated the machine-learning-derived white matter brain age gap, based on white matter microstructure integrity measured by fractional anisotropy derived from diffusion tensor imaging data, with a causal effect evidence found in late middle-aged women. This underscores the importance of blood pressure control in preventing brain aging, especially in post-menopausal women. Lastly, the impact of Life's Essential 8 (LE8), a comprehensive measure of cardiovascular health (lifestyle part: diet, smoke, physical activity, sleep; health part: BMI, blood sugar, blood pressure, blood lipid), on white matter brain aging was assessed, with a particular focus on how the APOE4 genotype modifies the relationship. Analyzing data from 18,817 European ancestries aged 40-60 from the UK Biobank, the study revealed that higher LE8 scores correlated with a younger brain age. Interestingly, the effect varied significantly with APOE4 status, highlighting the need for personalized health strategies based on genetic profiles. In conclusion, these studies collectively highlight the crucial role of modifiable lifestyle and health factors in managing chronic diseases, controlling blood pressure, and maintaining brain health, with an emphasis on the integration of genetic profiles for personalized healthcare.