Hippocampal Subfield Volumes and Spatial Memory Performance in Older Adults At‐Risk for Type 2 Diabetes

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 precise relationship between T2D risk factors, brain volumes (i.e., gray matter, white matter, hippocampus subfields), and hippocampus‐dependent functions (i.e., spatial pattern separation, a component of spatial memory) remains unexplored. To investigate these relationships in this cross‐sectional study, 60 older adults at risk for T2D (e.g., high BMI or elevated A1c levels) completed a touchscreen‐based spatial pattern separation behavioral task—the Trial‐Unique delayed Nonmatching‐to‐Location (TUNL) and magnetic resonance imaging (MRI). HippUnfold was utilized to segment the hippocampus from high‐resolution, T 1 ‐weighted images. We found positive correlations between A1c levels and volumes of the dentate gyrus (DG) and cornu ammonis (CA) 2, indicating that higher A1c was associated with larger volumes of hippocampal subregions. Additionally, TUNL accuracy was correlated with gray matter and distinct hippocampus subfield volumes (i.e., subiculum, CA1, and CA4), with larger volumes associated with better spatial memory performance. Understanding early structural changes in T2D risk allows us to further characterize changes in brain health associated with metabolic dysfunction.