Subacute functional connectivity correlates with cognitive recovery six months after stroke.

BACKGROUND AND PURPOSE: Cognitive impairment is a common consequence of stroke, and the rewiring of the surviving brain circuits might contribute to cognitive recovery. Studies investigating how the functional connectivity of networks change across time and whether their remapping relates to cognitive recovery in stroke patients are scarce. We aimed to investigate whether resting-state functional connectivity was associated with cognitive performance in stroke patients and if any alterations in these networks were correlated with cognitive recovery. METHODS: Using an fMRI ROI-ROI approach, we compared the ipsilesional, contralesional and interhemispheric functional connectivity of three resting-state networks involved in cognition - the Default Mode (DMN), Salience (SN) and Central Executive Networks (CEN), in subacute ischemic stroke patients (time 1, n = 37, stroke onset: 24.32 ± 7.44 days, NIHSS: 2.66 ± 3.45) with cognitively healthy controls (n = 20). Patients were reassessed six months after the stroke event (time 2, n = 20, stroke onset: 182.05 ± 8.17 days) to verify the subsequent reorganization of functional connections and whether such reorganization was associated with cognitive recovery. RESULTS: At time 1, patients had weaker interhemispheric connectivity in the DMN than controls; better cognitive performance at time 1 was associated with stronger interhemispheric and ipsilesional DMN connectivity, and weaker contralesional SN connectivity. At time 2, there were no changes in functional connectivity in stroke patients, compared to time 1. Better cognitive recovery measured at time 2 (time 2 - time 1) was associated with stronger functional connectivity in the DMN, and weaker interhemispheric subacute connectivity in the SN, both from time 1. CONCLUSIONS: Stroke disrupts the functional connectivity of the DMN, not only at the lesioned hemisphere but also between hemispheres. Six months after the stroke event, we could not detect the remapping of networks. Cognitive recovery was associated with the connectivity of both the DMN and SN of time 1. Our findings may be helpful for facilitating further understanding of the potential mechanisms underlying post-stroke cognitive performance.

Alzheimer's Disease Detection Through Whole-Brain 3D-CNN MRI.

The projected burden of dementia by Alzheimer's disease (AD) represents a looming healthcare crisis as the population of most countries grows older. Although there is currently no cure, it is possible to treat symptoms of dementia. Early diagnosis is paramount to the development and success of interventions, and neuroimaging represents one of the most promising areas for early detection of AD. We aimed to deploy advanced deep learning methods to determine whether they can extract useful AD biomarkers from structural magnetic resonance imaging (sMRI) and classify brain images into AD, mild cognitive impairment (MCI), and cognitively normal (CN) groups. We tailored and trained Convolutional Neural Networks (CNNs) on sMRIs of the brain from datasets available in online databases. Our proposed method, ADNet, was evaluated on the CADDementia challenge and outperformed several approaches in the prior art. The method's configuration with machine-learning domain adaptation, ADNet-DA, reached 52.3% accuracy. Contributions of our study include devising a deep learning system that is entirely automatic and comparatively fast, presenting competitive results without using any patient's domain-specific knowledge about the disease. We were able to implement an end-to-end CNN system to classify subjects into AD, MCI, or CN groups, reflecting the identification of distinctive elements in brain images. In this context, our system represents a promising tool in finding biomarkers to help with the diagnosis of AD and, eventually, many other diseases.

Cognitive Reserve Relates to Functional Network Efficiency in Alzheimer's Disease.

Alzheimer's disease (AD) is the most common form of dementia, with no means of cure or prevention. The presence of abnormal disease-related proteins in the population is, in turn, much more common than the incidence of dementia. In this context, the cognitive reserve (CR) hypothesis has been proposed to explain the discontinuity between pathophysiological and clinical expression of AD, suggesting that CR mitigates the effects of pathology on clinical expression and cognition. fMRI studies of the human connectome have recently reported that AD patients present diminished functional efficiency in resting-state networks, leading to a loss in information flow and cognitive processing. No study has investigated, however, whether CR modifies the effects of the pathology in functional network efficiency in AD patients. We analyzed the relationship between CR, pathophysiology and network efficiency, and whether CR modifies the relationship between them. Fourteen mild AD, 28 amnestic mild cognitive impairment (aMCI) due to AD, and 28 controls were enrolled. We used education to measure CR, cerebrospinal fluid (CSF) biomarkers to evaluate pathophysiology, and graph metrics to measure network efficiency. We found no relationship between CR and CSF biomarkers; CR was related to higher network efficiency in all groups; and abnormal levels of CSF protein biomarkers were related to more efficient networks in the AD group. Education modified the effects of tau-related pathology in the aMCI and mild AD groups. Although higher CR might not protect individuals from developing AD pathophysiology, AD patients with higher CR are better able to cope with the effects of pathology-presenting more efficient networks despite pathology burden. The present study highlights that interventions focusing on cognitive stimulation might be useful to slow age-related cognitive decline or dementia and lengthen healthy aging.

