Dataset Information

Aberrant Functional Connectivity Architecture in Alzheimer's Disease and Mild Cognitive Impairment: A Whole-Brain, Data-Driven Analysis.

ABSTRACT: The purpose of our study was to investigate whether the whole-brain functional connectivity pattern exhibits disease severity-related alterations in patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI). Resting-state functional magnetic resonance imaging data were acquired in 27 MCI subjects, 35 AD patients, and 27 age- and gender-matched subjects with normal cognition (NC). Interregional functional connectivity was assessed based on a predefined template which parcellated the brain into 90 regions. Altered whole-brain functional connectivity patterns were identified via connectivity comparisons between the AD and NC subjects. Finally, the relationship between functional connectivity strength and cognitive ability according to the mini-mental state examination (MMSE) was evaluated in the MCI and AD groups. Compared with the NC group, the AD group exhibited decreased functional connectivities throughout the brain. The most significantly affected regions included several important nodes of the default mode network and the temporal lobe. Moreover, changes in functional connectivity strength exhibited significant associations with disease severity-related alterations in the AD and MCI groups. The present study provides novel evidence and will facilitate meta-analysis of whole-brain analyses in AD and MCI, which will be critical to better understand the neural basis of AD.

SUBMITTER: Zhou B

PROVIDER: S-EPMC4475740 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Aberrant Functional Connectivity Architecture in Alzheimer's Disease and Mild Cognitive Impairment: A Whole-Brain, Data-Driven Analysis.

Zhou Bo B Yao Hongxiang H Wang Pan P Zhang Zengqiang Z Zhan Yafeng Y Ma Jianhua J Xu Kaibin K Wang Luning L An Ningyu N Liu Yong Y Zhang Xi X

BioMed research international 20150608

The purpose of our study was to investigate whether the whole-brain functional connectivity pattern exhibits disease severity-related alterations in patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI). Resting-state functional magnetic resonance imaging data were acquired in 27 MCI subjects, 35 AD patients, and 27 age- and gender-matched subjects with normal cognition (NC). Interregional functional connectivity was assessed based on a predefined template which parcellated ...[more]

PMID: 26167487

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Project description:Objectives: Although it is widely observed that chronic insomnia disorder (CID) is associated with cognitive impairment, the neurobiological mechanisms underlying this remain unclear. Prior neuroimaging studies have confirmed that a close correlation exists between functional connectivity and cognitive impairment. Based on this observation, in this study we used resting-state functional magnetic resonance imaging (rs-fMRI) to study the relationship between whole brain functional connectivity and cognitive function in CID. Methods: We included 39 patients with CID and 28 age-, gender-, and education-matched healthy controls (HC). Abnormalities in functional connectivity were identified by comparing the correlation coefficients for each pair of 116 brain regions between CID and HC. Results: Cognitive impairment was associated with reduced subjective insomnia scores after controlling for age, gender, and educational effects. Compared with HC, patients with CID had larger negative correlations within the task-negative network [medial prefrontal cortex (mPFC), precuneus, inferior temporal gyrus, cerebellum, and superior parietal gyrus], and between two intrinsic anti-correlation networks (mPFC and middle temporal gyrus; supplementary motor area and cerebellum). Patients with CID also had decreased positive correlations within the default mode network (DMN), and between the cerebellum and DMN, which mainly comprises the mPFC and posterior cingulated cortex. There were positive correlations of decreased positive connectivity with subjective sleep scores and MMSE scores, and increased negative correlations between the task-negative-network and MMSE scores in CID. Conclusions: Using rs-fMRI, our results support previous observations of cortical disconnection in CID in the prefrontal and DMN networks. Moreover, abnormal correlations within the task-negative network, and between two intrinsically anti-correlation networks, might be important neurobiological indicators of CID and associated cognitive impairment.

Project description:BackgroundResting-state functional magnetic resonance imaging studies using a regional homogeneity (ReHo) method have reported that amnestic mild cognitive impairment (aMCI) was associated with abnormalities in local functional connectivity. However, their results were not conclusive.MethodsSeed-based d Mapping was used to conduct a coordinate-based meta-analysis to identify consistent ReHo alterations in aMCI.ResultsWe identified 10 studies with 11 datasets suitable for inclusion, including 378 patients with aMCI and 435 healthy controls. This meta-analysis identified significant ReHo alterations in patients with aMCI relative to healthy controls, mainly within the default mode network (DMN) (bilateral posterior cingulate cortex [PCC], right angular gyrus, bilateral middle temporal gyri, and left parahippocampal gyrus/hippocampus), executive control network (right superior parietal lobule and dorsolateral prefrontal cortex), visual network (right lingual gyrus and left middle occipital gyrus), and sensorimotor network (right paracentral lobule/supplementary motor area, right postcentral gyrus and left posterior insula). Significant heterogeneity of ReHo alterations in the bilateral PCC, left parahippocampal gyrus/hippocampus, and right superior parietal lobule/angular gyrus was observed. Exploratory meta-regression analyses indicated that general cognitive function, gender distribution, age, and education level partially contributed to this heterogeneity.ConclusionsThis study provides provisional evidence that aMCI is associated with abnormal ReHo within the DMN, executive control network, visual network, and sensorimotor network. These local functional connectivity alterations suggest coexistence of functional deficits and compensation in these networks. These findings contribute to the modeling of brain functional connectomes and to a better understanding of the neural substrates of aMCI. Confounding factors merit much attention and warrant future investigations.

