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Dynamic functional connectivity in Parkinson's disease patients with mild cognitive impairment and normal cognition.

ABSTRACT: The objective was to assess dynamic functional connectivity (FC) and local/global connectivity in Parkinson's disease (PD) patients with mild cognitive impairment (PD-MCI) and with normal cognition (PD-NC). The sample included 35 PD patients and 26 healthy controls (HC). Cognitive assessment followed an extensive neuropsychological battery. For resting-state functional MRI (rs-fMRI) analysis, independent component analysis (ICA) was performed and components were located in 7 networks: Subcortical (SC), Auditory (AUD), Somatomotor (SM), visual (VI), cognitive-control (CC), default-mode (DMN), and cerebellar (CB). Dynamic FC analysis was performed using the GIFT toolbox. FC differences between groups in each FC state were analysed with the network-based statistic (NBS) approach. Finally, a graph-theoretical analysis for local/global parameters was performed. The whole sample showed 2 dynamic FC states during the rs-fMRI. PD-MCI patients showed decreased mean dwell time in the hypo-connectivity state (p = 0.030) and showed increased number of state transitions (p = 0.007) compared with the HC. In addition, in the hypo-connectivity state, PD-MCI patients showed reduced inter-network FC between the SM-CC, SM-VI, SM-AUD, CC-VI and SC-DMN compared with the HC (p < 0.05-FDR). These FC alterations in PD-MCI were accompanied by graph-topological alterations in nodes located in the SM network (p < 0.001). In contrast, no differences were found between the PD-NC and HC. Findings suggest the presence of dynamic functional brain deteriorations in PD-MCI that are not present in PD-NC, showing the PD-MCI group dynamic FC dysfunctions, reduced FC mostly between SM-CC networks and graph-topological deteriorations in the SM network. A dynamic FC approach could be helpful to understand cognitive deterioration in PD.

SUBMITTER: Diez-Cirarda M

PROVIDER: S-EPMC5842729 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Dynamic functional connectivity in Parkinson's disease patients with mild cognitive impairment and normal cognition.

Díez-Cirarda María M Strafella Antonio P AP Kim Jinhee J Peña Javier J Ojeda Natalia N Cabrera-Zubizarreta Alberto A Ibarretxe-Bilbao Naroa N

NeuroImage. Clinical 20171209

The objective was to assess dynamic functional connectivity (FC) and local/global connectivity in Parkinson's disease (PD) patients with mild cognitive impairment (PD-MCI) and with normal cognition (PD-NC). The sample included 35 PD patients and 26 healthy controls (HC). Cognitive assessment followed an extensive neuropsychological battery. For resting-state functional MRI (rs-fMRI) analysis, independent component analysis (ICA) was performed and components were located in 7 networks: Subcortica ...[more]

PMID: 29527489

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Project description:ObjectiveCognitive impairment occurs frequently in Parkinson's disease (PD) and negatively impacts the patient's quality of life. However, its pathophysiological mechanism remains unclear, hindering the development of new therapies. Changes in brain connectivity are related to cognitive impairment in patients with PD, with the dorsolateral prefrontal cortex (DLPFC) being considered the essential region related to PD cognitive impairment. Nevertheless, few studies have focused on the global connectivity responsible for communication with the DLPFC node, the posterior division of the middle frontal gyrus (PMFG) in patients with PD; this was the focus of this study.MethodsWe applied resting-state electroencephalography (EEG) and calculated a reliable functional connectivity measurement, the debiased weighted phase lag index (dWPLI), to examine inter-regional functional connectivity in 68 patients with PD who were classified into two groups according to their cognitive condition.ResultsWe observed that altered left and right PMFG-based functional connectivity associated with cognitive impairment in patients with PD in the theta frequency bands under the eyes closed condition (r = -0.426, p < 0.001 and r = -0.437, p < 0.001, respectively). Exploratory results based on the MoCA subdomains indicated that poorer visuospatial function was associated with higher right PMFG-based functional connectivity (r = -0.335, p = 0.005), and poorer attention function was associated with higher left and right PMFG-based functional connectivity (r = -0.380, p = 0.001 and r = -0.256, p = 0.035, respectively). Further analysis using logistic regression and receiver operating characteristic (ROC) curves found that this abnormal functional connectivity was an independent risk factor for cognitive impairment [odds ratio (OR): 2.949, 95% confidence interval (CI): 1.294-6.725, p = 0.01 for left PMFG; OR: 11.278, 95% CI: 2.578-49.335, p = 0.001 for right PMFG, per 0.1 U], and provided moderate classification power to discriminate between cognitive abilities in patients with PD [area under the ROC curve (AUC) = 0.770 for left PMFG; AUC = 0.809 for right PMFG].ConclusionThese preliminary findings indicate that abnormal PMFG-based functional connectivity patterns associated with cognitive impairment in the theta frequency bands under the eyes closed condition and altered functional connectivity patterns have the potential to act as reliable biomarkers for identifying cognitive impairment in patients with PD.

Project description:BACKGROUND:Alzheimer's Disease (AD) can be conceptualized as a continuum: patients progress from normal cognition to mild cognitive impairment (MCI) due to AD, followed by increasing severity of AD dementia. Prior research has measured transition probabilities among later stages of AD, but not for the complete spectrum. OBJECTIVE:To estimate annual progression rates across the AD continuum and evaluate the impact of a delay in MCI due to AD on the trajectory of AD dementia and clinical outcomes. METHODS:Patient-level longitudinal data from the National Alzheimer's Coordinating Center for n=18,103 patients with multiple visits over the age of 65 were used to estimate annual, age-specific transitional probabilities between normal cognition, MCI due to AD, and AD severity states (defined by Clinical Dementia Rating score). Multivariate models predicted the likelihood of death and institutionalization for each health state, conditional on age and time from the previous evaluation. These probabilities were used to populate a transition matrix describing the likelihood of progressing to a particular disease state or death for any given current state and age. Finally, a health state model was developed to estimate the expected effect of a reduction in the risk of transitioning from normal cognition to MCI due to AD on disease progression rates for a cohort of 65-year-old patients over a 35-year time horizon. RESULTS:Annual transition probabilities to more severe states were 8%, 22%, 25%, 36%, and 16% for normal cognition, MCI due to AD, and mild/moderate/severe AD, respectively, at age 65, and increased as a function of age. Progression rates from normal cognition to MCI due to AD ranged from 4% to 10% annually. Severity of cognitive impairment and age both increased the likelihood of institutionalization and death. For a cohort of 100 patients with normal cognition at age 65, a 20% reduction in the annual progression rate to MCI due to AD avoided 5.7 and 5.6 cases of MCI due to AD and AD, respectively. This reduction led to less time spent in severe AD dementia health states and institutionalized, and increased life expectancy. CONCLUSION:Transition probabilities from normal cognition through AD severity states are important for understanding patient progression across the AD spectrum. These estimates can be used to evaluate the clinical benefits of reducing progression from normal cognition to MCI due to AD on lifetime health outcomes.

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.

Dataset Information

Dynamic functional connectivity in Parkinson's disease patients with mild cognitive impairment and normal cognition.

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Dynamic functional connectivity in Parkinson's disease patients with mild cognitive impairment and normal cognition.

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