The Relations Between Physical Activity Level, Executive Function, and White Matter Microstructure in Older Adults.

The population of older adults is increasing, indicating a need to examine factors that may prevent or mitigate age-related cognitive decline. The current study examined whether microstructural white matter characteristics mediated the relation between physical activity and executive function in older adults without any self-reported psychiatric and neurological disorders or cognitive impairment (N = 43, mean age = 73 y). Physical activity was measured by average intensity and number of steps via accelerometry. Diffusion tensor imaging was used to examine microstructural white matter characteristics, and neuropsychological testing was used to examine executive functioning. Parallel mediation models were analyzed using microstructural white matter regions of interest as mediators of the association between physical activity and executive function. Results indicated that average steps was significantly related to executive function (ß = 0.0003, t = 2.829, P = .007), while moderate to vigorous physical activity was not (ß = 0.0007, t = 1.772, P = .08). White matter metrics did not mediate any associations. This suggests that microstructural white matter characteristics alone may not be the mechanism by which physical activity impacts executive function in aging.

The effects of lutein and zeaxanthin on resting state functional connectivity in older Caucasian adults: a randomized controlled trial.

The carotenoids lutein (L) and zeaxanthin (Z) accumulate in retinal regions of the eye and have long been shown to benefit visual health. A growing literature suggests cognitive benefits as well, particularly in older adults. The present randomized controlled trial sought to investigate the effects of L and Z on brain function using resting state functional magnetic resonance imaging (fMRI). It was hypothesized that L and Z supplementation would (1) improve intra-network integrity of default mode network (DMN) and (2) reduce inter-network connectivity between DMN and other resting state networks. 48 community-dwelling older adults (mean age = 72 years) were randomly assigned to receive a daily L (10 mg) and Z (2 mg) supplement or a placebo for 1 year. Resting state fMRI data were acquired at baseline and post-intervention. A dictionary learning and sparse coding computational framework, based on machine learning principles, was used to investigate intervention-related changes in functional connectivity. DMN integrity was evaluated by calculating spatial overlap rate with a well-established DMN template provided in the neuroscience literature. Inter-network connectivity was evaluated via time series correlations between DMN and nine other resting state networks. Contrary to expectation, results indicated that L and Z significantly increased rather than decreased inter-network connectivity (Cohen's d = 0.89). A significant intra-network effect on DMN integrity was not observed. Rather than restoring what has been described in the available literature as a "youth-like" pattern of intrinsic brain activity, L and Z may facilitate the aging brain's capacity for compensation by enhancing integration between networks that tend to be functionally segregated earlier in the lifespan.

The Effects of Lutein and Zeaxanthin Supplementation on Brain Morphology in Older Adults: A Randomized, Controlled Trial.

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.

Repeated Sport-Related Concussion Shows Only Minimal White Matter Differences Many Years After Playing High School Football.

OBJECTIVE: Multiple concussions sustained in youth sport may be associated with later-life brain changes and worse cognitive outcomes. We examined the association between two or more concussions during high school football and later-life white matter (WM) microstructure (i.e., 22-47 years following football retirement) using diffusion tensor imaging (DTI). METHOD: Forty former high school football players aged 40-65 who received 2+ concussions during high school football (N = 20), or denied concussive events (N = 20) were recruited. Participants underwent neurocognitive testing and DTI scanning. RESULTS: Groups did not statistically differ on age, education, or estimated pre-morbid intelligence. Tract-based Spatial Statistics (TBSS) correcting for Family-Wise Error (FWE)(p < .05) did not yield differences between groups at the whole-brain level. Region of interest analyses showed higher mean diffusivity (MD) in the anterior limb of the internal capsule (ALIC) in the concussed group compared to the non-concussed former players. More liberal analyses (i.e., p < .001, uncorrected for multiple comparisons, ≥8 voxels) also revealed that former players endorsing 2+ concussions had higher MD in the ALIC. Analyses that covaried for age did not reveal differences at either threshold. Concussive histories were not associated with worse cognitive functioning, nor did it impact the relationship between neuropsychological scores and DTI metrics. DISCUSSION: Results suggest only minimal neuroanatomical brain differences in former athletes many years following original concussive injuries compared to controls.

Intelligence moderates the relationship between age and inter-connectivity of resting state networks in older adults.

Age-related changes in the interactive behavior of default mode network (DMN) with other resting state networks are poorly understood. We hypothesized that age would positively correlate with inter-network connectivity in late life and intellectual functioning was expected to moderate this relationship. The sample consisted of 48 community-dwelling older adults with resting state functional magnetic resonance imaging data. Global inter-connectivity between DMN and 9 other resting state networks was calculated using a novel computational framework based on machine learning. Intellectual functioning (intelligence) was estimated using the Wechsler Test of Adult Reading. A significant, positive relationship was found between age and global inter-network connectivity (r = 0.31, p = 0.029). Moderation analyses yielded a significant age × intelligence interaction term (p = 0.003), such that intelligence attenuated the relationship between age and global inter-network connectivity. Taken together, these results suggest that age is positively associated with global DMN desegregation, possibly due to dedifferentiation or compensation. Intellectual functioning moderates this relationship, such that more intelligent older adults maintain a segregated DMN profile.

Education Differentially Buffers Cognitive Performance in Black and White Older Adults.

