Critical Flicker Fusion Predicts Executive Function in Younger and Older Adults.

Critical flicker fusion (CFF), a measure of visual processing speed, has often been regarded as a basic metric underlying a number of higher cognitive functions. To test this, we measured CFF, global cognition, and several cognitive subdomains. Because age is a strong covariate for most of these variables, both younger (n = 72) and older (n = 57) subjects were measured. Consistent with expectations, age was inversely related to CFF and performance on all of the cognitive measures except for visual memory. In contrast, age-adjusted CFF thresholds were only positively related to executive function. Results showed that CFF predicted executive function across both age groups and accounted for unique variance in performance above and beyond age and global cognitive status. The current findings suggest that CFF may be a unique predictor of executive dysfunction.

A double-blind, placebo-controlled study on the effects of lutein and zeaxanthin on neural processing speed and efficiency.

Lutein and zeaxanthin are major carotenoids in the eye but are also found in post-receptoral visual pathways. It has been hypothesized that these pigments influence the processing of visual signals within and post-retina, and that increasing lutein and zeaxanthin levels within the visual system will lead to increased visual processing speeds. To test this, we measured macular pigment density (as a biomarker of lutein and zeaxanthin levels in brain), critical flicker fusion (CFF) thresholds, and visual motor reaction time in young healthy subjects (n = 92). Changes in these outcome variables were also assessed after four months of supplementation with either placebo (n = 10), zeaxanthin only (20 mg/day; n = 29) or a mixed formulation containing 26 mg/day zeaxanthin, 8 mg/day lutein, and 190 mg/day mixed omega-3 fatty acids (n = 25). Significant correlations were found between retinal lutein and zeaxanthin (macular pigment) and CFF thresholds (p<0.01) and visual motor performance (overall p<0.01). Supplementation with zeaxanthin and the mixed formulation (considered together) produced significant (p<0.01) increases in CFF thresholds (∼12%) and visual motor reaction time (∼10%) compared to placebo. In general, increasing macular pigment density through supplementation (average increase of about 0.09 log units) resulted in significant improvements in visual processing speed, even when testing young, healthy individuals who tend to be at peak efficiency.

Lutein supplementation increases breast milk and plasma lutein concentrations in lactating women and infant plasma concentrations but does not affect other carotenoids.

Lutein is a carotenoid that varies in breast milk depending on maternal intake. Data are lacking with regard to the effect of dietary lutein supplementation on breast milk lutein concentration during lactation and subsequent plasma lutein concentration in breast-fed infants. This study was conducted to determine the impact of lutein supplementation in the breast milk and plasma of lactating women and in the plasma of breast-fed infants 2-3 mo postpartum. Lutein is the dominant carotenoid in the infant brain and the major carotenoid found in the retina of the eye. Eighty-nine lactating women 4-6 wk postpartum were randomly assigned to be administered either 0 mg/d of lutein (placebo), 6 mg/d of lutein (low-dose), or 12 mg/d of lutein (high-dose). The supplements were consumed for 6 wk while mothers followed their usual diets. Breast milk carotenoids were measured weekly by HPLC, and maternal plasma carotenoid concentrations were measured at the beginning and end of the study. Infant plasma carotenoid concentrations were assessed at the end of the study. No significant differences were found between dietary lutein + zeaxanthin intake and carotenoid concentrations in breast milk and plasma or body mass index at baseline. Total lutein + zeaxanthin concentrations were greater in the low- and high-dose-supplemented groups than in the placebo group in breast milk (140% and 250%, respectively; P < 0.0001), maternal plasma (170% and 250%, respectively; P < 0.0001), and infant plasma (180% and 330%, respectively; P < 0.05). Lutein supplementation did not affect other carotenoids in lactating women or their infants. Lactating women are highly responsive to lutein supplementation, which affects plasma lutein concentrations in the infant. This trial was registered at clinicaltrials.gov as NCT01747668.

Relationships between macular pigment optical density and cognitive function in unimpaired and mildly cognitively impaired older adults.

