Neurocognitive function and influence of diet among persons with multiple sclerosis

Martell, Shelby

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https://hdl.handle.net/2142/129505 Copy

Description

Title

Neurocognitive function and influence of diet among persons with multiple sclerosis

Author(s)

Martell, Shelby

Issue Date

2025-04-01

Director of Research (if dissertation) or Advisor (if thesis)

Khan, Naiman A

Doctoral Committee Chair(s)

Khan, Naiman A

Committee Member(s)

• Federmeier, Kara
• Liang, Nu-Chu
• Walk, Anne

Department of Study

Neuroscience Program

Discipline

Neuroscience

Degree Granting Institution

University of Illinois Urbana-Champaign

Degree Name

Ph.D.

Degree Level

Dissertation

Keyword(s)

• multiple sclerosis
• cognition
• diet
• event related potentials
• nutrition

Abstract

Objectives Multiple sclerosis (MS) is an inflammatory and demyelinating disease that disrupts the central nervous system causing a range of physical and cognitive impairments. Current treatments for MS have limited success addressing cognitive, motor, and visual impairments. Thus, there is a growing interest and evidence in lifestyle factors as complementary approaches to support MS management. Nutrition is of key interest for people with MS however, dietary recommendations for improving MS outcomes remain unknown. This dissertation aimed to address these gaps by exploring the interrelationships between nutrition, cognitive function, and MS disease markers in persons with MS. Aim 1 investigated the effects of lutein supplementation on carotenoid status and cognitive function in persons with MS. Aim 2 investigated how the lateralized readiness potential (LRP), an index of motor response and activation in the brain, differs in MS and HC as well as the relationships. Aim 3 assessed relationships between retinal morphologic markers of MS, cognitive performance, event-related potentials (ERP), and optic neuritis (ON) in persons with MS. Lastly, aim 4 investigated the feasibility of a Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet intervention in MS and the potential benefits for cognitive function. Methods We utilized both clinical pilot intervention trials and cross-sectional studies to explore cognitive function and nutrition in MS. Aim 1 was a single-blind placebo controlled RCT of 20 mg lutein supplementation in persons with MS (n = 21; active n = 12, placebo n = 9). Carotenoid status was evaluated utilizing skin carotenoids via reflection spectroscopy, macular pigment optical density (MPOD) via heterochromatic flicker photometry, and serum lutein. Cognitive function was assessed via a modified Eriksen flanker task with simultaneous EEG and the symbol digits modalities test (SDMT). Aim 2 utilized secondary data analysis in persons with MS (n = 53) and age-sex matched HC (n = 53) with flanker EEG data to explore the lateralized readiness potential (LRP) both in relation to the stimulus (LRP-S) and response (LRP-R) as well as flanker accuracy and reaction time. Aim 3 involved secondary data in persons with MS (n = 53) with optical coherence tomography (OCT) scans to assess three markers of retinal morphology: retinal nerve fiber layer (RNFL), total macular volume (TMV), and granule cell inter plexiform layer (GCIPL). Additionally, flanker EEG data was utilized with cognitive (P3, N2, and ERN) and motor (LRP-S and LRP-R) ERP components. Finally Aim 4, was a telehealth 12-week pilot RCT in persons with MS (n = 31) exploring feasibility and effects of MIND diet (n = 16) compared to control diet (n = 15) on cognitive function. Participants consumed a ready-to-eat meal per day and followed diet guidelines. Feasibility was assessed through descriptive analysis of retention, attrition, and compliance rates. Additionally, the effects of the intervention on diet indices were calculated from the dietary history questionnaire and adherence surveys. Cognitive function was assessed via the remote testing CANTAB cognitive battery. Results Analyses conducted for aim 1, after adjusting for baseline serum lutein and age, revealed significant group by time interactions for MPOD, skin carotenoids, and serum whereby the treatment group improved in all carotenoid outcomes. In the treatment group increase in MPOD was positively associated with incongruent accuracy and spatial memory. Aim 2 revealed that participants with MS had delayed LRP-S latency and reduced LRP-R amplitudes compared to HC. In Aim 3, significant relationships were observed with RNFL and accuracy, reaction time, P3 congruent latency, LRP-S amplitude and ERN peak latency. Additionally, GCIPL was significantly related to accuracy, SDMT score, LRP-R amplitude, LRP-S amplitude and LRP-S latency. Lastly TMV was significantly predictive of N2 amplitude. Finally, for the 12-week intervention conducted in Aim 4, the retention rate of 87.5% with an attrition rate of 12.5%. Compliance rates for consumption of the daily meal were high with overall compliance of 91.1% with the MIND group having 89.7% compliance and 92.6% compliance in the control diet. There was a significant time effects whereby HEI improved over time and only the MIND group had significant increases in MIND composite. Significant time effects were observed whereby post-test memory scores and attention reaction time improved. No other significant effects were observed for the cognitive outcomes. Conclusions These works provide evidence supporting the potential neuroprotective benefits of nutrition in MS and highlight neuroelectric indices of cognition and motor processes as potential biomarkers for MS. Specifically, Aim 1 demonstrated that four months of lutein supplementation significantly increased carotenoid status, with increases in macular pigment linked to improvements in attentional inhibition and spatial memory. Aim 2 revealed impairments in delayed pre-motor response selection and reduced neural activation for motor response initiation in MS. Aim 3 revealed novel relationships between proxy markers of white and gray brain matter and cognitive, motor, and error processes in MS. Finally, the remote pilot trial in Aim 4 demonstrated high feasibility and acceptability. While the MIND diet did not show greater cognitive benefits compared to the control diet, the findings support the need for larger fully powered RCTs to explore dietary patterns and cognition in MS. Collectively, this dissertation work informs future interventions and larger efficacy trials, offering valuable insights for researchers and clinicians to design interventions to provide neurocognitive benefits in persons with MS.

Graduation Semester

2025-05

Type of Resource

Thesis

Handle URL

https://hdl.handle.net/2142/129505

Copyright and License Information

Copyright 2025 Shelby Martell

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