DESCRIPTION (provided by applicant): Obesity is a leading cause of death and disability in the United States (US), affecting as many as 80 million Americans. It is well-established that obesity contributes to a number of risk factors for metabolic abnormalities and cardiovascular disease (CVD), including hypertension, diabetes, and hyperlipidemia. In addition, there is growing evidence that obesity is associated with cognitive deficits in multiple domains, even in otherwise healthy older adults. With the rapidly aging US population and the high prevalence of obesity among older adults, innovative strategies to prevent cognitive decline in this population are needed. Dietary patterns are central to the development and maintenance of obesity and evidence suggests that dietary factors also may affect cognition. Epidemiologic studies have shown that adherence to a Mediterranean Diet (MedDiet) is associated with less cognitive decline and reduced risk for dementia. Weight loss through caloric restriction also has been shown to improve cognitive function in obese adults. The identification of effective lifestyle interventions for diet/weight management to improve cognition among obese older adults is a public health priority. However, to our knowledge, no randomized clinical trials (RCTs) have examined the effect of the MedDiet, with and without caloric restriction, to promote weight loss on cognitive functioning in obese older adults. We propose a three-arm RCT in which 180 obese (body mass index [BMI] >30 and < 50 kg/m2) older adults, aged 55 years and older, will be randomized to an 8-month intervention consisting of: 1) MedDiet Alone, without caloric restriction/weight loss (MedDiet-A); 2) MedDiet lifestyle intervention with caloric restriction/weight loss (MedDiet-WL); or 3) typical diet control (TDC) without caloric restriction/weight loss. We will test the following hypotheses: 1) participants randomized to MedDiet-A and MedDiet-WL will achieve greater improvements in cognition compared to participants randomized to TDC; 2) participants randomized to MedDiet-WL will exhibit greater improvements in cognition compared to participants randomized to MedDiet-A; 3) participants randomized to MedDiet-A and MedDiet-WL will show greater improvements in CVD/metabolic risk factors, systemic inflammation, oxidative stress (OxStress), and body weight/composition compared to participants in TDC; 4) participants randomized to MedDiet-WL will exhibit greater improvements in CVD/metabolic risk factors, systemic inflammation, OxStress, and body weight/composition compared to MedDiet-A. We also we examine potential moderators of treatment (e.g., ethnicity and baseline cognitive function) and explore mediators by which neurocognition is improved by diet, including changes in CVD/metabolic risk factors, physical activity, systemic inflammation, and OxStress. We also will determine the extent to which changes in dietary habits, weight, and cognitive functioning are maintained over a 6-month follow-up period.

PUBLIC HEALTH RELEVANCE: The deleterious effects of obesity on cardiovascular disease (CVD) and metabolic risk factors (dyslipidemia, hypertension, and insulin resistance) are well-documented. Recent evidence also links obesity to cognitive decline and dementia. Dietary patterns are central to the development and maintenance of obesity and certain dietary patterns may contribute to the onset and progression of cognitive decline. With the rapid aging of the US population and the high prevalence of obesity among older adults, innovative lifestyle strategies to prevent cognitive decline among ethnically diverse obese older adults are critically needed.