Dietary carotenoids related to risk of incident Alzheimer dementia (AD) and brain AD neuropathology: a community-based cohort of older adults

Background: Studies have reported a protective relation to cognitive decline with long-term intake of total and individual dietary carotenoids. However, the underlying mechanisms have not yet been clearly established in humans. Objectives: To evaluate the prospective association between intakes of total and individual carotenoids and risk of incident Alzheimer dementia (AD) and explore the underlying neuropathological basis. Methods: Among 927 participants from the Rush Memory and Aging Project who were free from AD at baseline and were followed up for a mean of 7 y, we estimated HRs for AD using Cox proportional hazards models by intakes of energy-adjusted carotenoids. Brain AD neuropathology was assessed in postmortem brain autopsies among 508 deceased participants. We used linear regression to assess the association of carotenoid intake with AD-related neuropathology. Results: Higher intake of total carotenoids was associated with substantially lower hazard of AD after controlling for age, sex, education, ApoE-s4, participation in cognitively stimulating activities, and physical activity level. Comparing the top and bottom quintiles (median intake: 24.8 compared with 6.7 mg/d) of total carotenoids, the multivariate HR (95% CI) was 0.52 (0.33, 0.81), P-trend < 0.01. A similar association was observed for lutein zeaxanthin, a weaker linear inverse association was observed for beta-carotene, and a marginally significant linear inverse association was found for beta-cryptoxanthin. Among the deceased participants, consumers of higher total carotenoids (top compared with bottom tertile, 18.2 compared with 8.2 mg/d) had less global AD pathology (b: -0.10; SE = 0.04; P-trend = 0.01). For individual carotenoids, lutein-zeaxanthin and lycopene were inversely associated with brain global pathology, whereas lutein-zeaxanthin showed additional inverse associations with AD diagnostic score, neuritic plaque severity, and neurofibrillary tangle density and severity. Conclusions: Our findings support a beneficial role of total carotenoid consumption, in particular lutein/zeaxanthin, on AD incidence that may be related to the inhibition of brain beta-amyloid deposition and fibril formation.

Automated summary

This study found a protective relationship between long-term intake of total and individual dietary carotenoids and lower risk of cognitive decline. Results showed that higher intake of total carotenoids, particularly lutein/zeaxanthin, was significantly associated with lower hazard of AD. Examining the association of individual carotenoids with AD-related neuropathology revealed some components with inverse relationships.