Exploratory correlation of the human structural connectome with non-MRI variables in Alzheimer's disease.

Introduction: Discovery of the associations between brain structural connectivity and clinical and demographic variables can help to better understand the vulnerability and resilience of the brain architecture to neurodegenerative diseases and to discover biomarkers. Methods: We used four diffusion-MRI databases, three related to Alzheimer's disease (AD), to exploratorily correlate structural connections between 85 brain regions with non-MRI variables, while stringently correcting the significance values for multiple testing and ruling out spurious correlations via careful visual inspection. We repeated the analysis with brain connectivity augmented with multi-synaptic neural pathways. Results: We found 85 and 101 significant relationships with direct and augmented connectivity, respectively, which were generally stronger for the latter. Age was consistently linked to decreased connectivity, and healthier clinical scores were generally linked to increased connectivity. Discussion: Our findings help to elucidate which structural brain networks are affected in AD and aging and highlight the importance of including indirect connections.

Exploratory Correlation of The Human Structural Connectome with Non-MRI Variables in Alzheimer's Disease.

INTRODUCTION: Discovery of the associations between brain structural connectivity and clinical and demographic variables can help to better understand the vulnerability and resilience of the brain architecture to neurodegenerative diseases and to discover biomarkers. METHODS: We used four diffusion-MRI databases, three related to Alzheimer's disease, to exploratorily correlate structural connections between 85 brain regions with non-MRI variables, while stringently correcting the significance values for multiple testing and ruling out spurious correlations via careful visual inspection. We repeated the analysis with brain connectivity augmented with multi-synaptic neural pathways. RESULTS: We found 85 and 101 significant relationships with direct and augmented connectivity, respectively, which were generally stronger for the latter. Age was consistently linked to decreased connectivity, and healthier clinical scores were generally linked to increased connectivity. DISCUSSION: Our findings help to elucidate which structural brain networks are affected in Alzheimer's disease and aging and highlight the importance of including indirect connections.

Psychosocial and individual factors affecting Quality of Life (QoL) in patients suffering from Achilles tendinopathy: a systematic review.

BACKGROUND: Achilles tendinopathy (AT) is a joint condition that causes functional restrictions and pain. This condition negatively impacts patients' social connectedness and psychological well-being, reducing their quality of life (QoL). This review aims to summarise the current information on QoL in patients suffering from AT from different angles: compared to a healthy population, reported individual factors that influence it and the effects of some AT interventions on QoL. METHODS: A systematic review was conducted at PubMed, Cochrane, Google Scholar, and PsycINFO using tendinopathy and QoL-related keywords up to November 2021. Articles were included if they compared QoL to demographic factors such as age or gender, lifestyle factors (physical activity levels), comorbidity factors (diabetes, obesity), and/or a control group. RESULTS: Three hundred twenty-nine articles were reviewed; 23 met the inclusion criteria. SF-36, EQ-5D, and VISA-A were the most common instrument used. Patients with AT reported low QoL when compared to no AT population. When women were compared to men, women reported worse QoL. The patients who participated in different exercise programs (strengthening and stretching) showed improvements in QoL. Surgical AT intervention improved QoL, although results varied by age. CONCLUSION: AT has a substantial impact on QoL. In AT patients, QoL is also influenced by specific individual factors, including gender and physical activity. Exercise, education, and surgical treatment improve QoL. We suggest more research on AT patients to better understand the aspects leading to poor QoL.

Risk of ischaemic stroke among new users of glucosamine and chondroitin sulphate: a nested case-control study.

Background: Several studies have reported that the use of chondroitin sulphate (CS) and glucosamine may reduce the risk of acute myocardial infarction. Although it is thought that this potential benefit could be extended to ischaemic stroke (IS), the evidence is scarce. Objective: To test the hypothesis that the use of prescription glucosamine or CS reduces the risk of IS. Design: Case-control study nested in an open cohort. Methods: Patients aged 40-99 years registered in a Spanish primary healthcare database (BIFAP) during the 2002-2015 study period. From this cohort, we identified incident cases of IS, applying a case-finding algorithm and specific validation procedures, and randomly sampled five controls per case, individually matched with cases by exact age, gender and index date. Adjusted odds ratios (AORs) and 95% confidence interval (CI) were computed through a conditional logistic regression. Only new users of glucosamine or CS were considered. Results: A total of 13,952 incident cases of IS and 69,199 controls were included. Of them, 106 cases (0.76%) and 803 controls (1.16%) were current users of glucosamine or CS at index date, yielding an AOR of 0.66 (95% CI: 0.54-0.82) (for glucosamine, AOR: 0.55; 95% CI: 0.39-0.77; and for CS, AOR: 0.77; 95% CI: 0.60-0.99). The reduced risk among current users was observed in both sexes (men, AOR: 0.69; 95% CI: 0.49-0.98; women, AOR: 0.65; 95% CI: 0.50-0.85), in individuals above and below 70 years of age (AOR: 0.69; 95% CI: 0.53-0.89 and AOR: 0.59; 95% CI: 0.41-0.85, respectively), in individuals with vascular risk factors (AOR: 0.53; 95% CI: 0.39-0.74) and among current/recent users of nonsteroidal anti-inflammatory drugs (NSAIDs) (AOR: 0.71; 95% CI: 0.55-0.92). Regarding duration, the reduced risk was observed in short-term users (<365 days, AOR: 0.61; 95% CI: 0.48-0.78) while faded and became nonsignificant in long-term users (>364 days AOR: 0.86; 95% CI: 0.57-1.31). Conclusions: Our results support a protective effect of prescription CS and glucosamine in IS, which was observed even in patients at vascular risk. Mini abstract: Our aim was to analyse whether the use of glucosamine or chondroitin sulphate (CS) reduces the risk of ischaemic stroke (IS). We detected a significant decrease.

