Background Mild cognitive impairment (MCI) is an intermediate stage between normal aging and dementia. Amnestic MCI (aMCI) and non-amnestic MCI are the two subtypes of MCI with the former having a higher risk for progressing to Alzheimer's disease (AD). Compared with healthy elderly adults, individuals with MCI have specific functional alterations in the salience network (SN). However, no consistent results are documenting these changes. This meta-analysis aimed to investigate the specific functional alterations in the SN in MCI and aMCI. Methods: We systematically searched PubMed, Embase, and Web of Science for scientific neuroimaging literature based on three research methods, namely, functional connectivity (FC), regional homogeneity (ReHo), and the amplitude of low-frequency fluctuation or fractional amplitude of low-frequency fluctuation (ALFF/fALFF). Then, we conducted the coordinate-based meta-analysis by using the activation likelihood estimation algorithm. Results: In total, 30 functional neuroimaging studies were included. After extracting the data and analyzing it, we obtained specific changes in some brain regions in the SN including decreased ALFF/fALFF in the left superior temporal gyrus, the insula, the precentral gyrus, and the precuneus in MCI and aMCI; increased FC in the thalamus, the caudate, the superior temporal gyrus, the insula, and the cingulate gyrus in MCI; and decreased ReHo in the anterior cingulate gyrus in aMCI. In addition, as to FC, interactions of the SN with other networks including the default mode network and the executive control network were also observed mainly in the middle frontal gyrus and superior frontal gyrus in MCI and inferior frontal gyrus in aMCI. Conclusions: Specific functional alternations in the SN and interactions of the SN with other networks in MCI could be useful as potential imaging biomarkers for MCI or aMCI. Meanwhile, it provided a new insight in predicting the progression of health to MCI or aMCI and novel targets for proper intervention to delay the progression. Systematic Review Registration: [PROSPERO], identifier [No. CRD42020216259].

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Functional MRI-Specific Alterations in Salience Network in Mild Cognitive Impairment: An ALE Meta-Analysis.

Objective To characterize functional network changes related to conversion to cognitive impairment in a large sample of patients with multiple sclerosis (MS) over a period of 5 years. Methods Two hundred twenty-seven patients with MS and 59 healthy controls of the Amsterdam MS cohort underwent neuropsychological testing and resting-state fMRI at 2 time points (time interval 4.9 ± 0.9 years). At both baseline and follow-up, patients were categorized as cognitively preserved (CP; n = 123), mildly impaired (MCI; z Results Over time, 18.9% of patients converted to a worse phenotype; 22 of 123 patients who were CP (17.9%) converted from CP to MCI, 10 of 123 from CP to CI (8.1%), and 12 of 32 patients with MCI converted to CI (37.5%). At baseline, default-mode network (DMN) centrality was higher in CI individuals compared to controls (p = 0.05). Longitudinally, ventral attention network (VAN) importance increased in CP, driven by stable CP and CP-to-MCI converters (p Conclusions Of all patients, 19% worsened in their cognitive status over 5 years. Conversion from intact cognition to impairment is related to an initial disturbed functioning of the VAN, then shifting toward DMN dysfunction in CI. Because the VAN normally relays information to the DMN, these results could indicate that in MS normal processes crucial for maintaining overall network stability are progressively disrupted as patients clinically progress.

https://n.neurology.org/content/neurology/early/2021/06/07/WNL.0000000000012341.full.pdf

Longitudinal Network Changes and Conversion to Cognitive Impairment in Multiple Sclerosis

Magnetic Resonance Imaging (MRI) is an indispensable tool in the diagnosis of brain diseases due to painlessness and safety. Nevertheless, Rician noise is inevitably injected during the image acquisition process, which leads to poor observation and interferes with the treatment. Owing to the complexity of Rician noise, using the elimination method of Gaussian to remove it does not perform well. Therefore, the feature fusion and attention network (FFA-DMRI) is proposed to separate noise from observed MRI. Inspired by the attention-guided CNN network (ADNet) and Convolutional block attention module (CBAM), a spatial attention mechanism has been specially designed to obtain the area of interest in MRI. Furthermore, the feature fusion block concatenates local with global information, which makes full use of the multilevel structure and boosts the expressive ability of network. The comprehensive experiments on Alzheimer's disease neuroimaging initiative dataset (ADNI) have demonstrated high effectiveness of FFA-DMRI with maintaining the crucial brain details. Moreover, in terms of visual inspections, the denoising results are also consistent with human perception.

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FFA-DMRI: A Network Based on Feature Fusion and Attention Mechanism for Brain MRI Denoising.

Salience network (SN), playing a vital role in advanced cognitive function, is regarded to be impaired in subjective cognitive decline (SCD) and amnestic mild cognitive impairment (aMCI). The purpose of the study was to explore the importance of structural and functional features of SN in the diagnosis of SCD and aMCI. Structural and resting-state functional magnetic resonance imaging were collected from SCD, aMCI, and healthy control (HC). Cortex thickness, gray matter (GM) volume, spontaneous brain activity, functional connectivity (FC) within SN, and its relationship with cognitive function were analyzed. Moreover, the receiver operating characteristic analysis was performed to assess diagnostic efficacy of altered indictors for SCD and aMCI. Compared to HC, both SCD and aMCI showed decreased GM volume, decreased spontaneous brain activity, and increased FC within SN, while aMCI showed additional decreased cortex thickness. Furthermore, the altered FC in SCD and aMCI was significantly correlated with cognitive function. Particularly, the best-fitting classification models of SCD and aMCI were based on the combined multiple indicators. In conclusion, structure and function of SN were disrupted in SCD and aMCI, which involved in cognitive decline. The combined multiple indicators of SN provided powerful biomarkers for the diagnosis of SCD and aMCI.

