Plasma Proteins Associated with the Mediterranean-Dietary Approaches to Stop Hypertension Intervention for Neurodegenerative Delay (MIND) Diet and Incident Dementia

Background: The Mediterranean-Dietary Approaches to Stop Hypertension Intervention for Neurodegenerative Delay (MIND) diet slows cognitive decline and protects brain health, but the mechanisms are poorly understood. Objectives: We aimed to determine the plasma proteins associated with the MIND diet score and their ability to predict incident dementia in the Atherosclerosis Risk in Communities study. Methods: We analyzed 10,230 Black and White participants at visit 3 (1993–1995) with food frequency questionnaire and proteomics data and randomly divided them into discovery (n = 6850) and replication (n = 3380) samples. We examined associations between the MIND diet score and 4955 proteins using multivariable linear regression and elastic net regression. C-statistics were calculated to assess if proteins improved the prediction of high MIND diet adherence beyond participant characteristics. Cox proportional hazards models were used to assess associations between significant diet-related proteins and incident dementia over 2 decades. C-statistics assessed the ability of significant proteins to improve dementia prediction beyond known risk factors. Results: Of 316 proteins associated with the MIND diet score in the discovery sample at a false discovery rate <0.05, 62 were internally replicated. Of these, 21 proteins selected by the elastic net individually improved MIND diet score prediction. After a median follow-up of 21 y, there were 2311 dementia cases. Five diet-related proteins, thrombospondin-2 [hazard ratio (HR): 1.19; 95% confidence interval (CI): 1.11, 1.29], protein ABHD14A (HR: 1.23; 95% CI: 1.11, 1.37), structural maintenance of chromosomes protein 3 (HR: 1.19; 95% CI: 1.08, 1.31), epidermal growth factor receptor (HR: 0.68; 95% CI: 0.53, 0.86), and interleukin-12 subunit beta (HR: 1.14; 95% CI: 1.05, 1.25) were significantly associated with incident dementia. All 5 proteins individually and together improved the prediction of dementia risk. Conclusions: Using high-throughput proteomics, we identified candidate biomarkers of the MIND diet score and incident dementia, which are implicated in neural signaling, angiogenesis, and anti-inflammatory pathways.