Apolipoprotein E ε4-dependent associations between carotenoids and cognitive decline: Findings from the MIND (Mediterranean-DASH Intervention for Neurodegenerative delay) randomized controlled trial.

BACKGROUND: Alzheimer disease (AD) prevention is a public health priority, yet the impact of dietary carotenoids on cognitive decline, particularly in apolipoprotein E (APOE) ε4 carriers, remains unclear. OBJECTIVES: The objective of this study was to examine whether the APOE ε4 genotype modifies the relationship between blood carotenoid concentrations and global cognition. METHODS: This study was conducted within the Mediterranean-Dietary Approaches to Stop Hypertension intervention for neurodegenerative delay trial, a 3-y randomized controlled trial comparing the effects of the Mediterranean-Dietary Approaches to Stop Hypertension intervention for neurodegenerative delay diet with the usual diet on global cognition in older adults. Eligible participants were ≥65 y, had a body mass index (in kg/m2) >25, a family history of AD, suboptimal diets, and a Montreal cognitive assessment score ≥22. The primary outcome was 3-y change in global cognitive function, assessed using a validated composite cognitive score converted to standardized units (SUs). Baseline plasma carotenoid concentrations were measured in a subgroup of participants (n = 442). Mixed-effects models were used to test the interaction between APOE ε4 status and baseline carotenoid concentrations on cognitive trajectories. RESULTS: The mean age was 70.0 y for noncarriers (n = 308) and 69.4 y for APOE ε4 carriers (n = 134). Among APOE ε4 carriers, a 1-unit increment in plasma total carotenoids at baseline was associated with higher global cognitive scores [β = 0.17 SU; 95% confidence interval (CI): 0.06, 0.28 SU; P = 0.009]. Similar associations were observed for β-carotene (β = 0.13 SU; 95% CI: 0.05, 0.21 SU; P = 0.001), α-carotene (β = 0.09 SU; 95% CI: 0.02, 0.15 SU; P = 0.008), lutein plus zeaxanthin (β = 0.14 SU; 95% CI: 0.04, 0.25 SU; P = 0.008), lycopene (β = 0.17 SU; 95% CI: 0.07, 0.28 SU; P = 0.005), and β-cryptoxanthin (β = 0.13 SU; 95% CI: 0.05, 0.21 SU; P = 0.03). Associations in noncarriers were weaker or nonsignificant. CONCLUSIONS: Higher plasma carotenoid concentrations were associated with slower cognitive decline in APOE ε4 carriers, potentially mitigating genetic risk. This trial was registered at clinicaltrials.gov as NCT02817074.