Bias-free Regression Analysis in Nutrition (BRAiN) Index: A Predictive Model of Cognitive Function

Abstract Evidence suggests the development of age-related dementia is strongly associated with numerous modifiable risk factors, particularly lifestyle behaviours such as diet, sleep, and physical activity. Yet, when exploring the dietary predictors of cognitive function, many scoring systems apply linear scales to eating patterns in a way that prioritizes simplicity over predictive accuracy. The present study employed a cross-validated elastic net regression algorithm on a large dataset of self-reported dietary data (n=28,968 individuals, mean age 56.3, age range 16-100) to identify the greatest nutritional predictors of participants’ performance on a validated online cognitive function test. Bias-free Regression Analysis in Nutrition (BRAiN) scores were computed, and their predictive power was found to outperform a well-recognized cognition-focused scoring system (Mediterranean-DASH Intervention for Neurodegenerative Delay, MIND) in held-out data. Non-linear relationships between intake level and cognition were noted for most foods, with greater consumption of animal and vegetable proteins, vegetables, nuts and seeds, and wholegrains, being positively associated with cognitive function, while the regular consumption of both refined fats and refined carbohydrates was negatively associated with cognitive function. Shifts in dietary patterns by age suggested that some relationships between diet and cognitive function in nutritional epidemiology may be confounded by age-related dietary trends. Our data-driven model can be easily adjusted over time to reflect potential shifts in dietary practices at the population level and inform relevant health authorities in the timely design of effective nutritional recommendations and guidelines to prevent or slow down the onset of age-related cognitive decline. Competing Interest Statement T.R.W. is a paid scientific advisor for Hintsa Performance, Thriva LLC., and Better Brain LLC. Funding Statement This study did not receive any funding Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The University of Washington Institutional Review Board confirmed that this work did not constitute human subjects research and ethical approval was not necessary for the conduct of the present study. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data Availability All data produced in the present study are available upon reasonable request to the authors