Electronic Thesis and Dissertation Repository

Thesis Format

Integrated Article

Degree

Master of Science

Program

Neuroscience

Supervisor

Nagamatsu, Lindsay S.

Abstract

Older adults at risk for type 2 diabetes (T2D) are more likely to experience accelerated cognitive aging and neurodegeneration due to impaired metabolism in the hippocampus. However, the direct relationship between diabetes risk factors, brain volumes (i.e., grey matter, white matter, hippocampus subfields) and hippocampus-dependent functions (i.e., spatial pattern separation) remains unexplored. To investigate this, 60 older adults at risk for T2D (e.g., higher glycated hemoglobin [A1c]) completed touchscreen-based Trial-Unique Delayed Non-Matching to Location (TUNL) and magnetic resonance imaging (MRI). HippUnfold was utilized to segment the hippocampus from high-resolution, T1-weighted images. Findings indicate a relationship between A1c levels and volumes of the dentate gyrus (DG) and Cornu ammonis (CA) 2. Additionally, TUNL percent correct was correlated with grey matter and distinct hippocampus subfield volumes (i.e., subiculum, CA1, and CA4). Understanding the earliest structural changes in T2D risk allows us to uncover opportune moments to begin interventions aimed at preventing irreversible cognitive deficits.

Summary for Lay Audience

Dementia is a term used to describe a range of degenerative neurological conditions that impair memory, thinking, and daily functioning. One of the greatest modifiable risk factors for dementia is type 2 diabetes (T2D), a metabolic disorder most often developed in later life and characterized by high blood sugar levels and insulin resistance. Importantly, older adults at risk for T2D already show evidence of cognitive decline. Although the mechanisms underlying this relationship are not well understood, research suggests that loss of brain tissue and hippocampal volumes play a role. The hippocampus is divided into various subfields, each with their unique vulnerabilities to pathologies and memory functions. A function of the hippocampus is spatial pattern separation, which helps differentiate similar representations into non-overlapping memories. Currently, studies have not investigated the relationship between T2D risk factors, brain volumes (i.e., hippocampal subfields), and spatial pattern separation performance in older adults to uncover the onset and severity of structural and cognitive deficits in this context. To address this, 60 older adults with T2D risk completed anatomical neuroimaging and a touchscreen-based measure of spatial pattern separation. Larger hippocampal subfield volumes were associated with higher blood sugar levels, along with higher accuracy of spatial pattern separation. However, T2D risk was not associated with spatial memory. These results indicate early structural changes of the hippocampus in T2D risk and provide evidence of hippocampal subfield specificity in spatial pattern separation.

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