Conductance-Based Structural Brain Connectivity in Aging and Dementia.

Background: Structural brain connectivity has been shown to be sensitive to the changes that the brain undergoes during Alzheimer's disease (AD) progression. Methods: In this work, we used our recently proposed structural connectivity quantification measure derived from diffusion magnetic resonance imaging, which accounts for both direct and indirect pathways, to quantify brain connectivity in dementia. We analyzed data from the second phase of Alzheimer's Disease Neuroimaging Initiative and third release in the Open Access Series of Imaging Studies data sets to derive relevant information for the study of the changes that the brain undergoes in AD. We also compared these data sets to the Human Connectome Project data set, as a reference, and eventually validated externally on two cohorts of the European DTI Study in Dementia database. Results: Our analysis shows expected trends of mean conductance with respect to age and cognitive scores, significant age prediction values in aging data, and regional effects centered among subcortical regions, and cingulate and temporal cortices. Discussion: Results indicate that the conductance measure has prediction potential, especially for age, that age and cognitive scores largely overlap, and that this measure could be used to study effects such as anticorrelation in structural connections. Impact statement This work presents a methodology and a set of analyses that open new possibilities in the study of healthy and pathological aging. The methodology used here is sensitive to direct and indirect pathways in deriving brain connectivity measures from diffusion-weighted magnetic resonance imaging, and therefore provides information that many state-of-the-art methods do not account for. As a result, this technique may provide the research community with ways to detect subtle effects of healthy aging and Alzheimer's disease.

Lacunes, Microinfarcts, and Vascular Dysfunction in Cerebral Amyloid Angiopathy.

OBJECTIVE: To analyze the relationship of lacunes with cortical cerebral microinfarcts (CMIs), to assess their association with vascular dysfunction, and to evaluate their effect on the risk of incident intracerebral hemorrhage (ICH) in cerebral amyloid angiopathy (CAA). METHODS: The count and topography of lacunes (deep/lobar), CMIs, and white matter hyperintensity (WMH) volume were retrospectively analyzed in a prospectively enrolled CAA cohort that underwent high-resolution research MRIs. The relationship of lacunes with CMIs and other CAA-related markers including time to peak (TTP) of blood oxygen level-dependent signal, an established measure of vascular dysfunction, was evaluated in multivariate models. Adjusted Cox regression models were used to investigate the relationship between lacunes and incident ICH. RESULTS: The cohort consisted of 122 patients with probable CAA without dementia (mean age, 69.4 ± 7.6 years). Lacunes were present in 31 patients (25.4%); all but one were located in lobar regions. Cortical CMIs were more common in patients with lacunes compared to patients without lacunes (51.6% vs 20.9%, p = 0.002). TTP was not associated with either lacunes or CMIs (both p > 0.2) but longer TTP response independently correlated with higher WMH volume (p = 0.001). Lacunes were associated with increased ICH risk in univariate and multivariate Cox regression models (p = 0.048 and p = 0.026, respectively). CONCLUSIONS: Our findings show a high prevalence of lobar lacunes, frequently coexisting with CMIs in CAA, suggesting that these 2 lesion types may be part of a common spectrum of CAA-related infarcts. Lacunes were not related to vascular dysfunction but predicted incident ICH, favoring severe focal vessel involvement rather than global ischemia as their mechanism.

Optimizing the accuracy of cortical volumetric analysis in traumatic brain injury.

