INTERRELATIONSHIPS BETWEEN MACULAR CAROTENOIDS, RETINAL MORPHOMETRY, AND COGNITIVE FUNCTION IN PERSONS WITH MULTIPLE SCLEROSIS

Background: Multiple sclerosis (MS) is a neurodegenerative, autoimmune disease that affects oligodendrocyte-producing myelin cells and leads to cognitive, visual, affective, and motor problems, as well as fatigue, bowel dysfunction, among other symptoms. Although MS etiopathology is incompletely understood, it is known to be influenced by hereditary and environmental factors which can drastically affect the course of the disease. Amongst environmental factors, nutrition has gained significant attention. In 2015, The National Multiple Sclerosis Society published a report detailing that among various alternative approaches, diet was of the highest interest within the MS community, in part due to the limited dietary therapies as well as the poor efficacy of pharmacological approaches. Due to the health-promoting benefits that consumption of fruits and vegetables confer, their dietary components have gained substantial attention. Recently, lutein and zeaxanthin, dietary xanthophylls, have been shown to be associated with cognitive health. Although xanthophylls are not recognized to be essential, their lack of endogenous de novo synthesis necessitates regular dietary consumption to derive benefits. Macular xanthophylls are dietary carotenoids that comprise the macular pigment, serving as blue light filters and countering photooxidative damage. The robust antioxidant effects of carotenoids could support nerve health and protect against cognitive decline. However, macular xanthophyll status and its implications for markers of neuroaxonal degeneration, such as retinal morphometry, have not been examined among persons with MS. Specifically, the research presented herein aimed to explore the implications of macular and serum xanthophyll status for markers of retinal morphometry, and the associations between macular xanthophyll accumulation, retinal morphometry, and cognitive function in adults 18-64 years old with MS, with (MS-ON) and without ON (MS), and healthy controls (HC). Methods: Adults 18-64 years (HC, n=42; MS, n=40-42) participated in a cross-sectional study. Macular pigment optical density (MPOD) was measured via heterochromatic flicker photometry using a macular densitometer. Retinal morphometry was measured via optical coherence tomography (OCT). Serum carotenoids were quantified using high-performance liquid chromatography. Dietary carotenoids were assessed using 7-day dietary records. Cognitive function was assessed using an Eriksen Flanker task for attentional control with event-related potentials (ERPs). One-way analysis of variance was conducted to determine group effects on macular, serum, and dietary carotenoids. Partial correlations examined the relationships between MPOD, OCT metrics, dietary variables, and serum carotenoids (with a false discovery rate [FDR] correction implemented for exploratory analyses with serum and dietary variables). Independent sample t-test/Mann-Whitney U-test was conducted to assess between-group differences, and Spearman’s Rank correlations were used to examine the relationships between MPOD and retinal morphometry with covariates and cognitive variables of interest. Linear regressions were used to explore the relationship between retinal and cognitive measures. Results: Persons with MS-ON had lower MPOD and thickness and volume in OCT than HCs (i.e., optic disc retinal nerve fiber layer [odRNFL], macular retinal nerve fiber layer [mRNFL], total macular volume [TMV]). MS had significantly lower odRNFL thickness than HCs, and lower serum lutein than MS-ON subjects. Among MS, MPOD was positively correlated with odRNFL thickness and TMV, whereas odRNFL was negatively correlated with serum lutein and zeaxanthin. Between-group differences were observed in all cognitive outcomes showing lower attentional performance in persons with MS. After covariate adjustment, linear regressions showed that MPOD significantly predicted variance for incongruent P3 peak latency and odRNFL significantly predicted variance for congruent reaction time and congruent P3 peak latency. Interestingly, the interaction term between MPOD and odRNFL significantly predicted variance in all but one metric (congruent P3 peak latency). Conclusion: These findings provide initial evidence that persons with MS-ON have poorer xanthophyll status in the macula and serum. Further, MPOD was positively associated with beneficial anatomical features in the MS group. These results suggest that MPOD might be protective of AVP structural integrity. Additionally, higher carotenoid accumulation in the macula and higher retinal and optic nerve thickness were associated with greater attentional control, using both behavioral and neuroelectric indices, among people with MS.

Name thesis:degree_name

M.S.

Level thesis:degree_level

Thesis

Discipline thesis:degree_discipline

Nutritional Sciences

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2021

Author dc:creator

• Cerna, Jonathan

Contributors dc:contributor

• Khan, Naiman A.
• Erdman, John W.
• Steelman, Andrew J.
• Adamson, Brynn
• Burd, Nicholas A.

• Multiple Sclerosis
• macular pigment optical density
• optical coherence tomography
• retinal nerve fiber layer
• lutein
• zeaxanthin

Statement dc:rights

• Copyright 2021 Jonathan Cerna

Language dc:language

en

Handle dc:identifier

http://hdl.handle.net/2142/110730

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/110730