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Authors: Nolan, John M. | Mulcahy, Riona | Power, Rebecca | Moran, Rachel | Howard, Alan N.

Article Type: Research Article

Abstract: Background: A growing body of scientific evidence suggests that enrichment of certain nutritional compounds in the brain may reduce the risk of Alzheimer’s disease (AD). Objective: To investigate the impact of supplemental xanthophyll carotenoids plus omega-3 fatty acids on disease progression in patients with AD. Methods: Three trial experiments were performed. In Trials 1 and 2 (performed on patients with AD over an 18-month period), 12 patients (AD status at baseline: 4 mild and 8 moderate) were supplemented with a xanthophyll carotenoid only formulation (Formulation 1; lutein:meso-zeaxanthin:zeaxanthin 10:10:2 mg/day) and 13 patients (AD status at baseline: 2 mild, 10 moderate, and …1 severe) were supplemented with a xanthophyll carotenoid and fish oil combination (Formulation 2; lutein:meso-zeaxanthin:zeaxanthin 10:10:2 mg/day plus 1 g/day of fish oil containing 430 mg docohexaenoic acid [DHA] and 90 mg eicopentaenoic acid [EPA]), respectively. In Trial 3, 15 subjects free of AD (the control group) were supplemented for 6 months with Formulation 1. Blood xanthophyll carotenoid response was measured in all trials by HPLC. Omega-3 fatty acids were profiled by direct infusion mass spectrometry. Results: Xanthophyll carotenoid concentration increases were significantly greater for Formulation 2 compared to Formulation 1 (p  < 0.05), and progression of AD was less for this group (p  = 0.003), with carers reporting functional benefits in memory, sight, and mood. Conclusion: This preliminary report suggests positive outcomes for patients with AD who consumed a combination of xanthophyll carotenoids plus fish oil, but further study is required to confirm this important observation. Show more

Keywords: Alzheimer’s disease, dementia, DHA, fatty acids, lutein, meso-zeaxanthin, nutrition, omega-3, prevention, xanthophyll carotenoids

DOI: 10.3233/JAD-180160

Citation: Journal of Alzheimer's Disease, vol. 64, no. 2, pp. 367-378, 2018

Authors: Power, Rebecca | Coen, Robert F. | Beatty, Stephen | Mulcahy, Riona | Moran, Rachel | Stack, Jim | Howard, Alan N. | Nolan, John M.

Article Type: Research Article

Abstract: Background: There is a biologically plausible rationale whereby the dietary carotenoids lutein (L), zeaxanthin (Z), and meso -zeaxanthin (MZ), which are collectively referred to as macular pigment (MP) in the central retina (macula), support the maintenance of cognition via their antioxidant and anti-inflammatory properties. Objective: To investigate the impact of supplemental L, Z, and MZ on memory, executive function, and verbal fluency among healthy individuals with low MP levels. Methods: In this double-blind, placebo-controlled, randomized clinical trial, subjects (n  = 91; mean±SD age = 45.42±12.40; % male = 51.6) consumed a daily formulation of 10 mg L, 10 mg MZ, and 2 mg Z (n  = 45) or placebo …(n  = 46) for 12 months. Cognitive domains assessed included verbal and visual learning, immediate and delayed memory, executive function, and verbal fluency. MP and serum carotenoid concentrations of L, Z, and MZ were also measured. Results: Following 12-month supplementation, individuals in the active group exhibited statistically significant improvements in memory when compared to the placebo group (paired associated learning [PAL] memory score [rANOVA, p  = 0.009]; PAL errors [rANOVA, p  = 0.017]). Furthermore, the observed reduction in the number of errors made in the PAL task among those in the intervention group was positively and significantly related to observed increases in MP volume (p  = 0.005) and observed increases in serum concentrations of L (p  = 0.009). Conclusion: This randomized, double-blind, placebo-controlled clinical trial demonstrates a memory-enhancing effect of daily supplementation with L, Z, and MZ in healthy subjects with low MP at baseline. The implications of these findings for intellectual performance throughout life, and for risk of cognitive decline in later life, warrant further study. Show more

Keywords: Brain, CANTAB, carotenoids, cognitive function, episodic memory, lutein, meso-zeaxanthin, macular pigment, paired associated learning, zeaxanthin

