Abstract
A growing literature emphasizes the importance of lifestyle factors such as nutrition in successful aging. The current study examined if one year of supplementation with lutein (L) and zeaxanthin (Z), two nutrients with known antioxidative properties and cognitive benefits, impacted structural brain outcomes in older adults using a double-blind, randomized, placebo-controlled trial design. Community-dwelling older adults (20 males and 27 females) aged 65–87 years (M = 71.8 years, SD = 6.04 years) were randomized into supplement (N = 33) and placebo groups (N = 14) using simple randomization. The supplement group received 10 mg L + 2 mg Z daily for 12 months while the placebo group received a visually identical, inert placebo. L and Z were measured via retinal concentrations (macular pigment optical density or MPOD). Structural brain outcomes, focusing on global and frontal-temporal lobe regions, were acquired using both T1-weighted and DTI MRI sequences. We hypothesized that the supplement group would increase, maintain, or show attenuated loss in hypothesized regions-of-interest (ROIs) while the placebo group would show age-related declines in brain structural integrity over the course of the trial. While results showed age-related declines for frontal and temporal gray and white matter volumes, as well as fornix white matter microstructure across both groups, only minimal differences were found between the supplement and placebo groups. However, exploratory analyses showed that individuals who responded better to supplementation (i.e., showed greater increases in MPOD) showed less decline in global and prefrontal gray matter volume than supplement “nonresponders.” While results suggest that one year of L and Z supplementation may have limited effects on structural brain outcomes overall, there may be a subsample of individuals for whom supplementation of L and Z provides greater benefits. ClinicalTrials.gov number, NCT02023645.
Highlights
Aging is associated with many changes, both cognitive and neural, that contribute to negative outcomes such as decreased functional independence, significant personal and societal economic burden, and psychological distress for both aging individuals and their caregivers [1, 2]
L and Z are the dominant carotenoids in the central nervous system (CNS) in both early- and late-life, where they account for 66–77% of the total carotenoid concentration in human brain tissue [8, 9]
Recent randomized control trials (RCTs) have demonstrated that the effects of L and Z supplementation can be measured at a neural level using functional neuroimaging technology [11]
Summary
Aging is associated with many changes, both cognitive and neural, that contribute to negative outcomes such as decreased functional independence, significant personal and societal economic burden, and psychological distress for both aging individuals and their caregivers [1, 2]. To combat the negative effects of oxidation, researchers have studied nutrients such as vitamins, flavonoids, and carotenoids for their potential in preventing and treating age-related cognitive and neural decline. Intake of these nutrients, along with healthy fatty acids and adherence to a balanced healthy diet, has been associated with positive neural effects, including preserved gray and white matter volume, white matter microstructure, and lower risk of cerebral infarcts, even after controlling for demographics and vascular risk factors [5,6,7]. There remains limited literature on the structural brain effects of L and Z, and, to our knowledge, the only published study that examined the effect of L and Z on brain structure in vivo was crosssectional [12]. us, the aim of the current study was to extend previous literature on the relation between L and Z and brain structure in older adults by using a randomized, double-blind, placebo-controlled trial design to evaluate the impact of L and Z supplementation on several metrics of brain structure
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