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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.

SUBMITTER: Zhang M

PROVIDER: S-EPMC8498203 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Precuneus responds to a wide range of cognitive processes. Here, we examined how the patterns of resting state connectivity may define functional subregions in the precuneus. Using a K-means algorithm to cluster the whole-brain "correlograms" of the precuneus in 225 adult individuals, we corroborated the dorsal-anterior, dorsal-posterior, and ventral subregions, each involved in spatially guided behaviors, mental imagery, and episodic memory as well as self-related processing, with the ventral precuneus being part of the default mode network, as described extensively in earlier work. Furthermore, we showed that the lateral/medial volumes of dorsal anterior and dorsal posterior precuneus are each connected with areas of motor execution/attention and motor/visual imagery, respectively. Compared to the ventral precuneus, the dorsal precuneus showed greater connectivity with occipital and posterior parietal cortices, but less connectivity with the medial superior frontal and orbitofrontal gyri, anterior cingulate cortex as well as the parahippocampus. Compared to dorsal-posterior and ventral precuneus, the dorsal-anterior precuneus showed greater connectivity with the somatomotor cortex, as well as the insula, supramarginal, Heschl's, and superior temporal gyri, but less connectivity with the angular gyrus. Compared to ventral and dorsal-anterior precuneus, dorsal-posterior precuneus showed greater connectivity with the middle frontal gyrus. Notably, the precuneus as a whole has negative connectivity with the amygdala and the lateral and inferior orbital frontal gyri. Finally, men and women differed in the connectivity of precuneus. Men and women each showed greater connectivity with the dorsal precuneus in the cuneus and medial thalamus, respectively. Women also showed greater connectivity with ventral precuneus in the hippocampus/parahippocampus, middle/anterior cingulate gyrus, and middle occipital gyrus, compared to men. Taken together, these new findings may provide a useful platform upon which to further investigate sex-specific functional neuroanatomy of the precuneus and to elucidate the pathology of many neurological illnesses.

Project description:Background: Imaging studies in Alzheimer's disease (AD) have yet to answer the underlying questions concerning the relationship among tau retention, neuroinflammation, network disruption and cognitive decline. We compared the spatial retention patterns of 18F-THK5351 and resting state network (RSN) disruption in patients with early AD and healthy controls. Methods: We enrolled 23 11C-Pittsburgh compound B (PiB)-positive patients with early AD and 24 11C-PiB-negative participants as healthy controls. All participants underwent resting state functional MRI and 18F-THK5351 PET scans. We used scaled subprofile modeling/principal component analysis (SSM/PCA) to reduce the complexity of multivariate data and to identify patterns that exhibited the largest statistical effects (variances) in THK5351 concentration in AD and healthy controls. Findings: SSM/PCA identified a significant spatial THK5351 pattern composed by mainly three clusters including precuneus/posterior cingulate cortex (PCC), right and left dorsolateral prefrontal cortex (DLPFC) which accounted for 23.6% of the total subject voxel variance of the data and had 82.6% sensitivity and 79.1% specificity in discriminating AD from healthy controls. There was a significant relationship between the intensity of the 18F-THK5351 covariation pattern and cognitive scores in AD. The spatial patterns of 18F-THK5351 uptake showed significant similarity with intrinsic functional connectivity, especially in the PCC network. Seed-based connectivity analysis from the PCC showed significant decrease in connectivity over widespread brain regions in AD patients. An evaluation of an autopsied AD patient with Braak V showed that 18F-THK5351 retention corresponded to tau deposition, monoamine oxidase-B (MAO-B) and astrogliosis in the precuneus/PCC. Interpretation: We identified an AD-specific spatial pattern of 18F-THK5351 retention in the precuneus/PCC, an important connectivity hub region in the brain. Disruption of the functional connections of this important network hub may play an important role in developing dementia in AD.

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

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