Multimodal MRI reveals distinct hippocampal subregional alterations in de novo Parkinson's disease across the cognitive spectrum

Pan Chenxi¹Enchun Zhao²Jingru Ren³Gaiyan Zhou³Yajie Wang³Ronggui Zhang³Yang Shen⁴Jiu Chen⁵Weiguo Liu^3*

• ¹Department of Neurology, Nanjing Brain Hospital Affiliated to Nanjing Medical University, Nanjing, China
• ²Huai'an TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Huai’an, China
• ³The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China
• ⁴Xiaogan Hospital Affiliated to Wuhan University of Science and Technology, Xiaogan, China
• ⁵Nanjing University Medical School Affiliated Nanjing Drum Tower Hospital, Nanjing, China

Background: Hippocampal subregion atrophy has been associated with cognitive decline in Parkinson's disease (PD). Our study aimed to investigate functional and structural alterations of hippocampal subregion in newly-diagnosed PD patients depicting different cognitive states and explore potential associations between these neuroanatomical alterations and cognitive performance. Methods: Four participant groups were recruited, including a de novo PD patient with mild cognitive impairment (PD-MCI, n = 44), a de novo PD patient with subjective cognitive decline (PD-SCD, n = 11), a de novo PD patient with normal cognition (PD-NC, n = 28), and a healthy control (HC, n = 19). The functional connectivity (FC) and gray matter (GM) volume alterations in the anterior, middle, and posterior of left hippocampus were investigated. Moreover, we explored their relationship with cognition. Results: Compared with the PD-NC, the PD-SCD revealed significantly decreased FC between left middle hippocampus (HIPm) and right postcentral gyrus (PoCG.R). The PD-MCI had decreased FC value not only between HIPm and PoCG.R, but also between left anterior hippocampus (HIPa) and PoCG.R. The GM volume in HIPa of PD-NC patients was significantly higher than that of PD-MCI patients. Furthermore, partial correlation analysis indicated that the FC in HIPa-PoCG.R and HIPm-PoCG.R were positively associated with executive functions. The elevated GM volume in HIPa related to better visuospatial and language functions.