High-Resolution Diffusion Tensor Imaging of the Hippocampus and Associations With Neuropsychiatric Symptoms in Lewy...

Parkinson's disease (PD) encompasses motor and neuropsychiatric symptoms (NPS) including depression, anxiety, and apathy. Cognitive subtypes-PD with mild cognitive impairment (PD-MCI) and PD with dementia (PDD)-and the related Dementia with Lewy Bodies (DLB) exist within the spectrum of Lewy body disease (LBD). While NPS are a major comorbidity, established imaging biomarkers are not available, nor is the neuronal basis well known. Additionally, prevalence of NPS may be linked to cognitive status. The hippocampus is implicated in the development of NPS and may undergo microstructural changes that are not reflected in volume changes. High-resolution diffusion tensor imaging (DTI) was used to identify hippocampal changes in LBD compared to healthy controls (HC) and examine the relationship with NPS within the LBD group, both through association with DTI measures as well as comparison of cognitive subgroups. The hippocampus was manually segmented in 38 LB spectrum participants (aged 58-87 years, 32% female) and 35 HC (aged 50-83 years, 54% female) on high-resolution (1 × 1 × 1 mm³) DTI. The LBD group (LBD-All) was divided into LBD-Cognitively Impaired (LBD-CI) and LBD-Cognitively Unimpaired (LBD-CU). Hippocampal volume, mean diffusivity (MD), and fractional anisotropy (FA) were extracted and compared across groups. Relationships between significantly different hippocampal measures and depression, anxiety, and apathy were explored within the LBD-All group. Hippocampal FA was lower in LBD-All relative to HC; however, no differences in MD or volume were observed. Hippocampal FA was positively associated with depression scores within LBD-All. There were no differences in volume, MD, or FA between LBD-CI and LBD-CU. Lower hippocampal fractional anisotropy in the LBD spectrum relative to HC potentially reflects microstructure alterations; however, higher hippocampal FA in LBD with more severe depression suggests more complex microstructural changes such as altered synaptic density, Lewy neurite organization, or neuroplastic changes.