Hippocampal Subfield Vulnerability and Functional Connectivity in Cognitive Decline: a Comparison Between Parkinson's Disease and Mild Cognitive Impairmente.

Objective: To investigate the shared and distinct alterations in hippocampal subfield atrophy and functional connectivity (FC) in Parkinson's disease (PD) with normal cognition (PD-NC), PD with mild cognitive impairment (PD-MCI) and unspecified MCI (U-MCI).

Methods: A total of 294 participants were included from two centers (30 PD-NC, 86 PD-MCI, 76 U-MCI, and 102 healthy controls (HC)). Comparisons of hippocampal subfield volumes were conducted among groups. Seed-based FC was calculated to assess abnormalities between hippocampal subfields and cortical regions.

Results: Compared to HC, PD-NC group showed volumetric reductions in the right cornu ammonis (CA) 2/3, granule cell layer of the dentate gyrus (GC-DG), and CA4 subfields, while PD-MCI group exhibited bilateral volumetric reductions in the same subfields. PD-MCI patients exhibited increased FC between the bilateral GC-DG/CA4 subfield and the posterior default mode network (pDMN), as well as between the right GC-DG/CA4 subfield and the calcarine, in comparison to PD-NC. U‑MCI patients displayed smaller volume in the right CA4 compared to HC. Decreased FC of the hippocampus with the widespread visual network was observed in the PD-MCI group compared to the U‑MCI group.

Conclusions: PD-MCI is associated with structural vulnerability of hippocampal subfields in the CA2/3, GC-DG, and CA4 subfields, impacting FC with pDMN and visual network. Smaller scope of hippocampal subfields atrophy but weaker hippocampus-visual network FC abnormalities in U‑MCI relative to PD-MCI may suggest distinct progression mechanisms between these two conditions.