Lisa M. Renzi-Hammond

Lutein and Zeaxanthin Influence Brain Function in Older Adults: A Randomized Controlled Trial

OBJECTIVES The present study constitutes the first randomized controlled trial to investigate the relation of lutein (L) and zeaxanthin (Z) to brain function using functional magnetic resonance imaging (fMRI). It was hypothesized that L and Z supplementation in older adults would enhance neural efficiency (i.e., reduce activation) and cognitive performance on a verbal learning task relative to placebo. METHODS A total of 44 community-dwelling older adults (mean age=72 years) were randomly assigned to receive either placebo or L+Z supplementation (12 mg/daily) for 1 year. Neurocognitive performance was assessed at baseline and post-intervention on an fMRI-adapted task involving learning and recalling word pairs. Imaging contrasts of blood-oxygen-level-dependent (BOLD) signal were created by subtracting active control trials from learning and recall trials. A flexible factorial model was employed to investigate the expected group (placebo vs. supplement) by time (baseline vs. post-intervention) interaction in pre-specified regions-of-interest. RESULTS L and Z appeared to buffer cognitive decline on the verbal learning task (Cohens d=.84). Significant interactions during learning were observed in left dorsolateral prefrontal cortex and anterior cingulate cortex (p < .05, family-wise-error corrected). However, these effects were in the direction of increased rather than decreased BOLD signal. Although the omnibus interaction was not significant during recall, within-group contrasts revealed significant increases in left prefrontal activation in the supplement group only. CONCLUSIONS L and Z supplementation appears to benefit neurocognitive function by enhancing cerebral perfusion, even if consumed for a discrete period of time in late life. (JINS, 2018, 24, 77-90).

Effects of Lutein/Zeaxanthin Supplementation on the Cognitive Function of Community Dwelling Older Adults: A Randomized, Double-Masked, Placebo-Controlled Trial

Background: High levels of xanthophyll carotenoids lutein (L) and zeaxanthin (Z) in the central nervous system have been previously correlated with improved cognitive function in community-dwelling older adults. In this study, we tested the effects of supplementing L and Z on older men and women with a range of baseline cognitive abilities. Objective: The purpose of this study was to determine whether or not supplementation with L+Z could improve cognitive function in community-dwelling, older adults. Design: Double-masked, randomized, placebo-controlled trial. A total of 62 older adults were randomized into groups receiving either 12 mg L+Z or a visually identical placebo. Data from 51 participants (M = 73.7 years) were available for analysis. Retinal L+Z levels (macular pigment optical density, MPOD) were measured psychophysically using heterochromatic flicker photometry as a biomarker of cortical L+Z levels. Cognitive function was measured using the CNS Vital Signs computerized test platform. Results: Participants receiving the active L+Z supplement had statistically significant increases in MPOD (p < 0.03) and improvements in complex attention (p < 0.02) and cognitive flexibility domains (p < 0.04), relative to participants taking the placebo. A trend was also seen for the executive function domain (p = 0.073). In male participants only, supplementation yielded improved composite memory (p = 0.04). Conclusions: Supplementation with L+Z improved cognitive function in community-dwelling, older men and women.

Reliability of Heterochromatic Flicker Photometry in Measuring Macular Pigment Optical Density among Preadolescent Children

Macular pigment optical density (MPOD)—assessed using customized heterochromatic flicker photometry (cHFP)—is related to better cognition and brain lutein among adults. However, the reliability of MPOD assessed by cHFP has not been investigated in children. We assessed inter-session reliability of MPOD using modified cHFP. 7–10-year-olds (n = 66) underwent cHFP over 2 visits using 11 examiners. Reliability was also assessed in a subsample (n = 46) with only 2 examiners. Among all participants, there was no significant difference between the two sessions (p = 0.59—session 1: 0.61 ± 0.28; session 2: 0.62 ± 0.27). There was no significant difference in the MPOD of boys vs. girls (p = 0.56). There was a significant correlation between sessions (Y = 0.52x + 0.31; R2 = 0.29, p ≤ 0.005), with a reliability of 0.70 (Cronbach’s α). Among the subsample with 2 examiners, there was a significant correlation between sessions (Y = 0.54x + 0.31; R2 = 0.32, p < 0.005), with a reliability of 0.72 (Cronbach’s α). In conclusion, there is moderate reliability for modified cHFP to measure MPOD in preadolescents. These findings provide support for future studies aiming to conduct noninvasive assessments of retinal xanthophylls and study their association with cognition during childhood.

