Integrating light-based therapies and diagnostic tools for mild cognitive impairment: effects on neuroinflammation, amyloid beta, and alertness

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Authors
Leggett, Sagan
Issue Date
2024-07
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Electronic thesis
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en_US
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Biology
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Alzheimer's disease (AD) presents a significant public health challenge, with its prevalence expected to almost double in the next 25 years. Despite therapeutic advancements, mortality rates continue to rise, highlighting the need for effective interventions. Building on previous research demonstrating the efficacy of 40 Hz rhythmic light (RL) in clearing Aβ aggregates in AD mouse models, this aim of the dissertation explores the effects of varying exposure durations and light levels on neuroinflammation and Aβ42/40 ratios. Increasing exposure durations reduced IL-1β concentrations, while light levels had no significant impact on inflammatory markers. However, neither increased exposure durations nor light levels of 40 Hz RL decreased Aβ42/40 ratios, suggesting refinements are needed in RL administration for AD.Although light level and duration did not improve efficacy of RL on AD model mice, it is important to investigate other variables or effects of light. This aim of the dissertation explores the potential benefits of specific lighting schemes to induce alertness in environments such as hospitals and naval ships. To determine the most efficient wavelength for inducing alertness, nine different (quasi-)monochromatic stimuli were tested on healthy individuals. Electroencephalography (EEG), Go/NoGo (GNG) performance tests, and the Karolinska Sleepiness Scale (KSS) were used to measure subjective sleepiness and cognitive function. Findings indicated that 5 lux and 75 lux improved subjective sleepiness, but that different wavelengths did not impact subjective sleepiness. Longer wavelengths, such as orange and amber, stimulated more whole brain activity according to EEG. Additionally, it is imperative to establish baseline EEG patterns in those with mild cognitive impairment (MCI) – a transitional state between cognitively healthy and AD- compared to healthy controls (HCs) before implementing lighting therapies. This aim of the dissertation utilizes measures of functional connectivity (FC) and global field power (GFP) from EEG recordings to distinguish patterns of brain activity among various cohorts. Comparative analyses were conducted during rest among young healthy controls (YHC), old healthy controls (OHC), and individuals with MCI to identify potential biomarkers for cognitive decline in MCI. Results indicated significantly higher FC within the Central Executive Network (CEN), Default Mode Network (DMN), and Salience Network (SN) among MCI participants compared to both control groups. Additionally, MCI participants exhibited notably reduced GFP in the DMN compared to controls. A significant negative correlation was found between FC in the SN and sleep quality, as measured by the Pittsburgh Sleep Quality Index (PSQI). These findings suggest that FC and GFP metrics have potential clinical utility as early diagnostic indicators for cognitive decline in MCI.
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July2024
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Rensselaer Polytechnic Institute, Troy, NY
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