The MIND-BC Study: MIND diet for Breast cancer Cognition - PROJECT SUMMARY Cancer-related cognitive impairment (CRCI) is reported by up to 75% of breast cancer patients during treatment. Notably, up to 33% of survivors experience CRCI up to 20 years post-treatment. CRCI can be devastating among survivors, reducing return to work, self-confidence, social relationships, and day-to-day quality of life. Despite the well-documented CRCI burden, few efficacious interventions exist for this population. Likely biological mechanisms of CRCI include inflammation and oxidative stress, among others. Dietary interventions could be highly disseminable and acceptable to survivors but to our knowledge, none have been evaluated for CRCI. The “Mediterranean-DASH Intervention for Neurodegenerative Delay” (MIND) diet has been shown to improve neurocognitive outcomes (i.e., global cognition, working memory, verbal recognition memory, attention) and preserve brain structure (i.e., inferior frontal gyrus, a key region of language production) in randomized clinical trials (RCT) of women with obesity, adults with hypertension, and/or older adults at risk for Alzheimer’s disease. In an RCT in the New England Journal of Medicine, both the MIND diet and mild caloric restriction were associated with statistically significant improvements in overall cognition in overweight older adults with a family history of dementia. The MIND diet provides rich sources of polyphenols, vitamins (e.g., B6), and minerals (e.g., zinc) that act as anti-inflammatory and antioxidants. Thus, the MIND diet may target the putative mechanisms of CRCI. In the current study, we will conduct the first fully powered RCT to evaluate the efficacy the MIND diet among people with cancer. Breast cancer survivors who have completed adjuvant treatment 6 months to three years previously and reporting CRCI and low adherence to the MIND diet (N=200) will be randomized 1:1 to a 12-week feeding trial of the MIND diet versus their usual diet. Assessments will occur immediately before (baseline) and immediately after the 12-week feeding trial intervention (informed by previous RCTs showing cognitive benefits within this timeframe in non-cancer samples). To evaluate the longer-term effects of the MIND diet, we will also conduct a 3 month follow-up assessment. Assessments include: 1) self-reported cognitive functioning (i.e., subjective cognition), 2) a battery of neurocognitive tests (i.e., best objective performance), and 3) cognitive ecological momentary assessment (EMA) or smartphone-administered neurocognitive “brain games” in daily life (i.e., usual objective performance). Consistent with the notion that subjective cognition is the most clinically-relevant measure of CRCI, it will be evaluated as the primary outcome. Assessments will also include 24-hour recalls and food frequency questionnaires as measure of dietary intake, QOL, and body composition. Blood and stool will be collected at all three timepoints. Blood will be analyzed for change in putative biological mechanisms of CRCI (e.g., inflammation) and nutrient biomarkers. Stool will be banked for future analysis. Positive findings from this well-powered RCT would have high clinical impact for the many 2.3 million breast cancer survivors living with CRCI.