Cognitive and structural cerebral changes in amnestic mild cognitive impairment due to Alzheimer's disease after multicomponent training.

Introduction: Information about how physical exercise affects patients with amnestic mild cognitive impairment (aMCI) due to Alzheimer's disease (AD) is still missing. This study evaluated the impact of multicomponent exercise training on cognition and brain structure in aMCI subjects with cerebral spinal fluid positive AD biomarkers. Methods: Forty aMCI subjects were divided in training (multicomponent exercise thrice a week for 6 months) and nontraining groups. Assessments included cardiorespiratory fitness, neurocognitive tests, and a structural magnetic resonance imaging using 3.0 T scanner. FreeSurfer software analyzed hippocampal volume and cortical thickness. Results: The training group showed increased volume in both hippocampi and better performance in episodic memory test after 6 months. In contrast, the nontraining group declined in functional activities, recognition, and cardiorespiratory fitness for the same period. Discussion: Multicomponent exercise seems to improve hippocampal volume and episodic memory, and maintains VO2max in aMCI due to AD.

Depression and anxiety symptoms are associated to disruption of default mode network in subacute ischemic stroke.

Depression and anxiety symptoms are common after stroke and associated to reduction in quality of life and poor physical and social outcomes. The Default Mode Network (DMN) plays an important role in the emotional processing. We investigated whether these symptoms are associated to a disruption of DMN functional connectivity in the first month after stroke. Thirty-four subacute ischemic stroke patients were submitted to: 1) behavioral assessment through Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI) and Structured Clinical Interview for DSM Disorders; 2) neuropsychological assessment using Mini Mental State Examination and Montreal Cognitive Assessment; 3) resting state functional magnetic resonance imaging acquisition using a 3 T scanner (Philips Achieva). Patients with depression and/or anxiety symptoms showed an increased DMN functional connectivity in left inferior parietal gyrus and left basal nuclei, when compared to stroke controls. Specific correlation between BDI/BAI scores and DMN functional connectivity indicated that depression symptoms are correlated with increased functional connectivity in left inferior parietal gyrus, while anxiety symptoms are correlated with increased functional connectivity in cerebellum, brainstem and right middle frontal gyrus. Our study provides new insights into the underlying mechanisms of post stroke depression and anxiety, suggesting an alternate explanation other than regional structural damage following ischemic event, that these psychiatric symptoms are related to brain network dysfunction.

Relation between aerobic fitness and brain structures in amnestic mild cognitive impairment elderly.

Mild cognitive impairment (aMCI) is a clinical condition, with high risk to develop Alzheimer's disease. Physical exercise may have positive effect on cognition and brain structure in older adults. However, it is still under research whether these influences are true on aMCI subjects with low Ab_42 and high total tau in cerebrospinal fluid (CSF), which is considered a biomarker for AD. Therefore, we aimed to investigate a possible relation between aerobic fitness (AF) and gray matter (GM) volume and AF and white matter (WM) integrity in aMCI with a CSF biomarker. Twenty-two participants with aMCI acquired the images on a 3.0-T MRI. AF was assessed by a graded exercise test on a treadmill. Voxel-based morphometry and tract-based spatial statistic methods were used to analyze the GM volume and WM microstructural integrity, respectively. We correlated AF and GM volume and WM integrity in aMCI (p < 0.05, FWE corrected, cluster with at least five voxels). There was a positive relation between AF and GM volume mostly in frontal superior cortex. In WM integrity, AF was positively correlated with fractional anisotropy and negatively correlated with mean diffusivity and radial diffusivity, all in the same tracts that interconnect frontal, temporal, parietal, and occipital areas (longitudinal fasciculus, fronto-occipital fasciculus, and corpus callosum). These results suggest that aerobic fitness may have a positive influence on protection of brain even in aMCI CSF biomarker, a high-risk population to convert to AD.

Differences and the relationship in default mode network intrinsic activity and functional connectivity in mild Alzheimer's disease and amnestic mild cognitive impairment.