From neuro-pigments to neural efficiency: The relationship between retinal carotenoids and behavioral and neuroelectric indices of cognitive control in childhood

Lutein and zeaxanthin are plant pigments known to preferentially accumulate in neural tissue. Macular Pigment Optical Density (MPOD), a non-invasive measure of retinal carotenoids and surrogate measure of brain carotenoid concentration, has been associated with disease prevention and cognitive health. Superior MPOD status in later adulthood has been shown to provide neuroprotective effects on cognition. Given that childhood signifies a critical period for carotenoid accumulation in brain, it is likely that the beneficial impact would be evident during development, though this relationship has not been directly investigated. The present study investigated the relationship between MPOD and the behavioral and neuroelectric indices elicited during a cognitive control task in preadolescent children. 49 participants completed a modified flanker task while event-related potentials (ERPs) were recorded to assess the P3 component of the ERP waveform. MPOD was associated with both behavioral performance and P3 amplitude such that children with higher MPOD had more accurate performance and lower P3 amplitudes. These relationships were more pronounced for trials requiring greater amounts of cognitive control. These results indicate that children with higher MPOD may respond to cognitive tasks more efficiently, maintaining high performance while displaying neural indices indicative of lower cognitive load. These findings provide novel support for the neuroprotective influence of retinal carotenoids during preadolescence.

The Role of Retinal Carotenoids and Age on Neuroelectric Indices of Attentional Control among Early to Middle-Aged Adults

One apparent consequence of aging appears to be loss of some aspects of cognitive control. This loss is measurable as early as mid-adulthood. Since, like many aspects of cognition, there is wide variance among individuals, it is possible that behavior, such as one’s diet, could drive some of these differences. For instance, past data on older humans and non-human primates have suggested that dietary carotenoids could slow cognitive decline. In this study, we tested how early such protection might manifest by examining a sample (n = 60) of 25–45 year olds. Carotenoid status was assessed by directly measuring macular pigment optical density (MPOD) which has shown to be highly correlated with the primary carotenoid in brain, lutein. Cognitive control was measured using event-related potentials during the performance of cognitive control tasks designed to tap into different aspects of attentional (i.e., selective attention, attentional inhibition, and response inhibition) control. Our results showed that, across participants, MPOD was related to both age and the P3 component of participants’ neuroelectric profile (P3 amplitude) for attentional, but not response, inhibition. Although younger adults exhibited larger P3 amplitudes than their older adult counterparts, older subjects with higher MPOD levels displayed P3 indices similar to their younger adult counterparts in amplitude. Furthermore, hierarchical regression analyses showed that age was no longer a significant predictor of P3 amplitude when MPOD was included as a predictor in the model, suggesting that MPOD may partially contribute to the relationship between age and P3 amplitude. In addition, age and MPOD were shown to have independent associations with intraindividual variability of attentional control, such that younger individuals and individuals with higher MPOD showed less intraindividual variability. These results show a relationship between retinal carotenoids and neuroelectric indices underlying cognitive control. The protective role of carotenoids within the CNS may be evident during early and middle adulthood, decades prior to the onset of older age.

Macular pigment optical density is positively associated with academic performance among preadolescent children

Objective: Macular pigment optical density (MPOD) – a non-invasive indicator of retinal xanthophylls and correlate of brain lutein – has been associated with superior cognitive function among adult populations. Given that lutein accumulation in the brain occurs in early life, it is possible that the cognitive implications of greater MPOD may be evident in childhood. Methods: Participants aged 8–9 years (n = 56) completed MPOD measurements via heterochromatic flicker photometry. Academic performance was assessed using the Kaufman Test of Academic and Educational Achievement II (KTEA). Habitual dietary intake of L and Z was measured among a subsample of participants (n = 35) using averaged 3-day food records. Stepwise hierarchical regression models were developed to determine the relationship between MPOD and academic achievement tests, following the adjustment of key covariates including sex, aerobic fitness, body composition, and intelligence quotient (IQ). Results: The regression analyses revealed that MPOD improved the model, beyond the covariates, for overall academic achievement (ΔR2 = 0.10, P < 0.01), mathematics (ΔR2 = 0.07, P = 0.02), and written language composite standard scores (ΔR2 = 0.15, P < 0.01). Discussion: This is the first study to demonstrate that retinal L and Z, measured as MPOD, is positively related to academic achievement in children, even after accounting for the robust effects of IQ and other demographic factors. These findings extend the positive associations observed between MPOD and cognitive abilities to a pediatric population. Trail registration: The Fitness Improves Thinking in Kids 2 (FITKids2) trial was registered at www.clinicaltrials.gov as NCT01619826.

