Simultaneous PET/fMRI Detects Distinctive Alterations in Functional Connectivity and Glucose Metabolism of Precuneus Subregions in Alzheimer's Disease

Miao Zhang; Wanqing Sun; Ziyun Guan; Jialin Hu; Binyin Li; Guanyu Ye; Hongping Meng; Xinyun Huang; Xiaozhu Lin; Jin Wang; Jun Liu; Biao Li; Yaoyu Zhang; Yao Li

doi:10.3389/fnagi.2021.737002

Simultaneous PET/fMRI Detects Distinctive Alterations in Functional Connectivity and Glucose Metabolism of Precuneus Subregions in Alzheimer's Disease

Front Aging Neurosci. 2021 Sep 24:13:737002. doi: 10.3389/fnagi.2021.737002. eCollection 2021.

Authors

Miao Zhang¹, Wanqing Sun², Ziyun Guan², Jialin Hu², Binyin Li³, Guanyu Ye³, Hongping Meng¹, Xinyun Huang¹, Xiaozhu Lin¹, Jin Wang¹, Jun Liu³, Biao Li^{1

4}, Yaoyu Zhang², Yao Li²

Affiliations

¹ Department of Nuclear Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
² School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.
³ Department of Neurology & Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
⁴ Collaborative Innovation Center for Molecular Imaging of Precision Medicine, Ruijin Center, Shanghai, China.

Abstract

As a central hub in the interconnected brain network, the precuneus has been reported showing disrupted functional connectivity and hypometabolism in Alzheimer's disease (AD). However, as a highly heterogeneous cortical structure, little is known whether individual subregion of the precuneus is uniformly or differentially involved in the progression of AD. To this end, using a hybrid PET/fMRI technique, we compared resting-state functional connectivity strength (FCS) and glucose metabolism in dorsal anterior (DA_pcu), dorsal posterior (DP_pcu) and ventral (V_pcu) subregions of the precuneus among 20 AD patients, 23 mild cognitive impairment (MCI) patients, and 27 matched cognitively normal (CN) subjects. The sub-parcellation of precuneus was performed using a K-means clustering algorithm based on its intra-regional functional connectivity. For the whole precuneus, decreased FCS (p = 0.047) and glucose hypometabolism (p = 0.006) were observed in AD patients compared to CN subjects. For the subregions of the precuneus, decreased FCS was found in DP_pcu of AD patients compared to MCI patients (p = 0.011) and in V_pcu for both MCI (p = 0.006) and AD (p = 0.008) patients compared to CN subjects. Reduced glucose metabolism was found in DP_pcu of AD patients compared to CN subjects (p = 0.038) and in V_pcu of AD patients compared to both MCI patients (p = 0.045) and CN subjects (p < 0.001). For both FCS and glucose metabolism, DA_pcu remained relatively unaffected by AD. Moreover, only in V_pcu, disruptions in FCS (r = 0.498, p = 0.042) and hypometabolism (r = 0.566, p = 0.018) were significantly correlated with the cognitive decline of AD patients. Our results demonstrated a distinctively disrupted functional and metabolic pattern from ventral to dorsal precuneus affected by AD, with V_pcu and DA_pcu being the most vulnerable and conservative subregion, respectively. Findings of this study extend our knowledge on the differential roles of precuneus subregions in AD.

Keywords: Alzheimer’s disease; functional connectivity; glucose metabolism; hybrid PET/MRI; mild cognitive impairment; precuneus; subregions.