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

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.

Disrupted coupling between salience network segregation and glucose metabolism is associated with cognitive decline in Alzheimer's disease – A simultaneous resting-state FDG-PET/fMRI study

“…The intra-network functional connectivity (intra-FC) was evaluated by FCS ( Liang et al, 2013 , Zhang et al, 2021a ). The mean FCS of a given network module was denoted as , which was calculated as: where is the number of voxels within module ; and denotes the Fisher’s z-transformed correlation coefficient between voxel an within module .…”

Topographic metabolism‐function relationships in Alzheimer's disease: A simultaneous PET/MRI study

“…In order to support effective communications between functional hubs, the association cortices are highly energy‐demanded, which also makes them vulnerable to neurodegeneration and AD‐related pathologies (Badhwar et al, 2017 ; Manza et al, 2020 ; Tomasi et al, 2013 ). As a result, both metabolic and functional alterations have been extensively reported in the DMN (Badhwar et al, 2017 ; Buckner et al, 2005 ; Greicius et al, 2004 ; Sheline & Raichle, 2013 ), the FPT (Badhwar et al, 2017 ; Grothe, Teipel, & Initiative, 2016), and the COP/SAL in patients with AD (Brier et al, 2012 ; Thomas et al, 2014 ; Zhang et al, 2022 ). Some of these disruptions were partially attributed to, and further promoted the deposition of amyloid plaques in cortical hubs (Buckner et al, 2005 ; Drzezga et al, 2011 ; Grothe et al, 2016 ).…”

“…Participants were required to lay supine with eyes closed and remain awake without systematic thinking during scanning. The PET/MRI imaging protocols was the same as our previous studies (Zhang et al, 2022 ; M. Zhang, Sun, et al, 2021 ). After fasting for at least 6 h, participants received a bolus injection of the 18 F‐FDG using a mean dose of 217.2 MBq (range: 140.6–314.5 MBq).…”

“…On the other hand, Manza et al did not find metabolic‐functional associations in the association or sensorimotor cortices (Manza et al, 2020 ); and Shokri‐Kojori et al demonstrated a mismatch between energy consumption and neuroglial activity in particular brain regions (Shokri‐Kojori et al, 2019 ). Furthermore, several studies, including our previous research, have shown that the metabolic‐functional relationship could be altered during the progression of AD and might exert a detrimental effect on cognitive performance (Ding et al, 2021 ; Maleki Balajoo et al, 2022 ; Marchitelli et al, 2018 ; Martin Scherr et al, 2021 ; Zhang et al, 2022 ).…”

Tracers progress for positron emission tomography imaging of glial-related disease

“…Compared with PET/CT, it has an increased soft tissue contrast and lacks of ionizing radiation exposure, which outperforms PET/CT in many applications [ 156 ] . It has been used in both neurodegenerative disorders [ 157 – 159 ] and glioma [ 160 – 162 ] , with above-mentioned radiotracers, PET/MRI has achieved much better results than using PET or MRI individually, and also PET/CT.…”