Altered Insular Subregional Connectivity Associated With Cognitions for Distinguishing the Spectrum of Pre-clinical Alzheimer's Disease

Abstract

Background: Subjective cognitive decline (SCD) and amnestic mild cognitive impairment (aMCI) are regarded as part of the pre-clinical Alzheimer's disease (AD) spectrum. The insular subregional networks are thought to have diverse intrinsic connectivity patterns that are involved in cognitive and emotional processing. We set out to investigate convergent and divergent altered connectivity patterns of the insular subregions across the spectrum of pre-clinical AD and evaluated how well these patterns can differentiate the pre-clinical AD spectrum.Method: Functional connectivity (FC) analyses in insular subnetworks were carried out among 38 patients with SCD, 56 patients with aMCI, and 55 normal controls (CNs). Logistic regression analyses were used to construct models for aMCI and CN, as well as SCD and CN classification. Finally, we conducted correlation analyses to measure the relationship between FCs of altered insular subnetworks and cognition.Results: Patients with SCD presented with reduced FC in the bilateral cerebellum posterior lobe and increased FC in the medial frontal gyrus and the middle temporal gyrus. On the other hand, patients with aMCI largely presented with decreased FC in the bilateral inferior parietal lobule, the cerebellum posterior lobe, and the anterior cingulate cortex, as well as increased FC in the medial and inferior frontal gyrus, and the middle and superior temporal gyrus. Logistic regression analyses indicated that a model composed of FCs among altered insular subnetworks in patients with SCD was able to appropriately classify 83.9% of patients with SCD and CN, with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.876, 81.6% sensitivity, and 81.8% specificity. A model consisting of altered insular subnetwork FCs in patients with aMCI was able to appropriately classify 86.5% of the patients with aMCI and CNs, with an AUC of 0.887, 80.4% sensitivity, and 83.6% specificity. Furthermore, some of the FCs among altered insular subnetworks were significantly correlated with episodic memory and executive function.Conclusions: Patients with SCD and aMCI are likely to share similar convergent and divergent altered intrinsic FC patterns of insular subnetworks as the pre-clinical AD spectrum, and presented with abnormalities among subnetworks. Based on these abnormalities, individuals can be correctly differentiated in the pre-clinical AD spectrum. These results suggest that alterations in insular subnetworks can be utilized as a potential biomarker to aid in conducting a clinical diagnosis of the spectrum of pre-clinical AD.

Functional Integrity of Executive Control Network Contributed to Retained Executive Abilities in Mild Cognitive Impairment

“…The details of the NBH-ADsnp-related information are provided in Supplementary Material. The diagnostic and exclusion criteria of MCI and HC were in accordance with our previous studies (Xue et al, 2019;Wang et al, 2021b). This study was granted approval by the responsible Human Participants Ethics Committee of the Affiliated Brain Hospital of Nanjing Medical University (Nos.…”

Differential Abnormality in Functional Connectivity Density in Preclinical and Early-Stage Alzheimer's Disease

“…The data for the applied research were obtained from our domestic database, the Nanjing Brain Hospital Alzheimer's Disease Spectrum Neuroimaging Project (NBH-ADsnp) (Nanjing, China; Chen et al, 2020 ; Wang et al, 2021 ; Xu et al, 2021 ), which is regularly updated. Detailed information about NBH-ADsnp is available in the Supplementary Material .…”

“…Among them, eight participants were excluded due to excessive head motion (cumulative translation or rotation of > 3.0 mm or 3.0°). According to previous studies (Wang et al, 2021 ; Xue et al, 2021 ), a total of 194 participants, including 59 aMCI, 57 SCD, and 78 HC, were eventually included after strict exclusion. Detailed information about inclusive and exclusive criteria is summarized in the Supplementary Material .…”

“…Functional abnormalities of cortical or subcortical hubs are closely associated with cognitive dysfunction (Yu et al, 2017 ). Wang et al discovered altered intrinsic FC patterns with insular subnetworks in patients with SCD and aMCI, as opposed to healthy controls (HCs), and those specific changes were correlated with episodic memory (EM; Wang et al, 2021 ). Furthermore, using graph analysis, patients with AD or mild cognitive impairment (MCI) had global and local FC disruptions (Zhao et al, 2012 ; Wang et al, 2013 ).…”

Exploring dynamic functional connectivity alterations in the preclinical stage of Alzheimer’s disease: an exploratory study from SICOLDE

“…Resting-state functional magnetic resonance imaging (rs-fMRI) plays a key role in re ecting cognizance of brain functions, especially in exploring the abnormal connectivity patterns of brain regions in patients with AD (7)(8)(9). More speci cally, previous research on functional connectivity (FC) has explored the abnormal changes that occur in functional networks in the brains of SCD individuals (10,11). For instance, research shows that the global functional network is signi cantly increased in SCD (12), and that altered FC is primarily located in the posterior brain regions (13).…”