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Background: In the last decade, many studies have reported abnormal connectivity within the default mode network (DMN) in patients with Alzheimer disease. Few studies, however, have investigated other networks and their association with pathophysiological proteins obtained from cerebrospinal fluid (CSF). Methods: We performed 3 T imaging in patients with mild Alzheimer disease, patients with amnestic mild cognitive impairment (aMCI) and healthy controls, and we collected CSF samples from the patients with aMCI and mild Alzheimer disease. We analyzed 57 regions from 8 networks. Additionally, we performed correlation tests to investigate possible associations between the networks’ functional connectivity and the protein levels obtained from the CSF of patients with aMCI and Alzheimer disease. Results: Our sample included 41 patients with Alzheimer disease, 35 with aMCI and 48 controls. We found that the main connectivity abnormalities in those with Alzheimer disease occurred between the DMN and task-positive networks: these patients presented not only a decreased anticorrelation between some regions, but also an inversion of the correlation signal (positive correlation instead of anti-correlation). Those with aMCI did not present statistically different connectivity from patients with Alzheimer disease or controls. Abnormal levels of CSF proteins were associated with functional disconnectivity between several regions in both the aMCI and mild Alzheimer disease groups, extending well beyond the DMN or temporal areas. Limitations: The presented data are cross-sectional in nature, and our findings are dependent on the choice of seed regions used. Conclusion: We found that the main functional connectivity abnormalities occur between the DMN and task-positive networks and that the pathological levels of CSF biomarkers correlate with functional connectivity disruption in patients with Alzheimer disease.

Highlights • Stroke disrupts ipsilesional and inter-hemispheric functional connectivity of DMN. • Subacute cognition correlated to inter-hemispheric and ipsilesional DMN connectivity. • Subacute cognition correlated to weaker contralesional SN connectivity. • Functional connectivity remapping was not observed after six months. • Cognitive recovery correlated to DMN and SN connectivity from the subacute phase., 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.

Advanced magnetic resonance imaging (MRI) techniques are improving our understanding of cerebrovascular diseases. Elucidation of the critical pathways in post-stroke recovery would not only provide important fundamental insight in brain function and plasticity but could also lead the way toward development of new rehabilitation strategies for recovering stroke patients. Improvements in hardware and pulse sequences that decrease scan time while maintaining resolution will continue to impact the field. Post-processing strategies must evolve to encompass these increasingly complicated data sets. It also seems clear that multimodal imaging strategies are necessary to develop more detailed patient profiles that can be used for precision medicine.

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.

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.

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.

Neuropsychological and psychiatric disorders represent a major concern and cause of disabilities after the trauma, contributing to worse recovery after traumatic brain injury (TBI). However, the lack of well-defined parameters to evaluate patient’s psychiatric disorders leads to a wide range of diagnoses and symptoms. The aim of this study was to perform a review of literature in order to gather data of the most common scales and inventories used to assess and diagnose depression, anxiety, and posttraumatic stress disorder (PTSD) after TBI. We conducted a literature search via MEDLINE, PubMed, and Web of Science. We included reviews, systematic reviews, and meta-analysis studies, and we used the following keywords: “traumatic brain injury OR TBI,” “depression OR depressive disorder,” “anxiety,” and “posttraumatic stress disorder OR PTSD.” From 610 titles, a total of 68 systematic reviews or meta-analysis were included in the section “Results” of this review: depression (n = 32), anxiety (n = 9), and PTSD (n = 27). Depression after TBI is a more established condition, with more homogeneous studies. Anxiety and PTSD disorders have been studied in a heterogeneous way, usually as comorbidity with other psychiatric disorders. Some scales and inventories designed for the general community may not be appropriate for patients with TBI.