Low carotenoid status (especially of the xanthophylls, lutein [L], and zeaxanthin [Z]) is common in older adults and has been associated with a number of degenerative diseases of the central nervous system ranging from retina (e.g., macular degeneration) to brain (e.g., Alzheimer's disease). In this study, we tested whether retinal measures of L + Z (macular pigment optical density [MPOD]), used as a surrogate for brain L + Z levels, were related to cognitive function when comparing healthy older adults with mildly cognitively impaired older adults. Twenty-four subjects with mild cognitive impairment were compared with 24 matched controls. Subjects were matched with respect to age, body mass index, ethnicity, sex, and smoking status. Degree of cognitive impairment and cognitive ability was determined via structured clinical interview. MPOD was measured psychophysically. In healthy older adults, MPOD was only related to visual-spatial and constructional abilities (p = 0.04). For subjects with mild cognitive impairment (MCI), however, MPOD was broadly related to cognition including the composite score on the mini-mental state examination (p = 0.02), visual-spatial and constructional abilities (p = 0.04), language ability (p = 0.05), attention (p = 0.03), and the total scale on the Repeatable Battery for the Assessment of Neuropsychological Status (p = 0.03). It is possible that L/Z status may be more strongly related to cognition when individuals are considered with established onset of cognitive decline.

Macular pigment optical density is related to cognitive function in older people.

BACKGROUND: the xanthophylls lutein (L) and zeaxanthin (Z) exist in relatively high concentration in multiple central nervous tissues (e.g. cortex and neural retina). L + Z in macula (i.e. macular pigment, MP) are thought to serve multiple functions, including protection and improvement of visual performance. Also, L + Z in the macula are related to L + Z in the cortex. OBJECTIVE: to determine whether macular pigment optical density (MPOD, L + Z in the macula) is related to cognitive function in older adults. METHODS: participants were older adults (n = 108, 77.6 ± 2.7 years) sampled from the age-related maculopathy ancillary study of the Health Aging and Body Composition Study (Memphis, TN, USA). Serum carotenoids were measured using high performance liquid chromatography. MPOD was assessed using heterochromatic flicker photometry. Eight cognitive tests designed to evaluate several cognitive domains including memory and processing speed were administered. Partial correlation coefficients were computed to determine whether cognitive measures were related to serum L + Z and MPOD. RESULTS: MPOD levels were significantly associated with better global cognition, verbal learning and fluency, recall, processing speed and perceptual speed, whereas serum L + Z was significantly related to only verbal fluency. CONCLUSION: MPOD is related to cognitive function in older people. Its role as a potential biomarker of cognitive function deserves further study.

A role for the macular carotenoids in visual motor response.

OBJECTIVES: Lutein (L), zeaxanthin (Z), and meso-zeaxanthin are the dominant carotenoids within the central retina (there, termed macular pigment, MP). L is also the dominant carotenoid in the brain. The presence of L and Z in both motor and visual areas of the central nervous system is consistent with a role of these carotenoids in visual-motor behavior. The purpose of this study was to provide a first test of this hypothesis. METHODS: Balance ability (measured via the Standing Leg Test) and simple reaction time (measured via a stimulus appearing in one of four quadrants of a computer monitor) were measured in 49 subjects (mean age = 54.8 years). Fixed and variable reaction time, and coincidence anticipation ability (estimating the arrival of the stimulus at a target location moving at four velocities) were assessed in 106 younger subjects (mean age = 23 years) using a customized device. MP optical density was measured in all subjects via customized heterochromatic flicker photometry. RESULTS: MP optical density was significantly (P < 0.05) related to reaction time and to balance ability for the older subjects. Even for the younger group, MP optical density was significantly (P < 0.05) related to fixed and variable position reaction time, as well as coincidence anticipation errors, at high speed. DISCUSSION: L and Z status has been linked to benefits in cognitive function in past research. The present results, and the selective presence of L and Z in visual and motor areas in the brain, are consistent with these carotenoids having a role in visual and motor integration.

The relation between serum lipids and lutein and zeaxanthin in the serum and retina: results from cross-sectional, case-control and case study designs.

