Hippocampal-subfield macro- and microstructural changes in cerebral small vessel disease with mild cognitive...

Hippocampal subregions demonstrate a selective vulnerability to vascular injury, with pathological processes extensively affecting both microstructural and macrostructural characteristics. This phenomenon elucidates the intricate relationship between hippocampal dysfunction, cognitive deficits, and depressive symptoms. The present study investigated microstructural and volumetric changes in hippocampal subregions among patients with cerebral small vessel disease (CSVD), and their correlation with cognitive function.

A comprehensive neuroimaging and neuropsychological assessment was conducted on 169 participants, categorized into CSVD with mild cognitive impairment (MCI), CSVD without cognitive impairment (NCI), and healthy controls. An advanced multi-compartment diffusion (NODDI) model was employed to analyze hippocampal subregional characteristics.

Our findings revealed extensive hippocampal atrophy and microstructural abnormalities in CSVD patients, with the most pronounced changes observed in the cornu ammonis (CA) and dentate gyrus (DG) regions. Notably, orientation dispersion index (ODI) and free water fraction (FISO) demonstrated significant inter-group differences and exhibited broad correlations with cognitive performance. Notably, FISO metrics demonstrated more pronounced differences during early cognitive decline stages compared to volumetric analyses.

The study lacked a dementia cohort, which could have provided deeper insights into progressive hippocampal pathological changes.

The hippocampus plays a critical role in cognitive decline associated with small vessel disease. NODDI can provide pathological correlation information across different cognitive stages, offering a new perspective for early identification of pathological changes related to cognitive impairment in cerebral small vessel disease.