OBJECTIVES: Given that black American older adults are more likely to have lower educational attainment and perform worse on cognitive tests than white Americans, we examined whether increased education would confer greater cognitive advantage to black Americans on measures of global and specific domains of cognitive function. METHODS: The sample included 522 community-dwelling older adults from a larger study. An analysis of covariance was conducted with race and education as between-participant factors and global cognition as the dependent variable. A multivariate analysis of covariance was conducted with five cognitive domains (immediate memory, visuospatial/constructional ability, language, attention, and delayed memory) as the dependent variables. RESULTS: Significant main effects indicated that black Americans, F(1,516) = 29.18, p < .001, and individuals with less education, F(1,516) = 44.93, p < .001, evidenced lower cognitive functioning, controlling for age and overall health status, and the interaction term reached statistical significance, F(1,516) = 7.95, p = .005. The impact of education on global cognitive function for black participants was more than twice as large (Cohen's d = 1.30) than for white participants (Cohen's d = .52). There was a significant race × education interaction for the cognitive domain of attention (p < .001) and a composite measure of non-memory domains (i.e., language, visuospatial/constructional, and attention; p < .001). DISCUSSION: Our findings suggest that educational attainment is particularly important for black Americans with respect to global cognitive function, attention, and non-memory domains.

Lutein and Zeaxanthin Are Positively Associated with Visual-Spatial Functioning in Older Adults: An fMRI Study.

Lutein (L) and zeaxanthin (Z) are two xanthophyll carotenoids that have antioxidant and anti-inflammatory properties. Previous work has demonstrated their importance for eye health and preventing diseases such as age-related macular degeneration. An emerging literature base has also demonstrated the importance of L and Z in cognition, neural structure, and neural efficiency. The present study aimed to better understand the mechanisms by which L and Z relate to cognition, in particular, visual-spatial processing and decision-making in older adults. We hypothesized that markers of higher levels of L and Z would be associated with better neural efficiency during a visual-spatial processing task. L and Z were assessed via standard measurement of blood serum and retinal concentrations. Visual-spatial processing and decision-making were assessed via a judgment of line orientation task (JLO) completed during a functional magnetic resonance imaging (fMRI) scan. The results demonstrated that individuals with higher concentrations of L and Z showed a decreased blood-oxygen-level dependent (BOLD) signal during task performance (i.e., "neural efficiency") in key areas associated with visual-spatial perception, processing, decision-making, and motor coordination, including the lateral occipital cortex, occipital pole, superior and middle temporal gyri, superior parietal lobule, superior and middle frontal gyri, and pre- and post-central gyri. To our knowledge, this is the first investigation of the relationship of L and Z to visual-spatial processing at a neural level using in vivo methodology. Our findings suggest that L and Z may impact brain health and cognition in older adults by enhancing neurobiological efficiency in a variety of regions that support visual perception and decision-making.

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.

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 (Cohen's 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 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.

Cognitive Interventions for Cognitively Healthy, Mildly Impaired, and Mixed Samples of Older Adults: A Systematic Review and Meta-Analysis of Randomized-Controlled Trials.

Cognitive interventions may improve cognition, delay age-related cognitive declines, and improve quality of life for older adults. The current meta-analysis was conducted to update and expand previous work on the efficacy of cognitive interventions for older adults and to examine the impact of key demographic and methodological variables. EBSCOhost and Embase online databases and reference lists were searched to identify relevant randomized-controlled trials (RCTs) of cognitive interventions for cognitively healthy or mildly impaired (MCI) older adults (60+ years). Interventions trained a single cognitive domain (e.g., memory) or were multi-domain training, and outcomes were assessed immediately post-intervention using standard neuropsychological tests. In total, 279 effects from 97 studies were pooled based on a random-effects model and expressed as Hedges' g (unbiased). Overall, results indicated that cognitive interventions produce a small, but significant, improvement in the cognitive functioning of older adults, relative to active and passive control groups (g = 0.298, p < .001, 95% CI = 0.248-0.347). These results were confirmed using multi-level analyses adjusting for nesting of effect sizes within studies (g = 0.362, p < .001, 95% CI = 0.275, 0.449). Age, education, and cognitive status (healthy vs. MCI) were not significant moderators. Working memory interventions proved most effective (g = 0.479), though memory, processing speed, and multi-domain interventions also significantly improved cognition. Effects were larger for directly trained outcomes but were also significant for non-trained outcomes (i.e., "transfer effects"). Implications for future research and clinical practice are discussed. This project was pre-registered with PROSPERO (#42016038386).

Relationship of Lutein and Zeaxanthin Levels to Neurocognitive Functioning: An fMRI Study of Older Adults.

OBJECTIVES: It is well known that the carotenoids lutein (L) and zeaxanthin (Z) improve eye health and an accumulating evidence base suggests cognitive benefits as well. The present study investigated underlying neural mechanisms using functional magnetic resonance imaging (fMRI). It was hypothesized that lower L and Z concentrations would be associated with neurobiological inefficiency (i.e., increased activation) during cognitive performance. METHODS: Forty-three community-dwelling older adults (mean age=72 years; 58% female; 100% Caucasian) were asked to learn and recall pairs of unrelated words in an fMRI-adapted paradigm. L and Z levels were measured in retina (macular pigment optical density) and serum using validated procedures. RESULTS: Following first-level contrasts of encoding and retrieval trials minus control trials (p<.05, family-wise error corrected, minimum voxel cluster=8), L and Z were found to significantly and negatively relate to blood-oxygen-level-dependent signal in central and parietal operculum cortex, inferior frontal gyrus, supramarginal gyrus, planum polare, frontal and middle temporal gyrus, superior parietal lobule, postcentral gyrus, precentral gyrus, occipital cortex bilaterally, and cerebellar regions. CONCLUSIONS: To the authors' knowledge, the present study represents the first attempt to investigate neural mechanisms underlying the relation of L and Z to cognition using fMRI. The observed results suggest that L and Z promote cognitive functioning in old age by enhancing neural efficiency. (JINS, 2017, 23, 11-22).