Association of dietary macronutrients with MRI-detected vascular brain injury and cognition in 9886 middle-aged participants from four countries: for the Canadian Alliance of Healthy Hearts and Minds (CAHHM) and the Prospective Urban Rural Epidemiolog (PURE) Study Investigators.

Background: Epidemiologic evidence relating macronutrient intake and changes in the brain and cognition are limited. We assessed the associations of macronutrient consumption, including carbohydrate, protein, total fat, saturated fatty acids, monounsaturated fatty acids, and polyunsaturated fatty acids, with vascular brain injury and cognitive scores.

Methods: We analyzed cross-sectional data from 9886 middle-aged adults in four countries free of clinically apparent cardiovascular disease from the Canadian Alliance for Healthy Hearts and Minds (CAHHM) and the Prospective Urban Rural Epidemiological MIND (PURE-MIND) studies. Participants from CAHHM were recruited from January 1, 2014 to December 31, 2018, and PURE-MIND participants were recruited from January 1, 2010 to December 31, 2018. Dietary intakes were collected using validated ethnic or country-specific food frequency questionnaires. We report associations between macronutrient intakes and covert brain infarcts, high white matter hyperintensities (WMH), and the composite of vascular brain injury (defined as the presence of covert brain infarct or WMH) using multivariable logistic regression models adjusting for sociodemographic and vascular risk factors, and energy intake. Multivariable linear regression was used to examine the associations of macronutrient intakes with cognitive scores (Montreal Cognitive Assessment [MoCA] and Digit Symbol Substitution Test [DSST]).

Findings: In multivariable adjusted analyses, higher carbohydrate intake was significantly associated with higher covert brain infarct (highest third (T3) vs. lowest third (T1), OR 1·40; 95% CI 1·11-1·78), high WMH (T3 vs. T1, OR 1·51; 1·20-1·89), and composite vascular brain injury (T3 vs. T1, OR 1·48; 1·24-1·75), and lower MoCA and DSST z-scores. Total fat intake was associated with lower covert brain infarcts (T3 vs. T1, OR 0·75; 0·60-0·94), and composite vascular brain injury (T3 vs. T1, OR 0·77; 0·65-0·91). Intake of saturated fatty acids was associated with lower covert brain infarcts only, while intake of monounsaturated fatty acids was associated with lower covert brain infarcts, high WMH, and composite vascular brain injury, and a higher DSST z-score. Higher polyunsaturated fatty acid intake was associated with a DSST z-score.

Interpretation: In this cross-sectional study, high intake of carbohydrates was associated with higher MRI-detected vascular brain injury and lower cognitive scores, whereas higher intakes of total and individual types of fats were associated with lower vascular brain injury and higher cognitive scores.

Funding: Full funding sources are listed at the end of the paper.