Mapping the Interactive Effects of ApoE Gene Polymorphism on Caudate Functional Connectivity in Mild Cognitive Impairment Associated With Parkinson’s Disease

INTRODUCTION: Cognitive impairment (CI) is a frequent non-motor symptom of Parkinson’s disease (PD). Caudate and Apolipoprotein E (ApoE) are biomarkers linked to CI in PD. There is little known about whether ApoE affects caudate in mild CI of PD (PD-MCI). We investigated the possible interactive effect of ApoE genotypes on caudate functional connectivity (FC) in PD-MCI. METHODS: A total of 95 PD-MCI patients and 99 matched healthy controls underwent extensive neuropsychological assessment and magnetic resonance imaging. The two groups were separated into three subgroups according to their genotyping. Functional data were analyzed with FC analysis. RESULTS: Decreased FC between the caudate and the bilateral inferior orbit frontal gyrus and bilateral middle occipital gyrus (MOG) was found between groups, along with poor performance in general, executive, episodic memory, language, and visual–spatial function. Decreased FC between the caudate and right MOG, right middle temporal gyrus, and right superior occipital gyrus was found as an interaction effect. The FC values of ε4 carriers with PD-MCI were much lower than the other carriers, and FC was positively correlated with the impairment of global and language function. CONCLUSION: These results support the idea that altered FC between the bilateral caudate and posterior cortical regions was interactively influenced by ApoE genotype and PD-MCI status, and the ε4 subtype associated with underlying pathology of global cognitive decline and semantic fluency impairment in an interactive manner. Gene-based imaging approaches might strengthen the credibility in imaging genetic associations, which might provide new powerful insights into the neural mechanisms underlying PD-MCI.