PROJECT SUMMARY/ABSTRACT Accumulating basic, clinical, and population research suggests that high amounts of abdominal fat, particularly visceral adipose tissue (VAT) in the intra-abdominal depot, plays a crucial role in the pathophysiology of cardiometabolic diseases (i.e. type 2 diabetes (T2D), cardiovascular diseases (CVD) and stroke). Furthermore, VAT is the hypothesized driver of obesity-related Alzheimer's disease and Related Dementias (AD/ADRD), as all the aforementioned conditions/diseases are related to higher risk of AD/ADRD and poor brain health. The basis for this hypothesis is research that has elegantly described the intimate nature of VAT as a powerful, upstream metabolic driver of insulin resistance, dyslipidemia, and hypertension; all conditions that precipitate the etiology of AD/ADRD and changes in brain morphology related to AD/ADRD. Other related research suggests that total body fat, and more specifically subcutaneous adipose tissue (SAT), may be relatively less important in the pathophysiology of AD/ADRD. Despite this burgeoning framework of knowledge, much remains unknown about the relationship between abdominal VAT and SAT levels with AD/ADRD – a critical gap in the evidence base since further insight resulting from research on this topic would have major implications related to the importance of body composition and obesity in AD/ADRD prevention. As part of an active RO1, Dr. Odegaard and his team derived and validated repeated measures of VAT and SAT with novel technology in the existing Women's Health Initiative (WHI) Dual Energy X-Ray Absorptiometry (DXA) cohort, providing a solution to the basic data access problem. This sub-cohort is a minority enriched, analytic longitudinal cohort in the WHI with scans at baseline (N=10,607), year 3 (N=8,939), year 6 (N=8,239), and year 9 (N=4,595). We are now proposing to extend the framework originally created to address essential questions related to cardiometabolic disease risk by leveraging the WHI study design and structure and integrating the data with the WHI Memory Study (WHIMS) data, including 860 women with repeated, valid cognitive assessments and > 80 women with brain MRI's. This project leverages two significant scientific resources within the WHI and will address fundamental hypotheses that link visceral adiposity with AD/ADRD risk and brain health in postmenopausal women.