BACKGROUND: The xanthophyll carotenoids lutein (L) and zeaxanthin (Z) are found in and around the macula of the primate retina, where they are termed macular pigment (MP). Dietary L and Z are absorbed with fat in the gut and transported on lipoproteins to the retina. Both MP and serum lipoproteins have been related to risk for neurodegenerative diseases such as age-related macular degeneration (AMD). L and Z are carried on both HDL (related to reduced risk of AMD) and LDL (related to increased risk). The purpose of this set of studies was to analyze the relation between L and Z in the serum and retina with the circulating lipid profile. METHODS: In all experiments, lipoproteins were measured enzymatically from plasma, and MP optical density (MPOD) was measured using customized heterochromatic flicker photometry. Experiment 1: Relations between serum L and Z, MPOD and lipoprotein levels. 108 young, healthy subjects (M = 23.2, SD = 4.12 years) participated. Lipoprotein levels and MPOD were measured. In a subset of 66 participants, serum L and Z levels were also measured using high-performance liquid chromatography. Experiment 2: Relations between lipoprotein levels and MPOD in statin users. 20 subjects (M = 58.05, SD = 11.08 years) taking statin medication and 20 subjects (M = 57.95, SD = 11.03 years) not taking satin were recruited for participation. MPOD and lipoprotein levels were measured. Experiment 3: lowering lipoprotein levels to impact MPOD. One individual (aged 41 years) with high MP density adhered first to an atorvastatin regimen, then, after a wash-out period, to a rosuvastatin regimen. RESULTS: Experiment 1: HDL were significantly (p < 0.05) related to MPOD (r = 0.33), to serum L (r = 0.36) and to serum Z (r = 0.26). MPOD was also significantly related to total cholesterol (r = 0.19). Experiment 2: MPOD was not lower in statin users when compared to matched non-statin users, but MPOD decreased significantly with increased duration of statin use (r = -0.63). Experiment 3: Administration of a statin regimen reduced MPOD with atorvastatin (p < 0.05) but not with rosuvastatin. CONCLUSIONS: Serum xanthophylls, retinal xanthophylls and lipoprotein concentrations are significantly related, and changing lipoprotein levels may impact levels of retinal xanthophylls.

Contralateral comparison of blue-filtering and non-blue-filtering intraocular lenses: glare disability, heterochromatic contrast, and photostress recovery.

PURPOSE: To compare visual performance in eyes with intraocular lenses (IOLs) that filter short-wave blue light versus contralateral eyes with IOLs that do not filter visible blue light. METHODS: In this prospective, assessor-masked study that was conducted at five clinics in the US, eligible candidates were at least 12 months postimplantation of a control IOL and a contralateral IOL that filtered blue light. Glare disability was defined as the intensity of a white-light annulus that obscured a subject's ability to see a central target. Heterochromatic contrast thresholds were defined as the intensity of a blue-light disk that obscured a central target. Photostress recovery time was the duration required to regain sight of the target after a five-second flash of annulus light. RESULTS: Fifty-two subjects were evaluated. Mean glare disability was significantly less (P = 0.04) in the blue-filtering IOL group (1.97 ± 0.44 log µW/cm(2)) than in the control group (1.88 ± 0.43 log µW/cm(2)). Mean heterochromatic contrast threshold was significantly higher (P = 0.0003) in the blue-filtering IOL group (0.36 ± 0.43 log µW/cm(2)) than in the control IOL group (0.15 ± 0.49 log µW/cm(2)). Geometric mean photostress recovery time was significantly faster (P = 0.02) in the blue-filtering IOL group (21 ± 3 seconds) than in the control IOL group (26 ± 3 seconds). CONCLUSIONS: Glare disability was significantly lower, heterochromatic contrast threshold was significantly better, and recovery from photostress was significantly faster in the eyes with blue-filtering IOLs than in the contralateral control eyes with IOLs that did not filter blue light.

The effect of macular pigment on heterochromatic luminance contrast.

Macular pigment (MP) selectively filters short-wave light and may improve visual performance via this mechanism. This study was designed to test the hypothesis that MP alters contrast between an object and its background, and thus alters the object's detectability. In order to test this hypothesis, participants of a variety of ages were recruited into two groups. Group 1 consisted of 50 healthy elderly subjects (M = 72.7, SD = 7.3 years). Group 2 consisted of 28 healthy younger subjects (M = 22.7, SD = 3.6 years). For all subjects, contrast thresholds were assessed in Maxwellian-view. For subjects in Group 1, a circular grating target (600 nm, 1°; not absorbed by MP) was surrounded by a 10°, 460 nm field (strongly absorbed by MP). Subjects in Group 2 were measured using identical conditions with the exception that the surround was changed to 425 nm in one condition and to a broad-band (xenon) white in another. All subjects adjusted the intensity of the surround until the target was no longer visible. Finally, for a sub-sample of subjects in Group 2, a 1° bipartite field was used and wavelength was varied on one side to minimize the appearance of the border with the 460 nm reference side, foveally and parafoveally between 420-540 nm, with 20 nm steps, using the minimally distinct border (MDB) technique. MP density was assessed psychophysically. MP density was related to the amount of energy in the surround (at 425 and 460 nm, and for broad-band white) needed to lose sight of the central target. When the MDB technique was used to measure spectral sensitivity, the differences in the two curves yielded a spectrum that closely matched MP's ex vivo spectrum. Our data suggest that MP modifies an object's contrast against a short-wave background via simple filtration.