Cortical volumetric analysis is widely used to study the anatomic basis of neurological deficits in patients with traumatic brain injury (TBI). However, patients with TBI-related lesions are often excluded from MRI analyses because cortical lesions may compromise the accuracy of reconstructed surfaces upon which volumetric measurements are based. We developed a FreeSurfer-based lesion correction method and tested its impact on cortical volume measures in 87 patients with chronic moderate-to-severe TBI. We reconstructed cortical surfaces from T1-weighted MRI scans, then manually labeled and removed vertices on the cortical surfaces where lesions caused inaccuracies. Next, we measured the surface area of lesion overlap with seven canonical brain networks and the percent volume of each network affected by lesions.•The lesion correction method revealed that cortical lesions in patients with TBI are preferentially located in the limbic and default mode networks (95.7% each), with the limbic network also having the largest average surface area (4.4+/-3.7%) and percent volume affected by lesions (12.7+/-9.7%).•The method has the potential to improve the accuracy of cortical volumetric measurements and permit inclusion of patients with lesioned brains in MRI analyses.•The method also provides new opportunities to elucidate network-based mechanisms of neurological deficits in patients with TBI.

COMPENSATORY BRAIN CONNECTION DISCOVERY IN ALZHEIMER'S DISEASE.

Identification of the specific brain networks that are vulnerable or resilient in neurodegenerative diseases can help to better understand the disease effects and derive new connectomic imaging biomarkers. In this work, we use brain connectivity to find pairs of structural connections that are negatively correlated with each other across Alzheimer's disease (AD) and healthy populations. Such anti-correlated brain connections can be informative for identification of compensatory neuronal pathways and the mechanism of brain networks' resilience to AD. We find significantly anti-correlated connections in a public diffusion-MRI database, and then validate the results on other databases.

Ascending arousal network connectivity during recovery from traumatic coma.

BACKGROUND: It is not currently possible to predict which patients will develop chronic disorders of consciousness (DoC) after severe traumatic brain injury (TBI). Although the ascending arousal network (AAN) supports human consciousness, it is unknown which AAN pathways must be preserved for patients to recover consciousness. METHODS: Sixteen patients with acute traumatic coma and 16 matched healthy controls were scanned with high angular resolution diffusion imaging (HARDI). All patients recovered consciousness (Recovery Cohort). Nine were scanned longitudinally: first in the ICU (Acute), then at ≥5 months post-injury (Follow-up). Six separate patients with post-traumatic DoC were scanned ≥5 months post-injury (Chronic DoC Cohort). For each AAN pathway, we computed the median relative change in Acute-to-Follow-up Connectivity Probability (CP) in the Recovery Cohort. We then used Wilcoxon tests with Bonferroni correction to compare CP in each AAN pathway in the Recovery Cohort at Follow-up versus the Chronic DoC Cohort. In an exploratory analysis, we used principal component analysis (PCA) to determine whether linear combinations of AAN CP values could separate the Chronic DoC Cohort from the Recovery Cohort and the healthy controls. RESULTS: In the Recovery Cohort, the largest relative AAN CP changes were in the brainstem-to-thalamus (median [IQR] = 0.7 [0.09, 0.9]) and forebrain-to-occipital lobe (-0.8 [-0.9, -0.8]) pathways. The AAN connections that differed in the cross-sectional analysis between the Recovery Cohort at Follow-up and the Chronic DoC Cohort included brainstem-to-hypothalamus (W = 53, PBonf = 0.02), brainstem-to-temporal lobe (W = 52, PBonf = 0.04), and thalamus-to-temporal lobe (W = 54, PBonf = 0.009). Plotting the first two principal components of AAN connectivity resulted in a linear separation of Chronic DoC patients from other study groups. CONCLUSIONS: We provide evidence for a longitudinal increase in brainstem-thalamic connectivity during recovery of consciousness after traumatic coma. Cross-sectional analyses revealed that brainstem-hypothalamus, brainstem-temporal lobe, and thalamus-temporal lobe connectivity differed between patients who recovered consciousness and those with a chronic DoC. These observations provide the basis for further investigation into AAN connectivity as a biomarker for recovery of consciousness after traumatic coma.

Quantification of structural brain connectivity via a conductance model.

Connectomics has proved promising in quantifying and understanding the effects of development, aging and an array of diseases on the brain. In this work, we propose a new structural connectivity measure from diffusion MRI that allows us to incorporate direct brain connections, as well as indirect ones that would not be otherwise accounted for by standard techniques and that may be key for the better understanding of function from structure. From our experiments on the Human Connectome Project dataset, we find that our measure of structural connectivity better correlates with functional connectivity than streamline tractography does, meaning that it provides new structural information related to function. Through additional experiments on the ADNI-2 dataset, we demonstrate the ability of this new measure to better discriminate different stages of Alzheimer's disease. Our findings suggest that this measure is useful in the study of the normal brain structure, and for quantifying the effects of disease on the brain structure.