Relation of Retinal and Serum Lutein and Zeaxanthin to White Matter Integrity in Older Adults: A Diffusion Tensor Imaging Study

Objective Lutein (L) and zeaxanthin (Z) are phytonutrients that accumulate in human brain tissue and positively impact cognition. Given their antioxidant and anti-inflammatory properties and their role in stabilizing cell membranes, L&Z may relate to measures of white matter integrity (WMI). Method The current study tested the relation of retinal (macular pigment optical density/MPOD) and blood serum concentrations of L&Z to WMI in community-dwelling older adults (n = 54) using diffusion tensor imaging (DTI). Younger adults (n = 38) were recruited as a control group to confirm age-related changes in WMI. A priori analyses focused on four regions of interest (ROIs-genu of the corpus callosum, cingulum, fornix, and uncinate fasciculus). Exploratory whole-brain analyses were also conducted. Results Consistent with previous literature, age group (young vs. old) negatively predicted WMI globally, in the genu, cingulum, and fornix (p < .001). ROI analysis in the older adult sample showed relations of MPOD and serum L&Z to better WMI in the uncinate fasciculus and cingulum (p < .05, FWE-corrected). Whole-brain analysis suggested associations between L&Z and WMI in both anterior white matter tracts vulnerable to age-related decline and posterior tracts (p < .01, uncorrected). Conclusions The current study is among the first to use neuroimaging to measure the relation of L&Z to brain structure in vivo. Results confirm previous findings that L&Z influence white matter integrity, particularly in regions vulnerable to age-related decline. The current study contributes to a growing literature investigating the relationship between diet and neural integrity by identifying white matter tracts that may be associated with modifiable dietary factors in older adults.

Macular Carotenoids, Aerobic Fitness, and Central Adiposity Are Associated Differentially with Hippocampal-Dependent Relational Memory in Preadolescent Children

Objectives To examine the associations of macular pigment carotenoids (lutein, meso‐zeaxanthin, and zeaxanthin), aerobic fitness, and central adiposity with hippocampal‐dependent relational memory in prepubescent children. Study design Children between 7 and 10 years of age (n = 40) completed a task designed to assess relational memory performance and participated in aerobic fitness, adiposity, and macular pigment optical density (MPOD) assessment. Aerobic fitness was assessed via a modified Balke treadmill protocol designed to measure maximal oxygen volume. Central adiposity was assessed via dual‐energy x‐ray absorptiometry. MPOD was measured psychophysically by the use of customized heterochromatic flicker photometry. Statistical analyses included correlations and hierarchical linear regression. Results Aerobic fitness and MPOD were associated negatively with relational memory errors (P < .01), whereas central adiposity was associated positively with relational memory errors (P < .05). Hierarchical regression analysis revealed that MPOD accounted for a significant amount of the variance in relational memory performance even after we accounted for aerobic fitness (&bgr; = −0.388, P = .007). Conclusions Even after we adjusted for aerobic fitness and central adiposity, factors known to relate to hippocampal‐dependent memory, MPOD positively and significantly predicted hippocampal‐dependent memory performance. Trial registration ClinicalTrials.gov: NCT01619826.

Effects of a Lutein and Zeaxanthin Intervention on Cognitive Function: A Randomized, Double-Masked, Placebo-Controlled Trial of Younger Healthy Adults

Background: Past studies have suggested that higher lutein (L) and zeaxanthin (Z) levels in serum and in the central nervous system (as quantified by measuring macular pigment optical density, MPOD) are related to improved cognitive function in older adults. Very few studies have addressed the issue of xanthophylls and cognitive function in younger adults, and no controlled trials have been conducted to date to determine whether or not supplementation with L + Z can change cognitive function in this population. Objective: The purpose of this study was to determine whether or not supplementation with L + Z could improve cognitive function in young (age 18–30), healthy adults. Design: A randomized, double-masked, placebo-controlled trial design was used. Fifty-one young, healthy subjects were recruited as part of a larger study on xanthophylls and cognitive function. Subjects were randomized into active supplement (n = 37) and placebo groups (n = 14). MPOD was measured psychophysically using customized heterochromatic flicker photometry. Cognitive function was measured using the CNS Vital Signs testing platform. MPOD and cognitive function were measured every four months for a full year of supplementation. Results: Supplementation increased MPOD significantly over the course of the year, vs. placebo (p < 0.001). Daily supplementation with L + Z and increases in MPOD resulted in significant improvements in spatial memory (p < 0.04), reasoning ability (p < 0.05) and complex attention (p < 0.04), above and beyond improvements due to practice effects. Conclusions: Supplementation with L + Z improves CNS xanthophyll levels and cognitive function in young, healthy adults. Magnitudes of effects are similar to previous work reporting correlations between MPOD and cognition in other populations.

The effects of photochromic lenses on visual performance.

The purpose of the current study was to evaluate the effects of filtering by an activated photochromic lens on visual performance in healthy adults. Glare disability, glare discomfort, heterochromatic contrast thresholds and photostress recovery time were assessed.