DOI: 10.3233/JAD-170713

Citation: Journal of Alzheimer's Disease, vol. 61, no. 3, pp. 947-961, 2018

Authors: Nolan, John M. | Loskutova, Ekaterina | Howard, Alan N. | Moran, Rachel | Mulcahy, Riona | Stack, Jim | Bolger, Maggie | Dennison, Jessica | Akuffo, Kwadwo Owusu | Owens, Niamh | Thurnham, David I. | Beatty, Stephen

Article Type: Research Article

Abstract: Background: The macula (central retina) contains a yellow pigment, comprising the dietary carotenoids lutein (L), zeaxanthin (Z), and meso-zeaxanthin, known as macular pigment (MP). The concentrations of MP’s constituent carotenoids in retina and brain tissue correlate, and there is a biologically-plausible rationale, supported by emerging evidence, that MP’s constituent carotenoids are also important for cognitive function. Objective: To investigate if patients with Alzheimer’s disease (AD) are comparable to controls in terms of MP and visual function. Methods: 36 patients with moderate AD and 33 controls with the same age range participated. MP was measured using dual-wavelength autofluorescence (Heidelberg Spectralis® ); …cognitive function was assessed using a battery of cognition tests (including Cambridge Neuropsychological Test Automated Battery). Visual function was recorded by measuring best corrected visual acuity (BCVA) and contrast sensitivity (CS). Serum L and Z concentrations (by HPLC) and age-related macular degeneration (AMD, by retinal examination) status were also assessed. Results: In the AD group, central MP (i.e., at 0.23°) and MP volume were significantly lower than the control group (p < 0.001 for both), as were measures of BCVA, CS, and serum L and Z concentrations (p < 0.05, for all). Conclusion: AD patients were observed to exhibit significantly less MP, lower serum concentrations of L and Z, poorer vision, and a higher occurrence of AMD when compared to control subjects. A clinical trial in AD patients designed to investigate the impact of macular carotenoid supplementation with respect to MP, visual function, and cognitive function is merited. Show more

Keywords: Age-related macular degeneration, Alzheimer's disease, cognitive function, contrast sensitivity, lutein, meso-zeaxanthin, visual function, zeaxanthin

DOI: 10.3233/JAD-140507

Citation: Journal of Alzheimer's Disease, vol. 42, no. 4, pp. 1191-1202, 2014

Authors: Nolan, John M. | Power, Rebecca | Howard, Alan N. | Bergin, Paula | Roche, Warren | Prado-Cabrero, Alfonso | Pope, George | Cooke, John | Power, Tommy | Mulcahy, Ríona

Article Type: Research Article

Abstract: Background: Preliminary work by our center has reported behavior and functional benefits in patients with Alzheimer’s disease (AD) following targeted micronutritional supplementation. Objective: To build on the existing exploratory research and investigate the impact of these micronutrients on the natural progression of AD in a randomized controlled trial. Methods: Patients with mild-moderate AD consumed daily 1 g fish oil (of which 500 mg DHA, 150 mg EPA), 22 mg carotenoids (10 mg lutein, 10 mg meso -zeaxanthin, 2 mg zeaxanthin), and 15 mg vitamin E or placebo for 12 months in a double-blind, placebo-controlled, randomized clinical trial. Carotenoids, ω-3FAs, and vitamin E were quantified in blood. Carotenoids were …also measured in skin. AD severity was measured using the mini-mental state examination and dementia severity rating scale tools. Behavior, mood, and memory were measured using an informant-based questionnaire. Results: Following 12 months of supplementation, the active group (n  = 50) compared to the placebo group (n  = 27), demonstrated statistically significant improvements in skin carotenoid measurements, blood carotenoids, ω-3FAs, and vitamin E concentrations (p  < 0.05, for all). The active group also performed better in objective measures of AD severity (i.e., memory and mood), with a statistically significant difference reported in the clinical collateral for memory (p  < 0.001). Conclusion: Exponential increases in the prevalence of AD and its relentless progressive nature is driving the need for interventions that help to ameliorate symptoms and improve quality of life in AD patients. Given the positive outcomes demonstrated in this trial, this combined micronutrient dietary supplement should be considered in the overall management of AD. Show more

Keywords: Alzheimer’s disease, antioxidants, carotenoids, clinical collateral, disease management, disease progression, nutrition, omega-3 fatty acids, vitamin E

DOI: 10.3233/JAD-220556

Citation: Journal of Alzheimer's Disease, vol. 90, no. 1, pp. 233-249, 2022

Authors: Kelly, David | Coen, Robert F. | Akuffo, Kwadwo Owusu | Beatty, Stephen | Dennison, Jessica | Moran, Rachel | Stack, Jim | Howard, Alan N. | Mulcahy, Riona | Nolan, John M.

