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.
Highlights
The precuneus plays a critical role in fundamental cognitive functions including self-processing, memory, visual-spatial imagery, etc. (Cavanna and Trimble, 2006)
Decreased Mini-Mental State Examination (MMSE) scores were found in Alzheimer’s disease (AD) patients compared to the mild cognitive impairment (MCI) (p < 0.001) and cognitively normal (CN) (p < 0.001) groups, and in the MCI group compared to the CN group (p = 0.009)
The ventral precuneus was the earliest affected subregion and its compromised functional connectivity strength (FCS) and glucose metabolism were associated with cognitive decline of AD patients
Summary
The precuneus plays a critical role in fundamental cognitive functions including self-processing, memory, visual-spatial imagery, etc. (Cavanna and Trimble, 2006). (Cavanna and Trimble, 2006) It has been identified as a cortical hub for integrative processing of segregated systems in the brain (Buckner et al, 2009; Tomasi and Volkow, 2011). Based on its cytoarchitecture as well as anatomical and functional connectivities, the precuneus has been broadly subdivided, or hieratically classified, into three clusters, namely the dorsal-anterior, dorsal-posterior, and ventral/central subregions (Margulies et al, 2009; Zhang and Li, 2012; Wang et al, 2019; Luo et al, 2020; Ye et al, 2021). The dorsal anterior and posterior subregions are majorly involved in sensorimotor and visual-related functions, and the ventral/central subregion mostly participates in higher-order cognitive and self-related functions (Cauda et al, 2010). How the internal functional integrity of each subregion is affected by AD remains to be elucidated
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