Project description:(1) Background: Alzheimer's disease (AD), an age-progressive neurodegenerative disease that affects cognitive function, causes changes in the functional connectivity of the default-mode network (DMN). However, the question of whether AD-related changes occur in the functional connectivity of the basal ganglia has rarely been specifically analyzed. This study aimed to measure the changes in basal ganglia functional connectivity among patients with AD and mild cognitive impairment (MCI) in their resting state using the functional connectivity density (FCD) value, the functional connectivity (FC) intensity, and the graph theory index, and to confirm their influence on clinical manifestations. (2) Methods: Resting-state functional MRI (rs-fMRI) and neuropsychological data from 48 participants in the Alzheimer's Disease Neuroimaging Initiative (ADNI) were used for analyses. The 48 ADNI participants comprised 16 patients with AD, 16 patients with MCI, and 16 normal controls (NCs). The functional connectivity of basal ganglia was evaluated by FCDs, FC strength, and graph theory index. We compared voxel-based FCD values between groups to show specific regions with significant variation and significant connectivity from ROI conduction to ROI analysis. Pearson's correlation analyses between functional connectivity and several simultaneous clinical variables were also conducted. Additionally, receiver operating characteristic (ROC) analyses associated with classification were conducted for both FCD values and graph theory indices. (3) Results: The level of FCD in patients with cognitive impairment showed obvious abnormalities (including short-range and long-range FCD). In addition to DMN-related regions, aberrant functional connectivity was also found to be present in the basal ganglia, especially in the caudate and amygdala. The FCD values of the basal ganglia (involving the caudate and amygdala) were closely related to scores from the Mini-Mental State Examination (MMSE) and the Functional Activities Questionnaire (FAQ); meanwhile, the graph theory indices (involving global efficiency and degree) of the basal ganglia (involving the caudate, amygdala, and putamen) were also found to be closely correlated with MMSE scores. In ROC analyses of both FCD and graph theory, the amygdala was of the utmost importance in the early-stage detection of MCI; additionally, the caudate nucleus was found to be crucial in the progression of cognitive decline and AD diagnosis. (4) Conclusions: It was systematically confirmed that there is a phenomenon of change in the functional connections in the basal ganglia during cognitive decline. The findings of this study could improve our understanding of AD and MCI pathology in the basal ganglia and make it possible to propose new targets for AD treatment in further studies.

Project description:BackgroundAll cells accumulate insoluble protein aggregates throughout their lifespan. While many studies have characterized the canonical disease-associated protein aggregates, such as those associated with amyloid plaques, additional, undefined proteins aggregate in the brain and may be directly associated with disease and lifespan.MethodsA proteomics approach was used to identify a large subset of insoluble proteins in the mild cognitively impaired (MCI) and Alzheimer's disease (AD) human brain. Cortical samples from control, MCI, and AD patients were separated into detergent-soluble and detergent-insoluble fractions, and high-resolution LC/MS/MS technology was used to determine which proteins became more insoluble in the disease state. Bioinformatics analyses were used to determine if the alteration of protein aggregation between AD and control patients was associated with any specific biological process. Western blots were used to validate the proteomics data and to assess the levels of secondary protein modifications in MCI and AD.ResultsThere was a stage-dependent increase in detergent-insoluble proteins, with more extreme changes occurring in the AD cohort. Glycolysis was the most significantly overrepresented gene ontology biological process associated with the alteration of protein aggregation between AD and control patients. It was further shown that many low molecular weight proteins that were enriched in the AD brain were also highly aggregated, migrating on SDS-PAGE far above their predicted molecular masses. Glucose-6-phosphate isomerase, ubiquitin carboxyl-terminal hydrolase isoenzyme L1 (UCHL1/PARK5), and the DNA damage repair enzyme KU70 were among the top insoluble proteins identified by proteomics and validated by Western blot to be increased in the insoluble fractions of both MCI and AD brain samples.ConclusionsDiverse proteins became more detergent-insoluble in the brains of both MCI and AD patients compared to age-matched controls, suggesting that multiple proteins aggregate in these diseases, likely posing a direct toxic insult to neurons. Furthermore, detergent-insoluble proteins included those with important biological activities for critical cellular processes such as energetics, proteolysis, and DNA damage repair. Thus, reduced protein solubility likely promotes aggregation and limits functionality, reducing the efficiency of multiple aspects of cell physiology. Pharmaceutical interventions that increase autophagy may provide a useful therapeutic treatment to combat protein aggregation.

Dataset Information

Aberrant Functional Connectivity Architecture in Alzheimer's Disease and Mild Cognitive Impairment: A Whole-Brain, Data-Driven Analysis.

Publications

Aberrant Functional Connectivity Architecture in Alzheimer's Disease and Mild Cognitive Impairment: A Whole-Brain, Data-Driven Analysis.

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