Article Type: Research Article

Abstract: Background: Macular pigment (MP) levels correlate with brain concentrations of lutein (L) and zeaxanthin (Z), and have also been shown to correlate with cognitive performance in the young and elderly. Objective: To investigate the relationship between MP, serum concentrations of L and Z, and cognitive function in subjects free of retinal disease with low MP (Group 1, n  = 105) and in subjects with AMD (Group 2, n  = 121). Methods: MP was measured using customized heterochromatic flicker photometry and dual-wavelength autofluorescence; cognitive function was assessed using a battery of validated cognition tests; serum L and Z concentrations were determined by HPLC. …Results: Significant correlations were evident between MP and various measures of cognitive function in both groups (r  = –0.273 to 0.261, p ≤0.05, for all). Both serum L and Z concentrations correlated significantly (r  = 0.187, p ≤0.05 and r  = 0.197, p ≤0.05, respectively) with semantic (animal) fluency cognitive scores in Group 2 (the AMD study group), while serum L concentrations also correlated significantly with Verbal Recognition Memory learning slope scores in the AMD study group (r  = 0.200, p  = 0.031). Most of the correlations with MP, but not serum L or Z, remained significant after controlling for age, gender, diet, and education level. Conclusion: MP offers potential as a non-invasive clinical biomarker of cognitive health, and appears more successful in this role than serum concentrations of L or Z. Show more

Keywords: Age-related macular degeneration, biomarker, cognitive function, lutein, macular pigment, zeaxanthin

DOI: 10.3233/JAD-150199

Citation: Journal of Alzheimer's Disease, vol. 48, no. 1, pp. 261-277, 2015

Authors: Nolan, John M. | Loskutova, Ekaterina | Howard, Alan | Mulcahy, Riona | Moran, Rachel | Stack, Jim | Bolger, Maggie | Coen, Robert F. | Dennison, Jessica | Akuffo, Kwadwo Owusu | Owens, Niamh | Power, Rebecca | Thurnham, David | Beatty, Stephen

Article Type: Research Article

Abstract: Background: Patients with Alzheimer's disease (AD) exhibit significantly less macular pigment (MP) and poorer vision when compared to control subjects. Objective: To investigate supplementation with the macular carotenoids on MP, vision, and cognitive function in patients with AD versus controls. Methods: A randomized, double-blind clinical trial with placebo and active arms. 31 AD patients and 31 age-similar control subjects were supplemented for six months with either Macushield (10 mg meso-zeaxanthin [MZ]; 10 mg lutein [L]; 2 mg zeaxanthin [Z]) or placebo (sunflower oil). MP was measured using dual-wavelength autofluorescence (Heidelberg Spectralis® ). Serum L, Z, and MZ were quantified by …high performance liquid chromatography. Visual function was assessed by best corrected visual acuity and contrast sensitivity (CS). Cognitive function was assessed using a battery of cognition tests, including the Cambridge Neuropsychological Test Automated Battery (CANTAB)). Results: Subjects on the active supplement (for both AD and non-AD controls) exhibited statistically significant improvement in serum concentrations of L, Z, MZ, and MP (p < 0.001, for all) and also CS at (p = 0.039). Also, for subjects on the active supplement, paired samples t-tests exhibited four significant results (from five spatial frequencies tested) in the AD group, and two for the non-AD group, and all indicating improvements in CS. We found no significant changes in any of the cognitive function outcome variables measured (p > 0.05, for all). Conclusion: Supplementation with the macular carotenoids (MZ, Z, and L) benefits patients with AD, in terms of clinically meaningful improvements in visual function and in terms of MP augmentation. Show more

Keywords: Age-related macular degeneration, Alzheimer's disease, cognitive function, contrast sensitivity, lutein, meso-zeaxanthin, randomized clinical trial, visual function, zeaxanthin

DOI: 10.3233/JAD-142265

Citation: Journal of Alzheimer's Disease, vol. 44, no. 4, pp. 1157-1169, 2015