There is evidence that the default mode network (DMN) functional connectivity is impaired in Alzheimer's disease (AD) and few studies also reported a decrease in DMN intrinsic activity, measured by the amplitude of low-frequency fluctuations (ALFFs). In this study, we analyzed the relationship between DMN intrinsic activity and functional connectivity, as well as their possible implications on cognition in patients with mild AD and amnestic mild cognitive impairment (aMCI) and healthy controls. In addition, we evaluated the differences both in connectivity and ALFF values between these groups. We recruited 29 controls, 20 aMCI, and 32 mild AD patients. To identify the DMN, functional connectivity was calculated by placing a seed in the posterior cingulate cortex (PCC). Within the DMN mask obtained, we calculated regional average ALFFs. Compared with controls, aMCI patients showed decreased ALFFs in the temporal region; compared with AD, aMCI showed higher values in the PCC but lower in the temporal area. The mild AD group had lower ALFFs in the PCC compared with controls. There was no difference between the connectivity in the aMCI group compared with the other groups, but AD patients showed decreased connectivity in the frontal, parietal, and PCC. Also, PCC ALFFs correlated to functional connectivity in nearly all subregions. Cognitive tests correlated to connectivity values but not to ALFFs. In conclusion, we found that DMN connectivity and ALFFs are correlated in these groups. Decreased PCC ALFFs disrupt the DMN functional organization, leading to cognitive problems in the AD spectrum.

Structural connectivity of the default mode network and cognition in Alzheimer׳s disease.

Disconnectivity between the Default Mode Network (DMN) nodes can cause clinical symptoms and cognitive deficits in Alzheimer׳s disease (AD). We aimed to examine the structural connectivity between DMN nodes, to verify the extent in which white matter disconnection affects cognitive performance. MRI data of 76 subjects (25 mild AD, 21 amnestic Mild Cognitive Impairment subjects and 30 controls) were acquired on a 3.0T scanner. ExploreDTI software (fractional Anisotropy threshold=0.25 and the angular threshold=60°) calculated axial, radial, and mean diffusivities, fractional anisotropy and streamline count. AD patients showed lower fractional anisotropy (P=0.01) and streamline count (P=0.029), and higher radial diffusivity (P=0.014) than controls in the cingulum. After correction for white matter atrophy, only fractional anisotropy and radial diffusivity remained significantly lower in AD compared to controls (P=0.003 and P=0.05). In the parahippocampal bundle, AD patients had lower mean and radial diffusivities (P=0.048 and P=0.013) compared to controls, from which only radial diffusivity survived for white matter adjustment (P=0.05). Regression models revealed that cognitive performance is also accounted for by white matter microstructural values. Structural connectivity within the DMN is important to the execution of high-complexity tasks, probably due to its relevant role in the integration of the network.

Carotid stenting versus endarterectomy cognitive outcomes.

BACKGROUND: The objectives are to analyze the impact of carotid revascularization on cognitive performance after a 3-month period in patients, who have undergone carotid artery stenting (CAS) or carotid endarterectomy (CEA), and to compare the cognitive outcomes between these 2 groups of patients. This a nonrandomized and prospective single-center experience. METHODS: This study was performed in the University of Campinas Hospital from January 2010 to January 2012 and included 30 patients with carotid stenosis who received carotid interventions. Nineteen patients received CEA and 11 patients received CAS. Neuropsychologic evaluation included general cognitive, language, visuospatial, attentional, executive function, and memory tests. RESULTS: After the follow-up period, there was improvement in episodic memory, encoding subitem (P = 0.02), and delayed recall (P = 0.02) for the CEA group. The CAS group improved in episodic memory, encoding subitem (P = 0.009), working memory (P = 0.04), and executive functions (P = 0.02). Comparing the techniques, the CAS group showed higher scores only in executive functions (P = 0.02). CONCLUSIONS: Both groups had a similar performance in cognitive tests, comparing preoperative and postoperative results. However, patients who underwent CAS tended to achieve higher scores in executive function and operational memory/attention tests.

Volumetric brain changes in thalamus, corpus callosum and medial temporal structures: mild Alzheimer's disease compared with amnestic mild cognitive impairment.

BACKGROUND: It is widely known that atrophy of medial temporal structures is present in the mild stage of Alzheimer's disease (AD) and amnestic mild cognitive impairment (aMCI). However, structures such as the thalamus and corpus callosum are much less studied. METHODS: We compared the volumes of the entorhinal cortex, hippocampus, thalamus and the corpus callosum in 14 controls, 14 patients with mild AD and 15 with aMCI and correlated these volumes with neuropsychological data. MRI was obtained at 2 T followed by manual segmentation. RESULTS: We found atrophy in hippocampi and thalami of MCI patients compared to controls, and in the bilateral entorhinal cortex of aMCI compared to AD patients. All the structures showed atrophy in AD patients compared to controls, including the corpus callosum. CONCLUSIONS: Our study confirms that thalamic areas are atrophied in aMCI, and the corpus callosum might represent a good structural marker for mild AD. Those areas were associated with cognitive functions already described in the literature.