Structural and Functional Disruption of Salience Network in Distinguishing Subjective Cognitive Decline and Amnestic Mild Cognitive Impairment.

Background: Ginkgo biloba extract (GBE) and donepezil have been reported to be effective in patients with Alzheimer's disease (AD). Nonetheless, how these drugs impact spontaneous brain activities and how they consequently improve functional recovery are currently unclear. Objectives: This study was to explore the efficacy of GBE vs. donepezil and their add-on efficacy on functional recovery and the adaption of spontaneous brain activities following pharmacologic treatment in patients with AD. Methods: Patients with AD were enrolled and assigned to the GBE group (n = 50), the donepezil group (n = 50), or the combined group (n = 50). Neuropsychological assessments, including minimum mental state examination (MMSE), Alzheimer's disease assessment scale-cognition (ADAS-Cog), instrumental activity of daily living (IADL), geriatric depression scale (GDS), neuropsychiatric inventory (NPI), and quality of life in Alzheimer's disease (QOL-AD), were conducted at baseline, 1 month, 3 months, and 6 months. Resting-state functional magnetic resonance imaging (rs-fMRI) was collected to compare the amplitude of low-frequency fluctuation (ALFF), percent amplitude of fluctuation (PerAF), regional homogeneity (ReHo), and degree centrality (DC) at baseline and 6 months. Results: No major significant differences were detected in all comparisons between groups across all follow-up time points. For intragroup comparison, MMSE and ADAS-Cog scores differed significantly across all follow-ups in three groups. The combined group showed significant improvement of GDS scores between baseline and 6 months (p = 0.007). The GBE group (p = 0.044) and donepezil group (p = 0.012) demonstrated significant improvement of NPI scores between baseline and 6 months. Significant correlations were observed between IADL and ALFF in the right gyrus rectus (p = 0.03) and in the left superior cerebellum gyrus (p = 0.01), between GDS and ALFF in the right middle temporal gyrus (p = 0.01), between NPI and PerAF in the left fusiform gyrus (p = 0.03), and between MMSE and ReHo in right superior frontal gyrus (p = 0.04). Conclusion: GBE was comparable with donepezil in the improvement of functional recovery in patients with AD while the combined application of GBE and donepezil seems unnecessary. GBE-mediated improvement of functional recovery was characterized by decreased ALFF values in the right gyrus rectus and decreased PerAF values in the left fusiform gyrus. These featured variations of imaging metrics in specific brain regions may serve as biomarkers in the monitoring of the therapeutic efficacy of GBE.

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Ginkgo Biloba Extract Is Comparable With Donepezil in Improving Functional Recovery in Alzheimer's Disease: Results From a Multilevel Characterized Study Based on Clinical Features and Resting-State Functional Magnetic Resonance Imaging.

The subjective cognitive decline (SCD) may last for decades prior to the onset of dementia and has been proposed as a risk population for development to amnestic mild cognitive impairment (aMCI) and Alzheimer disease (AD). Disruptions of functional connectivity and causal connectivity (CC) in the salience network (SN) are generally perceived as prominent hallmarks of the preclinical AD. Nevertheless, the alterations in anterior SN (aSN), and posterior SN (pSN) remain unclear. Here, we hypothesized that both the functional connectivity (FC) and CC of the SN subnetworks, comprising aSN and pSN, were distinct disruptive in the SCD and aMCI. We utilized resting-state functional magnetic resonance imaging to investigate the altered FC and CC of the SN subnetworks in 28 healthy controls, 23 SCD subjects, and 29 aMCI subjects. In terms of altered patterns of FC in SN subnetworks, aSN connected to the whole brain was significantly increased in the left orbital superior frontal gyrus, left insula lobule, right caudate lobule, and left rolandic operculum gyrus (ROG), whereas decreased FC was found in the left cerebellum superior lobule and left middle temporal gyrus when compared with the HC group. Notably, no prominent statistical differences were obtained in pSN. For altered patterns of CC in SN subnetworks, compared to the HC group, the aberrant connections in aMCI group were separately involved in the right cerebellum inferior lobule (CIL), right supplementary motor area (SMA), and left ROG, whereas the SCD group exhibited more regions of aberrant connection, comprising the right superior parietal lobule, right CIL, left inferior parietal lobule, left post-central gyrus (PG), and right angular gyrus. Especially, SCD group showed increased CC in the right CIL and left PG, whereas the aMCI group showed decreased CC in the left pre-cuneus, corpus callosum, and right SMA when compared to the SCD group. Collectively, our results suggest that analyzing the altered FC and CC observed in SN subnetworks, served as impressible neuroimaging biomarkers, may supply novel insights for designing preclinical interventions in the preclinical stages of AD.

Altered Patterns of Functional Connectivity and Causal Connectivity in Salience Subnetwork of Subjective Cognitive Decline and Amnestic Mild Cognitive Impairment

Haijie Lu

Papers

Altered Patterns of Functional Connectivity and Causal Connectivity in Salience Subnetwork of Subjective Cognitive Decline and Amnestic Mild Cognitive Impairment