Nutrient-Wide Association Study for Dementia Risks: A Prospective Cohort Study in Middle-Aged and Older Adults

Background/Objectives: Evidence on associations between nutrients and dementia risk is limited and inconsistent. We aimed to systematically examine associations between 101 dietary nutrients and dementia incidence with a nutrient-wide association study (EWAS). Methods: We analyzed data from 6280 participants aged 50 years and older from the Health and Retirement Study. Levels of nutrient intake were measured with the food frequency questionnaire. Dementia status was assessed with the Lang-Weir Classification of Cognitive Function. In the EWAS analysis, the Cox proportional hazards regression model was used to estimate associations between each nutrient and dementia incidence, adjusting for multiple comparisons with a false discovery rate (FDR) of 0.05. Nutrients passing the EWAS selection were simultaneously included in the elastic net (ENET) regression model to construct a composite nutrient score (CNS), which was calculated as a weighted sum of the nutrients in the ENET regression model. Results: Over a mean (SD) follow-up of 6.76 (2.14) years, 495 individuals with incident dementia were identified. The results suggested that six nutrients were associated with increased dementia risks and five with decreased dementia risks. Compared with participants at the first tertile of CNS, individuals at the second (hazard ratio [HR] = 1.43, 95% confidence interval [CI] = 1.11 to 1.84) and third tertiles (HR = 1.80, 95% CI = 1.42 to 2.27) had increased risks of dementia. Furthermore, CNS-dementia associations were stronger in females than in males. Conclusions: We found that 11 dietary nutrients and their combinations were associated with dementia risks in middle-aged and older adults. Interventional studies with nutrients were warranted to confirm our findings.