Program Director/Principal Investigator (Last, First, Middle): Morris, Martha Clare and Aggarwal, Neelum T This is a resubmission of R01 application AG062637 that is retitled to, “MIND Diet and Dementia Prevention in Ischemic Stroke Patients.” The application is a Phase III randomized-controlled trial designed to test the effects of a 3-year intervention of the MIND diet plus usual post-stroke care versus usual post-stroke care on cognitive decline, brain biomarkers of AD and vascular disease, and on functional disability and depression in 500 patients hospitalized for acute ischemic stroke, aged 60-80 years and without dementia who are discharged home following hospitalization. More than 795,000 people in the U.S. have a stroke every year, the majority of which (87%) are ischemic. The estimated cost is $34 billion each year. Stroke is the leading cause of serious long-term disability. It is estimated that about half of survivors will experience cognitive impairment and depression, and one third will develop post-stroke dementia. Dementia is a major and growing public health problem that is amplified by the lack of effective cures or therapies to ameliorate the disease progression and symptoms. Lifestyle modifications, including dietary interventions using the DASH and Mediterranean diets, have been demonstrated to preserve or improve cognitive function and depression in older adults at high cardiovascular risk, however, it is unknown whether diet is an effective therapeutic intervention in stroke survivors. Importantly, dietary recommendations are highly desired by stroke patients and their families. The MIND diet (Mediterranean-DASH Intervention for Neurodegenerative Delay) is a hybrid of the Mediterranean and DASH diets but with selected modifications based on foods and nutrients that are important to brain health. The MIND diet has the same basic components of the DASH and Mediterranean diets, such as emphasis on natural plant-based foods and limited animal and high saturated fat foods, but uniquely specifies green leafy vegetables and berries as well as food component servings that reflect the nutrition-dementia evidence. The trial will employ a parallel group design comparing the effects of the MIND intervention (3 months of delivered MIND meals followed by dietary counseling) versus usual post-stroke care (3 months of delivered self-selected meals followed by general stroke health counseling) on decline in cognitive function and functional abilities, and depressive symptoms. Biological effects of the MIND diet will be assessed by change in measures of retinal imaging-derived amyloid beta plaque accumulation, and MRI-derived brain macro- and micro-structural integrity in 300 randomly selected participants. Other biochemical markers will be assessed over the treatment period in the entire cohort of 500 participants, including: plasma Abeta 42/Abeta 40, brain-derived neurotrophic factor (BDNF) and plasma markers of oxidative stress and inflam...