Objective: We aimed to investigate the interaction between hippocampus and dopaminergic pathways in PD with mild cognitive impairment (PD-MCI).

Background: Dysfunction of striatal dopaminergic neurotransmitter system and hippocampus are key contributors to cognitive disorders in Parkinson’s disease (PD). However, the interaction between dopaminergic deficits and hippocampal dysfunction in PD-related cognitive decline remains unclear.

Method: 33 PD-MCI and 20 PD with normal cognition (PD-NC) were included from the Parkinson’s Progression Markers Initiative (PPMI) (Table 1). All patients underwent motor and cognitive assessments, ¹⁸F-AV-133 vesicular monoamine transporter 2 PET imaging, and T1-weighted MRI. Asymmetry indices (AI) were calculated for striatal ¹⁸F-AV-133 standard uptake volume ratio (SUVR) and hippocampal subfield volumes. Partial correlation and multivariate regression models examined associations with cognition and potential interaction effects.

Results: PD-MCI showed higher AI in caudate and anterior putamen SUVR versus PD-NC (Table 2). Hippocampal CA2/3 AI negatively correlated with MoCA (p=0.045) and HVLT (p=0.022), and granule cell layer AI correlated with lower MoCA (p=0.047) . Striatal SUVR AI (caudate/anterior putamen) negatively linked to multiple cognitive domains (Table 3). Regression analysis revealed interactions between anterior putamen SUVR AI and CA2/3 AI on MoCA in PD group (p=0.039), and posterior putamen SUVR AI with CA2/3 AI in PD-MCI (p=0.002) (Table 4, Table 5).

Conclusion: Striatal dopaminergic denervation and hippocampal atrophy exhibit a cooperative interaction on cognitive decline in PD. Lateralized dopaminergic deficits in the anterior putamen and CA2/3 atrophy jointly contribute to cognitive impairment. These findings clarified the relationship between hippocampus and dopaminergic pathways in PD with cognitive decline, and deepen understanding of the pathophysiological mechanisms of cognitive impairment.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/hippocampal-striatal-interaction-and-cognitive-decline-in-parkinsons-disease-with-mild-cognitive-impairment/