477 The effect of short- and long-term diets on mechanisms of healthy brain aging: A protocol

Objectives/Goals: The second highest fear of the aging population is cognitive decline. Diet is associated with brain aging; therefore, the objective is to determine the effects of a Western diet (WD) on cognitive decline and the efficacy of a Mediterranean diet (MeDi) fecal microbiota transplant (FMT) in WD-induced cognitive deficit progression in aged rats. Methods/Study Population: For Study 1, 12-month-old Fischer344 rats (NIA Aging Colony) will be randomly assigned to a WD, MeDi, or control (positive control) for 6 or 12 months. Microbiota composition, blood pressure, and body composition (DXA Scan) will be longitudinally assessed. Groups will undergo a battery of neurobehavioral assessments to measure cognitive performance. At the end of the study, mitochondria bioenergetic assays in isolated cerebral microvessels will be used to determine changes in cerebrovascular function. For Study 2, 18-month-old Fischer344 rats (NIA Aging Colony) will be randomly assigned to a WD, MeDi, or control for 6 months. At month 4, the WD+ MeDi-FMT group will receive once weekly MeDi-FMT for two months. Assessments will be performed as described in Study 1. Results/Anticipated Results: It is anticipated that the WD-related gut dysbiosis will increase blood pressure, fat-free mass, neurovascular dysfunction, and induce cognitive impairment relative to a MeDi. When using a MeDi-FMT as an intervention, it is anticipated that there will be measurable improvements in cognitive function relative to a WD through the regulation of gut dysbiosis, blood pressure, fat-free mass, and neurovascular dysfunction. Discussion/Significance of Impact: These results are expected to have an important positive impact because they will provide insights into the WD-induced gut dysbiosis-associated cognitive impairments, and evaluate the roles and mechanisms of MeDi-FMT in the therapeutic intervention of aged rats.