To evaluate the structural integrity of white matter connections between the hypothalamus and hippocampus in the prodromal stages of Alzheimer’s disease and related dementias (AD/ADRD).
Stimulating the hypothalamus in animal models and human clinical studies have been found to modulate memory function, supporting the importance of hypothalamic connectivity to brain regions regulating cognition and memory. However, the structural connectivity between the hypothalamus and brain regions affected in AD/ADRD including the hippocampus remain relatively underexplored.
As an exploratory pilot study, we conducted propensity score matching using the Dallas Heart Study (DHS), a longitudinal population-based cohort, to identify 32 mild cognitive impairment (MCI) and 30 normal cognition (NC) representative participants from the most recent study visit (Age 61.3±9 years, Men:Women 23/39). To examine the structural connectivity between the hypothalamus and hippocampus in diffusion magnetic resonance imaging (dMRI) data, we performed probabilistic tractography using FSL’s probtrackx with the hypothalamus as the seed region, the hippocampus as the target, and the corpus callosum as an exclusion mask. Other parameters include 5000 samples, 2000 steps, 0.5 mm step length, and a curvature threshold of 0.2. To examine for microstructural changes, we used more conventional diffusion tensor imaging analytical methods (e.g., fractional anisotropy [FA] and mean diffusivity [MD]) in addition to neurite orientation dispersion and density index (NODDI) and diffusion kurtosis imaging.
The connection between the hypothalamus and hippocampus was projected primarily through the fornix, which had a significant decrease in FA in MCI compared to NC participants (MCI=0.36, CN=0.38; p=0.04). There were also non-significant trends of increased isotropic volume fraction, a measure of extracellular free water fraction, (p=0.1) and decreased mean kurtosis (p=0.1).
Collectively, these findings support that there are pathological changes in the structural connectivity between the hypothalamus and hippocampus occurring during early stages of AD/ADRD that may contribute to the cognitive impairment.