The relation between the macular carotenoids, lutein and zeaxanthin, and temporal vision.

Lutein (L) and zeaxanthin (Z) are the dominant carotenoids within the central retina (there, termed macular pigment, MP) and brain (approximately 70% of total carotenoid concentration). Past studies have shown that MP is related to many static indicators of visual performance, such as visibility and disability glare. It has also been shown that MP is related to a dynamic measure of visual performance, the critical flicker fusion threshold (CFF). In this study, we examine whether MP is related to CFF in a larger sample. We also test the relation between MP and the more complete temporal contrast sensitivity function (TCSF). A total of 70 participants were assessed for a comparison of MP and the full temporal function. A separate pool of 354 participants was assessed for a MP and CFF comparison. Peak MP density was measured psychophysically (via heterochromatic flicker photometry) using a 1-degree diameter test. CFF was measured using a 1-degree 570 nm test varied at 100% modulation. The full TCSF was measured centrally using a 1-degree, 660 nm test (the modulation depth of which could be adjusted directly by the subject) centered within a 5.5-degree, 660 nm surround. A small fixation point was used to test a 7-degree parafoveal site. MP density was positively related to temporal function as assessed by the full TCSF in the center (n = 70, r = -0.29, p < 0.01) but not at the parafoveal location (p < 0.07). MP was also positively related to critical flicker fusion thresholds (n = 354, r = 0.21, p < 0.0001).

A practical method of measuring the human temporal contrast sensitivity function.

One of the more significant indicators of neural age-related loss and disease is reduced temporal processing speed. It would, therefore, be useful to have an accurate and practical device that measures the full range of an individual's temporal processing abilities (characterized as the temporal contrast sensitivity function, TCSF). 70 subjects (15-84 yrs) were tested. A small tabletop device utilizing electronic control of light-emitting diodes (LEDs) was constructed that delivered a 1-degree, 660 nm test (the modulation depth of which could be adjusted directly by the subject) centered within a 10-degree 660 nm surround. The method provided a TCSF that had a shape consistent with past studies (peaking around 8 Hz). Also consistent with past work, the largest age-decline was found at the highest frequencies and for the central fovea (r = 0.47, p<0.0001, ~2 Hz per decade). Psychophysical assessment of temporal vision offers an easy and dynamic measure of central visual function.

Using scotopic and photopic flicker to measure lens optical density.

Many applications require knowledge of lens absorption. Measuring lens optical density (OD), however, is often difficult and time-consuming. For example, psychophysical measurement typically requires a long period of dark adaptation (e.g. about 40 min) and assessment of absolute scotopic thresholds. In this study, we examined efficient scotopic and photopic methods for measuring lens OD. In Experiment 1, 30 subjects were tested using a Maxwellian-view optical system. Relative scotopic thresholds were obtained after 15 min of dark adaptation using slow-rate (2 Hz) flicker photometry. A 3 degrees test stimulus, presented at 10 degrees nasal, was used that alternated between measuring wavelengths (420 and 460 nm) and a reference field (540 nm). The results showed that the relative scotopic method produces values that are consistent with published lens spectral curves. In Experiment 2, relative photopic measures (i.e. no dark adaptation period) were also obtained at 406 nm in natural view and compared with lens data obtained in Maxwellian view at 407 nm using the absolute scotopic method. The photopic method compared well with the absolute scotopic values obtained on the same subjects. Taken together, the two experiments showed that a relative method can yield valid lens density estimates. Using a relative rather than an absolute method reduces the time needed for dark adaptation and is an easier task for subjects to perform and may therefore be preferable when expeditious measures are desirable.

Lutein and age-related ocular disorders in the older adult: a review.

Lutein, a carotenoid found in dark green, leafy vegetables, has been implicated as being protective against the acquired ocular diseases, such as cataracts and age-related macular degeneration. In the eye, lutein may act as an antioxidant and as a blue light filter to protect the underlying tissues from phototoxic damage. Average intakes of lutein in the U.S. are below levels associated with eye disease prevention. Therefore, increased intakes of food sources rich in lutein may be warranted. Age-related factors, such as increased inflammation and body fat, are also related to increased risk of age-related eye disease. The mechanism by which these factors are related to risk may be partially due to adverse effects on lutein status.